WorldWideScience

Sample records for lung interstitial macrophages

  1. Enhancement of CD147 on M1 macrophages induces differentiation of Th17 cells in the lung interstitial fibrosis.

    Science.gov (United States)

    Geng, Jie-jie; Zhang, Kui; Chen, Li-na; Miao, Jin-lin; Yao, Meng; Ren, Ying; Fu, Zhi-guang; Chen, Zhi-nan; Zhu, Ping

    2014-09-01

    Lung interstitial fibrosis is a chronic lung disease, and few effective therapies are available to halt or reverse the progression of the disease. In murine and human lung fibrosis, the expression of CD147 is increased. However, the role of CD147 in lung fibrosis has not been identified, and it remains to be determined whether lung fibrosis would be improved by decreasing the expression of CD147. A murine bleomycin-induced lung interstitial fibrosis model was used in the experiments, and HAb18 mAbs and CsA were administered during the induction of lung fibrosis. In our study, we found that the HAb18 mAbs markedly reduced the collagen score and down-regulated M1 macrophages and Th17 cells. In vitro, flow cytometry analysis showed that M1 macrophages induced higher Th17 differentiation than M2 macrophages. After treatment with HAb18 mAbs or after reducing the expression of CD147 by lentivirus interference in M1 macrophages, the level of Th17 cells were significantly inhibited. In conclusion, HAb18 mAbs or CsA treatment ameliorates lung interstitial fibrosis. CD147 promoted M1 macrophage and induced the differentiation of Th17 cells in lung interstitial fibrosis, perhaps by regulating some cytokines such as IL-6, IL-1β, IL-12 and IL-23. These results indicated that CD147 may play an important role in the development of lung interstitial fibrosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Imaging of macrophage-related lung diseases

    International Nuclear Information System (INIS)

    Marten, Katharina; Hansell, David M.

    2005-01-01

    Macrophage-related pulmonary diseases are a heterogeneous group of disorders characterized by macrophage accumulation, activation or dysfunction. These conditions include smoking-related interstitial lung diseases, metabolic disorders such as Niemann-Pick or Gaucher disease, and rare primary lung tumors. High-resolution computed tomography abnormalities include pulmonary ground-glass opacification secondary to infiltration by macrophages, centrilobular nodules or interlobular septal thickening reflecting peribronchiolar or septal macrophage accumulation, respectively, emphysema caused by macrophage dysfunction, and honeycombing following macrophage-related lung matrix remodeling. (orig.)

  3. Smoking-related interstitial lung diseases: radiologic-pathologic correlation

    International Nuclear Information System (INIS)

    Hidalgo, Alberto; Franquet, Tomas; Gimenez, Ana; Pineda, Rosa; Madrid, Marta; Bordes, Ramon

    2006-01-01

    Smoking-related interstitial lung diseases (SRILD) are a heterogeneous group of entities of unknown cause. These diseases include desquamative interstitial pneumonia (DIP), respiratory-bronchiolitis-related interstitial lung disease (RB-ILD), pulmonary Langerhans' cell histiocytosis (LCH) and idiopathic pulmonary fibrosis (IPF). High-resolution CT is highly sensitive in the detection of abnormalities in the lung parenchyma and airways. Ground-glass attenuation can occur in DIP and RB-ILD. Whereas DIP is histologically characterized by intra-alveolar pigmented macrophages, RB-ILD shows alveolar macrophages in a patchy peribronchiolar distribution. LCH shows nodular infiltrates on histopathological examination containing varying amounts of characteristic Langerhans' histiocytes. The HRCT findings are characteristically bilateral, symmetrical and diffuse, involving the upper lobe zones with sparing of the costophrenic angles. The most prominent CT features are nodules (sometimes cavitary) measuring 1 to 10 mm in diameter, cysts and areas of ground-glass attenuation. Pathologically, IPF is characterized by its heterogeneity with areas of normal clung, alveolitis and end-stage fibrosis shown in the same biopsy specimen. High-resolution CT findings consist of honeycombing, traction bronchiectasis and intralobular interstitial thickening with subpleural and lower lung predominance. Since coexisting lesions in the same cases have been observed, a better understanding of the different smoking-related interstitial lung diseases (SRILD) allows a more confident and specific diagnosis. (orig.)

  4. Smoking-related interstitial lung diseases: radiologic-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Hidalgo, Alberto [Universidad Autonoma de Barcelona, Department of Radiology, Hospital de Sant Pau, Barcelona (Spain); Hospital de la Santa Creu i Sant Pau, Thoracic Radiology, Department of Radiology, Barcelona (Spain); Franquet, Tomas; Gimenez, Ana; Pineda, Rosa; Madrid, Marta [Universidad Autonoma de Barcelona, Department of Radiology, Hospital de Sant Pau, Barcelona (Spain); Bordes, Ramon [Universidad Autonoma de Barcelona, Department of Pathology, Hospital de Sant Pau, Barcelona (Spain)

    2006-11-15

    Smoking-related interstitial lung diseases (SRILD) are a heterogeneous group of entities of unknown cause. These diseases include desquamative interstitial pneumonia (DIP), respiratory-bronchiolitis-related interstitial lung disease (RB-ILD), pulmonary Langerhans' cell histiocytosis (LCH) and idiopathic pulmonary fibrosis (IPF). High-resolution CT is highly sensitive in the detection of abnormalities in the lung parenchyma and airways. Ground-glass attenuation can occur in DIP and RB-ILD. Whereas DIP is histologically characterized by intra-alveolar pigmented macrophages, RB-ILD shows alveolar macrophages in a patchy peribronchiolar distribution. LCH shows nodular infiltrates on histopathological examination containing varying amounts of characteristic Langerhans' histiocytes. The HRCT findings are characteristically bilateral, symmetrical and diffuse, involving the upper lobe zones with sparing of the costophrenic angles. The most prominent CT features are nodules (sometimes cavitary) measuring 1 to 10 mm in diameter, cysts and areas of ground-glass attenuation. Pathologically, IPF is characterized by its heterogeneity with areas of normal clung, alveolitis and end-stage fibrosis shown in the same biopsy specimen. High-resolution CT findings consist of honeycombing, traction bronchiectasis and intralobular interstitial thickening with subpleural and lower lung predominance. Since coexisting lesions in the same cases have been observed, a better understanding of the different smoking-related interstitial lung diseases (SRILD) allows a more confident and specific diagnosis. (orig.)

  5. Dysregulated Functions of Lung Macrophage Populations in COPD.

    Science.gov (United States)

    Kapellos, Theodore S; Bassler, Kevin; Aschenbrenner, Anna C; Fujii, Wataru; Schultze, Joachim L

    2018-01-01

    Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema. Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses. To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire. In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations. We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD. In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD.

  6. Dysregulated Functions of Lung Macrophage Populations in COPD

    Science.gov (United States)

    Bassler, Kevin; Aschenbrenner, Anna C.

    2018-01-01

    Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema. Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses. To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire. In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations. We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD. In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD. PMID:29670919

  7. Evidence for chronic inflammation as a component of the interstitial lung disease associated with progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Rossi, G.A.; Bitterman, P.B.; Rennard, S.I.; Ferrans, V.J.; Crystal, R.G.

    1985-01-01

    Progressive systemic sclerosis (PSS) is a generalized disorder characterized by fibrosis of many organs including the lung parenchyma. Unlike most other interstitial disorders, traditional concepts of the interstitial lung disease associated with PSS have held it to be a ''pure'' fibrotic disorder without a significant inflammatory component. To directly evaluate whether an active alveolitis is associated with this disorder, patients with chronic interstitial lung disease and PSS were studied by open lung biopsy, gallium-67 scanning, and bronchoalveolar lavage. Histologic evaluation of the biopsies demonstrated that the interstitial fibrosis of PSS is clearly associated with the presence of macrophages, lymphocytes, and polymorphonuclear leukocytes, both in the interstitium and on the alveolar epithelial surface. Gallium-67 scans were positive in 77% of the patients, showing diffuse, primarily lower zone uptake, suggestive of active inflammation. Consistent with the histologic findings, bronchoalveolar lavage studies demonstrated a mild increase in the proportions of neutrophils and eosinophils with occasional increased numbers of lymphocytes. Importantly, alveolar macrophages from patients with PSS showed increased release of fibronectin and alveolar-macrophage-derived growth factor, mediators that together stimulate lung fibroblasts to proliferate, thus suggesting at least one mechanism modulating the lung fibrosis of these patients

  8. CSF1R inhibition prevents radiation pulmonary fibrosis by depletion of interstitial macrophages.

    Science.gov (United States)

    Meziani, Lydia; Mondini, Michele; Petit, Benoît; Boissonnas, Alexandre; Thomas de Montpreville, Vincent; Mercier, Olaf; Vozenin, Marie-Catherine; Deutsch, Eric

    2018-03-01

    Radiation-induced lung fibrosis (RIF) is a delayed side-effect of chest radiotherapy, frequently associated with macrophage infiltration.We aimed to characterise the role of pulmonary macrophages in RIF using human lung biopsies from patients receiving radiotherapy for thorax malignancies and a RIF model developed in C57BL/6 mice after 16-Gy thorax irradiation.High numbers of macrophages (both interstitial and alveolar) were detected in clinical and preclinical RIF. In the preclinical model, upregulation of T-helper (Th)2 cytokines was measured, whereas Th1 cytokines were downregulated in RIF tissue lysate. Bronchoalveolar lavage demonstrated upregulation of both types of cytokines. At steady state, tissue-infiltrating macrophages (IMs) expressed 10-fold more arginase (Arg)-1 than alveolar macrophages (AMs), and a 40-fold upregulation of Arg-1 was found in IMs isolated from RIF. IMs, but not AMs, were able to induce myofibroblast activation in vitro In addition, whereas depletion of AMs using Clodrosome didn't affect RIF score, depletion of IMs using a clinically available colony-stimulating factor receptor-1 (CSF1R) neutralising antibody was antifibrotic.These findings suggest differential contributions of alveolar versus interstitial macrophages in RIF, highlighting the fibrogenic role of IMs. The CSF1/CSF1R pathway was identified as a new therapeutic target to inhibit RIF. Copyright ©ERS 2018.

  9. A Time- and Compartment-Specific Activation of Lung Macrophages in Hypoxic Pulmonary Hypertension.

    Science.gov (United States)

    Pugliese, Steven C; Kumar, Sushil; Janssen, William J; Graham, Brian B; Frid, Maria G; Riddle, Suzette R; El Kasmi, Karim C; Stenmark, Kurt R

    2017-06-15

    Studies in various animal models suggest an important role for pulmonary macrophages in the pathogenesis of pulmonary hypertension (PH). Yet, the molecular mechanisms characterizing the functional macrophage phenotype relative to time and pulmonary localization and compartmentalization remain largely unknown. In this study, we used a hypoxic murine model of PH in combination with FACS to quantify and isolate lung macrophages from two compartments over time and characterize their programing via RNA sequencing approaches. In response to hypoxia, we found an early increase in macrophage number that was restricted to the interstitial/perivascular compartment, without recruitment of macrophages to the alveolar compartment or changes in the number of resident alveolar macrophages. Principal component analysis demonstrated significant differences in overall gene expression between alveolar and interstitial macrophages (IMs) at baseline and after 4 and 14 d hypoxic exposure. Alveolar macrophages at both day 4 and 14 and IMs at day 4 shared a conserved hypoxia program characterized by mitochondrial dysfunction, proinflammatory gene activation, and mTORC1 signaling, whereas IMs at day 14 demonstrated a unique anti-inflammatory/proreparative programming state. We conclude that the pathogenesis of vascular remodeling in hypoxic PH involves an early compartment-independent activation of lung macrophages toward a conserved hypoxia program, with the development of compartment-specific programs later in the course of the disease. Thus, harnessing time- and compartment-specific differences in lung macrophage polarization needs to be considered in the therapeutic targeting of macrophages in hypoxic PH and potentially other inflammatory lung diseases. Copyright © 2017 by The American Association of Immunologists, Inc.

  10. Lung volumes and emphysema in smokers with interstitial lung abnormalities.

    Science.gov (United States)

    Washko, George R; Hunninghake, Gary M; Fernandez, Isis E; Nishino, Mizuki; Okajima, Yuka; Yamashiro, Tsuneo; Ross, James C; Estépar, Raúl San José; Lynch, David A; Brehm, John M; Andriole, Katherine P; Diaz, Alejandro A; Khorasani, Ramin; D'Aco, Katherine; Sciurba, Frank C; Silverman, Edwin K; Hatabu, Hiroto; Rosas, Ivan O

    2011-03-10

    Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema. Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; Ppulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation; ClinicalTrials.gov number, NCT00608764.).

  11. Smoking-related interstitial lung diseases

    International Nuclear Information System (INIS)

    Marten, K.

    2007-01-01

    The most important smoking-related interstitial lung diseases (ILD) are respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and Langerhans' cell histiocytosis. Although traditionally considered to be discrete entities, smoking-related ILDs often coexist, thus accounting for the sometimes complex patterns encountered on high-resolution computed tomography (HRCT). Further studies are needed to elucidate the causative role of smoking in the development of pulmonary fibrosis

  12. The diffuse interstitial lung disease - with emphasis in the idiopathic interstitial pneumonias

    International Nuclear Information System (INIS)

    Bustillo P, Jose G; Pacheco, Pedro M; Matiz, Carlos; Ojeda, Paulina; Carrillo B, Jorge A.

    2003-01-01

    The term diffuse interstitial lung disease, it refers to those diseases that commit the interstice basically, the space between the membrane basal epithelial and endothelial, although the damage can also commit the outlying air spaces and the vessels; the supplement is centered in the diffuse interstitial lung illness of unknown cause; well-known as idiopathic interstitial pneumonias, making emphasis in the more frequents, the pulmonary fibrosis idiopathic or cryptogenic fibrosant alveolitis

  13. [Modern Views on Children's Interstitial Lung Disease].

    Science.gov (United States)

    Boĭtsova, E V; Beliashova, M A; Ovsiannikov, D Iu

    2015-01-01

    Interstitial lung diseases (ILD, diffuse lung diseases) are a heterogeneous group of diseases in which a pathological process primarily involved alveoli and perialveolar interstitium, resulting in impaired gas exchange, restrictive changes of lung ventilation function and diffuse interstitial changes detectable by X-ray. Children's interstitial lung diseases is an topical problem ofpediatricpulmonoogy. The article presents current information about classification, epidemiology, clinical presentation, diagnostics, treatment and prognosis of these rare diseases. The article describes the differences in the structure, pathogenesis, detection of various histological changes in children's ILD compared with adult patients with ILD. Authors cite an instance of registers pediatric patients with ILD. The clinical semiotics of ILD, the possible results of objective research, the frequency of symptoms, the features of medical history, the changes detected on chest X-rays, CT semiotics described in detail. Particular attention was paid to interstitial lung diseases, occurring mainly in newborns and children during the first two years of life, such as congenital deficiencies of surfactant proteins, neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis. The diagnostic program for children's ILD, therapy options are presented in this article.

  14. Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation

    DEFF Research Database (Denmark)

    Kohno, M; Perch, M; Andersen, E

    2011-01-01

    A 44-year-old woman underwent left single-lung transplantation for end-stage emphysema due to α1-antitrypsin deficiency in January 2010. Cyclosporine, azathioprine, and prednisolone were administered for immunosuppression and antithymocyte globulin for induction therapy at the time...... of transplantation. Routine examination of a lung biopsy, 4 months after transplantation, showed nonspecific, diffuse interstitial inflammation with alveolar septal fibrosis. The patient's clinical status and imaging studies, consistent with nonspecific interstitial pneumonitis, which was considered as signs......, posttransplant antirejection drug regimen. We have since successfully treated with alemtuzumab three additional patients who developed interstitial lung injury after lung transplantation, who are also summarized in this report....

  15. Flock worker's lung: chronic interstitial lung disease in the nylon flocking industry.

    Science.gov (United States)

    Kern, D G; Crausman, R S; Durand, K T; Nayer, A; Kuhn, C

    1998-08-15

    Two young men working at a nylon flocking plant in Rhode Island developed interstitial lung disease of unknown cause. Similar clusters at the same company's Canadian plant were reported previously. To define the extent, clinicopathologic features, and potential causes of the apparent disease outbreak. Case-finding survey and retrospective cohort study. Academic occupational medicine program. All workers employed at the Rhode Island plant on or after 15 June 1990. Symptomatic employees had chest radiography, pulmonary function tests, high-resolution computed tomography, and serologic testing. Those with unexplained radiographic or pulmonary function abnormalities underwent bronchoalveolar lavage, lung biopsy, or both. The case definition of "flock worker's lung" required histologic evidence of interstitial lung disease (or lavage evidence of lung inflammation) not explained by another condition. Eight cases of flock worker's lung were identified at the Rhode Island plant. Three cases were characterized by a high proportion of eosinophils (25% to 40%) in lavage fluid. Six of the seven patients who had biopsy had histologic findings of nonspecific interstitial pneumonia, and the seventh had bronchiolitis obliterans organizing pneumonia. All seven of these patients had peribronchovascular interstitial lymphoid nodules, usually with germinal centers, and most had lymphocytic bronchiolitis and interstitial fibrosis. All improved after leaving work. Review of the Canadian tissue specimens showed many similar histologic findings. Among the 165-member study cohort, a 48-fold or greater increase was seen in the sex-adjusted incidence rate of all interstitial lung disease. Work in the nylon flocking industry poses substantial risk for a previously unrecognized occupational interstitial lung disease. Nylon fiber is the suspected cause of this condition.

  16. Peripheral-type benzodiazepine receptors in bronchoalveolar lavage cells of patients with interstitial lung disease

    International Nuclear Information System (INIS)

    Branley, Howard M.; Bois, Roland M. du; Wells, Athol U.; Jones, Hazel A.

    2007-01-01

    Introduction: PK11195 is a ligand with high affinity for peripheral benzodiazepine receptors (PBRs), which are present in large numbers in macrophages. PBRs play a role in antioxidant pathways and apoptosis, key factors in control of lung health. Intrapulmonary PBRs, assessed in vivo by positron emission tomography (PET), are decreased in interstitial lung disease (ILD) despite increased macrophage numbers. We wished to ascertain whether the observed decrease in in vivo expression of PBRs in the PET scans could be accounted for by a reduction in PBRs per cell by saturation-binding assays of R-PK11195 in cells obtained by bronchoalveolar lavage (BAL). Methods: We performed receptor saturation-binding assays with [ 3 H]-R-PK11195 on a mixed population of cells recovered by BAL to quantify the number of R-PK11195 binding sites per macrophage in 10 subjects with ILD and 10 normal subjects. Results: Receptor affinity [dissociation constant (Kd)] was similar in ILD patients and controls. However, R-PK11195 binding sites per cell [(maximal binding sites available (B max )] were decreased in macrophages obtained by BAL from subjects with ILD compared to normal (P<.0005). Microautoradiography confirmed localization of R-PK11195 to macrophages in a mixed inflammatory cell population obtained by BAL. Conclusion: These results demonstrate that in vitro PBR expression per cell on macrophages obtained by BAL is reduced in patients with ILD indicating a potentially functionally different macrophage phenotype. As PBRs are involved in the orchestration of lung inflammatory responses, this finding offers further insight into the role of macrophages in the pathogenesis of ILDs and offers a potential avenue for pharmacological strategy

  17. Activated prostaglandin D2 receptors on macrophages enhance neutrophil recruitment into the lung

    Science.gov (United States)

    Jandl, Katharina; Stacher, Elvira; Bálint, Zoltán; Sturm, Eva Maria; Maric, Jovana; Peinhaupt, Miriam; Luschnig, Petra; Aringer, Ida; Fauland, Alexander; Konya, Viktoria; Dahlen, Sven-Erik; Wheelock, Craig E.; Kratky, Dagmar; Olschewski, Andrea; Marsche, Gunther; Schuligoi, Rufina; Heinemann, Akos

    2016-01-01

    Background Prostaglandin (PG) D2 is an early-phase mediator in inflammation, but its action and the roles of the 2 D-type prostanoid receptors (DPs) DP1 and DP2 (also called chemoattractant receptor–homologous molecule expressed on TH2 cells) in regulating macrophages have not been elucidated to date. Objective We investigated the role of PGD2 receptors on primary human macrophages, as well as primary murine lung macrophages, and their ability to influence neutrophil action in vitro and in vivo. Methods In vitro studies, including migration, Ca2+ flux, and cytokine secretion, were conducted with primary human monocyte-derived macrophages and neutrophils and freshly isolated murine alveolar and pulmonary interstitial macrophages. In vivo pulmonary inflammation was assessed in male BALB/c mice. Results Activation of DP1, DP2, or both receptors on human macrophages induced strong intracellular Ca2+ flux, cytokine release, and migration of macrophages. In a murine model of LPS-induced pulmonary inflammation, activation of each PGD2 receptor resulted in aggravated airway neutrophilia, tissue myeloperoxidase activity, cytokine contents, and decreased lung compliance. Selective depletion of alveolar macrophages abolished the PGD2-enhanced inflammatory response. Activation of PGD2 receptors on human macrophages enhanced the migratory capacity and prolonged the survival of neutrophils in vitro. In human lung tissue specimens both DP1 and DP2 receptors were located on alveolar macrophages along with hematopoietic PGD synthase, the rate-limiting enzyme of PGD2 synthesis. Conclusion For the first time, our results show that PGD2 markedly augments disease activity through its ability to enhance the proinflammatory actions of macrophages and subsequent neutrophil activation. PMID:26792210

  18. Differential cell reaction upon Toll-like receptor 4 and 9 activation in human alveolar and lung interstitial macrophages

    Directory of Open Access Journals (Sweden)

    Meyerhans Andreas

    2010-09-01

    Full Text Available Abstract Background Investigations on pulmonary macrophages (MΦ mostly focus on alveolar MΦ (AM as a well-defined cell population. Characteristics of MΦ in the interstitium, referred to as lung interstitial MΦ (IM, are rather ill-defined. In this study we therefore aimed to elucidate differences between AM and IM obtained from human lung tissue. Methods Human AM and IM were isolated from human non-tumor lung tissue from patients undergoing lung resection. Cell morphology was visualized using either light, electron or confocal microscopy. Phagocytic activity was analyzed by flow cytometry as well as confocal microscopy. Surface marker expression was measured by flow cytometry. Toll-like receptor (TLR expression patterns as well as cytokine expression upon TLR4 or TLR9 stimulation were assessed by real time RT-PCR and cytokine protein production was measured using a fluorescent bead-based immunoassay. Results IM were found to be smaller and morphologically more heterogeneous than AM, whereas phagocytic activity was similar in both cell types. HLA-DR expression was markedly higher in IM compared to AM. Although analysis of TLR expression profiles revealed no differences between the two cell populations, AM and IM clearly varied in cell reaction upon activation. Both MΦ populations were markedly activated by LPS as well as DNA isolated from attenuated mycobacterial strains (M. bovis H37Ra and BCG. Whereas AM expressed higher amounts of inflammatory cytokines upon activation, IM were more efficient in producing immunoregulatory cytokines, such as IL10, IL1ra, and IL6. Conclusion AM appear to be more effective as a non-specific first line of defence against inhaled pathogens, whereas IM show a more pronounced regulatory function. These dissimilarities should be taken into consideration in future studies on the role of human lung MΦ in the inflammatory response.

  19. Chronic interstitial lung disease in children

    Directory of Open Access Journals (Sweden)

    Matthias Griese

    2018-02-01

    Full Text Available Children's interstitial lung diseases (chILD are increasingly recognised and contain many lung developmental and genetic disorders not yet identified in adult pneumology. Worldwide, several registers have been established. The Australasian Registry Network for Orphan Lung Disease (ARNOLD has identified problems in estimating rare disease prevalence; focusing on chILD in immunocompetent patients, a period prevalence of 1.5 cases per million children and a mortality rate of 7% were determined. The chILD-EU register highlighted the workload to be covered per patient included and provided protocols for diagnosis and initial treatment, similar to the United States chILD network. Whereas case reports may be useful for young physicians to practise writing articles, cohorts of patients can catapult progress, as demonstrated by recent studies on persistent tachypnoea of infancy, hypersensitivity pneumonitis in children and interstitial lung disease related to interferonopathies from mutations in transmembrane protein 173. Translational research has linked heterozygous mutations in the ABCA3 transporter to an increased risk of interstitial lung diseases, not only in neonates, but also in older children and adults. For surfactant dysfunction disorders in infancy and early childhood, lung transplantation was reported to be as successful as in adult patients. Mutual potentiation of paediatric and adult pneumologists is mandatory in this rapidly extending field for successful future development. This brief review highlights publications in the field of paediatric interstitial lung disease as reviewed during the Clinical Year in Review session presented at the 2017 European Respiratory Society (ERS Annual Congress in Milan, Italy. It was commissioned by the ERS and critically presents progress made as well as drawbacks.

  20. Smoking-related interstitial lung diseases: histopathological and imaging perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Desai, S.R.; Ryan, S.M.; Colby, T.V

    2003-04-01

    The present review focuses on the interstitial lung diseases related to smoking. Thus, the pathology and radiology of Langerhans cell histiocytosis, desquamative interstitial pneumonia, respiratory bronchiolitis and respiratory bronchiolitis-associated-interstitial lung disease are considered. The more tenuous association between pulmonary fibrosis and smoking is also discussed.

  1. Smoking-related interstitial lung diseases: histopathological and imaging perspectives

    International Nuclear Information System (INIS)

    Desai, S.R.; Ryan, S.M.; Colby, T.V.

    2003-01-01

    The present review focuses on the interstitial lung diseases related to smoking. Thus, the pathology and radiology of Langerhans cell histiocytosis, desquamative interstitial pneumonia, respiratory bronchiolitis and respiratory bronchiolitis-associated-interstitial lung disease are considered. The more tenuous association between pulmonary fibrosis and smoking is also discussed

  2. 67Gallium citrate lung scans in interstitial lung disease

    International Nuclear Information System (INIS)

    Niden, A.H.; Mishkin, F.S.; Khurana, M.M.L.

    1976-01-01

    Patients with diffuse interstitial lung disease often require a lung biopsy to determine the diagnosis and proper therapy. However, once the diagnosis is established, clinical evaluation of symptoms, chest roentgenogram and pulmonary function testing are the only noninvasive means currently available to assess activity of the disease process and response to the therapy. Although these measures appear adequate in the presence of acute active disease in which response to therapy results in readily demonstrable changes in the above parameters, they may be insensitive to subtle changes that can occur in minimally active disease with slowly progressive interstitial pulmonary fibrosis over a period of years. A more sensitive noninvasive technique for identifying these cases with a smoldering diffuse interstitial inflammatory process might greatly improve our ability to effectively manage such patients. With this in mind, the value of gallium lung scan was investigated to assess its ability to predict inflammatory activity in such a clinical setting

  3. [New toxicity of fotemustine: diffuse interstitial lung disease].

    Science.gov (United States)

    Bertrand, M; Wémeau-Stervinou, L; Gauthier, S; Auffret, M; Mortier, L

    2012-04-01

    Fotemustine is an alkylating cytostatic drug belonging to the nitrosourea family and is used in particular in the treatment of disseminated malignant melanoma. Herein, we report a case of interstitial lung disease associated with fotemustine. An 81-year-old man treated with fotemustine for metastatic melanoma presented acute interstitial lung disease 20 days after a fourth course of fotemustine monotherapy. The condition regressed spontaneously, with the patient returning to the clinical, radiological and blood gas status that had preceded fotemustine treatment. After other potential aetiologies had been ruled out, acute fotemustine-induced lung toxicity was considered and this treatment was definitively withdrawn. Other cytostatic agents belonging to the nitrosourea family can cause similar pictures, with a number of cases of interstitial lung disease thus being ascribed to fotemustine and dacarbazine. To our knowledge, this is the first case of interstitial lung disease induced by fotemustine monotherapy. This diagnosis should be considered where respiratory signs appear in melanoma patients undergoing fotemustine treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  4. Advanced sickle cell associated interstitial lung disease presenting ...

    African Journals Online (AJOL)

    Previous studies have reported abnormal pulmonary function and pulmonary hypertension among Nigerians with sickle cell disease, but there is no report of interstitial lung disease among them. We report a Nigerian sickle cell patient who presented with computed tomography proven interstitial lung disease complicated by ...

  5. Role of Oxidants in Interstitial Lung Diseases: Pneumoconioses, Constrictive Bronchiolitis, and Chronic Tropical Pulmonary Eosinophilia

    Directory of Open Access Journals (Sweden)

    William N. Rom

    2011-01-01

    Full Text Available Oxidants such as superoxide anion, hydrogen peroxide, and myeloperoxidase from activated inflammatory cells in the lower respiratory tract contribute to inflammation and injury. Etiologic agents include inorganic particulates such as asbestos, silica, or coal mine dust or mixtures of inorganic dust and combustion materials found in World Trade Center dust and smoke. These etiologic agents are phagocytosed by alveolar macrophages or bronchial epithelial cells and release chemotactic factors that recruit inflammatory cells to the lung. Chemotactic factors attract and activate neutrophils, eosinophils, mast cells, and lymphocytes and further activate macrophages to release more oxidants. Inorganic dusts target alveolar macrophages, World Trade Center dust targets bronchial epithelial cells, and eosinophils characterize tropical pulmonary eosinophilia (TPE caused by filarial organisms. The technique of bronchoalveolar lavage in humans has recovered alveolar macrophages (AMs in dust diseases and eosinophils in TPE that release increased amounts of oxidants in vitro. Interestingly, TPE has massively increased eosinophils in the acute form and after treatment can still have ongoing eosinophilic inflammation. A course of prednisone for one week can reduce the oxidant burden and attendant inflammation and may be a strategy to prevent chronic TPE and interstitial lung disease.

  6. /sup 67/Gallium citrate lung scans in interstitial lung disease

    Energy Technology Data Exchange (ETDEWEB)

    Niden, A.H.; Mishkin, F.S.; Khurana, M.M.L.

    1976-02-01

    Patients with diffuse interstitial lung disease often require a lung biopsy to determine the diagnosis and proper therapy. However, once the diagnosis is established, clinical evaluation of symptoms, chest roentgenogram and pulmonary function testing are the only noninvasive means currently available to assess activity of the disease process and response to the therapy. Although these measures appear adequate in the presence of acute active disease in which response to therapy results in readily demonstrable changes in the above parameters, they may be insensitive to subtle changes that can occur in minimally active disease with slowly progressive interstitial pulmonary fibrosis over a period of years. A more sensitive noninvasive technique for identifying these cases with a smoldering diffuse interstitial inflammatory process might greatly improve our ability to effectively manage such patients. With this in mind, the value of gallium lung scan was investigated to assess its ability to predict inflammatory activity in such a clinical setting.

  7. Interstitial lung disease: Diagnostic approach

    OpenAIRE

    Kaushik Saha

    2014-01-01

    Interstitial lung disease (ILD) is a final common pathway of a broad heterogeneous group of parenchymal lung disorders. It is characterized by progressive fibrosis of the lung leading to restriction and diminished oxygen transfer. Clinically, the presenting symptoms of ILD are non-specific (cough and progressive dyspnea on exertion) and are often attributed to other diseases, thus delaying diagnosis and timely therapy. Clues from the medical history along with the clinical context and radiolo...

  8. Smoking-related interstitial lung diseases; Interstitielle Lungenerkrankungen bei Rauchern

    Energy Technology Data Exchange (ETDEWEB)

    Marten, K. [Technische Univ. Muenchen (Germany). Klinikum rechts der Isar, Inst. fuer Roentgendiagnostik

    2007-03-15

    The most important smoking-related interstitial lung diseases (ILD) are respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and Langerhans' cell histiocytosis. Although traditionally considered to be discrete entities, smoking-related ILDs often coexist, thus accounting for the sometimes complex patterns encountered on high-resolution computed tomography (HRCT). Further studies are needed to elucidate the causative role of smoking in the development of pulmonary fibrosis.

  9. [Lung transplantation in pulmonary fibrosis and other interstitial lung diseases].

    Science.gov (United States)

    Berastegui, Cristina; Monforte, Victor; Bravo, Carlos; Sole, Joan; Gavalda, Joan; Tenório, Luis; Villar, Ana; Rochera, M Isabel; Canela, Mercè; Morell, Ferran; Roman, Antonio

    2014-09-15

    Interstitial lung disease (ILD) is the second indication for lung transplantation (LT) after emphysema. The aim of this study is to review the results of LT for ILD in Hospital Vall d'Hebron (Barcelona, Spain). We retrospectively studied 150 patients, 87 (58%) men, mean age 48 (r: 20-67) years between August 1990 and January 2010. One hundred and four (69%) were single lung transplants (SLT) and 46 (31%) bilateral-lung transplants (BLT). The postoperative diagnoses were: 94 (63%) usual interstitial pneumonia, 23 (15%) nonspecific interstitial pneumonia, 11 (7%) unclassifiable interstitial pneumonia and 15% miscellaneous. We describe the functional results, complications and survival. The actuarial survival was 87, 70 and 53% at one, 3 and 5 years respectively. The most frequent causes of death included early graft dysfunction and development of chronic rejection in the form of bronchiolitis obliterans (BOS). The mean postoperative increase in forced vital capacity and forced expiratory volume in the first second (FEV1) was similar in SLT and BLT. The best FEV1 was reached after 10 (r: 1-36) months. Sixteen percent of patients returned to work. At some point during the evolution, proven acute rejection was diagnosed histologically in 53 (35%) patients. The prevalence of BOS among survivors was 20% per year, 45% at 3 years and 63% at 5 years. LT is the best treatment option currently available for ILD, in which medical treatment has failed. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  10. Interstitial lung disease associated with Equine Infectious Anemia Virus infection in horses.

    Science.gov (United States)

    Bolfa, Pompei; Nolf, Marie; Cadoré, Jean-Luc; Catoi, Cornel; Archer, Fabienne; Dolmazon, Christine; Mornex, Jean-François; Leroux, Caroline

    2013-12-01

    EIA (Equine Infectious Anemia) is a blood-borne disease primarily transmitted by haematophagous insects or needle punctures. Other routes of transmission have been poorly explored. We evaluated the potential of EIAV (Equine Infectious Anemia Virus) to induce pulmonary lesions in naturally infected equids. Lungs from 77 EIAV seropositive horses have been collected in Romania and France. Three types of lesions have been scored on paraffin-embedded lungs: lymphocyte infiltration, bronchiolar inflammation, and thickness of the alveolar septa. Expression of the p26 EIAV capsid (CA) protein has been evaluated by immunostaining. Compared to EIAV-negative horses, 52% of the EIAV-positive horses displayed a mild inflammation around the bronchioles, 22% had a moderate inflammation with inflammatory cells inside the wall and epithelial bronchiolar hyperplasia and 6.5% had a moderate to severe inflammation, with destruction of the bronchiolar epithelium and accumulation of smooth muscle cells within the pulmonary parenchyma. Changes in the thickness of the alveolar septa were also present. Expression of EIAV capsid has been evidenced in macrophages, endothelial as well as in alveolar and bronchiolar epithelial cells, as determined by their morphology and localization. To summarize, we found lesions of interstitial lung disease similar to that observed during other lentiviral infections such as FIV in cats, SRLV in sheep and goats or HIV in children. The presence of EIAV capsid in lung epithelial cells suggests that EIAV might be responsible for the broncho-interstitial damages observed.

  11. An approach to interstitial lung disease in India

    Directory of Open Access Journals (Sweden)

    J N Pande

    2014-07-01

    Full Text Available Interstitial lung diseases are common and have varied etiology, clinical presentation, clinical course and outcome. They pose a diagnostic challenge to physicians and pulmonologists. Patients present with dry cough, exertional dyspnoea, interstitial lesions on X-ray of the chest and restrictive ventilatory defect on spirometry. A sharp decline in oxygen saturation with exercise is characteristic. Careful evaluation of the history of the patient and physical examination help in narrowing down diagnostic probabilities. HRCT of the chest has emerged as an important tool in the evaluation of these disorders. Idiopathic Interstitial Pneumonias (IIP are a group of conditions which are classified into several types based on pathological features. Bronchoscopic procedures are helpful in diagnosis of certain disorders but are of limited value in classification of IIP which requires surgical biopsy. Usual Interstitial Pneumonia (UIP, also referred to as Idiopathic Pulmonary Fibrosis, has a progressive course and an unfavourable outcome. Certain new drugs have recently become available for treatment of UIP. Our approach towards diagnosis and management of interstitial lung diseases based on personal experience over the past three decades is reported here. Key words: Usual interstitial pneumonia – sarcoidosis – pneumoconiosis – bronchoscopy – lung biopsy 

  12. Interstitial lung diseases with fibrosis - the pattern at high resolution

    International Nuclear Information System (INIS)

    Jarzemska, A.; Lasek, W.; Nawrocka, E.; Meder, G.; Zapala, M.

    2003-01-01

    Surgical lung biopsy, either open thoracotomy or video-assisted thoracoscopy is recommended in the diagnosis of interstitial lung diseases (ILD). In some cases, however, the repetitive pattern of radiological features in high-resolution computed tomography is often sufficient to confirm the diagnosis in a non-invasive manner. The purpose of the study was to determine whether patients with ILD can be selected on the basis of the HRCT pattern. Thin-section CT scans were performed in 40 patients with histologically proven idiopathic interstitial pneumonia (26 patients with usual interstitial pneumonia UIP, 2 patients with desquamative interstitial pneumonia DIP, 2 patients with bronchiolitis obliterans organizing pneumonia BOOP, 2 patients with non-specific interstitial pneumonia NSIP, 11 patients with hypersensitivity pneumonitis, and 3 patients with pulmonary histiocytosis X). The location and the intensity of lesions were taken into consideration. Clinical and histopathological findings were compared. HRCT features of interstitial lung diseases such as nodules and cystic spaces in hypersensitivity pneumonitis and pulmonary histiocytosis, and ground-glass opacities in idiopathic interstitial pneumonias (IIP) were statistically significant for differential diagnosis in ILD cases. Combination of honeycombing and ground-glass opacities found in UIP and nodules found in DIP were also statistically significant features in IIP subtypes diagnosis. In some cases, HRCT patterns of hypersensitivity pneumonitis, pulmonary histiocytosis X and IPF combined with clinical findings allowed for the accurate diagnosis without resorting to lung biopsy. Within a group of idiopathic interstitial pneumonia only in usual interstitial pneumonia characteristic pattern in thin-section CT can be defined. In other subgroups some typical features can imply a diagnosis. (author)

  13. Leflunomide-Induced Interstitial Lung Disease: A Case Report

    Directory of Open Access Journals (Sweden)

    Aygül Güzel

    2015-04-01

    Full Text Available Leflunomide (LEF induced interstitial pneumonitis is a very rare condition but potentially fatal. We report a case of LEF induced interstitial pneumonitis. A 63-year-old woman followed-up for 37 years with the diagnosis of rheumatoid arthritis treated with LEF (20 mg/day since 5 months were admitted to our hospital with cough, dyspnea, fever, and dark sputum.Chest radiography represented bilateral alveolar consolidation. High-resolution computed tomography demonstrated diffuse ground-glass appearance and interlobular septal thickening. Since the patient’s clinics and radiologic findings improved dramatically after the cessation of LEF and recieving oral steriod therapy, she was diagnosed as drug-induced interstitial lung disease. In conclusion, when nonspecific clinical signs such as respiratory distress, cough and fever seen during the use of LEF, drug-induced interstitial lung disease should be kept in mind for the differantial diagnosis.

  14. Rheumatoid arthritis associated interstitial lung disease: a review

    Directory of Open Access Journals (Sweden)

    Deborah Assayag

    2014-04-01

    Full Text Available Rheumatoid arthritis is a common inflammatory disease affecting about 1% of the population. Interstitial lung disease is a serious and frequent complication of rheumatoid arthritis. Rheumatoid arthritis associated interstitial lung disease (RA-ILD is characterized by several histopathologic subtypes. This article reviews the proposed pathogenesis and risk factors for RA-ILD. We also outline the important steps involved in the work-up of RA-ILD and review the evidence for treatment and prognosis.

  15. Interstitial lung abnormalities are associated with increased mortality in smokers

    DEFF Research Database (Denmark)

    Hoyer, Nils; Wille, Mathilde M W; Thomsen, Laura H

    2018-01-01

    OBJECTIVE: The aim of this study was to investigate whether smokers with incidental findings of interstitial lung abnormalities have an increased mortality during long-term follow-up, and review the contributing causes of death. METHODS: Baseline CT scans of 1990 participants from the Danish Lung...... in this lung cancer screening population of relatively healthy smokers and were associated with mortality regardless of the interstitial morphological phenotype. The increased mortality was partly due to an association with lung cancer and non-pulmonary malignancies....

  16. Lung lobar volume in patients with chronic interstitial pneumonia

    International Nuclear Information System (INIS)

    Harada, Hisao; Koba, Hiroyuki; Saitoh, Tsukasa; Abe, Shosaku.

    1997-01-01

    We measured lung lobar volume by using helical computed tomography (HCT) in 23 patients with idiopathic interstitial pneumonia (IIP), 7 patients with chronic interstitial pneumonia associated with collagen vascular disease (CVD-IP), and 5 healthy volunteers HCT scanning was done at the maximal inspiratory level and the resting end-expiratory level. To measure lung lobar volume, we traced the lobar margin on HCT images with a digitizer and calculated the lobar volume with a personal computer. The lower lobar volume and several factors influencing it in chronic interstitial pneumonia were studied. At the maximal inspiratory level, the lower lobar volume as a percent of the whole lung volume was 46.8±4.13% (mean ± SD) in the volunteers, 39.5±6.19% in the patients with IIP, and 27.7±7. 86% in the patients with CVD-IP. The lower lobar volumes in the patients were significantly lower than in the volunteers. Patients with IIP in whom autoantibody tests were positive had lower lobar volumes that were very low and were similar to those of patients with CVD-IP. These data suggest that collagen vascular disease may develop in patients with interstitial pneumonia. The patients with IIP who had emphysematous changes on the CT scans had smaller decreases in total lung capacity and lower ratios of forced expiratory volume in one second to forced vital capacity than did those who had no emphysematous changes, those two groups did not differ in the ratio of lower lobar volume to whole lung volume. This suggests that emphysematous change is not factor influencing lower lobar volume in patients with chronic interstitial pneumonia. We conclude that chronic interstitial pneumonia together with very low values for lower lobar volume may be a pulmonary manifestation of collagen vascular disease. (author)

  17. A CURIOUS CASE OF FEVER AND INTERSTITIAL LUNG DISEASE

    OpenAIRE

    Dr. Shahid Mahdi; Dr. Darpanarayan Hazra; Dr. Zainab Mahdi

    2017-01-01

    Antisynthetase syndrome is a rare chronic autoimmune inflammatory myopathy with fever, interstitial lung disease, Raynaud’s phenomenon and polyarthritis. The exact underlying cause of antisynthetase syndrome is not yet known. Diagnosis is made with presence of Jo-1 (Histydyl t RNA synthase) antigen in a patient with underlying interstitial lung disease, myositis, arthritis, Raynaud’s phenomenon and mechanic’s hand. Some of the other antisynthetase anti bodies are PL-7 (antigen – threonyl-tRNA...

  18. Drug-induced interstitial lung diseases. Often forgotten

    International Nuclear Information System (INIS)

    Poschenrieder, F.; Stroszczynski, C.; Hamer, O.W.

    2014-01-01

    Drug-induced interstitial lung diseases (DILD) are probably more common than diagnosed. Due to their potential reversibility, increased vigilance towards DILD is appropriate also from the radiologist's point of view, particularly as these diseases regularly exhibit radiological correlates in high-resolution computed tomography (HRCT) of the lungs. Based on personal experience typical relatively common manifestations of DILD are diffuse alveolar damage (DAD), eosinophilic pneumonia (EP), hypersensitivity pneumonitis (HP), organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). These patterns are presented based on case studies, whereby emphasis is placed on the clinical context. This is to highlight the relevance of interdisciplinary communication and discussion in the diagnostic field of DILD as it is a diagnosis of exclusion or of probability in most cases. Helpful differential diagnostic indications for the presence of DILD, such as an accompanying eosinophilia or increased attenuation of pulmonary consolidations in amiodarone-induced pneumopathy are mentioned and the freely available online database http://www.pneumotox.com is presented. (orig.) [de

  19. Bronchoalveolar lavage: role in the pathogenesis, diagnosis, and management of interstitial lung disease

    International Nuclear Information System (INIS)

    Daniele, R.P.; Elias, J.A.; Epstein, P.E.; Rossman, M.D.

    1985-01-01

    Bronchoalveolar lavage has emerged as a useful technique for the study of pulmonary interstitial disorders. Several types of information are provided by the evaluation of lavage fluid. First, the identification of cellular constituents helps to separate inflammatory processes in which lymphocytes predominate (for example, sarcoidosis, hypersensitivity pneumonitis, and berylliosis) from those in which neutrophils or macrophages predominate (for example, idiopathic pulmonary fibrosis and histiocytosis X). Second, the cells removed during lavage can be studied for their immune properties and function; tested with specific antigens, in diseases such as berylliosis and hypersensitivity pneumonitis; and examined for the presence of unique surface antigens with monoclonal antibodies (for example, histiocytosis X). Third, in conjunction with scanning electron microscopy and electron probe analysis, lavage makes possible the identification of inorganic particles in alveolar macrophages of patients with pneumoconiotic lung disease. Finally, although lavage is still an investigative procedure for most pulmonary disorders, it has an established role in the diagnosis of opportunistic infections in the immunocompromised patient

  20. Pulmonary interstitial glycogenosis in the setting of lung growth abnormality: radiographic and pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Castillo, Monette; Vade, Aruna; Lim-Dunham, Jennifer Eden [Loyola University Health System, Department of Radiology, Maywood, IL (United States); Masuda, Emi [Henry Ford Hospital, Department of Radiology, Detroit, MI (United States); Massarani-Wafai, Rasan [Loyola University Health System, Department of Pathology, Maywood, IL (United States)

    2010-09-15

    Pulmonary interstitial glycogenosis (PIG) is a rare pediatric interstitial lung disease. We report a case of a term boy presenting with tachypnea at birth requiring supplemental oxygen. Chest radiographs followed by high-resolution CT (HRCT) demonstrated hyperinflation and diffuse interstitial markings interspersed with multiple cystic spaces. An open lung biopsy demonstrated a minor component of PIG superimposed upon poor alveolarization. PIG in the setting of lung growth abnormality might be more common than previously described. Additionally, radiographic findings associated with most pediatric interstitial lung diseases are nonspecific, and histopathologic correlation is essential for diagnosis. (orig.)

  1. Intravascular Large B-Cell Lymphoma Presenting as Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Elham Vali Khojeini

    2014-01-01

    Full Text Available Intravascular large B-cell lymphoma (IVLBL is a rare subtype of diffuse large B-cell lymphoma that resides in the lumen of blood vessels. Patients typically present with nonspecific findings, particularly bizarre neurologic symptoms, fever, and skin lesions. A woman presented with shortness of breath and a chest CT scan showed diffuse interstitial thickening and ground glass opacities suggestive of an interstitial lung disease. On physical exam she was noted to have splenomegaly. The patient died and at autopsy was found to have an IVLBL in her lungs as well as nearly all her organs that were sampled. Although rare, IVLBL should be included in the differential diagnosis of interstitial lung disease and this case underscores the importance of the continuation of autopsies.

  2. Reversible Lansoprazole-Induced Interstitial Lung Disease Showing Improvement after Drug Cessation

    International Nuclear Information System (INIS)

    Hwang, Kyu Won; Woo, Ok Hee; Yong, Hwan Seok; Shin, Bong Kyung; Shim, Jae Jeong; Kang, Eun Young

    2008-01-01

    Lansoprazole is an acid proton-pump inhibitor that is similar to omeprazole. It is used to treat duodenal or gastric ulcers, H. pylori infection, gastroesophageal reflux disease (GERD) or Zollinger-Ellison syndrome. Common adverse effects of lansoprazole are diarrhea, abdominal pain, skin rash and/or itching. Information from U.S. National Library of Medicine warns that this drug can on rare occasion cause cough or cold-like symptoms. The pathophysiological mechanisms of lansoprazole-related pulmonary symptoms are not yet understood. In particular, there are no known reports regarding lansoprazole-induced interstitial lung diseases. We report here a case of interstitial lung disease (ILD) induced by oral administration of lansoprazole, which showed a pattern of nonspecific interstitial pneumonia (NSIP) as detected from a video-assisted thoracoscopic lung biopsy. We believe that this is the first report of a case of pathologically proven lansoprazole-induced ILD for which a surgical lung biopsy was performed. To the best of our knowledge, this is the first description of DI-ILD caused by lansoprazole. The diagnosis was made by considering the radiological, histopathological and clinical findings, including the close temporal relationship between lansoprazole exposure and symptom severity. Other possible causes were excluded due to a lack of a temporal relationship between the symptoms and work history or prednisolone therapy, and no other history of specific allergen exposure. When there is diffuse interstitial lung disease with an unknown etiology, it is important to remember that drugs can be the cause of pulmonary symptoms and it is crucial to take a careful patient history. If there is a recent history of taking lansoprazole in a patient with clinical and radiological findings of diffuse interstitial lung disease, we recommend stopping the medication to see if there is clinical and radiological improvement. That way, one can avoid using invasive procedures to

  3. Reversible Lansoprazole-Induced Interstitial Lung Disease Showing Improvement after Drug Cessation

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Kyu Won; Woo, Ok Hee; Yong, Hwan Seok; Shin, Bong Kyung; Shim, Jae Jeong; Kang, Eun Young [College of Medicine, Korea University, Guro Hospital, Seoul (Korea, Republic of)

    2008-04-15

    Lansoprazole is an acid proton-pump inhibitor that is similar to omeprazole. It is used to treat duodenal or gastric ulcers, H. pylori infection, gastroesophageal reflux disease (GERD) or Zollinger-Ellison syndrome. Common adverse effects of lansoprazole are diarrhea, abdominal pain, skin rash and/or itching. Information from U.S. National Library of Medicine warns that this drug can on rare occasion cause cough or cold-like symptoms. The pathophysiological mechanisms of lansoprazole-related pulmonary symptoms are not yet understood. In particular, there are no known reports regarding lansoprazole-induced interstitial lung diseases. We report here a case of interstitial lung disease (ILD) induced by oral administration of lansoprazole, which showed a pattern of nonspecific interstitial pneumonia (NSIP) as detected from a video-assisted thoracoscopic lung biopsy. We believe that this is the first report of a case of pathologically proven lansoprazole-induced ILD for which a surgical lung biopsy was performed. To the best of our knowledge, this is the first description of DI-ILD caused by lansoprazole. The diagnosis was made by considering the radiological, histopathological and clinical findings, including the close temporal relationship between lansoprazole exposure and symptom severity. Other possible causes were excluded due to a lack of a temporal relationship between the symptoms and work history or prednisolone therapy, and no other history of specific allergen exposure. When there is diffuse interstitial lung disease with an unknown etiology, it is important to remember that drugs can be the cause of pulmonary symptoms and it is crucial to take a careful patient history. If there is a recent history of taking lansoprazole in a patient with clinical and radiological findings of diffuse interstitial lung disease, we recommend stopping the medication to see if there is clinical and radiological improvement. That way, one can avoid using invasive procedures to

  4. Statin Use Is Associated with Reduced Mortality in Patients with Interstitial Lung Disease

    DEFF Research Database (Denmark)

    Vedel-Krogh, Signe; Nielsen, Sune F; Nordestgaard, Børge G

    2015-01-01

    INTRODUCTION: We hypothesized that statin use begun before the diagnosis of interstitial lung disease is associated with reduced mortality. METHODS: We studied all patients diagnosed with interstitial lung disease in the entire Danish population from 1995 through 2009, comparing statin use versus...... no statin use in a nested 1:2 matched study. RESULTS: The cumulative survival as a function of follow-up time from the date of diagnosis of interstitial lung disease (n = 1,786 + 3,572) and idiopathic lung fibrosis (n = 261 + 522) was higher for statin users versus never users (log-rank: P = 7 · 10......(-9) and P = 0.05). The median survival time in patients with interstitial lung disease was 3.3 years in statin users and 2.1 years in never users. Corresponding values in patients with idiopathic lung fibrosis were 3.4 versus 2.4 years. After multivariable adjustment, the hazard ratio for all...

  5. Esophageal involvement and interstitial lung disease in mixed connective tissue disease.

    Science.gov (United States)

    Fagundes, M N; Caleiro, M T C; Navarro-Rodriguez, T; Baldi, B G; Kavakama, J; Salge, J M; Kairalla, R; Carvalho, C R R

    2009-06-01

    Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonary and esophageal manifestations. We sought to evaluate the relationship between esophageal dysfunction and interstitial lung disease in patients with mixed connective tissue disease. We correlated the pulmonary function data and the high-resolution computed tomography findings of interstitial lung disease with the results of esophageal evaluation in manometry, 24-hour intraesophageal pH measurements, and the presence of esophageal dilatation on computed tomography scan. Fifty consecutive patients with mixed connective tissue disease, according to Kasukawa's classification criteria, were included in this prospective study. High-resolution computed tomography parenchymal abnormalities were present in 39 of 50 patients. Esophageal dilatation, gastroesophageal reflux, and esophageal motor impairment were also very prevalent (28 of 50, 18 of 36, and 30 of 36, respectively). The presence of interstitial lung disease on computed tomography was significantly higher among patients with esophageal dilatation (92% vs. 45%; pmotor dysfunction (90% vs. 35%; pesophageal and pulmonary involvement, our series revealed a strong association between esophageal motor dysfunction and interstitial lung disease in patients with mixed connective tissue disease.

  6. Interstitial Lung Disease due to Siderosis in a Lathe Machine Worker.

    Science.gov (United States)

    Gothi, D; Satija, B; Kumar, S; Kaur, Omkar

    2015-01-01

    Since its first description in 1936, siderosis of lung has been considered a benign pneumoconiosis due to absence of significant clinical symptoms or respiratory impairment. Subsequently, authors have questioned the non-fibrogenic property of iron. However, siderosis causing interstitial lung disease with usual interstitial pneumonia (UIP) pattern has not been described in the past. We report a case of UIP on high resolution computed tomography, proven to be siderosis on transbronchial lung biopsy in a lathe machine worker.

  7. Gastroesophageal Reflux Disease in Children with Interstitial Lung Disease.

    Science.gov (United States)

    Dziekiewicz, M A; Karolewska-Bochenek, K; Dembiński, Ł; Gawronska, A; Krenke, K; Lange, J; Banasiuk, M; Kuchar, E; Kulus, M; Albrecht, P; Banaszkiewicz, A

    2016-01-01

    Gastroesophageal reflux disease is common in adult patients with interstitial lung disease. However, no data currently exist regarding the prevalence and characteristics of the disease in pediatric patients with interstitial lung disease. The aim of the present study was to prospectively assess the incidence of gastroesophageal reflux disease and characterize its features in children with interstitial lung disease. Gastroesophageal reflux disease was established based on 24 h pH-impedance monitoring (MII-pH). Gastroesophageal reflux episodes (GERs) were classified according to widely recognized criteria as acid, weakly acid, weakly alkaline, or proximal. Eighteen consecutive patients (15 boys, aged 0.2-11.6 years) were enrolled in the study. Gastroesophageal reflux disease was diagnosed in a half (9/18) of children. A thousand GERs were detected by MII-pH (median 53.5; IQR 39.0-75.5). Of these, 585 (58.5 %) episodes were acidic, 407 (40.7 %) were weakly acidic, and eight (0.8 %) were weakly alkaline. There were 637 (63.7 %) proximal GERs. The patients in whom gastroesophageal reflux disease was diagnosed had a significantly higher number of proximal and total GERs. We conclude that the prevalence of gastroesophageal reflux disease in children with interstitial lung disease is high; thus, the disease should be considered regardless of presenting clinical symptoms. A high frequency of non-acid and proximal GERs makes the MII-pH method a preferable choice for the detection of reflux episodes in this patient population.

  8. 020. Coexistence of lung adenocarcinoma and usual interstitial pneumonia: a case report

    Science.gov (United States)

    Baliaka, Aggeliki; Papaemmanouil, Styliani; Spyratos, Dionysis; Zarogoulidis, Paul; Sakkas, Leonidas

    2015-01-01

    Background Usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia of unknown cause. The most common symptoms are progressively increased shortness of breath and dry cough. Some studies suggest an association between usual interstitial pneumonia and lung cancer through different pathogenetic mechanisms. Objective The case presentation of a patient with lung adenocarcinoma and UIP. Methods A 66-year-old male presented with persistent dry cough, hemoptysis and dyspnea. The chest radiographs revealed a mass in the lower lobe of the left lung, measuring 3 cm, as well as diffuse interstitial changes in the same lobe. Two partial lobectomies were performed. Results Histological examination of the mass showed moderately differentiated adenocarcinoma, focally with bronchoalveolar pattern (Immunohistochemical detection of EGFR: positive). The rest lung parenchyma presented histological appearance of UIP. Conclusions According to clinicopathological studies, the prevalence of lung cancer among patients with UIP/IPF varies between 4% and 9%. The overall median survival of IPF-Ca patients is seven months in comparison with IPF only patients (14 months).

  9. Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms.

    Science.gov (United States)

    Paulin, Francisco; Doyle, Tracy J; Fletcher, Elaine A; Ascherman, Dana P; Rosas, Ivan O

    2015-01-01

    The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.

  10. Desquamative interstitial pneumonia: A case report

    Directory of Open Access Journals (Sweden)

    Lovrenski Aleksandra

    2014-01-01

    Full Text Available Introduction. Desquamative interstitial pneumonia is one of the rarest idiopathic interstitial pneumonias and the rarest form of smoking-related interstitial lung diseases. It was first described by Liebow in 1965. Histologically, it is characterized by the presence of eosinophilic macrophages uniformly filling airspaces which often contain a finely granular light-brown pigment that does not stain for hemosiderin. The alveolar walls are usually mildly thickened by fibrous tissue and infiltrated by a moderate number of lymphocytes. Case Outline. Our patient was a 56-year-old male, heavy smoker, with bilateral lung infiltrations of unknown etiology and several months of discomfort in the form of dry cough and shortness of breath. Lung function tests showed a moderate restrictive ventilation disorder and a severe reduction of diffusing capacity. Since bronchoscopic specimens did not reveal lung lesion etiology, an open lung biopsy of the lower left pulmonary lobe was performed, and based on the obtained surgical material the pathohistologically diagnosis of desquamative interstitial pneumonia was established. The patient was started on corticosteroid and immunosuppressive therapy, and he ceased smoking. At the last control examination, two years after the onset of symptoms, the patient was feeling well, and high-resolution computed tomography (HRCT scan of the thorax showed regression of pathological changes. Conclusion. Although, as in our case, the majority of DIP patients improve on treatment, some patients still develop progressive irreversible fibrosis despite therapy.

  11. A comparison of visual and quantitative methods to identify interstitial lung abnormalities

    OpenAIRE

    Kliment, Corrine R.; Araki, Tetsuro; Doyle, Tracy J.; Gao, Wei; Dupuis, Jos?e; Latourelle, Jeanne C.; Zazueta, Oscar E.; Fernandez, Isis E.; Nishino, Mizuki; Okajima, Yuka; Ross, James C.; Est?par, Ra?l San Jos?; Diaz, Alejandro A.; Lederer, David J.; Schwartz, David A.

    2015-01-01

    Background: Evidence suggests that individuals with interstitial lung abnormalities (ILA) on a chest computed tomogram (CT) may have an increased risk to develop a clinically significant interstitial lung disease (ILD). Although methods used to identify individuals with ILA on chest CT have included both automated quantitative and qualitative visual inspection methods, there has been not direct comparison between these two methods. To investigate this relationship, we created lung density met...

  12. The Objective Identification and Quantification of Interstitial Lung Abnormalities in Smokers.

    Science.gov (United States)

    Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Hunninghake, Gary M; Putman, Rachel K; Onieva, Jorge; Martinez, Fernando J; Choi, Augustine M; Lynch, David A; Hatabu, Hiroto; Rosas, Ivan O; Estepar, Raul San Jose; Washko, George R

    2017-08-01

    Previous investigation suggests that visually detected interstitial changes in the lung parenchyma of smokers are highly clinically relevant and predict outcomes, including death. Visual subjective analysis to detect these changes is time-consuming, insensitive to subtle changes, and requires training to enhance reproducibility. Objective detection of such changes could provide a method of disease identification without these limitations. The goal of this study was to develop and test a fully automated image processing tool to objectively identify radiographic features associated with interstitial abnormalities in the computed tomography scans of a large cohort of smokers. An automated tool that uses local histogram analysis combined with distance from the pleural surface was used to detect radiographic features consistent with interstitial lung abnormalities in computed tomography scans from 2257 individuals from the Genetic Epidemiology of COPD study, a longitudinal observational study of smokers. The sensitivity and specificity of this tool was determined based on its ability to detect the visually identified presence of these abnormalities. The tool had a sensitivity of 87.8% and a specificity of 57.5% for the detection of interstitial lung abnormalities, with a c-statistic of 0.82, and was 100% sensitive and 56.7% specific for the detection of the visual subtype of interstitial abnormalities called fibrotic parenchymal abnormalities, with a c-statistic of 0.89. In smokers, a fully automated image processing tool is able to identify those individuals who have interstitial lung abnormalities with moderate sensitivity and specificity. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  13. Hypothalamic digoxin, hemispheric chemical dominance, and interstitial lung disease.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-10-01

    The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. This was assessed in patients with idiopathic pulmonary fibrosis and in individuals of differing hemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of idiopathic pulmonary fibrosis. All 15 cases of interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. The isoprenoidal metabolites--digoxin, dolichol, and ubiquinone, RBC membrane Na(+)-K+ ATPase activity, serum magnesium, tyrosine/tryptophan catabolic patterns, free radical metabolism, glycoconjugate metabolism, and RBC membrane composition--were assessed in idiopathic pulmonary fibrosis as well as in individuals with differing hemispheric dominance. In patients with idiopathic pulmonary fibrosis there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in patients with idiopathic pulmonary fibrosis. Isoprenoid pathway dysfunction con tributes to the pathogenesis of idiopathic pulmonary fibrosis. The biochemical patterns obtained in interstitial lung disease are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. However, all the patients with interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Interstitial lung disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

  14. The COPD Assessment Test as a Prognostic Marker in Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Fujiko Someya

    2016-01-01

    Full Text Available The chronic obstructive pulmonary disease (COPD Assessment Test (CAT, which was developed to measure the health status of patients with COPD, was applied to patients with interstitial lung disease, aiming to examine the CAT as a predictor of outcome. Over a follow-up period of more than one year, 101 consecutive patients with interstitial lung disease were evaluated by the CAT. The CAT scores of 40 in total were categorized into four subsets according to the severity. Patients with higher (more severe scores exhibited lower forced vital capacity and lung diffusion capacity for carbon monoxide. The survival rate was significantly lower in patients with higher scores (log-rank test, P = 0.0002, and the hazard ratios for death of the higher scores and lower lung diffusion capacity for carbon monoxide were independently significant. These findings suggest that CAT can indicate the risk of mortality in patients with interstitial lung disease.

  15. Tumorous interstitial lung disease

    International Nuclear Information System (INIS)

    Dinkel, E.; Meyer, E.; Mundinger, A.; Helwig, A.; Blum, U.; Wuertemberger, G.

    1990-01-01

    The radiological findings in pulmonary lymphangitic carcinomatosis and in leukemic pulmonary infiltrates mirror the tumor-dependent monomorphic interstitial pathology of lung parenchyma. It is a proven fact that pulmonary lymphangitic carcinomatosis is caused by hematogenous tumor embolization to the lungs; pathogenesis by contiguous lymphangitic spread is the exception. High-resolution CT performed as a supplement to the radiological work-up improves the sensitivity for pulmonary infiltrates in general and thus makes the differential diagnosis decided easier. Radiological criteria cannot discriminate the different forms of leukemia. Plain chest X-ray allows the diagnosis of pulmonary involvement in leukemia due to tumorous infiltrates and of tumor- or therapy-induced complications. It is essential that the radiological findings be interpreted with reference to the stage of tumor disease and the clinical parameters to make the radiological differential diagnosis of opportunistic infections more reliable. (orig.) [de

  16. Surfactant gene polymorphisms and interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Pantelidis Panagiotis

    2001-11-01

    Full Text Available Abstract Pulmonary surfactant is a complex mixture of phospholipids and proteins, which is present in the alveolar lining fluid and is essential for normal lung function. Alterations in surfactant composition have been reported in several interstitial lung diseases (ILDs. Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD. The role of surfactant in lung disease is therefore drawing increasing attention following the elucidation of the genetic basis underlying its surface expression and the proof of surfactant abnormalities in ILD.

  17. Fatal interstitial lung disease associated with icotinib

    OpenAIRE

    Zhang, Jiexia; Zhan, Yangqing; Ouyang, Ming; Qin, Yinyin; Zhou, Chengzhi; Chen, Rongchang

    2014-01-01

    The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and erlotinib is drug-associated interstitial lung disease (ILD), which has been often described. However, it has been less well described for icotinib, a similar orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old female patient with stage IV lung adenocarcinoma who developed fatal ILD is reported here. She denied chemotherapy, and received palliative treatment with icotinib (125 mg po, th...

  18. Paraseptal Emphysema: Prevalence and Distribution on CT and Association with Interstitial Lung Abnormalities

    Science.gov (United States)

    Araki, Tetsuro; Nishino, Mizuki; Zazueta, Oscar E.; Gao, Wei; Dupuis, Josée; Okajima, Yuka; Latourelle, Jeanne C.; Rosas, Ivan O.; Murakami, Takamichi; O’Connor, George T.; Washko, George R.; Hunninghake, Gary M.; Hatabu, Hiroto

    2015-01-01

    Objective To investigate the prevalence and distribution of paraseptal emphysema on chest CT images in the Framingham Heart Study (FHS) population, and assess its impact on pulmonary function. Also pursued was the association with interstitial lung abnormalities. Materials and Methods We assessed 2633 participants in the FHS for paraseptal emphysema on chest CT. Characteristics of participants, including age, sex, smoking status, clinical symptoms, and results of pulmonary function tests, were compared between those with and without paraseptal emphysema. The association between paraseptal emphysema and interstitial lung abnormalities was investigated. Results Of the 2633 participants, 86 (3%) had pure paraseptal emphysema (defined as paraseptal emphysema with no other subtypes of emphysema other than paraseptal emphysema or a very few centrilobular emphysema involved) in at least one lung zone. The upper zone of the lungs was almost always involved. Compared to the participants without paraseptal emphysema, those with pure paraseptal emphysema were significantly older, and were more frequently male and smokers (mean 64 years, 71% male, mean 36 pack-years, pemphysema and interstitial lung abnormalities (pemphysema was 3% in the FHS population, predominantly affects the upper lung zone, and contributes to decreased pulmonary function. Cigarette smoking, aging, and male gender were the factors associated with the presence of paraseptal emphysema. Significant association between paraseptal emphysema and interstitial lung abnormalities was observed. PMID:25868675

  19. Interstitial Lung Disease in a 70-Year-Old Man with Ulcerative Colitis.

    Science.gov (United States)

    Collins, Hampton W; Frye, Jeanetta W

    2018-01-01

    Interstitial lung disease is a rare but increasingly recognized extraintestinal manifestation of inflammatory bowel disease that can have devastating consequences if left untreated. We report a case of ulcerative colitis-associated interstitial lung disease presenting with acute hypoxic respiratory failure during an ulcerative colitis flare. Gastroenterologists and pulmonologists should be aware of the numerous bronchopulmonary signs and symptoms that can suggest systemic illness in inflammatory bowel disease.

  20. Progression of Common Variable Immunodeficiency Interstitial Lung Disease Accompanies Distinct Pulmonary and Laboratory Findings.

    Science.gov (United States)

    Maglione, Paul J; Overbey, Jessica R; Cunningham-Rundles, Charlotte

    2015-01-01

    Common variable immunodeficiency may be complicated by interstitial lung disease, which leads to worsened morbidity and mortality in some. Although immunomodulatory treatment has efficacy, choice of patient, duration of treatment, and long-term follow-up are not available. Interstitial lung disease appears stable in certain instances, so it is not known whether all patients will develop progressive disease or require immunomodulatory therapy. This study aims to determine if all common variable immunodeficiency patients with interstitial lung disease have physiological worsening, and if clinical and/or laboratory parameters may correlate with disease progression. A retrospective review of medical records at Mount Sinai Medical Center in New York was conducted for referred patients with common variable immunodeficiency, CT scan-confirmed interstitial lung disease, and periodic pulmonary function testing covering 20 or more months before immunomodulatory therapy. Fifteen patients were identified from the retrospective review and included in this study. Of the 15 patients with common variable immunodeficiency, 9 had physiological worsening of interstitial lung disease adapted from consensus guidelines, associated with significant reductions in forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of the lung for carbon monoxide. Those with progressive lung disease also had significantly lower mean immunoglobulin G levels, greater increases and highest levels of serum immunoglobulin M (IgM), and more significant thrombocytopenia. Interstitial lung disease resulted in physiological worsening in many, but not all subjects, and was associated with suboptimal immunoglobulin G replacement. Those with worsening pulmonary function tests, elevated IgM, and severe thrombocytopenic episodes appear to be at highest risk for progressive disease. Such patients may benefit from immunomodulatory treatment. Copyright © 2015 American Academy of Allergy

  1. MRI of interstitial lung diseases. What is possible?

    International Nuclear Information System (INIS)

    Biederer, J.; Wielpuetz, M.O.; Jobst, B.J.; Dinkel, J.

    2014-01-01

    Magnetic resonance imaging (MRI) of the lungs is becoming increasingly appreciated as a third diagnostic imaging modality besides chest x-ray and computed tomography (CT). Its value is well acknowledged for pediatric patients or for scientific use particularly when radiation exposure should be strictly avoided. However, the diagnosis of interstitial lung disease is the biggest challenge of all indications. The objective of this article is a summary of the current state of the art for diagnostic MRI of interstitial lung diseases. This article reflects the results of a current search of the literature and discusses them against the background of the authors own experience with lung MRI. Due to its lower spatial resolution and a higher susceptibility to artefacts MRI does not achieve the sensitivity of CT for the detection of small details for pattern recognition (e.g. fine reticulation and micronodules) but larger details (e.g. coarse fibrosis and honeycombing) can be clearly visualized. Moreover, it could be shown that MRI has the capability to add clinically valuable information on regional lung function (e.g. ventilation, perfusion and mechanical properties) and inflammation with native signal and contrast dynamics. In its present state MRI can be used for comprehensive cardiopulmonary imaging in patients with sarcoidosis or for follow-up of lung fibrosis after initial correlation with CT. Far more indications are expected when the capabilities of MRI for the assessment of regional lung function and activity of inflammation can be transferred into robust protocols for clinical use. (orig.) [de

  2. The safety and efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel in the treatment of non-small cell lung cancer patients with interstitial lung disease.

    Science.gov (United States)

    Yasuda, Yuichiro; Hattori, Yoshihiro; Tohnai, Rie; Ito, Shoichi; Kawa, Yoshitaka; Kono, Yuko; Urata, Yoshiko; Nogami, Munenobu; Takenaka, Daisuke; Negoro, Shunichi; Satouchi, Miyako

    2018-01-01

    The optimal chemotherapy regimen for non-small cell lung cancer patients with interstitial lung disease is unclear. We therefore investigated the safety and efficacy of carboplatin plus nab-paclitaxel as a first-line regimen for non-small cell lung cancer in patients with interstitial lung disease. We retrospectively reviewed advanced non-small cell lung cancer patients with interstitial lung disease who received carboplatin plus nab-paclitaxel as a first-line chemotherapy regimen at Hyogo Cancer Center between February 2013 and August 2016. interstitial lung disease was diagnosed according to the findings of pretreatment chest high-resolution computed tomography. Twelve patients were included (male, n = 11; female, n = 1). The overall response rate was 67% and the disease control rate was 100%. The median progression free survival was 5.1 months (95% CI: 2.9-8.3 months) and the median overall survival was 14.9 months (95% CI: 4.8-not reached). A chemotherapy-related acute exacerbation of interstitial lung disease was observed in one patient; the extent of this event was Grade 2. There were no treatment-related deaths. Carboplatin plus nab-paclitaxel, as a first-line chemotherapy regimen for non-small cell lung cancer, showed favorable efficacy and safety in patients with preexisting interstitial lung disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  3. Interstitial shadow on chest CT is associated with the onset of interstitial lung disease caused by chemotherapeutic drugs

    International Nuclear Information System (INIS)

    Niho, Seiji; Goto, Koichi; Yoh, Kiyotaka; Kim, Y.H.; Ohmatsu, Hironobu; Kubota, Kaoru; Saijo, Nagahiro; Nishiwaki, Yutaka

    2006-01-01

    Pretreatment computerized tomography (CT) films of the chest was studied to clarify the influence of interstitial shadow on developing interstitial lung disease (ILD). Eligible patients were those lung cancer patients who started to receive first-line chemotherapy between October 2001 and March 2004. Patients who received thoracic radiotherapy to the primary lesion, mediastinum, spinal or rib metastases were excluded. We reviewed pretreatment conventional CT and plain X-ray films of the chest. Ground-glass opacity, consolidation or reticular shadow without segmental distribution was defined as interstitial shadow, with this event being graded as mild, moderate or severe. If interstitial shadow was detected on CT films of the chest, but not via plain chest X-ray, it was graded as mild. Patients developing ILD were identified from medial records. A total of 502 patients were eligible. Mild, moderate and severe interstitial shadow was identified in 7, 8 and 5% of patients, respectively. A total of 188 patients (37%) received tyrosine kinase inhibitor (TKI) treatment, namely gefitinib or erlotinib. Twenty-six patients (5.2%) developed ILD either during or after chemotherapy. Multivariate analyses revealed that interstitial shadow on CT films of the chest and treatment history with TKI were associated with the onset of ILD. It is recommended that patients with interstitial shadow on chest CT are excluded from future clinical trials until this issue is further clarified, as it is anticipated that use of chemotherapeutic agents frequently mediate onset of ILD in this context. (author)

  4. Paraseptal emphysema: Prevalence and distribution on CT and association with interstitial lung abnormalities

    International Nuclear Information System (INIS)

    Araki, Tetsuro; Nishino, Mizuki; Zazueta, Oscar E.; Gao, Wei; Dupuis, Josée; Okajima, Yuka; Latourelle, Jeanne C.; Rosas, Ivan O.; Murakami, Takamichi; O’Connor, George T.; Washko, George R.; Hunninghake, Gary M.

    2015-01-01

    Highlights: • The prevalence of pure paraseptal emphysema was 3% (85/2633) in the Framingham Heart Study population, predominantly affects the upper lung zone, and contributes to slightly decreased pulmonary function. • There was significant association between paraseptal emphysema and interstitial lung abnormalities, which is a novel finding. • Prevalence of paraseptal emphysema and its impact on pulmonary function could have been underestimated in the previous reports. - Abstract: Objective: To investigate the prevalence and distribution of paraseptal emphysema on chest CT images in the Framingham Heart Study (FHS) population, and assess its impact on pulmonary function. Also pursued was the association with interstitial lung abnormalities. Materials and methods: We assessed 2633 participants in the FHS for paraseptal emphysema on chest CT. Characteristics of the participants, including age, sex, smoking status, clinical symptoms, and results of pulmonary function tests, were compared between those with and without paraseptal emphysema. The association between paraseptal emphysema and interstitial lung abnormalities was investigated. Results: Of the 2633 participants, 86 (3%) had pure paraseptal emphysema (defined as paraseptal emphysema with no other subtypes of emphysema other than paraseptal emphysema or a very few centrilobular emphysema involved) in at least one lung zone. The upper zone of the lungs was almost always involved. Compared to the participants without paraseptal emphysema, those with pure paraseptal emphysema were significantly older, and were more frequently male and smokers (mean 64 years, 71% male, mean 36 pack-years, P < 0.001) and had significantly decreased FEV 1 /FVC% (P = 0.002), and diffusion capacity of carbon monoxide (DLCO) (P = 0.002). There was a significant association between pure paraseptal emphysema and interstitial lung abnormalities (P < 0.001). Conclusions: The prevalence of pure paraseptal emphysema was 3% in the FHS

  5. Paraseptal emphysema: Prevalence and distribution on CT and association with interstitial lung abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Araki, Tetsuro, E-mail: taraki@partners.org [Department of Radiology, Center for Pulmonary Functional Imaging, Brigham and Women' s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02215 (United States); Department of Radiology, Kinki University Faculty of Medicine, Osaka-Sayama (Japan); Nishino, Mizuki [Department of Radiology, Center for Pulmonary Functional Imaging, Brigham and Women' s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02215 (United States); Zazueta, Oscar E. [The Pulmonary and Critical Care Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Gao, Wei [Department of Biostatistics, Boston University School of Public Health, Boston, MA (United States); Dupuis, Josée [Department of Biostatistics, Boston University School of Public Health, Boston, MA (United States); The National Heart Lung and Blood Institute' s Framingham Heart Study, Framingham, MA (United States); Okajima, Yuka [Department of Radiology, Center for Pulmonary Functional Imaging, Brigham and Women' s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02215 (United States); Latourelle, Jeanne C. [Department of Medicine and Neurology, Boston University School of Medicine, Boston, MA (United States); Rosas, Ivan O. [The Pulmonary and Critical Care Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Murakami, Takamichi [Department of Radiology, Kinki University Faculty of Medicine, Osaka-Sayama (Japan); O’Connor, George T. [The National Heart Lung and Blood Institute' s Framingham Heart Study, Framingham, MA (United States); Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA (United States); Washko, George R.; Hunninghake, Gary M. [The Pulmonary and Critical Care Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); and others

    2015-07-15

    Highlights: • The prevalence of pure paraseptal emphysema was 3% (85/2633) in the Framingham Heart Study population, predominantly affects the upper lung zone, and contributes to slightly decreased pulmonary function. • There was significant association between paraseptal emphysema and interstitial lung abnormalities, which is a novel finding. • Prevalence of paraseptal emphysema and its impact on pulmonary function could have been underestimated in the previous reports. - Abstract: Objective: To investigate the prevalence and distribution of paraseptal emphysema on chest CT images in the Framingham Heart Study (FHS) population, and assess its impact on pulmonary function. Also pursued was the association with interstitial lung abnormalities. Materials and methods: We assessed 2633 participants in the FHS for paraseptal emphysema on chest CT. Characteristics of the participants, including age, sex, smoking status, clinical symptoms, and results of pulmonary function tests, were compared between those with and without paraseptal emphysema. The association between paraseptal emphysema and interstitial lung abnormalities was investigated. Results: Of the 2633 participants, 86 (3%) had pure paraseptal emphysema (defined as paraseptal emphysema with no other subtypes of emphysema other than paraseptal emphysema or a very few centrilobular emphysema involved) in at least one lung zone. The upper zone of the lungs was almost always involved. Compared to the participants without paraseptal emphysema, those with pure paraseptal emphysema were significantly older, and were more frequently male and smokers (mean 64 years, 71% male, mean 36 pack-years, P < 0.001) and had significantly decreased FEV{sub 1}/FVC% (P = 0.002), and diffusion capacity of carbon monoxide (DLCO) (P = 0.002). There was a significant association between pure paraseptal emphysema and interstitial lung abnormalities (P < 0.001). Conclusions: The prevalence of pure paraseptal emphysema was 3% in the

  6. Viral infection of human lung macrophages increases PDL1 expression via IFNβ.

    Directory of Open Access Journals (Sweden)

    Karl J Staples

    Full Text Available Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophages in response to viral infection. Ex-vivo viral infection models using influenza and RSV were established in human lung explants, isolated lung macrophages and monocyte-derived macrophages (MDM and analysed by flow cytometry and RT-PCR. Incubation of lung explants, lung macrophages and MDM with X31 resulted in mean cellular infection rates of 18%, 18% and 29% respectively. Viral infection significantly increased cell surface expression of PDL1 on explant macrophages, lung macrophages and MDM but not explant epithelial cells. Infected MDM induced IFNγ release from autologous CD8+ T cells, an effect enhanced by PDL1 blockade. We observed increases in PDL1 mRNA and IFNβ mRNA and protein release by MDM in response to influenza infection. Knockdown of IFNβ by siRNA, resulted in a 37.5% reduction in IFNβ gene expression in response to infection, and a significant decrease in PDL1 mRNA. Furthermore, when MDM were incubated with IFNβ, this cytokine caused increased expression of PDL1 mRNA. These data indicate that human macrophage PDL1 expression modulates CD8+ cell IFNγ release in response to virus and that this expression is regulated by autologous IFNβ production.

  7. T2 mapping of CT remodelling patterns in interstitial lung disease

    Energy Technology Data Exchange (ETDEWEB)

    Buzan, Maria T.A. [Iuliu Hatieganu University of Medicine and Pharmacy, Department of Pneumology, Cluj-Napoca (Romania); Thoraxklinik at Heidelberg University Hospital, Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Heidelberg (Germany); University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology, Heidelberg (Germany); Eichinger, Monika; Heussel, Claus Peter [Thoraxklinik at Heidelberg University Hospital, Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg (Germany); Kreuter, Michael; Herth, Felix J. [Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg (Germany); Thoraxklinik at Heidelberg University Hospital, Department of Pneumology, Center for Rare and Interstitial Lung Diseases, Heidelberg (Germany); Kauczor, Hans-Ulrich [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology, Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg (Germany); Warth, Arne [Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg (Germany); University Hospital Heidelberg, Institute for Pathology, Heidelberg (Germany); Pop, Carmen Monica [Iuliu Hatieganu University of Medicine and Pharmacy, Department of Pneumology, Cluj-Napoca (Romania); Dinkel, Julien [Thoraxklinik at Heidelberg University Hospital, Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg (Germany); Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research (DZL), Munich (Germany); Ludwig-Maximilians-University Hospital Munich, Institute for Clinical Radiology, Munich (Germany)

    2015-11-15

    To evaluate lung T2 mapping for quantitative characterization and differentiation of ground-glass opacity (GGO), reticulation (RE) and honeycombing (HC) in usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). Twelve patients with stable UIP or NSIP underwent thin-section multislice CT and 1.5-T MRI of the lung. A total of 188 regions were classified at CT into normal (n = 29) and pathological areas, including GGO (n = 48), RE (n = 60) and HC (n = 51) predominant lesions. Entire lung T2 maps based on multi-echo single shot TSE sequence (TE: 20, 40, 79, 140, 179 ms) were generated from each subject with breath-holds at end-expiration and ECG-triggering. The median T2 relaxation of GGO was 67 ms (range 60-72 ms). RE predominant lesions had a median relaxation of 74 ms (range 69-79 ms), while for HC pattern this was 79 ms (range 74-89 ms). The median T2 relaxation for normal lung areas was 41 ms (ranged 38-49 ms), and showed significant difference to pathological areas (p < 0.001). A statistical difference was found between the T2 relaxation of GGO, RE and HC (p < 0.05). The proposed method provides quantitative information for pattern differentiation, potentially allowing for monitoring of progression and response to treatment, in interstitial lung disease. (orig.)

  8. T2 mapping of CT remodelling patterns in interstitial lung disease

    International Nuclear Information System (INIS)

    Buzan, Maria T.A.; Eichinger, Monika; Heussel, Claus Peter; Kreuter, Michael; Herth, Felix J.; Kauczor, Hans-Ulrich; Warth, Arne; Pop, Carmen Monica; Dinkel, Julien

    2015-01-01

    To evaluate lung T2 mapping for quantitative characterization and differentiation of ground-glass opacity (GGO), reticulation (RE) and honeycombing (HC) in usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). Twelve patients with stable UIP or NSIP underwent thin-section multislice CT and 1.5-T MRI of the lung. A total of 188 regions were classified at CT into normal (n = 29) and pathological areas, including GGO (n = 48), RE (n = 60) and HC (n = 51) predominant lesions. Entire lung T2 maps based on multi-echo single shot TSE sequence (TE: 20, 40, 79, 140, 179 ms) were generated from each subject with breath-holds at end-expiration and ECG-triggering. The median T2 relaxation of GGO was 67 ms (range 60-72 ms). RE predominant lesions had a median relaxation of 74 ms (range 69-79 ms), while for HC pattern this was 79 ms (range 74-89 ms). The median T2 relaxation for normal lung areas was 41 ms (ranged 38-49 ms), and showed significant difference to pathological areas (p < 0.001). A statistical difference was found between the T2 relaxation of GGO, RE and HC (p < 0.05). The proposed method provides quantitative information for pattern differentiation, potentially allowing for monitoring of progression and response to treatment, in interstitial lung disease. (orig.)

  9. Mechanisms of macrophage accumulation in the lungs of asbestos-exposed subjects

    International Nuclear Information System (INIS)

    Spurzem, J.R.; Saltini, C.; Rom, W.; Winchester, R.J.; Crystal, R.G.

    1987-01-01

    Chronic asbestos exposure is associated with the accumulation of mononuclear phagocytes in the lower respiratory tract. This process can be both protective and injurious, since macrophages can aid in asbestos clearance yet also modulate structural derangements of the alveolar walls. To understand why macrophages accumulate in the lungs of asbestos-exposed persons, 2 possible mechanisms were evaluated using alveolar macrophages from subjects with histories of chronic high exposure to airborne asbestos: enhanced recruitment of blood monocytes to the lung, and an increased rate of replication of macrophages in situ. Monoclonal antibody analysis with antibodies that detect surface antigens on the majority of circulating blood monocytes but only on a minority of mature alveolar macrophages demonstrated that an increased proportion of alveolar macrophages of asbestos workers expressed monocyte lineage antigens, suggesting the presence of young newly recruited macrophages and thus enhanced recruitment. Culture of the alveolar macrophages from these subjects with [ 3 H]thymidine followed by autoradiography demonstrated an increased proportion of alveolar macrophages synthesizing DNA, suggesting the macrophages are replicating at an increased rate in situ. These observations are consistent with the concept that both enhanced recruitment of blood monocytes and increased local proliferation of alveolar macrophages contribute to the accumulation mononuclear phagocytes in the lung of persons with chronic asbestos exposure

  10. Host lung immunity is severely compromised during tropical pulmonary eosinophilia: role of lung eosinophils and macrophages.

    Science.gov (United States)

    Sharma, Pankaj; Sharma, Aditi; Vishwakarma, Achchhe Lal; Agnihotri, Promod Kumar; Sharma, Sharad; Srivastava, Mrigank

    2016-04-01

    Eosinophils play a central role in the pathogenesis of tropical pulmonary eosinophilia, a rare, but fatal, manifestation of filariasis. However, no exhaustive study has been done to identify the genes and proteins of eosinophils involved in the pathogenesis of tropical pulmonary eosinophilia. In the present study, we established a mouse model of tropical pulmonary eosinophilia that mimicked filarial manifestations of human tropical pulmonary eosinophilia pathogenesis and used flow cytometry-assisted cell sorting and real-time RT-PCR to study the gene expression profile of flow-sorted, lung eosinophils and lung macrophages during tropical pulmonary eosinophilia pathogenesis. Our results show that tropical pulmonary eosinophilia mice exhibited increased levels of IL-4, IL-5, CCL5, and CCL11 in the bronchoalveolar lavage fluid and lung parenchyma along with elevated titers of IgE and IgG subtypes in the serum. Alveolar macrophages from tropical pulmonary eosinophilia mice displayed decreased phagocytosis, attenuated nitric oxide production, and reduced T-cell proliferation capacity, and FACS-sorted lung eosinophils from tropical pulmonary eosinophilia mice upregulated transcript levels of ficolin A and anti-apoptotic gene Bcl2,but proapoptotic genes Bim and Bax were downregulated. Similarly, flow-sorted lung macrophages upregulated transcript levels of TLR-2, TLR-6, arginase-1, Ym-1, and FIZZ-1 but downregulated nitric oxide synthase-2 levels, signifying their alternative activation. Taken together, we show that the pathogenesis of tropical pulmonary eosinophilia is marked by functional impairment of alveolar macrophages, alternative activation of lung macrophages, and upregulation of anti-apoptotic genes by eosinophils. These events combine together to cause severe lung inflammation and compromised lung immunity. Therapeutic interventions that can boost host immune response in the lungs might thus provide relief to patients with tropical pulmonary eosinophilia.

  11. Visual assessment of early emphysema and interstitial abnormalities on CT is useful in lung cancer risk analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wille, Mathilde M.W.; Dirksen, Asger; Shaker, Saher B. [Gentofte Hospital, Department of Respiratory Medicine, Hellerup (Denmark); Thomsen, Laura H. [Hvidovre Hospital, Department of Respiratory Medicine, Hvidovre (Denmark); Petersen, Jens [University of Copenhagen, Department of Computer Science, DIKU, Koebenhavn Oe (Denmark); Bruijne, Marleen de [University of Copenhagen, Department of Computer Science, DIKU, Koebenhavn Oe (Denmark); Erasmus MC -University Medical Center Rotterdam, Biomedical Imaging Group Rotterdam, Departments of Radiology and Medical Informatics, Rotterdam (Netherlands); Pedersen, Jesper H. [Copenhagen University Hospital, Department of Thoracic Surgery, Rigshospitalet, Koebenhavn Oe (Denmark)

    2016-02-15

    Screening for lung cancer should be limited to a high-risk-population, and abnormalities in low-dose computed tomography (CT) screening images may be relevant for predicting the risk of lung cancer. Our aims were to compare the occurrence of visually detected emphysema and interstitial abnormalities in subjects with and without lung cancer in a screening population of smokers. Low-dose chest CT examinations (baseline and latest possible) of 1990 participants from The Danish Lung Cancer Screening Trial were independently evaluated by two observers who scored emphysema and interstitial abnormalities. Emphysema (lung density) was also measured quantitatively. Emphysema was seen more frequently and its extent was greater among participants with lung cancer on baseline (odds ratio (OR), 1.8, p = 0.017 and p = 0.002) and late examinations (OR 2.6, p < 0.001 and p < 0.001). No significant difference was found using quantitative measurements. Interstitial abnormalities were more common findings among participants with lung cancer (OR 5.1, p < 0.001 and OR 4.5, p < 0.001).There was no association between presence of emphysema and presence of interstitial abnormalities (OR 0.75, p = 0.499). Even early signs of emphysema and interstitial abnormalities are associated with lung cancer. Quantitative measurements of emphysema - regardless of type - do not show the same association. (orig.)

  12. Visual assessment of early emphysema and interstitial abnormalities on CT is useful in lung cancer risk analysis

    International Nuclear Information System (INIS)

    Wille, Mathilde M.W.; Dirksen, Asger; Shaker, Saher B.; Thomsen, Laura H.; Petersen, Jens; Bruijne, Marleen de; Pedersen, Jesper H.

    2016-01-01

    Screening for lung cancer should be limited to a high-risk-population, and abnormalities in low-dose computed tomography (CT) screening images may be relevant for predicting the risk of lung cancer. Our aims were to compare the occurrence of visually detected emphysema and interstitial abnormalities in subjects with and without lung cancer in a screening population of smokers. Low-dose chest CT examinations (baseline and latest possible) of 1990 participants from The Danish Lung Cancer Screening Trial were independently evaluated by two observers who scored emphysema and interstitial abnormalities. Emphysema (lung density) was also measured quantitatively. Emphysema was seen more frequently and its extent was greater among participants with lung cancer on baseline (odds ratio (OR), 1.8, p = 0.017 and p = 0.002) and late examinations (OR 2.6, p < 0.001 and p < 0.001). No significant difference was found using quantitative measurements. Interstitial abnormalities were more common findings among participants with lung cancer (OR 5.1, p < 0.001 and OR 4.5, p < 0.001).There was no association between presence of emphysema and presence of interstitial abnormalities (OR 0.75, p = 0.499). Even early signs of emphysema and interstitial abnormalities are associated with lung cancer. Quantitative measurements of emphysema - regardless of type - do not show the same association. (orig.)

  13. Fetal lung interstitial tumor: the first Japanese case report and a comparison with fetal lung tissue and congenital cystic adenomatoid malformation/congenital pulmonary airway malformation type 3.

    Science.gov (United States)

    Yoshida, Mariko; Tanaka, Mio; Gomi, Kiyoshi; Iwanaka, Tadashi; Dehner, Louis P; Tanaka, Yukichi

    2013-10-01

    Fetal lung interstitial tumor, a newly recognized lung lesion in infants, was first reported in 2010. Here, we report the first Japanese case of fetal lung interstitial tumor which was originally diagnosed as atypical congenital cystic adenomatoid malformation/congenital pulmonary airway malformation type 3. A 7-day-old girl was referred to our hospital with respiratory distress and a left lung mass and she subsequently underwent left lower lobectomy. The specimen showed a 5 cm solid mass with a fibrous capsule. Histological examination revealed immature airspaces and interstitium, containing bronchioles and cartilage. The epithelial and interstitial cells contained abundant glycogen granules. Immunohistochemistry showed nuclear/cytoplasmic expression of β-catenin in the epithelial and interstitial cells. β-catenin gene mutations and trisomy 8 were not detected, so a neoplastic origin could not be confirmed. The histological findings were partly consistent with normal fetal lung at the canalicular stage, pulmonary interstitial glycogenosis, and congenital cystic adenomatoid malformation/congenital pulmonary airway malformation type 3. In this report, we compare the above conditions and discuss the pathogenesis of fetal lung interstitial tumor. © 2013 The Authors. Pathology International © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  14. Soluble ICAM-1 activates lung macrophages and enhances lung injury

    DEFF Research Database (Denmark)

    Schmal, H; Czermak, B J; Lentsch, A B

    1998-01-01

    production of TNF-alpha and the CXC chemokine, macrophage inflammatory protein-2 (MIP-2). Alveolar macrophages exhibited cytokine responses to both sICAM-1 and immobilized sICAM-1, while rat PBMCs failed to demonstrate similar responses. Exposure of alveolar macrophages to sICAM-1 resulted in NFkappa......B activation (which was blocked by the presence of the aldehyde peptide inhibitor of 28S proteosome and by genistein, a tyrosine kinase inhibitor). As expected, cross-linking of CD18 on macrophages with Ab resulted in generation of TNF-alpha and MIP-2. This response was also inhibited in the presence...... of TNF-alpha and MIP-2 and increased neutrophil recruitment. Therefore, through engagement of beta2 integrins, sICAM-1 enhances alveolar macrophage production of MIP-2 and TNF-alpha, the result of which is intensified lung injury after intrapulmonary disposition of immune complexes....

  15. Rheumatoid arthritis-associated interstitial lung disease: lung inflammation evaluated with high resolution computed tomography scan is correlated to rheumatoid arthritis disease activity.

    Science.gov (United States)

    Pérez-Dórame, Renzo; Mejía, Mayra; Mateos-Toledo, Heidegger; Rojas-Serrano, Jorge

    2015-01-01

    To describe the association between rheumatoid arthritis disease activity (RA) and interstitial lung damage (inflammation and fibrosis), in a group of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). A retrospective study of RA patients with interstitial lung disease (restrictive pattern in lung function tests and evidence of interstitial lung disease in high resolution computed tomography (HRCT)). Patients were evaluated to exclude other causes of pulmonary disease. RA disease activity was measured with the CDAI index. Interstitial lung inflammation and fibrosis were determined by Kazerooni scale. We compared Kazerooni ground-glass score with the nearest CDAI score to HRCT date scan of the first medical evaluation at our institution. In nine patients, we compared the first ground-glass score with a second one after treatment with DMARDs and corticosteroids. Spearman's rank correlation coefficient was used to evaluate association between RA disease activity and the Kazerooni ground-glass and fibrosis scores. Thirty-four patients were included. A positive correlation between CDAI and ground-glass scores was found (rs=0.3767, P<0.028). Fibrosis and CDAI scores were not associated (rs=-0.0747, P<0.6745). After treatment, a downward tendency in the ground-glass score was observed (median [IQR]): (2.33 [2,3] vs. 2 [1.33-2.16]), P<0.056, along with a lesser CDAI score (27 [8-43] vs. 9 [5-12]), P<0.063. There is a correlation between RA disease activity and ground-glass appearance in the HRCT of RA-ILD patients. These results suggest a positive association between RA disease activity and lung inflammation in RA-ILD. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  16. Distinct Properties of Human M-CSF and GM-CSF Monocyte-Derived Macrophages to Simulate Pathological Lung Conditions In Vitro: Application to Systemic and Inflammatory Disorders with Pulmonary Involvement.

    Science.gov (United States)

    Lescoat, Alain; Ballerie, Alice; Augagneur, Yu; Morzadec, Claudie; Vernhet, Laurent; Fardel, Olivier; Jégo, Patrick; Jouneau, Stéphane; Lecureur, Valérie

    2018-03-17

    Macrophages play a central role in the pathogenesis of inflammatory and fibrotic lung diseases. However, alveolar macrophages (AM) are poorly available in humans to perform in vitro studies due to a limited access to broncho-alveolar lavage (BAL). In this study, to identify the best alternative in vitro model for human AM, we compared the phenotype of AM obtained from BAL of patients suffering from three lung diseases (lung cancers, sarcoidosis and Systemic Sclerosis (SSc)-associated interstitial lung disease) to human blood monocyte-derived macrophages (MDMs) differentiated with M-CSF or GM-CSF. The expression of eight membrane markers was evaluated by flow cytometry. Globally, AM phenotype was closer to GM-CSF MDMs. However, the expression levels of CD163, CD169, CD204, CD64 and CD36 were significantly higher in SSc-ILD than in lung cancers. Considering the expression of CD204 and CD36, the phenotype of SSc-AM was closer to MDMs, from healthy donors or SSc patients, differentiated by M-CSF rather than GM-CSF. The comparative secretion of IL-6 by SSc-MDMs and SSc-AM is concordant with these phenotypic considerations. Altogether, these results support the M-CSF MDM model as a relevant in vitro alternative to simulate AM in fibrotic disorders such as SSc.

  17. Interstitial Lung Disease in Rheumatoid Arthritis in the Era of Biologics

    Directory of Open Access Journals (Sweden)

    A. Picchianti Diamanti

    2011-01-01

    Full Text Available Interstitial lung disease (ILD represents a severe manifestation in connective tissue diseases (CTD, with an overall incidence of 15%, and it is still a challenge for clinicians evaluation and management. ILD is the most common manifestation of lung involvement in Rheumatoid Arthritis (RA, observed in up to 80% of biopsies, 50% of chest Computed Tomography (CT and only 5% of chest radiographs. Histopatological patterns of ILD in RA may present with different patterns, such as: usual interstitial pneumonia, non specific interstitial pneumonia, desquamative interstitial pneumonia, organizing pneumonia, and eosinophilic infiltration. The incidence of ILD in RA patients is not only related to the disease itself, many drugs may be in fact associated with the development of pulmonary damage. Some reports suggest a causative role for TNFα inhibitors in RA-ILD development/worsening, anyway, no definitive statement can be drawn thus data are incomplete and affected by several variables. A tight control (pulmonary function tests and/or HRCT is mandatory in patients with preexisting ILD, but it should be also performed in those presenting risk factors for ILD and mild respiratory symptoms. Biologic therapy should be interrupted, and, after excluding triggering infections, corticosteroids should be administered.

  18. β-elemene inhibits tumor-promoting effect of M2 macrophages in lung cancer.

    Science.gov (United States)

    Yu, Xiaomu; Xu, Maoyi; Li, Na; Li, Zongjuan; Li, Hongye; Shao, Shujuan; Zou, Kun; Zou, Lijuan

    2017-08-19

    Macrophages in tumor are mostly M2-polarized and have been reported to promote tumorigenesis, which are also defined as tumor-associated macrophages (TAMs). β-elemene has therapeutic effects against several cancers, however, it remains unknown whether β-elemene could inhibit cancer by targeting TAMs. Herein, we examined the effect of β-elemene on macrophages to elucidate a novel mechanism of β-elemene in tumor therapy. We showed that the conditioned medium of M2 macrophages promoted lung cancer cells to migration, invasion and epithelial mesenchymal transition, which could be inhibited by β-elemene. Moreover, β-elemene regulated the polarization of macrophages from M2 to M1. β-elemene also inhibited the proliferation, migration, invasion of lung cancer cells and enhanced its radiosensitivity. These results indicate β-elemene suppresses lung cancer by regulating both macrophages and lung cancer cells, it is a promising drug for combination with chemotherapy or radiotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. IgG4-related lung disease presenting as interstitial lung disease with bronchiolitis: A case report.

    Science.gov (United States)

    Chen, Chiu-Fan; Chu, Kuo-An; Tseng, Yen-Chiang; Wu, Chang-Che; Lai, Ruay-Sheng

    2017-12-01

    IgG4-related disease is a rare and novel disease entity that tends to involve multiple organs. The pulmonary manifestation of this disease is highly variable and may mimic lung cancer, pneumonia, interstitial lung disease (ILD), sarcoidosis, and so forth. Small airway disease is rarely reported in IgG4-related lung disease (IgG4-RLD). In the current study, we describe a rare case of IgG4-RLD with patterns of ILD and bronchiolitis. A 43-year-old man had chronic cough and dyspnea on exertion for 4 years. Initial chest radiography showed diffuse interstitial infiltration. Follow-up chest computed tomography 4 years later revealed bilateral diffuse centrilobular nodules with tree-in-bud pattern, bronchial wall thickening, and mediastinal lymph nodes. Bilateral diffuse multifocal ground-glass opacities and mosaic attenuation were also observed. Pulmonary function test revealed mixed restrictive and obstructive ventilatory impairment. Video-assisted thoracoscopic surgery (VATS) lung biopsy showed interstitial fibrosis with lymphoplasmacytic infiltration rich in IgG4-positive plasma cells. Serum IgG4 level also showed remarkable elevation. Therefore, IgG4-RLD is confirmed. VATS wedge resection of right upper lobe and mediastinal lymph node. The patient responded well to steroid and immunosuppression therapy, and was regular followed-up in outpatient clinic. IgG4-RLD should be considered not only in ILD, but also in small airway disease. Serum IgG4 level may be a useful tool for screening.

  20. Clinical Outcomes in Interstitial Lung Diseases : Measuring and improving quality of life

    NARCIS (Netherlands)

    M.J.G. Van Manen (Mirjam)

    2017-01-01

    markdownabstractInterstitial lung diseases (ILDs) contain a wide variety of disorders, usually affecting both lungs diffusely. The most common ILDs are idiopathic pulmonary fibrosis and sarcoidosis. ILDs have a major impact on quality of life. Although it is well-known that quality of life is

  1. Interstitial lung disease associated with connective tissue diseases

    International Nuclear Information System (INIS)

    Medina, Yimy F; Restrepo, Jose Felix; Iglesias, Antonio; Ojeda, Paulina; Matiz, Carlos

    2007-01-01

    An interstitial lung disease (ILD) belongs to a group of diffuse parenchyma lung diseases it should be differentiated from other pathologies among those are idiopathic and ILD associated to connective tissue diseases (CTD) New concepts have been developed in the last years and they have been classified in seven defined subgroups. It has been described the association of each one of these subgroups with CTD. Natural history and other aspects of its treatment is not known completely .For complete diagnose it is required clinical, image and histopathologic approaches. The biopsy lung plays an essential role. It is important to promote and to stimulate the subclasification of each subgroup with the purpose of knowing their natural history directing the treatment and to improve their outcome

  2. Interstitial Lung disease in Systemic Sclerosis

    International Nuclear Information System (INIS)

    Ooi, G.C.; Mok, M.Y.; Tsang, K.W.T.; Khong, P.L.; Fung, P.C.W.; Chan, S.; Tse, H.F.; Wong, R.W.S.; Lam, W.K.; Lau, C.S.; Wong, Y.

    2003-01-01

    Purpose: To evaluate high-resolution CT (HRCT) parameters of inflammation and fibrosis in systemic sclerosis (SSc), for correlation with lung function, skin scores and exercise tolerance. Material and Methods: : 45 SSc patients (40 women, 48.5±13.4 years), underwent thoracic HRCT, lung function assessment, and modified Rodnan skin scores. Exercise tolerance was also graded. HRCT were scored for extent of 4 HRCT patterns of interstitial lung disease (ILD): ground glass opacification (GGO), reticular, mixed and honeycomb pattern in each lobe. Total HRCT score, inflammation index (GGO and mixed score) and fibrosis index (reticular and honeycomb scores) were correlated with lung function and clinical parameters. Results: ILD was present in 39/45 (86.7%) patients. Abnormal (<80% predicted) forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusion factor (DLco) were detected in 30%, 22% and 46% of patients. Total HRCT score correlated with FVC (r=0.43, p=0.008), FEV1 (forced expiratory volume) (r=-0.37, p=0.03), TLC (r=-0.47, p=0.003), and DLCO (r=-0.43, p=0.008); inflammatory index with DLCO (r=-0.43, p=0.008) and exercise tolerance (r=-0.39, p < 0.05); and fibrosis index with FVC (r=-0.31, p=0.05) and TLC (r=-0.38, p=0.02). Higher total HRCT score, and inflammation and fibrosis indices were found in patients with abnormal lung function. Conclusion: Qualitative HRCT is able to evaluate inflammation and fibrosis, showing important relationships with diffusion capacity and lung volume, respectively

  3. Immune complexes, gallium lung scans, and bronchoalveolar lavage in idiopathic interstitial pneumonitis-fibrosis

    International Nuclear Information System (INIS)

    Gelb, A.F.; Dreisen, R.B.; Epstein, J.D.; Silverthorne, J.D.; Bickel, Y.; Fields, M.; Border, W.A.; Taylor, C.R.

    1983-01-01

    We obtained results of lung immune complexes (LIC), circulating immune complexes (CIC), 48-hour gallium lung scans (scans), bronchoalveolar lavage (BAL), and pulmonary function tests in 20 patients with idiopathic interstitial pneumonitis-fibrosis. Sixteen patients had predominantly interstitial (13 cases UIP) and/or intraalveolar (3 cases DIP) cellular disease (group 1). Prior to corticosteroid therapy in group 1, scans were positive in 75 percent, CIC were elevated in 86 percent, LIC were present in 64 percent, and BAL was abnormal in 90 percent. Duration of follow-up after treatment was 3.5 +/- 1.0 year. In group 1 after treatment with corticosteroids in 13 patients and corticosteroids and penicillamine (three patients) and plasmapheresis (one patient), only four patients remain stable or improved. After corticosteroid therapy, elevated CIC returned to normal values despite progressive patient deterioration. In three patients, lung immune complexes were still detected after circulating immune complexes had returned to normal after corticosteroid therapy. In group 2 were four patients with fibrotic disease; scans and CIC were uniformly negative, LIC were weakly present in only one patient, and BAL was abnormal in all. Despite corticosteroid therapy, all have died or deteriorated. These results suggest that positive gallium lung scans, BAL, circulating immune complexes, and to a lesser extent, lung immune complexes are associated with the cellular phase of interstitial pneumonia, but do not reliably identify a corticosteroid-responsive group

  4. Ultrasound lung comets: new echographic sign of lung interstitial fibrosis in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    C. Giacomelli

    2011-09-01

    Full Text Available Objective: Interstitial lung disease (ILD and pulmonary arterial hypertension (PAH are common complications of systemic sclerosis (SSc. Echocardiography evaluates PAH, and chest sonography detects even mild ILC as ultrasound lung comets (ULC, i.e. multiple comet-tails fanning out from the lung surface and originating from subpleural interlobular septa thickened by fibrosis. Aim: to assess ILaD and PAH by integrated cardiac and chest ultrasound in SSc. Methods: We enrolled 30 consecutive SSc patients (age= 54±13 years, 23 females in the Rheumatology Clinic of Pisa University. In all, we assessed systolic pulmonary arterial pressure (SPAP, from maximal velocity of tricuspid regurgitation flow, and ULC score with chest sonography (summing the number of ULC from each scanning space of anterior and posterior right and left chest, from second to fifth intercostal space. All patients underwent plasma assay for anti-topoisomerase antibodies (anti-Scl70, and antiicentromere associated with development of pulmonary involvement. Twenty-eight patients also underwent high resolution computed tomography, HRCT (from 0= no fibrosis to 3= honey combing. Results: ULC number - but not SPAP - was correlated to HRCT fibrosis and presence Scl-70 antibodies. ULC number was similar in localized or diffuse forms (16±20 vs 21±19, p=ns and was unrelated to SPAP (r=0.216, p=ns. Conclusions: Chest sonography assessment and ULC allow a complete, simple, radiation-free characterization of interstitial lung involvement in SSc - all in one setting and with the same instrument, same transducer and the same sonographer. In particular, ULC number is associated with HRCT evidence of lung fibrosis and presence of Scl-70 antibodies.

  5. Systems medicine advances in interstitial lung disease.

    Science.gov (United States)

    Greiffo, Flavia R; Eickelberg, Oliver; Fernandez, Isis E

    2017-09-30

    Fibrotic lung diseases involve subject-environment interactions, together with dysregulated homeostatic processes, impaired DNA repair and distorted immune functions. Systems medicine-based approaches are used to analyse diseases in a holistic manner, by integrating systems biology platforms along with clinical parameters, for the purpose of understanding disease origin, progression, exacerbation and remission.Interstitial lung diseases (ILDs) refer to a heterogeneous group of complex fibrotic diseases. The increase of systems medicine-based approaches in the understanding of ILDs provides exceptional advantages by improving diagnostics, unravelling phenotypical differences, and stratifying patient populations by predictable outcomes and personalised treatments. This review discusses the state-of-the-art contributions of systems medicine-based approaches in ILDs over the past 5 years. Copyright ©ERS 2017.

  6. Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study.

    Directory of Open Access Journals (Sweden)

    Federica Novelli

    Full Text Available Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H₂O₂ was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons. Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r² = .27 and .31, respectively; p<.05 for both correlations. Exposure of lung epithelial cells to H₂O₂ caused an increase in microparticle-bound tissue factor

  7. Interstitial lung involvement in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    David Vladimirovich Bestaev

    2014-01-01

    Full Text Available Rheumatoid arthritis (RA is a systemic autoimmune rheumatic disease of unknown etiology, characterized by chronic erosive arthritis and extraarticular manifestations. Pulmonary involvement is one of the common extraarticular manifestations of RA and may show itself as bronchial tree lesions, rheumatoid nodules, Caplan's syndrome, and lesions in the pleura or pulmonary interstitium (interstitial lung involvement (ILI. High-resolution computed tomography allows the diagnosis of ILI in RA in nearly 70% of cases although the incidence of ILI may be lower (4 to 30% depending on diagnostic methods and patient selection criteria. There are several histopathological types of ILI, the differential diagnosis of which can be troublesome. Usual interstitial pneumonia (UIP and nonspecific interstitial pneumonia are major types of RA-associated ILI. UIP-pattern ILI has a more severe course than ILI with other histological patterns. The clinical presentation of ILI may be complicated by the likely toxic effect of a number of disease-modifying antirheumatic drugs (DMARDs used to treat RA, such as methotrexate and leflunomide, and biological agents (BAs, tumor necrosis factor-α (TNF-α inhibitors. The pathogenesis of pulmonary involvement in RA and the role of synthetic DMARDs and BAs in the development of ILI call for further investigations.An extraarticular manifestation, such as ILI, affects the choice of treatment policy in patients with RA.The relevance of a study of ILI is beyond question. The paper discusses the state-of-the-art of investigations in this area.

  8. Drug-induced interstitial lung diseases. Often forgotten; Medikamenteninduzierte interstitielle Lungenerkrankungen. Haeufig vergessen

    Energy Technology Data Exchange (ETDEWEB)

    Poschenrieder, F.; Stroszczynski, C. [Universitaetsklinikum Regensburg, Institut fuer Roentgendiagnostik, Regensburg (Germany); Hamer, O.W. [Universitaetsklinikum Regensburg, Institut fuer Roentgendiagnostik, Regensburg (Germany); Lungenfachklinik Donaustauf, Donaustauf (Germany)

    2014-12-15

    Drug-induced interstitial lung diseases (DILD) are probably more common than diagnosed. Due to their potential reversibility, increased vigilance towards DILD is appropriate also from the radiologist's point of view, particularly as these diseases regularly exhibit radiological correlates in high-resolution computed tomography (HRCT) of the lungs. Based on personal experience typical relatively common manifestations of DILD are diffuse alveolar damage (DAD), eosinophilic pneumonia (EP), hypersensitivity pneumonitis (HP), organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). These patterns are presented based on case studies, whereby emphasis is placed on the clinical context. This is to highlight the relevance of interdisciplinary communication and discussion in the diagnostic field of DILD as it is a diagnosis of exclusion or of probability in most cases. Helpful differential diagnostic indications for the presence of DILD, such as an accompanying eosinophilia or increased attenuation of pulmonary consolidations in amiodarone-induced pneumopathy are mentioned and the freely available online database http://www.pneumotox.com is presented. (orig.) [German] Medikamenteninduzierte interstitielle Lungenerkrankungen (engl. ''drug-induced interstitial lung diseases'', DILD) sind wahrscheinlich haeufiger, als sie diagnostiziert werden. Aufgrund ihrer potenziellen Reversibilitaet ist eine erhoehte Vigilanz gegenueber DILD auch seitens der Radiologie angebracht, da diese regelmaessig ein radiomorphologisches Korrelat in der hochaufloesenden Computertomographie (''high-resolution CT'', HRCT) der Lunge aufweisen. Typische, nach eigener Erfahrung relativ haeufige Manifestationsformen von DILD sind der diffuse Alveolarschaden (engl. ''diffuse alveolar damage'', DAD), die eosinophile Pneumonie (EP), die Hypersensitivitaetspneumonitis (HP), die organisierende

  9. Fibred confocal fluorescence microscopy in the diagnosis of interstitial lung diseases.

    Science.gov (United States)

    Meng, Peng; Tan, Gan Liang; Low, Su Ying; Takano, Angela; Ng, Yuen Li; Anantham, Devanand

    2016-12-01

    Accurate diagnosis is critical to both therapeutic decisions and prognostication in interstitial lung diseases (ILD). However, surgical lung biopsies carry high complication rates. Fibred confocal fluorescence microscopy (FCFM) offers an alternative as it can visualize lung tissue in vivo at the cellular level with minimal adverse events. We wanted to investigate the diagnostic utility, and safety of using FCFM for patients with ILD. In patients with suspected ILD, FCFM images were obtained from multiple bronchopulmonary segments using a miniprobe inserted through the working channel of a flexible bronchoscope. The procedure was performed under moderate sedation in an outpatient setting. Morphometric measurements and fibre pattern analyses were co-related with computed tomography (CT) findings and patients' final diagnoses based on multi-disciplinary consensus. One hundred and eighty four segments were imaged in 27 patients (18 males) with a median age of 67 years (range, 24-79 years). They were grouped into chronic fibrosing interstitial pneumonia (16 patients) and other ILDs. Six distinct FCFM patterns were observed: normal, increased fibres, densely packed fibres, hypercellular, thickened fibres and others/non-specific. The pattern resembling densely packed fibres was seen in at least one segment in 68.8% patients with chronic fibrosing interstitial pneumonia, but only 36.4% in other ILD (P=0.097). An association between inflammatory patterns on CT and a hypercellular pattern on FCFM was also found (P<0.001). Our study shows the potential of FCFM in classifying ILD, but its role in further diagnosis remains limited.

  10. Interstitial lung disease associated with human papillomavirus vaccination

    Directory of Open Access Journals (Sweden)

    Yasushi Yamamoto

    2015-01-01

    Full Text Available Vaccinations against the human papillomavirus (HPV have been recommended for the prevention of cervical cancer. HPV-16/18 AS04-adjuvanted vaccines (Cervarix are said to have favourable safety profiles. Interstitial lung diseases (ILDs can occur following exposure to a drug or a biological agent. We report a case of ILD associated with a Cervarix vaccination. A woman in her 40's, with a history of conisation, received three inoculations of Cervarix. Three months later, she presented with a cough and shortness of breath. Findings from a computed tomography of the chest and a transbronchial lung biopsy were consistent with non-specific interstitial pneumonia. Workup eliminated all other causes of the ILD, except for the vaccination. Over the 11 months of the follow-up period, her symptoms resolved without steroid therapy. The onset and spontaneous resolution of the ILD showed a chronological association with the HPV vaccination. The semi-quantitative algorithm revealed that the likelihood of an adverse drug reaction to Cervarix was “Probable”. The outcome was relatively good, but more attention should be paid to a potential risk for HPV vaccinations to cause ILDs. Wherever possible, chest radiographic examinations should be performed in order not to overlook any ILDs.

  11. Coal Mine Dust Desquamative Chronic Interstitial Pneumonia: A Precursor of Dust-Related Diffuse Fibrosis and of Emphysema.

    Science.gov (United States)

    Jelic, Tomislav M; Estalilla, Oscar C; Sawyer-Kaplan, Phyllis R; Plata, Milton J; Powers, Jeremy T; Emmett, Mary; Kuenstner, John T

    2017-07-01

    Diseases associated with coal mine dust continue to affect coal miners. Elucidation of initial pathological changes as a precursor of coal dust-related diffuse fibrosis and emphysema, may have a role in treatment and prevention. To identify the precursor of dust-related diffuse fibrosis and emphysema. Birefringent silica/silicate particles were counted by standard microscope under polarized light in the alveolar macrophages and fibrous tissue in 25 consecutive autopsy cases of complicated coal worker's pneumoconiosis and in 21 patients with tobacco-related respiratory bronchiolitis. Coal miners had 331 birefringent particles/high power field while smokers had 4 (pcoal miner had intra-alveolar macrophages with silica/silicate particles and interstitial fibrosis ranging from minimal to extreme. All coal miners, including those who never smoked, had emphysema. Fibrotic septa of centrilobular emphysema contained numerous silica/silicate particles while only a few were present in adjacent normal lung tissue. In coal miners who smoked, tobacco-associated interstitial fibrosis was replaced by fibrosis caused by silica/silicate particles. The presence of silica/silicate particles and anthracotic pigment-laden macrophages inside the alveoli with various degrees of interstitial fibrosis indicated a new disease: coal mine dust desquamative chronic interstitial pneumonia, a precursor of both dust-related diffuse fibrosis and emphysema. In studied coal miners, fibrosis caused by smoking is insignificant in comparison with fibrosis caused by silica/silicate particles. Counting birefringent particles in the macrophages from bronchioalveolar lavage may help detect coal mine dust desquamative chronic interstitial pneumonia, and may initiate early therapy and preventive measures.

  12. Initial experience with lung-MRI at 3.0 T: Comparison with CT and clinical data in the evaluation of interstitial lung disease activity

    International Nuclear Information System (INIS)

    Lutterbey, G.; Grohe, C.; Gieseke, J.; Falkenhausen, M. von; Morakkabati, N.; Wattjes, M.P.; Manka, R.; Trog, D.; Schild, H.H.

    2007-01-01

    Objectives: We evaluated the feasibility of highfield lung-MRI at 3.0 T. A comparison with Computed Tomography (CT) and clinical data regarding the assessment of inflammatory activity in patients with diffuse lung disease was performed. Material and methods: Prospective evaluation of 21 patients (15 males, 6 females, 43-80 y) with diffuse lung diseases who underwent clinical work-up inclusive laboratory tests, lung-function tests and transbronchial biopsy. After routine helical CT (additional 12 HRCT) a lung-MRI (3.0 Intera, Philips Medical Systems, Best, The Netherlands) using a T2-weighted, cardiac and respiratory triggered Fast-Spinecho-Sequence (TE/TR = 80/1500-2500 ms, 22 transverse slices, 7/2 mm slice-thickness/-gap) was performed. A pneumologist classified the cases into two groups: A = temporary acute interstitial disease or chronic interstitial lung disease with acute episode or superimposed infection/B = burned out interstitial lung disease without activity. Two blinded CT-radiologists graded the cases in active/inactive disease on the basis of nine morphological criteria each. A third radiologist rated the MRI-cases as active/inactive, depending on the signal-intensities of lung tissues. Results: The pneumologist classified 14 patients into group A and 7 patients into group B. Using CT, 6 cases were classified as active, 15 cases as inactive disease. With MRI 12 cases were classified as active and 9 cases as inactive. In the complete group of 21 patients MRI decisions and CT decisions respectively were false positive/false negative/correct in 2/4/15 respectively 0/8/13 cases. Correct diagnoses were obtained in 72% (MRI) respectively 62% (CT). In the subgroup of 12 cases including HRCT, MRI respectively CT were false positive/false negative/correct in 2/1/9 respectively 0/5/7 cases. Correct diagnoses were obtained in 75% (MRI) respectively 58% (CT). Conclusion: Highfield MRI of the lung is feasible and performed slightly better compared to CT in the

  13. Initial experience with lung-MRI at 3.0 T: Comparison with CT and clinical data in the evaluation of interstitial lung disease activity

    Energy Technology Data Exchange (ETDEWEB)

    Lutterbey, G. [Department of Radiology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn (Germany)]. E-mail: goetz.lutterbey@ukb.uni-bonn.de; Grohe, C. [Department of Internal Medicine, University of Bonn (Germany); Gieseke, J. [PHILIPS Medical Systems, Best (Netherlands); Falkenhausen, M. von [Department of Radiology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn (Germany); Morakkabati, N. [Department of Radiology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn (Germany); Wattjes, M.P. [Department of Radiology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn (Germany); Manka, R. [Department of Internal Medicine, University of Bonn (Germany); Trog, D. [Department of Radiology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn (Germany); Schild, H.H. [Department of Radiology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn (Germany)

    2007-02-15

    Objectives: We evaluated the feasibility of highfield lung-MRI at 3.0 T. A comparison with Computed Tomography (CT) and clinical data regarding the assessment of inflammatory activity in patients with diffuse lung disease was performed. Material and methods: Prospective evaluation of 21 patients (15 males, 6 females, 43-80 y) with diffuse lung diseases who underwent clinical work-up inclusive laboratory tests, lung-function tests and transbronchial biopsy. After routine helical CT (additional 12 HRCT) a lung-MRI (3.0 Intera, Philips Medical Systems, Best, The Netherlands) using a T2-weighted, cardiac and respiratory triggered Fast-Spinecho-Sequence (TE/TR = 80/1500-2500 ms, 22 transverse slices, 7/2 mm slice-thickness/-gap) was performed. A pneumologist classified the cases into two groups: A = temporary acute interstitial disease or chronic interstitial lung disease with acute episode or superimposed infection/B = burned out interstitial lung disease without activity. Two blinded CT-radiologists graded the cases in active/inactive disease on the basis of nine morphological criteria each. A third radiologist rated the MRI-cases as active/inactive, depending on the signal-intensities of lung tissues. Results: The pneumologist classified 14 patients into group A and 7 patients into group B. Using CT, 6 cases were classified as active, 15 cases as inactive disease. With MRI 12 cases were classified as active and 9 cases as inactive. In the complete group of 21 patients MRI decisions and CT decisions respectively were false positive/false negative/correct in 2/4/15 respectively 0/8/13 cases. Correct diagnoses were obtained in 72% (MRI) respectively 62% (CT). In the subgroup of 12 cases including HRCT, MRI respectively CT were false positive/false negative/correct in 2/1/9 respectively 0/5/7 cases. Correct diagnoses were obtained in 75% (MRI) respectively 58% (CT). Conclusion: Highfield MRI of the lung is feasible and performed slightly better compared to CT in the

  14. Functional ability and fate of pulmonary alveolar macrophages after intratracheal instillation into rats

    International Nuclear Information System (INIS)

    Snipes, M.B.; Feddersen, D.; Mueller, H.L.; Guilmette, R.A.; Haley, P.J.

    1988-01-01

    Pulmonary alveolar macrophages (PAM) from donor rats were intratracheally instilled into recipient rats to determine if donor macrophages were functionally similar to the recipient's own macrophages. Recipient and donor (extrinsic) PAM were equivalent in their ability to phagocytize 1.7 μm and 3.9 μm latex microspheres in vivo and sensitized sheep red blood cells in vitro. Also, the extrinsic PAM appeared functionally equivalent to recipient PAM with respect to ability to translocate into interstitial tissue and migrate to the lung-associated lymph nodes (LALN). The recipient PAN appeared to phagocytize the extrinsic PAM, but the extrinsic PAM did not appear to phagocytize the recipient PAM. This could represent a different degree of physiological coordination of intrinsic and extrinsic PAM activities in the lung. Overall, results indicated that extrinsic PAM can live and function in the lungs of recipient rats, and perform most or all of the functions ascribed to recipient PAM. Results also support the hypothesis that PAM are able to move into the pulmonary interstitium and translocate to the LALM without the involvement of other pulmonary macrophages. (author)

  15. Interstitial lung disease in patients with polymyositis, dermatomyositis and amyopathic dermatomyositis.

    Science.gov (United States)

    Kang, E H; Lee, E B; Shin, K C; Im, C H; Chung, D H; Han, S K; Song, Y W

    2005-10-01

    To assess the prevalence, characteristics and prognostic factors of interstitial lung disease (ILD) in Korean patients with polymyositis (PM), dermatomyositis (DM) and amyopathic dermatomyositis (ADM). We reviewed the medical records of 72 consecutive PM and DM patients, including six patients with ADM, who were seen at the Rheumatology Clinic of Seoul National University Hospital between 1984 and 2003. Twenty-nine PM/DM patients (40.3%) developed ILD. Anti-Jo-1 antibody and arthralgia were associated with the presence of ILD (P = 0.022 and P = 0.041, respectively), whereas dysphagia was more frequently found in patients without ILD (P = 0.041). Lung biopsies revealed diffuse alveolar damage (DAD) (n = 2), usual interstitial pneumonia (UIP) with DAD (n = 2), UIP (n = 1), and non-specific interstitial pneumonia (n = 2). Of the 29 patients, 11 (37.9%) died. The mean survival time in ILD patients was significantly shorter than in those without ILD (13.8+/-1.8 vs 19.2+/-0.9 yr, P = 0.017). Poor survival in ILD patients was associated with a Hamman-Rich-like presentation (P = 0.0000), ADM features (P = 0.0001) and an initial forced vital capacity (FVC) poor survival. A Hamman-Rich-like presentation, ADM features and an initial FVC poor survival in ILD.

  16. The role of nailfold capillaroscopy in interstitial lung diseases - can it differentiate idiopathic cases from collagen tissue disease associated interstitial lung diseases?

    Science.gov (United States)

    Çakmakçı Karadoğan, Dilek; Balkarlı, Ayşe; Önal, Özgür; Altınışık, Göksel; Çobankara, Veli

    2015-01-01

    Nailfold capillaroscopy (NFC) is a non-invasive diagnostic test that is mostly used for early diagnosis of collagen tissue diseases (CTDs). We aimed to evaluate whether NFC findings could be a clue for discriminating idiopathic interstitial lung diseases (ILD) from CTD associated ILDs (CTD-ILD). Additionally it was aimed to determine whether NFC could be helpful in discriminating usual interstitial pneumonia (UIP) pattern from non-specific interstitial pneumonia (NSIP) pattern. We grouped patients into three main groups: 15 CTD-ILD, 18 idiopathic ILD, and 17 patients in the control group. The CTD-ILD group was split into two subgroups: 8 patients with Sjögren's syndrome (SJS)-associated ILD and 7 with rheumatoid arthritis (RA)-associated ILD. The idiopathic-ILD group consisted of 10 idiopathic NSIP and 8 IPF patients. The control group consisted of 10 SJS and 7 RA patients without lung disease. None of the patients were on acute exacerbation at the time of examination, and none had Reynaud's phenomenon. Mean capillary density was significantly reduced only in the CTD-ILD group as compared to the control group (p= 0.006). In subgroup analysis, it was determined that RA-ILD, IPF, and SJS-ILD subgroups had more severe capillaroscopic abnormalities. Mean capillary density in patients with the UIP pattern was reduced compared to patients with the NSIP pattern and those in the control group; p values were 0.008 and nailfold capillaroscopic findings of patients with NSIP and UIP patterns. NFC findings can be helpful in discriminating UIP patterns from NSIP patterns. But to show its role in differentiating idiopathic disease, more studies with more patients are needed.

  17. Interstitial lung disease induced by fluoxetine: Systematic review of literature and analysis of Vigiaccess, Eudravigilance and a national pharmacovigilance database.

    Science.gov (United States)

    Deidda, Arianna; Pisanu, Claudia; Micheletto, Laura; Bocchetta, Alberto; Del Zompo, Maria; Stochino, Maria Erminia

    2017-06-01

    We investigated a pulmonary adverse drug reaction possibly induced by fluoxetine, the Interstitial Lung Disease, by performing a systematic review of published case reports on this subject, a review of the World Health Organization VigiAccess database, of the European EudraVigilance database and of a national Pharmacovigilance database (Italian Pharmacovigilance Network). The research found a total of seven cases linking fluoxetine to Interstitial Lung Disease in the literature. 36 cases of interstitial lung disease related to fluoxetine were retrieved from the VigiAccess database (updated to July 2016), and 36 reports were found in EudraVigilance database (updated to June 2016). In the Italian Pharmacovigilance database (updated to August 2016), we found only one case of Interstitial Lung Disease, codified as "pulmonary disease". Our investigation shows that fluoxetine might be considered as a possible cause of Interstitial Lung Disease. In particular, although here we do not discuss the assessment of benefits and harms of fluoxetine, since this antidepressant is widely used, our review suggests that fluoxetine-induced Interstitial Lung Disease should be considered in patients with dyspnea, associated or not with dry cough, who are treated with this drug. An early withdrawn of fluoxetine could be useful to obtain a complete remission of this adverse drug reaction and special attention should be particularly devoted to long-term therapy, and to female and elderly patients. Although the spontaneous reporting system is affected by important limitations, drug post- marketing surveillance represents an important tool to evaluate the real world effectiveness and safety of drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Pulmonary function tests as outcomes for systemic sclerosis interstitial lung disease.

    Science.gov (United States)

    Caron, Melissa; Hoa, Sabrina; Hudson, Marie; Schwartzman, Kevin; Steele, Russell

    2018-06-30

    Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc). We performed a systematic review to characterise the use and validation of pulmonary function tests (PFTs) as surrogate markers for systemic sclerosis-associated interstitial lung disease (SSc-ILD) progression.Five electronic databases were searched to identify all relevant studies. Included studies either used at least one PFT measure as a longitudinal outcome for SSc-ILD progression ( i.e. outcome studies) and/or reported at least one classical measure of validity for the PFTs in SSc-ILD ( i.e. validation studies).This systematic review included 169 outcome studies and 50 validation studies. Diffusing capacity of the lung for carbon monoxide ( D LCO ) was cumulatively the most commonly used outcome until 2010 when it was surpassed by forced vital capacity (FVC). FVC (% predicted) was the primary endpoint in 70.4% of studies, compared to 11.3% for % predicted D LCO Only five studies specifically aimed to validate the PFTs: two concluded that D LCO was the best measure of SSc-ILD extent, while the others did not favour any PFT. These studies also showed respectable validity measures for total lung capacity (TLC).Despite the current preference for FVC, available evidence suggests that D LCO and TLC should not yet be discounted as potential surrogate markers for SSc-ILD progression. Copyright ©ERS 2018.

  19. Coal Mine Dust Desquamative Chronic Interstitial Pneumonia: A Precursor of Dust-Related Diffuse Fibrosis and of Emphysema

    Directory of Open Access Journals (Sweden)

    Tomislav M Jelic

    2017-07-01

    Full Text Available Background: Diseases associated with coal mine dust continue to affect coal miners. Elucidation of initial pathological changes as a precursor of coal dust-related diffuse fibrosis and emphysema, may have a role in treatment and prevention. Objective: To identify the precursor of dust-related diffuse fibrosis and emphysema. Methods: Birefringent silica/silicate particles were counted by standard microscope under polarized light in the alveolar macrophages and fibrous tissue in 25 consecutive autopsy cases of complicated coal worker's pneumoconiosis and in 21 patients with tobacco-related respiratory bronchiolitis. Results: Coal miners had 331 birefringent particles/high power field while smokers had 4 (p<0.001. Every coal miner had intra-alveolar macrophages with silica/silicate particles and interstitial fibrosis ranging from minimal to extreme. All coal miners, including those who never smoked, had emphysema. Fibrotic septa of centrilobular emphysema contained numerous silica/silicate particles while only a few were present in adjacent normal lung tissue. In coal miners who smoked, tobacco-associated interstitial fibrosis was replaced by fibrosis caused by silica/silicate particles. Conclusion: The presence of silica/silicate particles and anthracotic pigment-laden macrophages inside the alveoli with various degrees of interstitial fibrosis indicated a new disease: coal mine dust desquamative chronic interstitial pneumonia, a precursor of both dust-related diffuse fibrosis and emphysema. In studied coal miners, fibrosis caused by smoking is insignificant in comparison with fibrosis caused by silica/silicate particles. Counting birefringent particles in the macrophages from bronchioalveolar lavage may help detect coal mine dust desquamative chronic interstitial pneumonia, and may initiate early therapy and preventive measures.

  20. Rheumatoid Arthritis (RA) associated interstitial lung disease (ILD).

    LENUS (Irish Health Repository)

    O'Dwyer, David N

    2013-10-01

    Rheumatoid Arthritis (RA) is the most common Connective Tissue Disease (CTD) and represents an increasing burden on global health resources. Interstitial lung disease (ILD) has been recognised as a complication of RA but its potential for mortality and morbidity has arguably been under appreciated for decades. New studies have underscored a significant lifetime risk of ILD development in RA. Contemporary work has identified an increased risk of mortality associated with the Usual Interstitial Pneumonia (UIP) pattern which shares similarity with the most devastating of the interstitial pulmonary diseases, namely Idiopathic Pulmonary Fibrosis (IPF). In this paper, we discuss recent studies highlighting the associated increase in mortality in RA-UIP. We explore associations between radiological and histopathological features of RA-ILD and the prognostic implications of same. We emphasise the need for translational research in this area given the growing burden of RA-ILD. We highlight the importance of the respiratory physician as a key stakeholder in the multidisciplinary management of this disorder. RA-ILD focused research offers the opportunity to identify early asymptomatic disease and define the natural history of this extra articular manifestation. This may provide a unique opportunity to define key regulatory fibrotic events driving progressive disease. We also discuss some of the more challenging and novel aspects of therapy for RA-ILD.

  1. Visual assessment of early emphysema and interstitial abnormalities on CT is useful in lung cancer risk analysis

    DEFF Research Database (Denmark)

    Wille, Mathilde M. W.; Thomsen, Laura H.; Petersen, Jens

    2016-01-01

    Objectives: Screening for lung cancer should be limited to a high-risk-population, and abnormalities in low-dose computed tomography (CT) screening images may be relevant for predicting the risk of lung cancer. Our aims were to compare the occurrence of visually detected emphysema and interstitial...... abnormalities in subjects with and without lung cancer in a screening population of smokers. Methods: Low-dose chest CT examinations (baseline and latest possible) of 1990 participants from The Danish Lung Cancer Screening Trial were independently evaluated by two observers who scored emphysema and interstitial...... abnormalities. Emphysema (lung density) was also measured quantitatively. Results: Emphysema was seen more frequently and its extent was greater among participants with lung cancer on baseline (odds ratio (OR), 1.8, p = 0.017 and p = 0.002) and late examinations (OR 2.6, p

  2. Fatal interstitial lung disease associated with icotinib.

    Science.gov (United States)

    Zhang, Jiexia; Zhan, Yangqing; Ouyang, Ming; Qin, Yinyin; Zhou, Chengzhi; Chen, Rongchang

    2014-12-01

    The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and erlotinib is drug-associated interstitial lung disease (ILD), which has been often described. However, it has been less well described for icotinib, a similar orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old female patient with stage IV lung adenocarcinoma who developed fatal ILD is reported here. She denied chemotherapy, and received palliative treatment with icotinib (125 mg po, three times daily) on March 1, 2013. One month after treatment initiation, the patient complained of continuous dry cough and rapid progressive dyspnea. Forty one days after icotinib treatment, icotinib associated ILD was suspected when the patient became increasingly dyspnoeic despite of treatment of pericardial effusion, left pleural effusion and lower respiratory tract infection, and X-ray computed tomography (CT) of chest revealed multiple effusion shadows and ground-glass opacities in bilateral lungs. Then, icotinib was discontinued and intravenous corticosteroid was started (methylprednisolone 40 mg once daily, about 1 mg per kilogram) respectively. Forty three days after icotinib treatment, the patient died of hypoxic respiratory failure. ILD should be considered as a rare, but often fatal side effect associated with icotinib treatment.

  3. Classical and alternative macrophage activation in the lung following ozone-induced oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Sunil, Vasanthi R., E-mail: sunilva@pharmacy.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 (United States); Patel-Vayas, Kinal; Shen, Jianliang [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 (United States)

    2012-09-01

    Ozone is a pulmonary irritant known to cause oxidative stress, inflammation and tissue injury. Evidence suggests that macrophages play a role in the pathogenic response; however, their contribution depends on the mediators they encounter in the lung which dictate their function. In these studies we analyzed the effects of ozone-induced oxidative stress on the phenotype of alveolar macrophages (AM). Exposure of rats to ozone (2 ppm, 3 h) resulted in increased expression of 8-hydroxy-2′-deoxyguanosine (8-OHdG), as well as heme oxygenase-1 (HO-1) in AM. Whereas 8-OHdG was maximum at 24 h, expression of HO-1 was biphasic increasing after 3 h and 48–72 h. Cleaved caspase-9 and beclin-1, markers of apoptosis and autophagy, were also induced in AM 24 h post-ozone. This was associated with increased bronchoalveolar lavage protein and cells, as well as matrix metalloproteinase (MMP)-2 and MMP-9, demonstrating alveolar epithelial injury. Ozone intoxication resulted in biphasic activation of the transcription factor, NFκB. This correlated with expression of monocyte chemotactic protein‐1, inducible nitric oxide synthase and cyclooxygenase‐2, markers of proinflammatory macrophages. Increases in arginase-1, Ym1 and galectin-3 positive anti-inflammatory/wound repair macrophages were also observed in the lung after ozone inhalation, beginning at 24 h (arginase-1, Ym1), and persisting for 72 h (galectin-3). This was associated with increased expression of pro-surfactant protein-C, a marker of Type II cell proliferation and activation, important steps in wound repair. These data suggest that both proinflammatory/cytotoxic and anti-inflammatory/wound repair macrophages are activated early in the response to ozone-induced oxidative stress and tissue injury. -- Highlights: ► Lung macrophages are highly sensitive to ozone induced oxidative stress. ► Ozone induces autophagy and apoptosis in lung macrophages. ► Proinflammatory and wound repair macrophages are activated

  4. Percutaneous evacuation of diffuse pulmonary interstitial emphysema by lung puncture in a baby with extremely low birth weight: a case report

    Directory of Open Access Journals (Sweden)

    Watanabe Masahiro

    2012-09-01

    Full Text Available Abstract Introduction Pulmonary interstitial emphysema is a serious complication of mechanical ventilation and can become life-threatening if progression occurs. Therapeutic lung puncture is a treatment option for severe pulmonary interstitial emphysema but has a limited use in babies with extremely low birth weight. We present a case of pulmonary interstitial emphysema in a Japanese baby (1-day-old boy with extremely low birth weight. The emphysema was successfully decompressed by therapeutic lung puncture performed with a trocar catheter. Case presentation The baby was born with a weight of 420g, which, to the best of our knowledge, is the lowest reported birth weight among babies with pulmonary interstitial emphysema. A chest X-ray on postnatal day 2 revealed pulmonary interstitial emphysema, which gradually progressed to diffuse pseudocystic changes. His condition became life-threatening despite the use of high-frequency oscillatory ventilation and lateral decubitus positioning. We evacuated the pulmonary interstitial emphysema by lung puncture with a trocar catheter to avoid respiratory and cardiovascular collapse. This resulted in adequate evacuation of the emphysema and a dramatic improvement in his clinical condition. Conclusions Therapeutic lung puncture performed with a trocar catheter is beneficial in babies with extremely low birth weight and diffuse pulmonary interstitial emphysema. This treatment option may be broadly applicable, especially in an emergency situation.

  5. Role of macrophages and oxygen radicals in IgA induced lung injury in the rat

    International Nuclear Information System (INIS)

    Johnson, K.J.; Ward, P.A.; Kunkel, R.G.; Wilson, B.S.

    1986-01-01

    Acute lung injury in the rat has been induced by the instillation of affinity-purified mouse monoclonal IgA antibody with specific reactivity to dinitrophenol (DNP) coupled to albumin. This model of lung injury requires an intact complement system but not neutrophils, and evidence suggests that pulmonary macrophages are the critical effector cell. Macrophages retrievable from the lungs of the IgA immune complex treated rats are considerably increased in number as compared to control animals which received only the antibody. In addition these cells show evidence of activation in vivo with greater spontaneous generation of the superoxide anion (O 2 - ) as well as significantly enhanced O 2 - response in the presence of a second stimulus. Inhibition studies in vivo suggest that the lung injury is mediated by oxygen radical generation by the pulmonary macrophages. Pretreatment of rats with superoxide dismutase (SOD), catalase, the iron chelator deferoxamine or the hydroxyl radical scavenger dimethyl sulfoxide (DMSO) all markedly suppressed the development of the lung injury. In summary, these studies suggest that IgA immune complex injury in the rat lung is mediated by oxygen radical formation from pulmonary macrophages

  6. High-resolution computed tomography versus chest radiography in the diagnosis of interstitial lung disease in systemic sclerosis

    International Nuclear Information System (INIS)

    Azevedo, Ana Beatriz Cordeiro de; Calderaro, Debora; Moreira, Caio; Guimaraes, Silvana Mangeon Meirelles; Tavares Junior, Wilson Campos; Leao Filho, Hilton Muniz; Andrade, Diego Correa de; Ferreira, Cid Sergio; Vieira, Jose Nelson Mendes

    2005-01-01

    Objective: To compare the accuracy of high-resolution computed tomography (HRCT) with chest radiography in the diagnosis of interstitial lung disease in systemic sclerosis (SSc). Materials And Methods: HRCT scans and chest radiographs in postero-anterior and lateral views were performed in 34 patients with systemic sclerosis, according to the American College of Rheumatology preliminary criteria for the diagnosis of SSc. The prevalence of radiological findings suggestive of interstitial lung disease in SSc seen on both imaging methods was compared. Results: Interstitial disease was observed on HRCT images of 31 patients (91%) and in the chest radiographs of 16 patients (47%). The most frequent findings observed on HRCT were septal lines (74%), honeycombing (56%) and parenchymal bands (26%). Chest radiographs showed reticular areas of attenuation in 11 patients (32%) and parenchymal distortion in 12% of the patients. In 18 patients (53%) with normal chest radiographs HRCT showed septal lines in 55%, ground glass in 44%, honeycombing in 38.5% and cysts in 33%. Conclusion: HRCT is more sensitive than chest radiography in the evaluation of incipient interstitial lung involvement in patients with SSc and can provide a justification for immunosuppressive therapy in patients with early disease. (author)

  7. Importance of Bacterial Replication and Alveolar Macrophage-Independent Clearance Mechanisms during Early Lung Infection with Streptococcus pneumoniae

    Science.gov (United States)

    Camberlein, Emilie; Cohen, Jonathan M.; José, Ricardo; Hyams, Catherine J.; Callard, Robin; Chimalapati, Suneeta; Yuste, Jose; Edwards, Lindsey A.; Marshall, Helina; van Rooijen, Nico; Noursadeghi, Mahdad

    2015-01-01

    Although the importance of alveolar macrophages for host immunity during early Streptococcus pneumoniae lung infection is well established, the contribution and relative importance of other innate immunity mechanisms and of bacterial factors are less clear. We have used a murine model of S. pneumoniae early lung infection with wild-type, unencapsulated, and para-amino benzoic acid auxotroph mutant TIGR4 strains to assess the effects of inoculum size, bacterial replication, capsule, and alveolar macrophage-dependent and -independent clearance mechanisms on bacterial persistence within the lungs. Alveolar macrophage-dependent and -independent (calculated indirectly) clearance half-lives and bacterial replication doubling times were estimated using a mathematical model. In this model, after infection with a high-dose inoculum of encapsulated S. pneumoniae, alveolar macrophage-independent clearance mechanisms were dominant, with a clearance half-life of 24 min compared to 135 min for alveolar macrophage-dependent clearance. In addition, after a high-dose inoculum, successful lung infection required rapid bacterial replication, with an estimated S. pneumoniae doubling time of 16 min. The capsule had wide effects on early lung clearance mechanisms, with reduced half-lives of 14 min for alveolar macrophage-independent and 31 min for alveolar macrophage-dependent clearance of unencapsulated bacteria. In contrast, with a lower-dose inoculum, the bacterial doubling time increased to 56 min and the S. pneumoniae alveolar macrophage-dependent clearance half-life improved to 42 min and was largely unaffected by the capsule. These data demonstrate the large effects of bacterial factors (inoculum size, the capsule, and rapid replication) and alveolar macrophage-independent clearance mechanisms during early lung infection with S. pneumoniae. PMID:25583525

  8. HRCT patterns of the most important interstitial lung diseases; HRCT-Muster der wichtigsten interstitiellen Lungenerkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer-Prokop, C. [Meander Medisch Centrum, Abt. Radiologie, Amersfoort (Netherlands); Radboud Universitaet, Abt. Radiologie und Nuklearmedizin, Nijmegen (Netherlands)

    2014-12-15

    Interstitial lung diseases are a mixed group of diffuse parenchymal lung diseases which can have an acute or chronic course. Idiopathic diseases and diseases with an underlying cause (e.g. collagen vascular diseases) share the same patterns. Thin section computed tomography (CT) plays a central role in the diagnostic work-up. The article describes the most important interstitial lung diseases following a four pattern approach with a predominant nodular or reticular pattern or a pattern with increased or decreased lung density. (orig.) [German] Interstitielle Lungenerkrankungen stellen eine gemischte Gruppe diffuser Lungenparenchymerkrankungen dar, die einen akuten oder chronischen Verlauf haben koennen. Idiopathische Erkrankungen und Erkrankungen mit definierter Ursache (z. B. kollagenvaskulaere Erkrankungen) weisen ein gemeinsames Muster auf. Die Duennschichtcomputertomographie spielt eine zentrale Rolle in der diagnostischen Abklaerung. In dem vorliegenden Beitrag werden die wichtigsten interstitiellen Lungenerkrankungen beschrieben. Dabei gibt es 4 Grundmuster: ueberwiegend nodulaere Verdichtungen, vorwiegend retikulaere Verdichtungen, erhoehte oder erniedrigte Lungenparenchymdichte. (orig.)

  9. Intravenous Immunoglobulin Monotherapy for Granulomatous Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency.

    Science.gov (United States)

    Hasegawa, Mizue; Sakai, Fumikazu; Okabayashi, Asako; Sato, Akitoshi; Yokohori, Naoko; Katsura, Hideki; Asano, Chihiro; Kamata, Toshiko; Koh, Eitetsu; Sekine, Yasuo; Hiroshima, Kenzo; Ogura, Takashi; Takemura, Tamiko

    2017-11-01

    Common variable immunodeficiency (CVID) is a heterogeneous subset of immunodeficiency disorders. Recurrent bacterial infection is the main feature of CVID, but various non-infectious complications can occur. A 42-year-old woman presented with cough and abnormal chest X-ray shadows. Laboratory tests showed remarkable hypogammaglobulinemia. Computed tomography revealed multiple consolidation and nodules on the bilateral lung fields, systemic lymphadenopathy, and splenomegaly. A surgical lung biopsy specimen provided the final diagnosis of lymphoproliferative disease in CVID, which was grouped under the term granulomatous lymphocytic interstitial lung disease. Interestingly, the lung lesions of this case resolved immediately after the initiation of intravenous immunoglobulin monotherapy.

  10. Classical patterns of interstitial lung diseases

    International Nuclear Information System (INIS)

    Mueller-Mang, C.

    2014-01-01

    High resolution computed tomography (HRCT) is the most important non-invasive tool in the diagnostics and follow-up of patients with interstitial lung disease (ILD). A systematic review of the HRCT patterns of ILD was carried out and the most relevant differential diagnoses are discussed in order to provide a road map for the general radiologist to successfully navigate the complex field of ILD. Using HRCT four basic patterns of ILD can be identified: linear and reticular patterns, the nodular pattern, the high attenuation and low attenuation patterns. These patterns can be further differentiated according to their localization within the secondary pulmonary lobule (SPL), e.g. centrilobular or perilymphatic and their distribution within the lungs (e.g. upper or lower lobe predominance). Relevant clinical data, such as smoking history and course of the disease provide useful additional information in the diagnosis of ILD. On the basis of the pattern and anatomical distribution on HRCT, an accurate diagnosis can be achieved in some cases of ILD; however, due to morphological and clinical overlap the final diagnosis of many ILDs requires close cooperation between clinicians, radiologists and pathologists. (orig.) [de

  11. Classification of interstitial lung disease patterns with topological texture features

    Science.gov (United States)

    Huber, Markus B.; Nagarajan, Mahesh; Leinsinger, Gerda; Ray, Lawrence A.; Wismüller, Axel

    2010-03-01

    Topological texture features were compared in their ability to classify morphological patterns known as 'honeycombing' that are considered indicative for the presence of fibrotic interstitial lung diseases in high-resolution computed tomography (HRCT) images. For 14 patients with known occurrence of honey-combing, a stack of 70 axial, lung kernel reconstructed images were acquired from HRCT chest exams. A set of 241 regions of interest of both healthy and pathological (89) lung tissue were identified by an experienced radiologist. Texture features were extracted using six properties calculated from gray-level co-occurrence matrices (GLCM), Minkowski Dimensions (MDs), and three Minkowski Functionals (MFs, e.g. MF.euler). A k-nearest-neighbor (k-NN) classifier and a Multilayer Radial Basis Functions Network (RBFN) were optimized in a 10-fold cross-validation for each texture vector, and the classification accuracy was calculated on independent test sets as a quantitative measure of automated tissue characterization. A Wilcoxon signed-rank test was used to compare two accuracy distributions and the significance thresholds were adjusted for multiple comparisons by the Bonferroni correction. The best classification results were obtained by the MF features, which performed significantly better than all the standard GLCM and MD features (p < 0.005) for both classifiers. The highest accuracy was found for MF.euler (97.5%, 96.6%; for the k-NN and RBFN classifier, respectively). The best standard texture features were the GLCM features 'homogeneity' (91.8%, 87.2%) and 'absolute value' (90.2%, 88.5%). The results indicate that advanced topological texture features can provide superior classification performance in computer-assisted diagnosis of interstitial lung diseases when compared to standard texture analysis methods.

  12. Gigantocellular macrophagal reaction in epidermoid cancer of the lung in patients exposed to preoperative irradiation

    International Nuclear Information System (INIS)

    Galil-Ogly, G.A.; Kharchenko, V.P.; Poroshin, K.K.; Pereslegin, O.I.; Krylov, L.M.; Ivanov, E.D.

    1980-01-01

    The histologic and electron microscopic study of frequently occurring gigantocellular macrophagal reaction in the stroma of 83 irradiated epidermoid carcinomas of the lung is carried out. It is found that gigantic multinuclear macrophages take part in the resorption of necrotic and corneous masses as well as in the absorption of viable tumour cells. The presence of gigantocellular macrophagal reaction in the stroma of irradiated tumoUr evidences a more favourable prognosis in patients after the combined treatment of epidermoid lung cancer. Gigantocellular macrophagal reaction should be considered as the manifestation of cell antitumour immunity which makes stronger the tumour irradiation damage

  13. Interstitial lung disease: Diagnostic accuracy and safety of surgical lung biopsy

    Directory of Open Access Journals (Sweden)

    Miguel Guerra

    2009-05-01

    Full Text Available This study reports our experience, diagnostic accuracy and safety of surgical lung biopsy in patients with interstitial lung diseases. From January 1998 – December 2007 surgical lung biopsy was performed in 53 patients (22 female [41.5%]; age 47.2 ± 13 years. A total of 37 patients (69.8% underwent videothoracoscopic lung biopsy and minithoracotomy was performed in 16 patients (30.2%. Right lung was the choice in 47 patients (88.7%. Postoperative complications were rare (9.4% and included three prolonged air leaks (5.7%, one pneumothorax re-quiring a chest drain (1.9%, and one haemothorax requiring reoperation (1.9%. One patient died of cardiac arrest of unknown cause. Average chest tube duration was 4.4 ± 3 days and average hospital stay 5.4 ± 4 days. Lung biopsy contributed to the diagnosis in 50 patients (94.3%. In conclusion, the potential benefits of diagnostic surgical lung biopsy must be considered against the risks of the procedure especially in patients with severe cardiopulmonary dysfunction. Resumo: Os autores descrevem a sua casuística de biópsias pulmonares cirúrgicas em doentes com doença pulmonar intersticial, de forma a determinar a acuidade diagnóstica, os riscos e a morbimortalidade associados ao procedimento. Entre Janeiro de 1998 e Dezembro de 2007, 53 doentes (idade média de 47,2 ± 13 anos foram referenciados para a realização de biópsia pulmonar cirúrgica, dos quais 22 eram mulheres (41,5%. As biópsias pulmonares foram realizadas quer por videotoracoscopia (37 doentes, 69,8%, quer por minitoracotomia (16 doentes, 30,2%. Foi escolhido o pulmão direito para biopsar em 88,7% dos casos. Registaram-se complicações pós-operatórias em 5 doentes (9,4%: fuga aérea prolongada em 3 doentes (5,7%, persistência de loca de pneumotórax num doente (1,9% e hemorragia com necessidade de revisão de hemostase noutro doente (1,9%. Ocorreu um

  14. Clinical use of pulmonary function tests and high-resolution tomography in interstitial lung diseases

    International Nuclear Information System (INIS)

    Garcia C, Clara P; Mejia M, Luis F

    2010-01-01

    Diagnosis of interstitial lung diseases is generally arrived at by clinical history, physical examination, and radiologic images, especially high-resolution CT-scanning. It is important to note that, while these diseases have different clinical and histological characteristics, they share a basic pattern of abnormal lung function. With regard to high-resolution tomography, the characteristics of these diseases are similar, although there are specific differences that can be helpful for correct diagnosis. These diseases have severe consequences on respiratory gas exchange. These alterations, combined with other abnormalities of lung function, cause the signs and symptoms and have an impact on quality of life. The use of physiologic parameters is not only helpful for diagnosis, but can also assess severity, help to define the consequences of treatment, and aid in the follow-up. Although some pulmonary function tests can remain completely normal with severe radiographic findings, 10% of patients have impaired lung function before radiologic changes. High-resolution tomography is an essential imaging tool for the study of these patients. This is true not only for diagnosis, but also with regard to clinical parameters and follow-up. Its prognostic use is continually gaining importance. In this article we assess the clinical use of pulmonary function tests and high-resolution tomography in interstitial lung diseases.

  15. Early structural changes in sheep lung following thoracic irradiation

    International Nuclear Information System (INIS)

    Guerry-Force, M.L.; Perkett, E.A.; Brigham, K.L.; Meyrick, B.

    1988-01-01

    Using a large animal model of radiation lung injury--the sheep exposed to bilateral thoracic irradiation--we have recently shown the development of sustained pulmonary hypertension during the first 4 weeks following radiation. This is the period prior to the onset of pneumonitis and pulmonary fibrosis. In the present study, we have examined biopsy and autopsy lung tissue from these same sheep and assessed the sequential changes in lung morphology. Six unanesthetized sheep received bilateral thoracic irradiation (a total of 15 Gy); control sheep were sham irradiated. Lung biopsy tissue was taken prior to and at weekly or biweekly intervals during the 4 weeks immediately following radiation. The lungs were also removed at autopsy for light and electron microscopic examination. Our results show early (Week 1) interstitial and progressive intraalveolar edema accompanied by endothelial and epithelial injury. A gradual increase in number of interstitial mononuclear cells was evident from Week 1, both in the lung tissue and in perivascular cuffs. The number of peripheral lung interstitial mononuclear cells was twice baseline from Week 3 and included accumulation of lymphocytes, fibroblasts, and intravascular macrophages. The increased numbers of mononuclear cells paralleled the development of chronic pulmonary hypertension, perhaps suggesting their involvement in the pathogenesis of this disease. Alternatively, it may be that increased mononuclear cell number represents a stage of lung repair

  16. Subclinical interstitial lung involvement in rheumatic diseases. Correlations of high-resolution Computed Tomography patterns with functional and cytologic findings

    International Nuclear Information System (INIS)

    Salaffi, F.; Baldelli, S.

    1999-01-01

    The aims of this study were to quantify the severity and extent of subclinical interstitial lung disease as depicted on HRCT and to study the relationship between the patterns of lung disease quantified by HRCT and the functional parameters and bronchoalveolar lavage findings in patients with rheumatic diseases. The results confirm that HRCT is a sensitive tool in detecting interstitial lung disease in patients with rheumatic diseases with no signs and symptoms of pulmonary involvement. The relationship between the different HRCT patterns and bronchoalveolar lavage cell profiles can identify patients at higher risk of developing irreversible lung fibrosis. A long-term, prospective follow-up study is needed to determine whether these patients will develop over pulmonary disease [it

  17. Serial perfusion in native lungs in patients with idiopathic pulmonary fibrosis and other interstitial lung diseases after single lung transplantation.

    Science.gov (United States)

    Sokai, Akihiko; Handa, Tomohiro; Chen, Fengshi; Tanizawa, Kiminobu; Aoyama, Akihiro; Kubo, Takeshi; Ikezoe, Kohei; Nakatsuka, Yoshinari; Oguma, Tsuyoshi; Hirai, Toyohiro; Nagai, Sonoko; Chin, Kazuo; Date, Hiroshi; Mishima, Michiaki

    2016-04-01

    Lung perfusions after single lung transplantation (SLT) have not been fully clarified in patients with interstitial lung disease (ILD). The present study aimed to investigate temporal changes in native lung perfusion and their associated clinical factors in patients with ILD who have undergone SLT. Eleven patients were enrolled. Perfusion scintigraphy was serially performed up to 12 months after SLT. Correlations between the post-operative perfusion ratio in the native lung and clinical parameters, including pre-operative perfusion ratio and computed tomography (CT) volumetric parameters, were evaluated. On average, the perfusion ratio of the native lung was maintained at approximately 30% until 12 months after SLT. However, the ratio declined more significantly in idiopathic pulmonary fibrosis (IPF) than in other ILDs (p = 0.014). The perfusion ratio before SLT was significantly correlated with that at three months after SLT (ρ = 0.64, p = 0.048). The temporal change of the perfusion ratio in the native lung did not correlate with those of the CT parameters. The pre-operative perfusion ratio may predict the post-operative perfusion ratio of the native lung shortly after SLT in ILD. Perfusion of the native lung may decline faster in IPF compared with other ILDs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Management of Myositis-Related Interstitial Lung Disease.

    Science.gov (United States)

    Morisset, Julie; Johnson, Cheilonda; Rich, Eric; Collard, Harold R; Lee, Joyce S

    2016-11-01

    Interstitial lung disease (ILD) is a frequent pulmonary manifestation and an important cause of morbidity and mortality in patients with idiopathic inflammatory myopathy. Myositis-related ILD presents a therapeutic challenge for clinicians, as there are no available guidelines to help with management decisions. This review covers the existing evidence on the pharmacologic and nonpharmacologic management of myositis-related ILD, highlighting the lack of randomized controlled data to guide treatment. Given the absence of existing guidelines to inform treatment decisions, we provide a comprehensive summary, including dosing, side effects, and suggested monitoring of the commonly used immunosuppressive agents and a proposed treatment algorithm based on the existing literature. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  19. Calcium Channel Blockers and Esophageal Sclerosis: Should We Expect Exacerbation of Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Charalampos Seretis

    2012-01-01

    Full Text Available Esophageal sclerosis is the most common visceral manifestation of systemic sclerosis, resulting in impaired esophageal clearance and retention of ingested food; in addition, co-existence of lung fibrosis with esophageal scleroderma is not uncommon. Both the progression of generalized connective tissue disorders and the damaging effect of chronic aspiration due to esophageal dysmotility appear to be involved in this procedure of interstitial fibrosis. Nifedipine is a widely prescribed calcium antagonist in a significant percentage of rheumatologic patients suffering from Raynaud syndrome, in order to inhibit peripheral vasospasm. Nevertheless, blocking calcium channels has proven to contribute to exacerbation of gastroesophageal reflux, which consequently can lead to chronic aspiration. We describe the case of severe exacerbation of interstitial lung disease in a 76-year-old female with esophageal sclerosis who was treated with oral nifedipine for Raynaud syndrome.

  20. Pulmonary hypertension due to unclassified interstitial lung disease in a Pembroke Welsh corgi.

    Science.gov (United States)

    Morita, Tomoya; Nakamura, Kensuke; Tatsuyuki, Osuga; Kobayashi, Atsushi; Ichii, Osamu; Yabuki, Akira; Takiguchi, Mitsuyoshi

    2018-04-23

    A 12 year-old intact male Pembroke Welsh corgi weighing 10.8 kg was presented for evaluation of a 3-month history of dyspnea, and a 1-week history of exercise intolerance and anorexia. Severe hypoxemia (PaO 2 56 mmHg), diffuse lung alveolar infiltration, and severe pulmonary hypertension (tricuspid regurgitation pressure gradient was 81 mmHg) were identified. A tentative diagnosis of severe PH due to lung disease or pulmonary thromboembolism was made and treated intensively. After 5 days of hospitalization, the dog died despite oxygen supplementation and anticoagulant therapy. This dog was diagnosed as unclassified interstitial lung disease based on histopathological findings.

  1. Doença pulmonar intersticial associada a bronquiolite respiratória Respiratory bronchilitis-associated interstitial lung disease

    Directory of Open Access Journals (Sweden)

    Sílvia CS. Rodrigues

    2004-12-01

    Full Text Available A doença pulmonar intersticial associada a bronquiolite respiratória faz parte do espectro anatomopatológico das lesões pulmonares infiltrativas difusas induzidas pela fumaça de cigarro. Raramente tem apresentação clínico-funcional exuberante. Descrevemos dois casos diagnosticados por biópsia pulmonar aberta, caracterizados por dispnéia de evolução insidiosa, baqueteamento digital, lesões císticas à tomografia computadorizada e hipoxemia ao exercício. Enfatizamos considerar, em indivíduos tabagistas, a doença pulmonar intersticial associada a bronquiolite respiratória no contexto das pneumopatias intersticiais císticas, juntamente com a linfangioleiomiomatose, o granuloma eosinofílico e a fibrose pulmonar idiopática.Respiratory bronchiolitis-associated interstitial lung disease is one of many within the spectrum of smoking-related diffuse infiltrative lung diseases. The clinical and functional characteristics are typically subtle. Herein, we describe two cases of diagnosed through open-lung biopsy, and characterized by insidious evolution of dyspnea, digital clubbing, cystic lesions on computed tomography scans, and hipoxemia upon exertion. We emphasize that, when smokers are evaluated, it is imprtant to consider a diagnosis of respiratory bronchiolitis-associated interstitial lung disease in the context of interstitial cystitis, as well as in that of lymphangioleiomyomatosis, eosinophilic granuloma and idiophatic pulmonary fibrosis.

  2. Increase in a distinct pulmonary macrophage subset possessing an antigen-presenting cell phenotype and in vitro APC activity following silica exposure

    International Nuclear Information System (INIS)

    Migliaccio, Christopher T.; Hamilton, Raymond F.; Holian, Andrij

    2005-01-01

    Silica inhalation results in chronic lung inflammation and fibrosis. While the role of the alveolar macrophage (AM) is considered key to the effects of silica on lung pathology, the etiology is not completely understood. Evidence suggests an increase in antigen presenting cell (APC) activity as a contributing factor to this process, as well as potential roles for both AM and interstitial macrophages (IM) in silicosis. In order to study the effects of crystalline silica on the APC activity of pulmonary macrophages, mice were exposed intranasally and changes in pulmonary macrophage populations were assessed using flow cytometry. Following intranasal instillation of silica, a significant increase in the APC activity of AM was observed, as well as a significant increase in a subset of IM expressing classic APC markers (MHC class II, CD11c). In addition, an in vitro system using bone marrow-derived macrophages (BMDM) was generated to assess the effects of silica on the APC activity of macrophages in vitro. Data using BMDM in the in vitro APC assay demonstrated a significant increase in APC activity following silica exposure, but not following exposure to saline or a control particle (TiO 2 ). Using a combination of in vivo and in vitro experiments, the current study describes a significant increase in an interstitial macrophage subset with an APC phenotype, as well as an increase in the APC activity of both AM and BMDM, as a direct result of exposure to crystalline silica. These studies suggest a specific mechanism, macrophage subset activation, by which crystalline silica exposure results in chronic pulmonary inflammation and, eventually, fibrosis

  3. Lung cancer in connective tissue disease-associated interstitial lung disease: clinical features and impact on outcomes.

    Science.gov (United States)

    Watanabe, Satoshi; Saeki, Keigo; Waseda, Yuko; Murata, Akari; Takato, Hazuki; Ichikawa, Yukari; Yasui, Masahide; Kimura, Hideharu; Hamaguchi, Yasuhito; Matsushita, Takashi; Yamada, Kazunori; Kawano, Mitsuhiro; Furuichi, Kengo; Wada, Takashi; Kasahara, Kazuo

    2018-02-01

    Lung cancer (LC) adversely impacts survival in patients with idiopathic pulmonary fibrosis. However, little is known about LC in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The aim of this study was to evaluate the prevalence of and risk factors for LC in CTD-ILD, and the clinical characteristics and survival of CTD-ILD patients with LC. We conducted a single-center, retrospective review of patients with CTD-ILD from 2003 to 2016. Patients with pathologically diagnosed LC were identified. The prevalence, risk factors, and clinical features of LC and the impact of LC on CTD-ILD patient outcomes were observed. Of 266 patients with CTD-ILD, 24 (9.0%) had LC. CTD-ILD with LC was more likely in patients who were older, male, and smokers; had rheumatoid arthritis, a usual interstitial pneumonia pattern, emphysema on chest computed tomography scan, and lower diffusing capacity of the lung carbon monoxide (DLco)% predicted; and were not receiving immunosuppressive therapy. Multivariate analysis indicated that the presence of emphysema [odds ratio (OR), 8.473; 95% confidence interval (CI), 2.241-32.033] and nonuse of immunosuppressive therapy (OR, 8.111; 95% CI, 2.457-26.775) were independent risk factors for LC. CTD-ILD patients with LC had significantly worse survival than patients without LC (10-year survival rate: 28.5% vs. 81.8%, P<0.001). LC is associated with the presence of emphysema and nonuse of immunosuppressive therapy, and contributes to increased mortality in patients with CTD-ILD.

  4. Interstitial lung disease during trimethoprim/sulfamethoxazole administration

    International Nuclear Information System (INIS)

    Yuzurio, Syota; Horita, Naokatsu; Shiota, Yutaro; Kanehiro, Arihiko; Tanimoto, Mitsune

    2010-01-01

    We studied clinical and radiographic features of interstitial lung disease (ILD) during trimethoprim/sulfamethoxazole (TMP/SMX) administration. Ten patients who had received prednisolone treatment for underlying diffuse pulmonary disease showed various ILDs after introduction of TMP/SMX. The radiographic features of the ILDs were not consistent with infectious disease or exacerbation of the underlying disease, and these diagnoses were excluded radiographically and on clinical grounds during the differential diagnosis of the ILDs. These ILDs emerged relatively early after introduction of TMP/SMX, which is consistent with the former case report of drug-induced ILD (DI-ILD) caused by TMP/SMX. Therefore DI-ILDs caused by TMP/SMX were suspected in these cases. In most of these cases, the ILDs were clinically mild and disappeared immediately although administration of TMP/SMX was continued. (author)

  5. Dynamic Gd-DTPA enhanced breath-hold 1.5 t MRI of normal lungs and patients with interstitial lung disease and pulmonary nodules: preliminary results

    International Nuclear Information System (INIS)

    Semelka, R.C.; Maycher, B.; Shoenut, J.P.; Kroeker, R.; Griffin, P.; Lertzman, M.

    1992-01-01

    A FLASH technique was used, which encompassed the entire thorax in the transverse plane, before and after dynamic intravenous injection of godalinium DTPA (Gd-DTPA) to study 7 patients with normal lungs, 12 patients with interstitial lung disease (ILD), and 11 patients with pulmonary nodules. Comparative CT studies were obtained within 2 weeks of the MRI study in the patients with lung disease. Quantitative signal intensity (SI) measurements were performed. Qualitative evaluation of lung parenchyma was determined in a prospective blinded fashion, and in the normal group comparison was made with the CT images. In normal patients, SI of lung parenchyma increased by 7.7±1.3%. On precontrast images, second-order pulmonary branchings were visible while post-contrast, fifth- to sixth-order branches were apparent. In patients with ILD, interstitial changes enhanced to a variable extent, increases in SI ranging from minimal (49.9%) to substantial (308.4%). Detection of pulmonary nodules improved following contrast injection. The minimum lesion size detectable decreased from 8 mm precontrast to 5 mm post-contrast. Percentage contrast enhancement was greater for malignant nodules (124.2±79.7%) than benign nodules (5.8±4.7%) (p<0.01). (orig.)

  6. Stimulation of alveolar macrophages by BCG vaccine enhances the process of lung fibrosis induced by bleomycin.

    Science.gov (United States)

    Chyczewska, E; Chyczewski, L; Bańkowski, E; Sułkowski, S; Nikliński, J

    1993-01-01

    It was found that the BCG vaccine injected subcutaneously to the rats enhances the process of lung fibrosis induced by bleomycin. Pretreatment of rats with this vaccine results in accumulation of activated macrophages in lung interstitium and in the bronchoalveolar spaces. It may be suggested that the activated macrophages release various cytokines which may stimulate the proliferation of fibroblasts and biosynthesis of extracellular matrix components.

  7. Acute exacerbation of idiopathic interstitial pneumonia complicated by lung cancer, caused by treatment for lung cancer

    International Nuclear Information System (INIS)

    Takenaka, Kiyoshi; Okano, Tetsuya; Yoshimura, Akinobu

    1999-01-01

    In 64 patients with lung cancer complicated by idiopathic interstitial pneumonia (IIP), we retrospectively studied the outcome of the treatment for lung cancer and clinical features of acute exacerbation of IIP after treatment for lung cancer. The incidence of acute exacerbation of IIP was 8.7% (2 of 23 patients) after anticancer chemotherapy, 14.3% (2 of 14 patients) after operation, and 25% (2 of 8 patients) after radiation therapy. Serum C-reactive protein level was significantly higher in the patients who developed acute exacerbation of IIP than in those who did not (CRP=5.12±2.27, 2.26±2.29, respectively). On the contrary, there were no differences in the levels of serum lactate dehydrogenase, white blood cell count, erythrocyte sedimentation rate, PaO 2 , and %VC between the two groups. Pathologic presentations of surgically resected lungs did not show significant differences in the activity of IIP between the two groups. Five of 6 patients who developed acute exacerbation of IIP died within 3 months after the treatment for lung cancer. We conclude that we should evaluate the activity of IIP more precisely using new markers for activity of IIP and on that basis select patients to be treated for lung cancer. (author)

  8. Estimating local scaling properties for the classification of interstitial lung disease patterns

    Science.gov (United States)

    Huber, Markus B.; Nagarajan, Mahesh B.; Leinsinger, Gerda; Ray, Lawrence A.; Wismueller, Axel

    2011-03-01

    Local scaling properties of texture regions were compared in their ability to classify morphological patterns known as 'honeycombing' that are considered indicative for the presence of fibrotic interstitial lung diseases in high-resolution computed tomography (HRCT) images. For 14 patients with known occurrence of honeycombing, a stack of 70 axial, lung kernel reconstructed images were acquired from HRCT chest exams. 241 regions of interest of both healthy and pathological (89) lung tissue were identified by an experienced radiologist. Texture features were extracted using six properties calculated from gray-level co-occurrence matrices (GLCM), Minkowski Dimensions (MDs), and the estimation of local scaling properties with Scaling Index Method (SIM). A k-nearest-neighbor (k-NN) classifier and a Multilayer Radial Basis Functions Network (RBFN) were optimized in a 10-fold cross-validation for each texture vector, and the classification accuracy was calculated on independent test sets as a quantitative measure of automated tissue characterization. A Wilcoxon signed-rank test was used to compare two accuracy distributions including the Bonferroni correction. The best classification results were obtained by the set of SIM features, which performed significantly better than all the standard GLCM and MD features (p < 0.005) for both classifiers with the highest accuracy (94.1%, 93.7%; for the k-NN and RBFN classifier, respectively). The best standard texture features were the GLCM features 'homogeneity' (91.8%, 87.2%) and 'absolute value' (90.2%, 88.5%). The results indicate that advanced texture features using local scaling properties can provide superior classification performance in computer-assisted diagnosis of interstitial lung diseases when compared to standard texture analysis methods.

  9. Tumor necrosis factor-α accelerates the resolution of established pulmonary fibrosis in mice by targeting profibrotic lung macrophages.

    Science.gov (United States)

    Redente, Elizabeth F; Keith, Rebecca C; Janssen, William; Henson, Peter M; Ortiz, Luis A; Downey, Gregory P; Bratton, Donna L; Riches, David W H

    2014-04-01

    Idiopathic pulmonary fibrosis (IPF) is a relentless, fibrotic parenchymal lung disease in which alternatively programmed macrophages produce profibrotic molecules that promote myofibroblast survival and collagen synthesis. Effective therapies to treat patients with IPF are lacking, and conventional therapy may be harmful. We tested the hypothesis that therapeutic lung delivery of the proinflammatory cytokine tumor necrosis factor (TNF)-α into wild-type fibrotic mice would reduce the profibrotic milieu and accelerate the resolution of established pulmonary fibrosis. Fibrosis was assessed in bleomycin-instilled wild-type and TNF-α(-/-) mice by measuring hydroxyproline levels, static compliance, and Masson's trichrome staining. Macrophage infiltration and programming status was assessed by flow cytometry of enzymatically digested lung and in situ immunostaining. Pulmonary delivery of TNF-α to wild-type mice with established pulmonary fibrosis was found to reduce their fibrotic burden, to improve lung function and architecture, and to reduce the number and programming status of profibrotic alternatively programmed macrophages. In contrast, fibrosis and alternative macrophage programming were prolonged in bleomycin-instilled TNF-α(-/-) mice. To address the role of the reduced numbers of alternatively programmed macrophages in the TNF-α-induced resolution of established pulmonary fibrosis, we conditionally depleted macrophages in MAFIA (MAcrophage Fas-Induced Apoptosis) mice. Conditional macrophage depletion phenocopied the resolution of established pulmonary fibrosis observed after therapeutic TNF-α delivery. Taken together, our results show for the first time that TNF-α is involved in the resolution of established pulmonary fibrosis via a mechanism involving reduced numbers and programming status of profibrotic macrophages. We speculate that pulmonary delivery of TNF-α or augmenting its signaling pathway represent a novel therapeutic strategy to resolve

  10. Up-to-Date Information on Rheumatoid Arthritis-Associated Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Takafumi Suda

    2015-01-01

    Full Text Available Pulmonary involvement is common in rheumatoid arthritis (RA and affects all the components of the lung. Interstitial lung disease (ILD is the most predominant pulmonary manifestation and has been identified as the main cause of morbidity and mortality in RA. Clinically significant RA-ILD occurs in approximately 10% of RA patients. Several risk factors, such as old age, male gender, and smoking, have been reported to date. Histologically, the proportion of the usual interstitial pneumonia (UIP pattern is higher in RA-ILD than in ILD associated with other connective tissue diseases, and RA-ILD also shows nonspecific interstitial pneumonia and organizing pneumonia patterns. High-resolution computed tomography scans are highly predictive of the histological UIP pattern with a specificity of 96%-100%. Acute exacerbation, which is the acute deterioration of the respiratory status characterized by newly developed bilateral infiltrates with unknown etiologies, has been reported in RA-ILD. Although acute exacerbation of RA-ILD has high mortality, similar to that of idiopathic pulmonary fibrosis, its incidence is lower in RA-ILD than in idiopathic pulmonary fibrosis. A consensus treatment has not yet been established. Current therapeutic regimens typically include corticosteroids with or without cytotoxic agents. Recent large longitudinal studies reported that the prognosis of RA-ILD was poor with a median survival of 2.6-3.0 years. Furthermore, histological and/or radiological patterns, such as UIP or non-UIP, have significant prognostic implications. RA-ILD patients with histological or radiological UIP patterns have poorer prognoses than those with non-UIP patterns. This review assessed the characteristics of RA-ILD by overviewing recent studies in the field and focused on the clinical significance of histological and/or radiological patterns in RA-ILD.

  11. Is a linear probe helpful in diagnosing diseases of pulmonary interstitial spaces?

    Directory of Open Access Journals (Sweden)

    Natalia Buda

    2017-06-01

    Full Text Available In a lung ultrasound examination, interstitial lung lesions are visible as numerous B-line artifacts, and are best recorded with the use of a convex probe. Interstitial lung lesions may result from many conditions, including cardiogenic pulmonary oedema, non-cardiogenic pulmonary oedema, or interstitial lung disease. Hence difficulties in the differential diagnostics of the above clinical conditions. This article presents cases of patients suffering from interstitial lung lesions discovered in the course of lung ultrasound examination. The patients were examined with a 3.5–5.0 MHz convex probe and a 7.0–11.0 MHz linear probe. Ultrasound images have been analysed, and differences in the imaging with both probes in patients with interstitial lung lesions have been detailed. The use of a linear probe in patients with interstitial lung lesions (discovered with a convex or a micro-convex probe provides additional information on the source of the origin of the lesions.

  12. Early aggressive intra-venous pulse cyclophosphamide therapy for interstitial lung disease in a patient with systemic sclerosis. A case report.

    LENUS (Irish Health Repository)

    Peshin, R

    2009-06-01

    Interstitial lung disease is an important cause of mortality and morbidity in patients with systemic sclerosis (SSc). There are currently no recommended guidelines for management of these patients. This is probably due to the rarity of this condition, as well as clinical trials with only a small number of cases. There are published case report and case series along with the two main trials, viz. Scleroderma Lung Study and the Fibrosing Alveolitis Study, but again, there is no consensus on treatment protocols. In this report, we present a case of aggressive interstitial lung disease in a patient with SSc, which improved dramatically on treatment with intra-venous cyclophosphamide and high dose prednisolone therapy.

  13. Ex vivo expansion of alveolar macrophages with Mycobacterium tuberculosis from the resected lungs of patients with pulmonary tuberculosis

    Science.gov (United States)

    Petrunina, Ekaterina; Umpeleva, Tatiana; Karskanova, Svetlana; Bayborodin, Sergey; Vakhrusheva, Diana; Kravchenko, Marionella; Skornyakov, Sergey

    2018-01-01

    Tuberculosis (TB), with the Mycobacterium tuberculosis (Mtb) as the causative agent, remains to be a serious world health problem. Traditional methods used for the study of Mtb in the lungs of TB patients do not provide information about the number and functional status of Mtb, especially if Mtb are located in alveolar macrophages. We have developed a technique to produce ex vivo cultures of cells from different parts of lung tissues surgically removed from patients with pulmonary TB and compared data on the number of cells with Mtb inferred by the proposed technique to the results of bacteriological and histological analyses used for examination of the resected lungs. The ex vivo cultures of cells obtained from the resected lungs of all patients were largely composed of CD14-positive alveolar macrophages, foamy or not, with or without Mtb. Lymphocytes, fibroblasts, neutrophils, and multinucleate Langhans giant cells were also observed. We found alveolar macrophages with Mtb in the ex vivo cultures of cells from the resected lungs of even those TB patients, whose sputum smears and lung tissues did not contain acid-fast Mtb or reveal growing Mtb colonies on dense medium. The detection of alveolar macrophages with Mtb in ex vivo culture as soon as 16–18 h after isolation of cells from the resected lungs of all TB patients suggests that the technique proposed for assessing the level of infection in alveolar macrophages of TB patients has higher sensitivity than do prolonged bacteriological or pathomorphological methods. The proposed technique allowed us to rapidly (in two days after surgery) determine the level of infection with Mtb in the cells of the resected lungs of TB patients and, by the presence or absence of Mtb colonies, including those with cording morphology, the functional status of the TB agent at the time of surgery. PMID:29401466

  14. Critical role of macrophages and their activation via MyD88-NFκB signaling in lung innate immunity to Mycoplasma pneumoniae.

    Directory of Open Access Journals (Sweden)

    Jen-Feng Lai

    2010-12-01

    Full Text Available Mycoplasma pneumoniae (Mp, a common cause of pneumonia, is associated with asthma; however, the mechanisms underlying this association remain unclear. We investigated the cellular immune response to Mp in mice. Intranasal inoculation with Mp elicited infiltration of the lungs with neutrophils, monocytes and macrophages. Systemic depletion of macrophages, but not neutrophils, resulted in impaired clearance of Mp from the lungs. Accumulation and activation of macrophages were decreased in the lungs of MyD88(-/- mice and clearance of Mp was impaired, indicating that MyD88 is a key signaling protein in the anti-Mp response. MyD88-dependent signaling was also required for the Mp-induced activation of NFκB, which was essential for macrophages to eliminate the microbe in vitro. Thus, MyD88-NFκB signaling in macrophages is essential for clearance of Mp from the lungs.

  15. Exertional dyspnoea in interstitial lung diseases: the clinical utility of cardiopulmonary exercise testing

    Directory of Open Access Journals (Sweden)

    Matteo Bonini

    2017-02-01

    Full Text Available Interstitial lung diseases (ILDs represent a heterogeneous group of pathologies characterised by alveolar and interstitial damage, pulmonary inflammation (usually associated with fibrosis, decreased lung function and impaired gas exchange, which can be attributed to either a known or an unknown aetiology. Dyspnoea is one of the most common and disabling symptoms in patients with ILD, significantly impacting quality of life. The mechanisms causing dyspnoea are complex and not yet fully understood. However, it is recognised that dyspnoea occurs when there is an imbalance between the central respiratory efferent drive and the response of the respiratory musculature. The respiratory derangement observed in ILD patients at rest is even more evident during exercise. Pathophysiological mechanisms responsible for exertional dyspnoea and reduced exercise tolerance include altered respiratory mechanics, impaired gas exchange, cardiovascular abnormalities and peripheral muscle dysfunction. This review describes the respiratory physiology of ILD, both at rest and during exercise, and aims to provide comprehensive and updated evidence on the clinical utility of the cardiopulmonary exercise test in the assessment and management of these pathological entities. In addition, the role of exercise training and pulmonary rehabilitation programmes in the ILD population is addressed.

  16. Effect of porcine reproductive and respiratory syndrome virus (PRRSV) on alveolar lung macrophage survival and function

    DEFF Research Database (Denmark)

    Oleksiewicz, Martin B.; Nielsen, Jens

    1999-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) recently emerged as an important cause of reproductive disorders and pneumonia in domestic pigs throughout the world. Acute cytocidal replication of PRRSV in alveolar lung macrophages causes the acute pneumonia; however, it remains largely...... infection in this system. In short, in our minimal system containing only a single cell type, phagocytosis-suppressive effects of PRRSV infection were detected, that acted at the culture level by reducing the total number of alveolar lung macrophages....

  17. IRAK-M regulates chromatin remodeling in lung macrophages during experimental sepsis.

    Directory of Open Access Journals (Sweden)

    Kenneth Lyn-Kew

    2010-06-01

    Full Text Available Sepsis results in a profound state of immunosuppression, which is temporally associated with impaired leukocyte function. The mechanism of leukocyte reprogramming in sepsis is incompletely understood. In this study, we explored mechanisms contributing to dysregulated inflammatory cytokine expression by pulmonary macrophages during experimental sepsis. Pulmonary macrophages (PM recovered from the lungs of mice undergoing cecal ligation and puncture (CLP display transiently reduced expression of some, but not all innate genes in response to LPS. Impaired expression of TNF-alpha and iNOS was associated with reduced acetylation and methylation of specific histones (AcH4 and H3K4me3 and reduced binding of RNA polymerase II to the promoters of these genes. Transient impairment in LPS-induced cytokine responses in septic PM temporally correlated with induction of IRAK-M mRNA and protein, which occurred in a MyD88-dependent fashion. PM isolated from IRAK-M(-/- mice were largely refractory to CLP-induced impairment in cytokine expression, chromatin remodeling, recruitment of RNA polymerase II, and induction of histone deacetylase-2 observed during sepsis. Our findings indicate that systemic sepsis induces epigenetic silencing of cytokine gene expression in lung macrophages, and IRAK-M appears to be a critical mediator of this response.

  18. Pulmonary scan in evaluating alveolar-interstitial syndrome in ER

    Directory of Open Access Journals (Sweden)

    Giovanni Volpicelli

    2006-10-01

    Full Text Available Diffuse comet-tail artifacts at lung ultrasound are due to thickened interlobular septa and extravascular lung water. This condition is typical of the alveolar-interstitial syndrome due to pulmonary edema, diffuse parenchymal lung disease or ARDS. Aim of our study is to assess the potential of bedside lung ultrasound to diagnose the alveolar-interstitial syndrome in patients admitted to our emergency medicine unit. The ultrasonic feature of multiple and diffuse comet-tail artifacts was investigated during 5 months, in 121 consecutive patients admitted to our unit. Each patient was studied bedside in a supine position, by 8 antero-lateral pulmonary intercostal scans. Ultrasonic results were compared with chest radiograph and clinical outcome. Lung ultrasound showed a sensitivity of 84% and a specificity of 98% in diagnosing the radiologic alveolar-interstitial syndrome. Corresponding figures in the identification of a disease involving lung interstitium were 83% and 96%. These preliminary data show that the study of comet-tail artifacts at lung ultrasound is a method reasonably accurate for diagnosing the alveolar-interstitial syndrome at bedside. This conclusion opens the hypothesis of the usefullness of bedside lung ultrasound in the evaluation of dyspnoeic patients in the emergency setting.

  19. Lewis Lung Cancer Cells Promote SIGNR1(CD209b)-Mediated Macrophages Polarization Induced by IL-4 to Facilitate Immune Evasion.

    Science.gov (United States)

    Yan, Xiaolong; Li, Wenhai; Pan, Lei; Fu, Enqing; Xie, Yonghong; Chen, Min; Mu, Deguang

    2016-05-01

    Tumor-associated macrophages are a prominent component of lung cancer and contribute to tumor progression by facilitating the immune evasion of cancer cells. DC-SIGN (CD209) assists in the immune evasion of a broad spectrum of pathogens and neoplasms by inhibiting the maturation of DCs and subsequent cytokines production. However, the expression of DC-SIGN in macrophages and its role in mediating immune evasion in lung cancer and the underlying mechanism remain unclear. Our study aimed to identify the immunosuppressive role of SIGNR1 in murine macrophage differentiation and lung cancer progression. We found that SIGNR1-positive RAW264.7 macrophages were enriched in mixed cultures with Lewis lung cancer cells (LLC) (ratio of RAW 264.7 to LLC being 1:1) after stimulation with IL-4. Moreover, LLC-educated macrophages exhibited significantly higher levels of IL-10 but lower IL-12 in response to IL-4 treatment as determined by RT-PCR and ELISA. However, inhibition of SIGNR1 markedly hampered the production of IL-10, indicating that SIGNR1 was indispensable for IL-4+LLC induced macrophage polarization towards the M2 subtype. Furthermore, polarized M2 cells immersed in a tumor microenvironment promoted the migration of LLCs, as measured by transwell assays, but migration was suppressed after blockade of SIGNR1 using CD209b antibody. In addition, IL-4+LLC-educated macrophages reduced the proliferation of the activated T cells and reduced IFN-γ-mediated Th1 response in T cells, while SIGNR1 inhibition rescued Th1 cell functions. In conclusion, murine SIGNR1 expressed in LLC-educated macrophages appears to mediate IL-4-induced RAW264.7 macrophage polarization and thus facilitate lung cancer evasion. © 2015 Wiley Periodicals, Inc.

  20. MRI of interstitial lung diseases. What is possible?; MRT bei interstitiellen Lungenerkrankungen. Was ist moeglich

    Energy Technology Data Exchange (ETDEWEB)

    Biederer, J. [Kreisklinik Gross-Gerau, Radiologie Darmstadt, Gross-Gerau (Germany); Universitaetsklinikum Heidelberg, Klinik fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany); Deutsches Zentrum fuer Lungenforschung (DZL), Translational Lung Research Center (TLRC) Heidelberg, Heidelberg (Germany); Thoraxklinik, Universitaetsklinikum Heidelberg, Klinik fuer Diagnostische und Interventionelle Radiologie mit Nuklearmedizin, Heidelberg (Germany); Wielpuetz, M.O.; Jobst, B.J.; Dinkel, J. [Universitaetsklinikum Heidelberg, Klinik fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany); Deutsches Zentrum fuer Lungenforschung (DZL), Translational Lung Research Center (TLRC) Heidelberg, Heidelberg (Germany); Thoraxklinik, Universitaetsklinikum Heidelberg, Klinik fuer Diagnostische und Interventionelle Radiologie mit Nuklearmedizin, Heidelberg (Germany)

    2014-12-15

    Magnetic resonance imaging (MRI) of the lungs is becoming increasingly appreciated as a third diagnostic imaging modality besides chest x-ray and computed tomography (CT). Its value is well acknowledged for pediatric patients or for scientific use particularly when radiation exposure should be strictly avoided. However, the diagnosis of interstitial lung disease is the biggest challenge of all indications. The objective of this article is a summary of the current state of the art for diagnostic MRI of interstitial lung diseases. This article reflects the results of a current search of the literature and discusses them against the background of the authors own experience with lung MRI. Due to its lower spatial resolution and a higher susceptibility to artefacts MRI does not achieve the sensitivity of CT for the detection of small details for pattern recognition (e.g. fine reticulation and micronodules) but larger details (e.g. coarse fibrosis and honeycombing) can be clearly visualized. Moreover, it could be shown that MRI has the capability to add clinically valuable information on regional lung function (e.g. ventilation, perfusion and mechanical properties) and inflammation with native signal and contrast dynamics. In its present state MRI can be used for comprehensive cardiopulmonary imaging in patients with sarcoidosis or for follow-up of lung fibrosis after initial correlation with CT. Far more indications are expected when the capabilities of MRI for the assessment of regional lung function and activity of inflammation can be transferred into robust protocols for clinical use. (orig.) [German] Die MRT der Lunge entwickelt sich zu einer ernstzunehmenden dritten Saeule der Thoraxdiagnostik neben dem Thoraxroentgen und der Computertomographie (CT). Ihr Wert in der paediatrischen Lungendiagnostik oder fuer den wissenschaftlichen Einsatz, insbesondere wenn eine Strahlenexposition vermieden werden soll, ist unbestritten. Von allen Indikationen stellt die Diagnostik

  1. Normal expiratory flow rate and lung volumes in patients with combined emphysema and interstitial lung disease: a case series and literature review.

    Science.gov (United States)

    Heathcote, Karen L; Cockcroft, Donald W; Fladeland, Derek A; Fenton, Mark E

    2011-01-01

    Pulmonary function tests in patients with idiopathic pulmonary fibrosis characteristically show a restrictive pattern including small lung volumes and increased expiratory flow rates resulting from a reduction in pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. When the diseases coexist, pulmonary volumes are compensated, and a smaller than expected reduction or even normal lung volumes can be found. The present report describes 10 patients with progressive breathlessness, three of whom experienced severe limitation in their quality of life. All patients showed lung interstitial involvement and emphysema on computed tomography scan of the chest. The 10 patients showed normal spirometry and lung volumes with severe compromise of gas exchange. Normal lung volumes do not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

  2. Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features

    Directory of Open Access Journals (Sweden)

    Daniel Antunes Silva Pereira

    2015-04-01

    Full Text Available OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD. METHODS: This was a retrospective study of patients with interstitial lung disease (ILD, positive antinuclear antibody (ANA results (≥ 1/320, with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD. RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89% and anti-SSA (anti-Ro, 27%. The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05. Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria.

  3. Introduction of cryobiopsies in the diagnostics of interstitial lung diseases - experiences in a referral center

    DEFF Research Database (Denmark)

    Kronborg-White, Sissel; Folkersen, Birgitte; Rasmussen, Torben Riis

    2017-01-01

    Introduction: Transbronchial cryobiopsies (cTBB) has emerged as a new method for obtaining lung tissue biopsies in the diagnosis of interstitial lung diseases (ILDs). Until now, it has been used in a few highly specialized interventional centers and has shown promising results in obtaining a defi...... bleeding occurred during the procedure and was easily controlled by a Fogarty catheter balloon and in some cases tranexamic acid. Conclusion: Performing cTBB in the diagnostics of ILDs is a safe and feasible procedure. cTBB resulted in a confident diagnosis in 74% of cases....

  4. Clinical and Genetic Associations of Objectively Identified Interstitial Changes in Smokers.

    Science.gov (United States)

    Ash, Samuel Y; Harmouche, Rola; Putman, Rachel K; Ross, James C; Diaz, Alejandro A; Hunninghake, Gary M; Onieva Onieva, Jorge; Martinez, Fernando J; Choi, Augustine M; Lynch, David A; Hatabu, Hiroto; Rosas, Ivan O; San Jose Estepar, Raul; Washko, George R

    2017-10-01

    Smoking-related lung injury may manifest on CT scans as both emphysema and interstitial changes. We have developed an automated method to quantify interstitial changes and hypothesized that this measurement would be associated with lung function, quality of life, mortality, and a mucin 5B (MUC5B) polymorphism. Using CT scans from the Genetic Epidemiology of COPD Study, we objectively labeled lung parenchyma as a tissue subtype. We calculated the percentage of the lung occupied by interstitial subtypes. A total of 8,345 participants had clinical and CT scanning data available. A 5% absolute increase in interstitial changes was associated with an absolute decrease in FVC % predicted of 2.47% (P percentage of lung with interstitial changes. Objective interstitial changes on CT scans were associated with impaired lung function, worse quality of life, increased mortality, and more copies of a MUC5B promoter polymorphism, suggesting that these changes may be a marker of susceptibility to smoking-related lung injury, detectable even in those who are healthy by other measures. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  5. Occupational Exposures and Subclinical Interstitial Lung Disease. The MESA (Multi-Ethnic Study of Atherosclerosis) Air and Lung Studies.

    Science.gov (United States)

    Sack, Coralynn S; Doney, Brent C; Podolanczuk, Anna J; Hooper, Laura G; Seixas, Noah S; Hoffman, Eric A; Kawut, Steven M; Vedal, Sverre; Raghu, Ganesh; Barr, R Graham; Lederer, David J; Kaufman, Joel D

    2017-10-15

    The impact of a broad range of occupational exposures on subclinical interstitial lung disease (ILD) has not been studied. To determine whether occupational exposures to vapors, gas, dust, and fumes (VGDF) are associated with high-attenuation areas (HAA) and interstitial lung abnormalities (ILA), which are quantitative and qualitative computed tomography (CT)-based measurements of subclinical ILD, respectively. We performed analyses of participants enrolled in MESA (Multi-Ethnic Study of Atherosclerosis), a population-based cohort aged 45-84 years at recruitment. HAA was measured at baseline and on serial cardiac CT scans in 5,702 participants. ILA was ascertained in a subset of 2,312 participants who underwent full-lung CT scanning at 10-year follow-up. Occupational exposures were assessed by self-reported VGDF exposure and by job-exposure matrix (JEM). Linear mixed models and logistic regression were used to determine whether occupational exposures were associated with log-transformed HAA and ILA. Models were adjusted for age, sex, race/ethnicity, education, employment status, tobacco use, and scanner technology. Each JEM score increment in VGDF exposure was associated with 2.64% greater HAA (95% confidence interval [CI], 1.23-4.19%). Self-reported vapors/gas exposure was associated with an increased odds of ILA among those currently employed (1.76-fold; 95% CI, 1.09-2.84) and those less than 65 years old (1.97-fold; 95% CI, 1.16-3.35). There was no consistent evidence that occupational exposures were associated with progression of HAA over the follow-up period. JEM-assigned and self-reported exposures to VGDF were associated with measurements of subclinical ILD in community-dwelling adults.

  6. Classical patterns of interstitial lung diseases; Klassische Muster der interstitiellen Lungenerkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Mang, C. [Institut fuer CT und MRT, Gaenserndorf (Austria); Medizinische Universitaet Wien, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Wien (Austria)

    2014-12-15

    High resolution computed tomography (HRCT) is the most important non-invasive tool in the diagnostics and follow-up of patients with interstitial lung disease (ILD). A systematic review of the HRCT patterns of ILD was carried out and the most relevant differential diagnoses are discussed in order to provide a road map for the general radiologist to successfully navigate the complex field of ILD. Using HRCT four basic patterns of ILD can be identified: linear and reticular patterns, the nodular pattern, the high attenuation and low attenuation patterns. These patterns can be further differentiated according to their localization within the secondary pulmonary lobule (SPL), e.g. centrilobular or perilymphatic and their distribution within the lungs (e.g. upper or lower lobe predominance). Relevant clinical data, such as smoking history and course of the disease provide useful additional information in the diagnosis of ILD. On the basis of the pattern and anatomical distribution on HRCT, an accurate diagnosis can be achieved in some cases of ILD; however, due to morphological and clinical overlap the final diagnosis of many ILDs requires close cooperation between clinicians, radiologists and pathologists. (orig.) [German] Die hochaufloesende CT (High-resolution[HR]-CT) ist das wichtigste nichtinvasive Verfahren zur Identifikation und Verlaufsbeurteilung von Patienten mit interstitiellen Lungenerkrankungen (''interstitial lung diseases'', ILD). Systematische Darstellung der HRCT-Muster interstitieller Lungenerkrankungen und Diskussion der relevanten Differenzialdiagnosen, um dem Radiologen eine erfolgreiche Analyse der komplexen CT-Morphologie der ILD zu ermoeglichen. Mit der HRCT koennen 4 Grundmuster interstitieller Grunderkrankungen identifiziert werden: das retikulaere und lineare Muster, das nodulaere Muster, das Muster mit erhoehter Lungendichte und das Muster mit verminderter Lungendichte. Diese Muster koennen anhand ihrer Lage im sekundaeren

  7. Changes of bronchoalveolar cell pattern and lecithin content in experimental interstitial pneumonia

    International Nuclear Information System (INIS)

    Manabe, Hideki; Yasuoka, Susumu; Tsubura, Eiro

    1978-01-01

    The pathogenesis of diffuse interstitial fibrosing pneumonitis (DIFP) was studied by histological observations and analysis of the cells and lecithin content of bronchoalveolar lavage of rats with cyclophosphamide (CY)-induced pneumonitis or irradiation pneumonitis. The rats developed diffuse interstitial pneumonitis one week after the last of 5 intraperitoneal injections of 50 mg/kg of CY and gradually recovered in the next 14 weeks. The number of alveolar macrophages and the lecithin content in the bronchoalveolar lavage from these rats corresponded to the degree of inflammatory change of the lung tissue. The results of cell counts and analysis of the bronchoalveolar lavage from rats with irradiated pneumonitis were similar to those on rats with CY-induced pneumonitis, except that in irradiated rats the lecithin content of the lavage decreased with increase in severity of pulmonary fibrosis. These results indicate that the cell number and lecithin content of bronchoalveolar lavage are good parameters for use in diagnosis of DIFP. (auth.)

  8. Autophagy deficiency in macrophages enhances NLRP3 inflammasome activity and chronic lung disease following silica exposure

    International Nuclear Information System (INIS)

    Jessop, Forrest; Hamilton, Raymond F.; Rhoderick, Joseph F.; Shaw, Pamela K.; Holian, Andrij

    2016-01-01

    Autophagy is an important metabolic mechanism that can promote cellular survival following injury. The specific contribution of autophagy to silica-induced inflammation and disease is not known. The objective of these studies was to determine the effects of silica exposure on the autophagic pathway in macrophages, as well as the general contribution of autophagy in macrophages to inflammation and disease. Silica exposure enhanced autophagic activity in vitro in Bone Marrow derived Macrophages and in vivo in Alveolar Macrophages isolated from silica-exposed mice. Impairment of autophagy in myeloid cells in vivo using Atg5 fl/fl LysM-Cre + mice resulted in enhanced cytotoxicity and inflammation after silica exposure compared to littermate controls, including elevated IL-18 and the alarmin HMGB1 in the whole lavage fluid. Autophagy deficiency caused some spontaneous inflammation and disease. Greater silica-induced acute inflammation in Atg5 fl/fl LysM-Cre + mice correlated with increased fibrosis and chronic lung disease. These studies demonstrate a critical role for autophagy in suppressing silica-induced cytotoxicity and inflammation in disease development. Furthermore, this data highlights the importance of basal autophagy in macrophages and other myeloid cells in maintaining lung homeostasis. - Highlights: • Silica exposure increases autophagy in macrophages. • Autophagy deficient mice have enhanced inflammation and silicosis. • Autophagy deficiency in macrophages results in greater silica-induced cytotoxicity. • Autophagy deficiency in macrophages increases extracellular IL-18 and HMGB1.

  9. Respiratory bronchiolitis-associated interstitial lung disease secondary to electronic nicotine delivery system use confirmed with open lung biopsy.

    Science.gov (United States)

    Flower, Mark; Nandakumar, Lakshmy; Singh, Mahendra; Wyld, David; Windsor, Morgan; Fielding, David

    2017-05-01

    As a modern phenomenon, there is currently limited understanding of the possible toxic effects and broader implications of electronic nicotine delivery systems (ENDS). Large volumes of aerosolized particles are inhaled during "vaping" and there are now an increasing number of case reports demonstrating toxic effects of ENDS, as well as human studies demonstrating impaired lung function in users. This article presents a case of respiratory bronchiolitis interstitial lung disease (RB-ILD) precipitated by vaping in a 33-year-old male with 10 pack years of traditional cigarette and prior treatment for mixed germ cell tumour. The patient had started vaping 10-15 times per day while continuing to smoke 10 traditional cigarettes per day. After 3 months of exposure to e-cigarette vapour, chest computed tomography demonstrated multiple new poorly defined pulmonary nodules with fluffy parenchyma opacification centred along the terminal bronchovascular units. Video-assisted thoracoscopy with lung biopsy of the right upper and right middle lobes was undertaken. The microscopic findings were overall consistent with RB-ILD. This case demonstrates toxicity with use of ENDS on open lung biopsy with resolution of radiographic findings on cessation. We believe that this is the first case where open lung biopsy has demonstrated this and our findings are consistent with RB-ILD.

  10. A systematic review of occupational exposure to coal dust and the risk of interstitial lung diseases

    DEFF Research Database (Denmark)

    Beer, Christiane; Kolstad, Henrik A; Søndergaard, Klaus

    2017-01-01

    Objective: Exposure to coal dust can cause interstitial lung disease (ILD), but whether this is due to pure coal or to the contents of quartz in coal is less clear. Here, we systematically reviewed the relation between 'pure coal' and ILD. Methods: In a systematic review based on PRISMA criteria...

  11. A systematic review of occupational exposure to coal dust and the risk of interstitial lung diseases

    NARCIS (Netherlands)

    Beer, Christiane; Kolstad, Henrik A; Søndergaard, Klaus; Bendstrup, Elisabeth; Heederik, Dick; Olsen, Karen E; Omland, Øyvind; Petsonk, Edward; Sigsgaard, Torben; Sherson, David L; Schlünssen, Vivi

    2017-01-01

    Objective: Exposure to coal dust can cause interstitial lung disease (ILD), but whether this is due to pure coal or to the contents of quartz in coal is less clear. Here, we systematically reviewed the relation between 'pure coal' and ILD. Methods: In a systematic review based on PRISMA criteria

  12. Normal Expiratory Flow Rate and Lung Volumes in Patients with Combined Emphysema and Interstitial Lung Disease: A Case Series and Literature Review

    Directory of Open Access Journals (Sweden)

    Karen L Heathcote

    2011-01-01

    Full Text Available Pulmonary function tests in patients with idiopathic pulmonary fibrosis characteristically show a restrictive pattern including small lung volumes and increased expiratory flow rates resulting from a reduction in pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. When the diseases coexist, pulmonary volumes are compensated, and a smaller than expected reduction or even normal lung volumes can be found. The present report describes 10 patients with progressive breathlessness, three of whom experienced severe limitation in their quality of life. All patients showed lung interstitial involvement and emphysema on computed tomography scan of the chest. The 10 patients showed normal spirometry and lung volumes with severe compromise of gas exchange. Normal lung volumes do not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

  13. Improved pulmonary function following pirfenidone treatment in a patient with progressive interstitial lung disease associated with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Zarir F Udwadia

    2015-01-01

    Full Text Available Pirfenidone is an anti-fibrotic drug which has been approved for the management of patients with Idiopathic Pulmonary Fibrosis (IPF. However, its role in interstitial lung disease (ILD due to other causes such as systemic sclerosis (SSc is not clear. We present a case of a patient with SSc associated ILD who showed a subjective as well as objective improvement in lung function with pirfenidone.

  14. Interstitial Lung Disease

    Science.gov (United States)

    ... propranolol (Inderal, Innopran), may harm lung tissue. Some antibiotics. Nitrofurantoin (Macrobid, Macrodantin, others) and ethambutol (Myambutol) can cause lung damage. Anti-inflammatory drugs. Certain anti-inflammatory drugs, such as rituximab ( ...

  15. PLASMA AND LUNG MACROPHAGE CAROTENOID RESPONSIVENESS TO SUPPLEMENTATION AND OZONE EXPOSURE IN HUMANS

    Science.gov (United States)

    OBJECTIVE:: To examine the effect of ozone exposure and vegetable juice supplementation on plasma and lung macrophage concentrations of carotenoids. DESIGN:: A randomized trial. SETTING:: Subjects were exposed to ambient air prior to antioxidant supplementation and to ozone after...

  16. Pulmonary hypertension in childhood interstitial lung disease: A systematic review of the literature.

    Science.gov (United States)

    Bromley, Susan; Vizcaya, David

    2017-05-01

    Childhood interstitial lung disease (chILD) comprises a wide heterogeneous group of rare parenchymal lung disorders associated with substantial morbidity and mortality. Pulmonary hypertension is a common comorbidity in adults with interstitial lung disease (ILD) and associated with poor survival. We aimed to systematically review the literature regarding the occurrence of pulmonary hypertension (PH) in chILD, its effect on prognosis and healthcare use, and its treatment in clinical practice. Searches of PubMed and EMBASE databases (up to February 2016), and American Thoracic Society conference abstracts (2009-2015) were conducted using relevant keywords. References from selected articles and review papers were scanned to identify further relevant articles. A total of 20 articles were included; estimates of PH in chILD ranged from 1% to 64% with estimates among specific chILD entities ranging from 0% to 43%. Comparisons between studies were limited by differences in the study populations, including the size, age range, and heterogeneous composition of the ILD case series in terms of the nature and severity of the clinical entities, and also the methods used to diagnose PH. Three studies found that among patients with chILD, those with PH had a significantly higher risk (up to sevenfold) of death compared with those without PH. Information on the treatment of pulmonary hypertension in chILD or the effect of PH on healthcare use was not available. Data on the use and effectiveness of treatments for pulmonary hypertension in chILD are required to address this area of unmet need. Pediatr Pulmonol. 2017;52:689-698. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Macrophage phenotype is associated with disease severity in preterm infants with chronic lung disease.

    Directory of Open Access Journals (Sweden)

    Lynne R Prince

    Full Text Available The etiology of persistent lung inflammation in preterm infants with chronic lung disease of prematurity (CLD is poorly characterized, hampering efforts to stratify prognosis and treatment. Airway macrophages are important innate immune cells with roles in both the induction and resolution of tissue inflammation.To investigate airway innate immune cellular phenotypes in preterm infants with respiratory distress syndrome (RDS or CLD.Bronchoalveolar lavage (BAL fluid was obtained from term and preterm infants requiring mechanical ventilation. BAL cells were phenotyped by flow cytometry.Preterm birth was associated with an increase in the proportion of non-classical CD14(+/CD16(+ monocytes on the day of delivery (58.9 ± 5.8% of total mononuclear cells in preterm vs 33.0 ± 6.1% in term infants, p = 0.02. Infants with RDS were born with significantly more CD36(+ macrophages compared with the CLD group (70.3 ± 5.3% in RDS vs 37.6 ± 8.9% in control, p = 0.02. At day 3, infants born at a low gestational age are more likely to have greater numbers of CD14(+ mononuclear phagocytes in the airway (p = 0.03, but fewer of these cells are functionally polarized as assessed by HLA-DR (p = 0.05 or CD36 (p = 0.05 positivity, suggesting increased recruitment of monocytes or a failure to mature these cells in the lung.These findings suggest that macrophage polarization may be affected by gestational maturity, that more immature macrophage phenotypes may be associated with the progression of RDS to CLD and that phenotyping mononuclear cells in BAL could predict disease outcome.

  18. Macrophage phenotype is associated with disease severity in preterm infants with chronic lung disease.

    Science.gov (United States)

    Prince, Lynne R; Maxwell, Nicola C; Gill, Sharonjit K; Dockrell, David H; Sabroe, Ian; McGreal, Eamon P; Kotecha, Sailesh; Whyte, Moira K

    2014-01-01

    The etiology of persistent lung inflammation in preterm infants with chronic lung disease of prematurity (CLD) is poorly characterized, hampering efforts to stratify prognosis and treatment. Airway macrophages are important innate immune cells with roles in both the induction and resolution of tissue inflammation. To investigate airway innate immune cellular phenotypes in preterm infants with respiratory distress syndrome (RDS) or CLD. Bronchoalveolar lavage (BAL) fluid was obtained from term and preterm infants requiring mechanical ventilation. BAL cells were phenotyped by flow cytometry. Preterm birth was associated with an increase in the proportion of non-classical CD14(+)/CD16(+) monocytes on the day of delivery (58.9 ± 5.8% of total mononuclear cells in preterm vs 33.0 ± 6.1% in term infants, p = 0.02). Infants with RDS were born with significantly more CD36(+) macrophages compared with the CLD group (70.3 ± 5.3% in RDS vs 37.6 ± 8.9% in control, p = 0.02). At day 3, infants born at a low gestational age are more likely to have greater numbers of CD14(+) mononuclear phagocytes in the airway (p = 0.03), but fewer of these cells are functionally polarized as assessed by HLA-DR (p = 0.05) or CD36 (p = 0.05) positivity, suggesting increased recruitment of monocytes or a failure to mature these cells in the lung. These findings suggest that macrophage polarization may be affected by gestational maturity, that more immature macrophage phenotypes may be associated with the progression of RDS to CLD and that phenotyping mononuclear cells in BAL could predict disease outcome.

  19. Lipid-derived free radical production in superantigen-induced interstitial pneumonia

    Science.gov (United States)

    Miyakawa, Hisako; Mason, Ronald P.; Jiang, JinJie; Kadiiska, Maria B.

    2009-01-01

    We studied the free radical generation involved in the development of interstitial pneumonia (IP) in an animal model of autoimmune disease. We observed an electron spin resonance (ESR) spectrum of α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) radical adducts detected in the lipid extract of lungs in autoimmune-prone mice after intratracheal instillation of staphylococcal enterotoxin B. The POBN adducts detected by ESR were paralleled by infiltration of macrophages and neutrophils in the bronchoalveolar lavage fluid. To further investigate the mechanism of free radical generation, mice were pretreated with the macrophage toxicant gadolinium chloride, which significantly suppressed the radical generation. Free radical generation was also decreased by pretreatment with the xanthine oxidase (XO) inhibitor allopurinol, the iron chelator Desferal, and the inducible nitric oxide synthase (iNOS) inhibitor 1400W. Histopathologically, these drugs significantly reduced both the cell infiltration to alveolar septal walls and the synthesis of pulmonary collagen fibers. Experiments with NADPH oxidase knockout mice showed that NADPH oxidase did not contribute to lipid radical generation. These results suggest that lipid-derived carbon-centered free radical production is important in the manifestation of IP and that a macrophage toxicant, an XO inhibitor, an iron chelator, and an iNOS inhibitor protect against both radical generation and the manifestation of IP. PMID:19376221

  20. Interstitial lung disease in an adult with Fanconi anemia: Clues to the pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Rubinstein, W.S.; Wenger, S.L.; Hoffman, R.M. [Univ. of Pittsburgh, PA (United States)] [and others

    1997-03-31

    We have studied a 38-year-old man with a prior diagnosis of Holt-Oram syndrome, who presented with diabetes mellitus. He had recently taken prednisone for idiopathic interstitial lung disease and trimethoprim-sulfamethoxazole for sinusitis. Thrombocytopenia progressed to pancytopenia. The patient had skeletal, cardiac, renal, cutaneous, endocrine, hepatic, neurologic, and hematologic manifestations of Fanconi anemia (FA). Chest radiographs showed increased interstitial markings at age 25, dyspnea began in his late 20s, and he stopped smoking at age 32. At age 38, computerized tomography showed bilateral upper lobe fibrosis, lower lobe honeycombing, and bronchiectasis. Pulmonary function tests, compromised at age 29, showed a moderately severe obstructive and restrictive pattern by age 38. Serum alpha-1 antitrypsin level was 224 (normal 85-213) mg/dL and PI phenotype was M1. Karyotype was 46,X-Y with a marked increase in chromosome aberrations induced in vitro by diepoxybutane. The early onset and degree of pulmonary disease in this patient cannot be fully explained by environmental or known genetic causes. The International Fanconi Anemia Registry (IFAR) contains no example of a similar pulmonary presentation. Gene-environment (ecogenetic) interactions in FA seem evident in the final phenotype. The pathogenic mechanism of lung involvement in FA may relate to oxidative injury and cytokine anomalies. 49 refs., 2 figs., 1 tab.

  1. Automated diagnosis of interstitial lung diseases and emphysema in MDCT imaging

    Science.gov (United States)

    Fetita, Catalin; Chang Chien, Kuang-Che; Brillet, Pierre-Yves; Prêteux, Françoise

    2007-09-01

    Diffuse lung diseases (DLD) include a heterogeneous group of non-neoplasic disease resulting from damage to the lung parenchyma by varying patterns of inflammation. Characterization and quantification of DLD severity using MDCT, mainly in interstitial lung diseases and emphysema, is an important issue in clinical research for the evaluation of new therapies. This paper develops a 3D automated approach for detection and diagnosis of diffuse lung diseases such as fibrosis/honeycombing, ground glass and emphysema. The proposed methodology combines multi-resolution 3D morphological filtering (exploiting the sup-constrained connection cost operator) and graph-based classification for a full characterization of the parenchymal tissue. The morphological filtering performs a multi-level segmentation of the low- and medium-attenuated lung regions as well as their classification with respect to a granularity criterion (multi-resolution analysis). The original intensity range of the CT data volume is thus reduced in the segmented data to a number of levels equal to the resolution depth used (generally ten levels). The specificity of such morphological filtering is to extract tissue patterns locally contrasting with their neighborhood and of size inferior to the resolution depth, while preserving their original shape. A multi-valued hierarchical graph describing the segmentation result is built-up according to the resolution level and the adjacency of the different segmented components. The graph nodes are then enriched with the textural information carried out by their associated components. A graph analysis-reorganization based on the nodes attributes delivers the final classification of the lung parenchyma in normal and ILD/emphysematous regions. It also makes possible to discriminate between different types, or development stages, among the same class of diseases.

  2. Evaluation of chronic infectious interstitial pulmonary disease in children by low-dose CT-guided transthoracic lung biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Heyer, Christoph M.; Lemburg, Stefan P.; Kagel, Thomas; Nicolas, Volkmar [Ruhr-University of Bochum, Institute of Diagnostic Radiology, Interventional Radiology and Nuclear Medicine, BG Clinics Bergmannsheil, Bochum (Germany); Mueller, Klaus-Michael [Ruhr-University of Bochum, Institute of Pathology, BG Clinics Bergmannsheil, Bochum (Germany); Nuesslein, Thomas G.; Rieger, Christian H.L. [Ruhr-University of Bochum, Pediatric Hospital, Bochum (Germany)

    2005-07-01

    Children with chronic infectious interstitial lung disease often have to undergo open lung biopsy to establish a final diagnosis. Open lung biopsy is an invasive procedure with major potential complications. Transthoracic lung biopsy (TLB) guided by computed tomography (CT) is a less-invasive well-established procedure in adults. Detailing the role of low-dose CT-guided TLB in the enhanced diagnosis of chronic lung diseases related to infection in children. A group of 11 children (age 8 months to 16 years) underwent CT-guided TLB with a 20-gauge biopsy device. All investigations were done under general anaesthesia on a multidetector CT scanner (SOMATOM Volume Zoom, Siemens, Erlangen, Germany) using a low-dose protocol (single slices, 120 kV, 20 mAs). Specimens were processed by histopathological, bacteriological, and virological techniques. All biopsies were performed without major complications; one child developed a small pneumothorax that resolved spontaneously. A diagnosis could be obtained in 10 of the 11 patients. Biopsy specimens revealed chronic interstitial alveolitis in ten patients. In five patients Chlamydia pneumoniae PCR was positive, in three Mycoplasma pneumoniae PCR was positive, and in two Cytomegalovirus PCR was positive. The average effective dose was 0.83 mSv. Low-dose CT-guided TLB can be a helpful tool in investigating chronic infectious inflammatory processes in children with minimal radiation exposure. It should be considered prior to any open surgical procedure performed for biopsy alone. In our patient group no significant complication occurred. A disadvantage of the method is that it does not allow smaller airways and vessels to be assessed. (orig.)

  3. [Macrophage colony stimulating factor enhances non-small cell lung cancer invasion and metastasis by promoting macrophage M2 polarization].

    Science.gov (United States)

    Li, Y J; Yang, L; Wang, L P; Zhang, Y

    2017-06-23

    Objective: To investigate the key cytokine which polarizes M2 macrophages and promotes invasion and metastasis in non-small cell lung cancer (NSCLC). Methods: After co-culture with A549 cells in vitro, the proportion of CD14(+) CD163(+) M2 macrophages in monocytes and macrophage colony stimulating factor (M-CSF) levels in culture supernatant were detected by flow cytometry, ELISA assay and real-time qPCR, respectively. The effects of CD14(+) CD163(+) M2 macrophages on invasion of A549 cells and angiogenesis of HUVEC cells were measured by transwell assay and tubule formation assay, respectively. The clinical and prognostic significance of M-CSF expression in NSCLC was further analyzed. Results: The percentage of CD14(+) CD163(+) M2 macrophages in monocytes and the concentration of M-CSF in the supernatant followed by co-culture was (12.03±0.46)% and (299.80±73.76)pg/ml, respectively, which were significantly higher than those in control group [(2.80±1.04)% and (43.07±11.22)pg/ml, respectively, P macrophages in vitro . M2 macrophages enhanced the invasion of A549 cells (66 cells/field vs. 26 cells/field) and the angiogenesis of HUVEC cells (22 tubes/field vs. 8 tubes/field). The mRNA expression of M-CSF in stage Ⅰ-Ⅱ patients (16.23±4.83) was significantly lower than that in stage Ⅲ-Ⅳ (53.84±16.08; P macrophages, which can further promote the metastasis and angiogenesis of NSCLC. M-CSF could be used as a potential therapeutic target of NSCLC.

  4. Chronic interstitial lung disease in nylon flocking industry workers--Rhode Island, 1992-1996.

    Science.gov (United States)

    1997-09-26

    Interstitial lung disease (ILD) occurs infrequently; some cases are attributed to sarcoidosis, pulmonary hemorrhage syndromes, connective tissue diseases, hypersensitivity pneumonitis, drugs, radiation, and mineral dusts (e.g., silica or asbestos). However, most cases of ILD are of uncertain classification or etiology. This report describes preliminary findings of the investigation in Rhode Island of an outbreak of ILD among workers involved in the manufacture of finely cut nylon (flock) and flocked fabric (used for upholstery, clothing, and automobiles); the findings provide evidence of a newly recognized occupational illness.

  5. Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis

    International Nuclear Information System (INIS)

    Zhang, Yan; Choksi, Swati; Liu, Zheng-Gang

    2013-01-01

    Tumor-associated macrophages (TAMs) promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA) blocks occurrence of tumor associated macrophages (TAMs) in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA), a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80 + macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF) confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206 + TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer

  6. 18FDG uptake associated with CT density on PET/CT in lungs with and without chronic interstitial lung diseases

    International Nuclear Information System (INIS)

    Inoue, Kentaro; Okada, Ken; Taki, Yasuyuki; Goto, Ryoi; Kinomura, Shigeo; Fukuda, Hiroshi

    2009-01-01

    The dependent-density of computed tomography (CT) images of positron emission tomography (PET)/CT is sometimes difficult to distinguish from chronic interstitial lung disease (ILD) when it accompanies increased 18 F-fluorodeoxy-D-glucose ( 18 FDG) uptake. Though the possible utility of 18 FDG-PET for the diagnosis of active ILD has been reported, the clinical relevance of mild lung 18 FDG uptake in ILD cases without signs and symptoms suggesting acute progression has not been described. This study aimed to test relationships between 18 FDG uptake and lung density on CT using PET/CT in patients with normal lung as well as clinically stable chronic ILD. Thirty-six patients with normal lungs (controls) and 28 patients with chronic ILD (ILD cases) without acute exacerbation were retrospectively selected from 18 FDG PET/CT scans performed in examination of malignant neoplasms. Elliptical regions of interest (ROIs) were placed on the lung. The relationships between CT density and 18 FDG uptake between the control and ILD cases were tested. The CT density and 18 FDG uptake had a linear correlation in both the controls and the ILD cases without a difference in their regression slopes, and they were overlapped between the controls and the ILD cases with higher mean values in the ILD cases. Lung 18 FDG uptake was considered to reflect a gravity-dependent tissue density in the normal lung. Though the lung 18 FDG uptake as well as the CT density tended to be higher in chronic ILD patients, it may be difficult to distinguish them in normal dependent regions from those related to chronic ILD in some cases. (author)

  7. Rare pneumoconiosis induced by long-term amorphous silica exposure: the histological characteristics and expression of cyclooxygenase-2 as an antifibrogenic mediator in macrophages.

    Science.gov (United States)

    Kumasaka, Toshio; Akaike, Yasushi; Nakamura, Osamu; Yamazaki, Kazuma; Moriyama, Hiroshi; Takemura, Tamiko

    2011-11-01

    Pneumoconiosis induced by non-crystalline silica is considered rare, although silicosis resulting from contact with crystalline silica is a well-known hazard associated with progressive pulmonary fibrosis. Here we describe a patient with pneumoconiosis induced by diatomaceous earth composed of amorphous silica detected by two-dimensional imaging of chemical elements. The histology revealed that the disease was characterized by a granulomatous reaction in the lung. A large number of macrophages laden with yellow and black pigments accumulated in alveolar spaces and were incorporated into the interstitial sites. Bronchiolar walls were destroyed by palisade macrophages, suggesting airflow obstruction. Packed macrophages adhering to and covering the denuded interstitium indicated that macrophages might be incorporated into pulmonary interstitium in this fashion. Immunohistochemistry showed that cyclooxygenase-2, an antifibrogenic mediator, was intensely expressed in the macrophages compared with macrophages in control lungs. No birefringent material was found in the tissues. When two-dimensional analysis of chemical elements was performed using an electron probe microanalyzer with a wavelength-dispersive spectrometer, the resultant fine mapping of silicon and oxygen on the tissue indicated that the pigments phagocytosed by macrophages corresponded to amorphous silica. In conclusion, two-dimensional analysis of elements is very useful for pathologists in correlating the presence of chemical elements with histological changes. © 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.

  8. Lung macrophages contribute to house dust mite driven airway remodeling via HIF-1α.

    Directory of Open Access Journals (Sweden)

    Adam J Byrne

    Full Text Available HIF-1α is a transcription factor that is activated during hypoxia and inflammation and is a key regulator of angiogenesis in vivo. During the development of asthma, peribronchial angiogenesis is induced in response to aeroallergens and is thought to be an important feature of sustained chronic allergic inflammation. Recently, elevated HIF-1α levels have been demonstrated in both the lung tissue and bronchoalveolar lavage of allergic patients, respectively. Therefore, we investigated the role of HIF-1α on the development of angiogenesis and inflammation following acute and chronic allergen exposure. Our data shows that intranasal exposure to house dust mite (HDM increases the expression of HIF-1α in the lung, whilst reducing the expression of the HIF-1α negative regulators, PHD1 and PHD3. Blockade of HIF-1α in vivo, significantly decreased allergic inflammation and eosinophilia induced by allergen, due to a reduction in the levels of IL-5 and Eotaxin-2. Importantly, HIF-1α blockade significantly decreased levels of VEGF-A and CXCL1 in the lungs, which in turn led to a profound decrease in the recruitment of endothelial progenitor cells and a reduction of peribronchial angiogenesis. Furthermore, HDM or IL-4 treatment of primary lung macrophages resulted in significant production of both VEGF-A and CXCL1; inhibition of HIF-1α activity abrogated the production of these factors via an up-regulation of PHD1 and PHD3. These findings suggest that novel strategies to reduce the expression and activation of HIF-1α in lung macrophages may be used to attenuate allergen-induced airway inflammation and angiogenesis through the modulation of VEGF-A and CXCL1 expression.This study provides new insights into the role of HIF-1α in the development of peribronchial angiogenesis and inflammation in a murine model of allergic airway disease. These findings indicate that strategies to reduce activation of macrophage derived HIF-1α may be used as a target to

  9. [Clinical and radiological features of pulmonary tuberculosis manifested as interstitial lung diseases.].

    Science.gov (United States)

    Shi, Ju-Hong; Feng, Rui-E; Tian, Xin-Lun; Xu, Wen-Bing; Xu, Zuo-Jun; Liu, Hong-Rui; Zhu, Yuan-Jue

    2009-12-01

    The purpose of this paper was to investigate the clinical and radiological features of pulmonary tuberculosis presenting as interstitial lung diseases (ILD). We analyzed the data of cases suspected of diffuse parenchyma lung diseases at this hospital between October 2003 and October 2007. The diagnosis of active pulmonary tuberculosis was based on epithelioid granuloma or positive acid-fast bacilli in lung biopsy and changes on serial radiographs obtained during treatment. The data of a series of 230 consecutive patients with suspected ILD were retrospectively analyzed. The diagnosis was confirmed by lung biopsy. Twelve patients were confirmed to have pulmonary tuberculosis. There were 5 males and 7 females with a mean age of 38 +/- 11 years (range, 17 - 68). The median course of disease in these patients was 3 months (range, 0.5 - 18 months). Patients with pulmonary tuberculosis presented with fever (11/12), cough (9/12), weight loss (7/12), dyspnea (7/12), lymphadenopathy (4/12), and splenohepatomegaly (2/12). On chest CT scan, ground-glass attenuation was identified in 4, bilateral patchy infiltration in 5, tree-in-bud appearance 1, and centrilobular lesions in 2 of the 12 patients. During the follow-up period (median, 9 month, range from 3 to 12 month), 11 patients improved, but 1 died of diabetic ketoacidosis. The diagnosis of pulmonary tuberculosis should be considered in suspected ILD patients presenting with fever, splenohepatomegaly and lymphadenopathy.

  10. Radiographic and microscopic correlation of diffuse interstitial and bronchointerstitial pulmonary patterns in the caudodorsal lung of adult Thoroughbred horses in race training

    International Nuclear Information System (INIS)

    Wisner, E.R.; O'Brien, T.R.; Lakritz, J.; Pascoe, J.R.; Wilson, D.W.; Tyler, W.S.

    1993-01-01

    Complete thoracic radiographic examinations were performed on 7 horses ranging in age from 24 to 60 months, followed by in-situ lung fixation. Radiographs were examined by 3 radiologists for the presence, degree and distribution of generalised pulmonary patterns within a region of interest in the caudodorsal lung. Pulmonary tissue was obtained from 12 sites within a designated volume of interest in the caudodorsal lung, corresponding to the area of interest evaluated radiographically, and examined for the presence, character and severity of microscopic lesions. Radiographic findings within the volume of interest consisted of mild to moderate bronchial, bronchointerstitial, or interstitial pulmonary patterns. Interstitial and bronchointerstitial radiographic findings were related to severity of peribronchiolar mononuclear cell infiltrates, the degree of bronchiolar mucosal plication, and alveolar capillary and peribronchial blood vessel erythrocyte content. The severity of the interstitial radiographic pattern was inversely associated with the perceived diagnostic quality of the radiographic examinations. There was no evidence of spatial variation in the severity of the microscopic changes examined in this limited pulmonary region. Inter-rater reliability between radiologists was good in the assessment of diagnostic quality of the radiographic examinations but poor in assessing severity of the primary generalised pulmonary patterns within the radiographic region of interest

  11. HRCT appearances of pulmonary interstitial diseases. The pathologic basis and clinical diagnostic significance

    International Nuclear Information System (INIS)

    Ma Daqing; Li Tieyi; Guan Yansheng; He Wen; Nie Yongkang

    1999-01-01

    Objective: To evaluate the CT appearances, the pathologic basis and diagnostic significance of pulmonary interstitial diseases. methods: 14 isolated lungs with interstitial diseases were obtained at autopsy and surgery. The lungs were inflated and fixed. HRCT and 1 cm thin slice soft X-ray radiograph were performed and then histologic examination was done. HRCT images of 72 cases with interstitial diseases were analysed. The HRCT appearances of 10 cases were followed up for 1.5-7.0 years. Results: According to HRCT-pathologic correlation, pulmonary interstitial diseases had the following HRCT findings: (1) Intralobular interstitial thickening (33 cases, 46%), including fine linear, reticular and radiating appearances and the interface sign. (2) Interlobular septal thickening (24 cases, 33%). (3) Thickening of bronchovesicular bundles (35 cases, 49%), with coarse, blurred or smooth bundle, and nodular shape. (4) Subpleural lines (31 cases, 43%). (5) Ground-glass opacity (22 cases, 31%) with peripheral, diffuse or locular distribution. (6) Honeycombing (27 cases, 38%), having sizes: 5 mm. Of the 10 cases with follow-up, 2 cases became normal on CT and 8 cases progressing to honeycombed lung. Conclusions: The HRCT findings of pulmonary interstitial diseases represent abnormalities of axial, peripheral and septal interstitium. Interstitial fibrosis of the lung can be differentiated from that without fibrosis by HRCT. Ground-glass opacity, intralobular interstitial thickening and subpleural lines are preliminary findings of pulmonary interstitial fibrosis

  12. High-resolution computed tomography to differentiate chronic diffuse interstitial lung diseases with predominant ground-glass pattern using logical analysis of data

    International Nuclear Information System (INIS)

    Martin, Sophie Grivaud; Brauner, Michel W.; Rety, Frederique; Kronek, Louis-Philippe; Brauner, Nadia; Valeyre, Dominique; Nunes, Hilario; Brillet, Pierre-Yves

    2010-01-01

    We evaluated the performance of high-resolution computed tomography (HRCT) to differentiate chronic diffuse interstitial lung diseases (CDILD) with predominant ground-glass pattern by using logical analysis of data (LAD). A total of 162 patients were classified into seven categories: sarcoidosis (n = 38), connective tissue disease (n = 32), hypersensitivity pneumonitis (n = 18), drug-induced lung disease (n = 15), alveolar proteinosis (n = 12), idiopathic non-specific interstitial pneumonia (n = 10) and miscellaneous (n = 37). First, 40 CT attributes were investigated by the LAD to build up patterns characterising a category. From the association of patterns, LAD determined models specific to each CDILD. Second, data were recomputed by adding eight clinical attributes to the analysis. The 20 x 5 cross-folding method was used for validation. Models could be individualised for sarcoidosis, hypersensitivity pneumonitis, connective tissue disease and alveolar proteinosis. An additional model was individualised for drug-induced lung disease by adding clinical data. No model was demonstrated for idiopathic non-specific interstitial pneumonia and the miscellaneous category. The results showed that HRCT had a good sensitivity (≥64%) and specificity (≥78%) and a high negative predictive value (≥93%) for diseases with a model. Higher sensitivity (≥78%) and specificity (≥89%) were achieved by adding clinical data. The diagnostic performance of HRCT is high and can be increased by adding clinical data. (orig.)

  13. Radiographic and high resolution CT findings of non-specific interstitial pneumonia/fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Kondoh, Yasuhiro; Taniguchi, Hiroyuki; Nishiyama, Satoshi [Tosei General Hospital, Seto, Aichi (Japan); Yokoi, Toyoharu; Suzuki, Ryujiro; Noda, Yasunobu; Kato, Toshiyuki; Kaneko, Michie

    1999-01-01

    We evaluated the radiographic and high resolution CT findings in fifteen patients with biopsy proven nonspecific interstitial pneumonia. The most common radiographic findings in NSIP were bilateral infiltrates involving alveolar pattern, interstitial pattern, and mixed alveolar-interstitial pattern, which distributed mainly in the middle and lower lung zones. Loss of lung volumes were common. The predominant findings of linear and reticular opacities on HRCT were peribronchovascular interstitial thickening, parenchymal bands, intralobular interstitial thickening, and traction bronchiectasis. Honeycombing was not noted in any patient on initial CT scans. The predominant findings of increased lung opacity were mixed pattern of ground glass opacity and consolidation. Because these findings mimic those of idiopathic pulmonary fibrosis/usual interstitial pneumonia, distinction between NSIP and IPF/UIP seems to be difficult by radiographic and HRCT findings. The response to corticosteroid therapy was good. At follow up HRCT, the pulmonary abnormalities observed on initial scans had disappeared or were diminished in most cases. Intralobular interstitial thickening and traction bronchiectasis, that have been considered to be an indicator of irreversible fibrosis, occasionally disappeared after corticosteroid therapy. (author)

  14. Outcome and prognostic factors in a French cohort of patients with myositis-associated interstitial lung disease.

    Science.gov (United States)

    Obert, Julie; Freynet, Olivia; Nunes, Hilario; Brillet, Pierre-Yves; Miyara, Makoto; Dhote, Robin; Valeyre, Dominique; Naccache, Jean-Marc

    2016-12-01

    Interstitial lung disease (ILD) is a common form of extramuscular involvement in patients with polymyositis/dermatomyositis and is associated with poor prognosis. This study was designed to describe the long-term outcome of myositis-associated ILD. This retrospective observational study was conducted in 48 consecutive patients. Two groups defined according to outcome were compared to determine prognostic factors: a "severe" group (vital capacity [VC] myositis-associated ILD had severe initial PFT results but a low mortality rate. Independent prognostic factors at presentation were initial VC and myopathic changes on electromyography. This study highlights the need for studies focusing on the correlation between muscle and lung pathogenic mechanisms.

  15. MARS variant associated with both recessive interstitial lung and liver disease and dominant Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Rips, Jonathan; Meyer-Schuman, Rebecca; Breuer, Oded; Tsabari, Reuven; Shaag, Avraham; Revel-Vilk, Shoshana; Reif, Shimon; Elpeleg, Orly; Antonellis, Anthony; Harel, Tamar

    2018-04-12

    Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes responsible for charging tRNA with cognate amino acids during protein translation. Non-canonical functions are increasingly recognized, and include transcription and translation control and extracellular signaling. Monoallelic mutations in genes encoding several ARSs have been identified in axonal Charcot-Marie-Tooth (CMT2) disease, whereas biallelic mutations in ARS loci have been associated with multi-tissue syndromes, variably involving the central nervous system, lung, and liver. We report a male infant of non-consanguineous origin, presenting with successive onset of transfusion-dependent anemia, hypothyroidism, cholestasis, interstitial lung disease, and developmental delay. Whole-exome sequencing (WES) revealed compound heterozygosity for two variants (p.Tyr307Cys and p.Arg618Cys) in MARS, encoding methionyl-tRNA synthetase. Biallelic MARS mutations are associated with interstitial lung and liver disease (ILLD). Interestingly, the p.Arg618Cys variant, inherited from an unaffected father, was previously reported in a family with autosomal dominant late-onset CMT2. Yeast complementation assays confirmed pathogenicity of p.Arg618Cys, yet suggested retained function of p.Tyr307Cys. Our findings underscore the phenotypic variability associated with ARS mutations, and suggest genetic or environmental modifying factors in the onset of monoallelic MARS-associated CMT2. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  16. Myofibroblasts in interstitial lung diseases show diverse electron microscopic and invasive features.

    Science.gov (United States)

    Karvonen, Henna M; Lehtonen, Siri T; Sormunen, Raija T; Harju, Terttu H; Lappi-Blanco, Elisa; Bloigu, Risto S; Kaarteenaho, Riitta L

    2012-09-01

    The characteristic features of myofibroblasts in various lung disorders are poorly understood. We have evaluated the ultrastructure and invasive capacities of myofibroblasts cultured from small volumes of diagnostic bronchoalveolar lavage (BAL) fluid samples from patients with different types of lung diseases. Cells were cultured from samples of BAL fluid collected from 51 patients that had undergone bronchoscopy and BAL for diagnostic purposes. The cells were visualized by transmission electron microscopy and immunoelectron microscopy to achieve ultrastructural localization of alpha-smooth muscle actin (α-SMA) and fibronectin. The levels of α-SMA protein and mRNA and fibronectin mRNA were measured by western blot and quantitative real-time reverse transcriptase polymerase chain reaction. The invasive capacities of the cells were evaluated. The cultured cells were either fibroblasts or myofibroblasts. The structure of the fibronexus, and the amounts of intracellular actin, extracellular fibronectin and cell junctions of myofibroblasts varied in different diseases. In electron and immunoelectron microscopy, cells cultured from interstitial lung diseases (ILDs) expressed more actin filaments and α-SMA than normal lung. The invasive capacity of the cells obtained from patients with idiopathic pulmonary fibrosis was higher than that from patients with other type of ILDs. Cells expressing more actin filaments had a higher invasion capacity. It is concluded that electron and immunoelectron microscopic studies of myofibroblasts can reveal differential features in various diseases. An analysis of myofibroblasts cultured from diagnostic BAL fluid samples may represent a new kind of tool for diagnostics and research into lung diseases.

  17. Radionuclide study for the interstitial lung disease

    International Nuclear Information System (INIS)

    Kawakami, Kenji; Mori, Yutaka; Ujita, Masuo

    1991-01-01

    The contribution of pulmonary nuclear medicine was evaluated in 105 patients with interstitial pulmonary diseases (IPD). Ventilation study (V) with 81m Kr, distribution of compliance in thoraco-pulmonary system (C) by 81m Kr gas bolus inhalation method, perfusion study (Q) with 99m Tc-MAA, 67 Ga scintigraphy and an assessment of pulmonary epithelial permeability with 99m Tc-DTPA aerosol were performed as nuclear medicine procedures. Pulmonary function test (%DLco, vital capacity and functional residual capacity) and blood gas analysis were also examined. Abnormalities in V were larger than that in Q which was high V/Q mismatch finding, in the interstitial pneumonia. Correlation between V/Q mismatch and PaO 2 was, therefore, not significant. %DLco was decreased in cases with larger V/Q mismatches. 67 Ga accumulated in the early stage of interstitial pneumonia when CT or chest X-ray did not show any finding. %DLco was decreased in cases with strong accumulation of 67 Ga. 67 Ga might be useful to evaluate activity of the diseases. Pulmonary epithelial permeability was assessed by 99m Tc-DTPA inhalation study. This permeability accelerated in idiopathic interstitial fibrosis and sarcoidosis. Pulmonary epithelial permeability may be useful as an indicator for epithelial cell injury. (author)

  18. Detection and classification of interstitial lung diseases and emphysema using a joint morphological-fuzzy approach

    Science.gov (United States)

    Chang Chien, Kuang-Che; Fetita, Catalin; Brillet, Pierre-Yves; Prêteux, Françoise; Chang, Ruey-Feng

    2009-02-01

    Multi-detector computed tomography (MDCT) has high accuracy and specificity on volumetrically capturing serial images of the lung. It increases the capability of computerized classification for lung tissue in medical research. This paper proposes a three-dimensional (3D) automated approach based on mathematical morphology and fuzzy logic for quantifying and classifying interstitial lung diseases (ILDs) and emphysema. The proposed methodology is composed of several stages: (1) an image multi-resolution decomposition scheme based on a 3D morphological filter is used to detect and analyze the different density patterns of the lung texture. Then, (2) for each pattern in the multi-resolution decomposition, six features are computed, for which fuzzy membership functions define a probability of association with a pathology class. Finally, (3) for each pathology class, the probabilities are combined up according to the weight assigned to each membership function and two threshold values are used to decide the final class of the pattern. The proposed approach was tested on 10 MDCT cases and the classification accuracy was: emphysema: 95%, fibrosis/honeycombing: 84% and ground glass: 97%.

  19. Bilateral pleural effusion and interstitial lung disease as unusual manifestations of kikuchi-fujimoto disease: case report and literature review

    Directory of Open Access Journals (Sweden)

    Magdalena Fernandez-Martinez

    2010-11-01

    Full Text Available Abstract Background Kikuchi-Fujimoto's disease (KFD, also called histiocytic necrotizing lymphadenitis, is a rare, idiopathic and self-limited condition usually characterized by cervical lymphadenopathy and fever, most often affecting young patients. Aetiology is unknown. Differential diagnosis includes mainly malignant lymphoma, tuberculous lymphadenitis and systemic lupus erythematosus (SLE, so early diagnosis is crucial. Pleuropulmonary involvement due to isolated KFD has been seldom reported. Case Presentation a 32-year-old man, on treatment for iatrogenic hypothyroidism, was admitted due to high grade fever and painful cervical lymphadenopathies. KFD was diagnosed by lymph node biopsy. Some days after admission the patient got worse, he developed generalized lymphadenopathy, bilateral pleural effusion and interstitial lung disease. All of them resolved with prednisone and after two years of following up he remains asymptomatic and without evidence of any other associated disease. Conclusion Pleural effusion and interstitial lung disease are very uncommon manifestations of KFD. In our experience, treatment with oral prednisone was effective.

  20. Life history of plutonium dioxide in the lung: from macrophage to carcinoma

    International Nuclear Information System (INIS)

    Sanders, C.L.; Adee, R.R.; Rhoads, K.; Madison, R.M.

    1976-01-01

    The pulmonary macrophage exerts a large influence upon the distribution of alpha energy from inhaled 239 PuO 2 , while the pulmonary epithelium serves as the prime 'target' cell for neoplastic transformation. In the rat, of the total radiation energy absorbed in the lung, about 80 percent is delivered to the alveolar septae, 19 percent to the vascular tissues and less than 1 percent to the bronchial epithelium. Of the radiation energy delivered to the alveolar septae, about 10 percent is absorbed by alveolar epithelium, 10 percent by macrophage, 10 percent by endothelium and 70 percent by other cellular and noncellular elements. Both the type II alveolar epithelium and the bronchiolar epithelium serve as the probable cells of origin for induced adenocarcinoma

  1. Monocyte to macrophage differentiation-associated (MMD) targeted by miR-140-5p regulates tumor growth in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Li, Weina; He, Fei

    2014-01-01

    Highlights: • Expression of MMD is increased in lung cancer tissues. • Knockdown of MMD inhibits growth of A549 and LLC cells in vitro and in vivo. • MMD is a direct functional target of miR-140-5p. • MiR-140-5p/MMD axis regulates Erk1/2 signaling. - Abstract: Monocyte to macrophage differentiation-associated (MMD) is identified in macrophages as a gene associated with the differentiation from monocytes to macrophages. Recent microarray analysis for non-small cell lung cancer (NSCLC) suggests that MMD is an important signature associated with relapse and survival among patients with NSCLC. Therefore, we speculate that MMD likely plays a role in lung cancer. In this study, we found that the protein level of MMD was increased in lung cancer compared to benign lung tissues, and knockdown of MMD inhibited the growth of A549 and Lewis lung cancer cells (LLC) in vitro and in vivo. Integrated analysis demonstrated that MMD was a direct functional target of miR-140-5p. Furthermore, we found that miR-140-5p/MMD axis could affect the cell proliferation of lung cancer cells by regulating Erk signaling. Together, our results highlight the significance of miR-140-5p/MMD axis in lung cancer, and miR-140-5p/MMD axis could serve as new molecular targets for the therapy against lung cancer

  2. Radionuclide study for the interstitial lung disease

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Kenji; Mori, Yutaka; Ujita, Masuo (Jikei Univ., Tokyo (Japan). School of Medicine)

    1991-07-01

    The contribution of pulmonary nuclear medicine was evaluated in 105 patients with interstitial pulmonary diseases (IPD). Ventilation study (V) with {sup 81m}Kr, distribution of compliance in thoraco-pulmonary system (C) by {sup 81m}Kr gas bolus inhalation method, perfusion study (Q) with {sup 99m}Tc-MAA, {sup 67}Ga scintigraphy and an assessment of pulmonary epithelial permeability with {sup 99m}Tc-DTPA aerosol were performed as nuclear medicine procedures. Pulmonary function test (%DLco, vital capacity and functional residual capacity) and blood gas analysis were also examined. Abnormalities in V were larger than that in Q which was high V/Q mismatch finding, in the interstitial pneumonia. Correlation between V/Q mismatch and PaO{sub 2} was, therefore, not significant. %DLco was decreased in cases with larger V/Q mismatches. {sup 67}Ga accumulated in the early stage of interstitial pneumonia when CT or chest X-ray did not show any finding. %DLco was decreased in cases with strong accumulation of {sup 67}Ga. {sup 67}Ga might be useful to evaluate activity of the diseases. Pulmonary epithelial permeability was assessed by {sup 99m}Tc-DTPA inhalation study. This permeability accelerated in idiopathic interstitial fibrosis and sarcoidosis. Pulmonary epithelial permeability may be useful as an indicator for epithelial cell injury. (author).

  3. Nicaraven reduces cancer metastasis to irradiated lungs by decreasing CCL8 and macrophage recruitment.

    Science.gov (United States)

    Yan, Chen; Luo, Lan; Urata, Yoshishige; Goto, Shinji; Li, Tao-Sheng

    2018-04-01

    Radiotherapy for cancer patients damages normal tissues, thereby inducing an inflammatory response and promoting cancer metastasis. We investigated whether nicaraven, a compound with radioprotective and anti-inflammatory properties, could attenuate radiation-induced cancer metastasis to the lungs of mice. Nicaraven and amifostine, another commercial radioprotective agent, had limited effects on both the radiosensitivity of Lewis lung carcinoma cells in vitro and radiation-induced tumor growth inhibition in vivo. Using experimental and spontaneous metastasis models, we confirmed that thorax irradiation with 5 Gy X-rays dramatically increased the number of tumors in the lungs. Interestingly, the number of tumors in the lungs was significantly reduced by administering nicaraven but not by administering amifostine daily after radiation exposure. Furthermore, nicaraven administration effectively inhibited CCL8 expression and macrophage recruitment in the lungs 1 day after thorax irradiation. Our data suggest that nicaraven attenuates radiation-induced lung metastasis, likely by regulating the inflammatory response after radiation exposure. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Effects of pure and hybrid iterative reconstruction algorithms on high-resolution computed tomography in the evaluation of interstitial lung disease.

    Science.gov (United States)

    Katsura, Masaki; Sato, Jiro; Akahane, Masaaki; Mise, Yoko; Sumida, Kaoru; Abe, Osamu

    2017-08-01

    To compare image quality characteristics of high-resolution computed tomography (HRCT) in the evaluation of interstitial lung disease using three different reconstruction methods: model-based iterative reconstruction (MBIR), adaptive statistical iterative reconstruction (ASIR), and filtered back projection (FBP). Eighty-nine consecutive patients with interstitial lung disease underwent standard-of-care chest CT with 64-row multi-detector CT. HRCT images were reconstructed in 0.625-mm contiguous axial slices using FBP, ASIR, and MBIR. Two radiologists independently assessed the images in a blinded manner for subjective image noise, streak artifacts, and visualization of normal and pathologic structures. Objective image noise was measured in the lung parenchyma. Spatial resolution was assessed by measuring the modulation transfer function (MTF). MBIR offered significantly lower objective image noise (22.24±4.53, PASIR (39.76±7.41) and FBP (51.91±9.71). MTF (spatial resolution) was increased using MBIR compared with ASIR and FBP. MBIR showed improvements in visualization of normal and pathologic structures over ASIR and FBP, while ASIR was rated quite similarly to FBP. MBIR significantly improved subjective image noise (PASIR and FBP. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Childhood Interstitial Lung Disease

    Science.gov (United States)

    ... rule out conditions such as asthma , cystic fibrosis , acid reflux, heart disease, neuromuscular disease, and immune deficiency. Various ... a lung infection. Acid-blocking medicines can prevent acid reflux, which can lead to aspiration. Lung Transplant A ...

  6. Ultrastructural characterization of the pulmonary cellular defences in the lung of a bird, the rock dove, Columba livia

    Science.gov (United States)

    Maina, J. N.; Cowley, H. M.

    1998-01-01

    Free (surface) avian respiratory macrophages (FARMs) were harvested by lavage of the lung/air-sac system of the rock dove, Columba livia. The presence of FARMs in the atria and infundibula was confirmed by scanning electron microscopy. The respiratory system has developed several cellular defence lines that include surface macrophages, epithelial, subepithelial and interstitial phagocytes, and pulmonary intravascular macrophages (PIMs). Hence, C. livia appears to have a multiple pulmonary cellular protective armoury. Ultrastructurally, the FARMs and the PIMs were similar to the corresponding cells of mammals. The purported high susceptibility of birds to respiratory diseases, a state that has largely been deduced from morbidities and mortalities of commercial birds, and which has chiefly been attributed to paucity of the FARMs, is not supported by the present observations.

  7. Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

    Energy Technology Data Exchange (ETDEWEB)

    Nishino, Mizuki, E-mail: Mizuki_Nishino@DFCI.HARVARD.EDU [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Cardarella, Stephanie [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Dahlberg, Suzanne E. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Araki, Tetsuro [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Lydon, Christine; Jackman, David M.; Rabin, Michael S. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Hatabu, Hiroto [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Johnson, Bruce E. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States)

    2015-05-15

    Highlights: • Interstitial lung abnormalities were present in 14% of stage IV NSCLC patients. • ILA was more common in older patients with heavier smoking history. • ILA was associated with shorter survival after adjusting for smoking and therapy. • ILA could be an additional independent marker for survival in advanced NSCLC. - Abstract: Objective: Interstitial lung diseases are associated with increased risk of lung cancer. The prevalence of ILA at diagnosis of advanced non-small-cell lung cancer (NSCLC) and its impact on overall survival (OS) remain to be investigated. Materials and method: The study included 120 treatment-naïve stage IV NSCLC patients (53 males, 67 females). ILA was scored on CT prior to any systemic therapy using a 4-point scale [0 = no evidence of ILA, 1 = equivocal for ILA, 2 = suspicious for ILA, 3 = ILA] by a sequential reading method previously reported. ILA scores of 2 or 3 indicated the presence of ILA. Results: ILA was present in 17 patients (14%) with advanced NSCLC prior to any treatment (score3: n = 2, score2: n = 15). These 17 patients were significantly older (median age: 69 vs. 63, p = 0.04) and had a heavier smoking history (median: 40 vs. 15.5 pack-year, p = 0.003) than those with ILA score 0 or 1. Higher ILA scores were associated with shorter OS (p = 0.001). Median OS of the 17 patients with ILA was 7.2 months [95%CI: 2.9–9.4] compared to 14.8 months [95%CI: 11.1–18.4] in patients with ILA score 0 or 1 (p = 0.002). In a multivariate model, the presence of ILA remained significant for increased risk for death (HR = 2.09, p = 0.028) after adjusting for first-line systemic therapy (chemotherapy, p < 0.001; TKI, p < 0.001; each compared to no therapy) and pack years of smoking (p = 0.40). Conclusion: Radiographic ILA was present in 14% of treatment-naïve advanced NSCLC patients. Higher ILA scores were associated with shorter OS, indicating that ILA could be a marker of shorter survival in advanced NSCLC.

  8. Mechanisms underlying the redistribution of particles among the lung's alveolar macrophages during alveolar phase clearance

    Energy Technology Data Exchange (ETDEWEB)

    Lehnert, B.E.; Oritz, J.B.; Steinkamp, J.A.; Tietjen, G.L.; Sebring, R.J. (Los Alamos National Lab., NM (United States)); Oberdorster, G. (Rochester Univ., NY (United States))

    1991-01-01

    In order to obtain information about the particle redistribution phenomenon following the deposition of inhaled particles, as well as to obtain information about some of the mechanisms that may be operable in the redistribution of particles, lavaged lung free cell analyses and transmission electron microscopic (TEM) analyses of lung tissue and were performed using lungs from rats after they were subchronically exposed to aerosolized dioxide (TiO{sub 2}). TEM analyses indicated that the in situ autolysis of particle-containing Alveolar Macropages (AM) is one important mechanism involved in the redistribution of particles. Evidence was also obtained that indicated that the engulfment of one particle-containing phagocyte by another phagocyte also occurs. Another prominent mechanism of the particle redistribution phenomenon may be the in situ proliferation of particle-laden AM. We used the macrophage cell line J774A.1 as a surrogate for AM to investigate how different particulate loads in macrophages may affect their abilities to proliferate. These in vitro investigations indicated that the normal rate of proliferation of macrophages is essentially unaffected by the containment of relatively high particulate burdens. Overall, the results of our investigations suggest that in situ autolysis of particle-containing AM and the rephagocytosis of freed particles by other phagocytes, the phagocytosis of effete and disintegrating particle-containing phagocytes by other AM, and the in situ division of particle-containing AM are likely mechanisms that underlie the post-depositional redistribution of particles among the lung's AM during alveolar phase clearance. 19 refs., 8 figs., 2 tabs.

  9. Assessment and management of refractory breathlessness in interstitial lung disease.

    Science.gov (United States)

    Speakman, Lucy; Walthall, Helen

    2017-09-02

    Interstitial lung disease (ILD) refers to a cluster of fibroinflammatory conditions. There are limited treatment options and most patients have severe dyspnoea. The prognosis is poor. This study aims to evaluate current literature on the assessment and management of refractory breathlessness in ILD. Few tools are available to assess dyspnoea in advanced respiratory disease. Holistic assessment requires a combination of tools but there are few disease specific tools. The role of opioids is well established in the reduction of breathlessness, but there is insufficient evidence that benzodiazepines are beneficial. Non-pharmcolological breathlessness intervention services can give patients mastery of their disease, reduced distress due to breathlessness and were more cost effective. More research on holistic interventions for use in advanced disease needs to be done. Patient-reported outcome measures could elicit valuable evidence to describe the benefit of breathlessness management services in advanced respiratory disease.

  10. The importance of determining surgical indications in cases of lung cancer and interstitial pneumonia with multiple intrapulmonary lymph nodes

    Directory of Open Access Journals (Sweden)

    Yuki Nakajima

    2016-01-01

    Discussion and conclusions: The greatest problem in treating pulmonary cancer complicated with interstitial pneumonia is acute exacerbation, wherein, in the absence of any surgical indications, alternative treatment is limited. Thus, contra-indicating surgery for a patient due to a diagnosis of metastasis within the lungs, based only on nodule images, should be avoided. If nodules are noted in the area of the pleura, the possibility exists that these could be intrapulmonary lymph nodes, along with metastasis within the lung, and thoracoscopic surgery should be implemented proactively while keeping these in mind.

  11. PATTERN OF INTERSTITIAL LUNG DISEASE AS SEEN BY HIGH RESOLUTION COMPUTERISED TOMOGRAPHY.

    Science.gov (United States)

    Onyambu, C K; Waigwa, M N

    2012-09-01

    Diffuse lung diseases constitute a major cause of morbidity and mortality worldwide. High Resolution Computed Tomography (HRCT) is the recommended imaging technique in the diagnosis, assessment and followup of these diseases. To describe the pattern of HRCT findings in patients with suspected interstitial lung disease. Kenyatta National Hospital (KNH), Nairobi Hospital and MP Shah Hospital; all situated in Nairobi, during the period February to August 2010. One hundred and one patients sent for HRCT in the six month study period. A total of 101 patients were recruited with age range 18 to 100 years, with a mean age of 53.6 (SD 19.7) years and a median age of 54 years. The male-female ratio was 1.2:1. Cough [80.2% (n = 81)] was the most common presenting complaint followed by dyspnoea (53.5%, n = 53) and chest pain [24.8% (n = 25)]. Overall, the predominant pattern of involvement on chest HRCT was reticular pattern seen in 56.1% (n = 82) of patients, followed by honey-comb pattern (37.8%, n = 82). The study demonstrated marked lung parenchymal destruction in most cases; a poor prognostic indicator which could have been due to delayed referral. HRCT has a high pick up rate of subtle parenchymal lung lesions as well as defining the lesions and their distribution compared to plain chest radiography. This is important in narrowing the differential diagnosis as well as for pre-biopsy planning. The diagnosis of ILD requires a multidisciplinary approach including a detailed clinical history, physical findings, and laboratory investigations, radiological and histological assessment.

  12. Four Cases of Interstitial Lung Disease Induced by Erlotinib 
and A Review of the Literatures

    Directory of Open Access Journals (Sweden)

    Xiaoling WU

    2012-08-01

    Full Text Available Erlotinib is an agent of oral epidermal growth factor receptor (EGFR tyrosine kinase inhibitors which are used for non-small cell lung cancer. Although this class of agents is considered to be relatively safe, the most serious, but rare, adverse reaction is drug-associated interstitial lung disease (ILD. ILD induced by gefitinib been often described, but the ILD induced by erlotinib is relatively less well known. We here describle four cases of ILD related to erlotinib and review recent literatures to help physicians earlier alert erlotinib-induced ILD. It is important to carefully monitor pulmonary symptoms in all patients who are receiving erlotinib. Early diagnosis and timely intervention is critical in the treatment of drug-induced ILD.

  13. Tritiated thymidine incorporation and the development of an interstitial lesion in the bronchiolar-alveolar regions of the lungs of normal and complement deficient mice after inhalation of chrysotile asbestos

    International Nuclear Information System (INIS)

    McGavran, P.D.; Butterick, C.J.; Brody, A.R.

    1989-01-01

    Inhaled asbestos causes the proliferation of bronchiolar-alveolar epithelial and interstitial cells in rats and mice 19 to 72 hours after a single 5-hour exposure. This condition is associated with rapid macrophage accumulation and development of an interstitial fibrotic lesion at alveolar duct bifurcations. In an attempt to define the mechanisms mediating asbestos-induced cell proliferation and fibrogenesis, we studied mice exposed to chrysotile asbestos for five hours. The mice were normal and a congenic strain (B10.D2/oSn), deficient in the fifth component of complement (C5-). We knew that the latter exhibit a depressed asbestos-induced macrophage response and wanted to learn whether the depressed response correlated with measurements of cell proliferation and progression of an interstitial lesion. Sections of first alveolar duct bifurcations were prepared for light microscopic autoradiography and ultrastructural morphometry at varying times after animal exposure to asbestos. In sham-exposed C5+ and C5- animals, less than 1% of epithelial and interstitial cells of the terminal bronchioles and alveolar ducts incorporated tritiated thymidine (3H-TdR) at any time after exposure to asbestos. Between 19 and 72 hours after exposure, epithelial and interstitial cells in both strains of mice exhibited significantly increased levels of 3H-TdR incorporation. The response decreased by eight days postexposure, and 3H-TdR incorporation was normal one month after exposure. Similarly, morphometry showed that both the C5+ and C5- asbestos-exposed mice exhibited significant increases in the volume density of epithelial and interstitial cells 48 hours after exposure. However, one month after exposure, the normal C5+ asbestos-exposed mice developed a fibrotic lesion, whereas the C5- asbestos-exposed animals were no different from sham-exposed C5- controls

  14. Computer-aided detection of early interstitial lung diseases using low-dose CT images

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sang Cheol; Kim, Soo Hyung [School of Electronics and Computer Engineering, Chonnam National University, Gwangju 500-757 (Korea, Republic of); Tan, Jun; Wang Xingwei; Lederman, Dror; Leader, Joseph K; Zheng Bin, E-mail: zhengb@upmc.edu [Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15213 (United States)

    2011-02-21

    This study aims to develop a new computer-aided detection (CAD) scheme to detect early interstitial lung disease (ILD) using low-dose computed tomography (CT) examinations. The CAD scheme classifies each pixel depicted on the segmented lung areas into positive or negative groups for ILD using a mesh-grid-based region growth method and a multi-feature-based artificial neural network (ANN). A genetic algorithm was applied to select optimal image features and the ANN structure. In testing each CT examination, only pixels selected by the mesh-grid region growth method were analyzed and classified by the ANN to improve computational efficiency. All unselected pixels were classified as negative for ILD. After classifying all pixels into the positive and negative groups, CAD computed a detection score based on the ratio of the number of positive pixels to all pixels in the segmented lung areas, which indicates the likelihood of the test case being positive for ILD. When applying to an independent testing dataset of 15 positive and 15 negative cases, the CAD scheme yielded the area under receiver operating characteristic curve (AUC = 0.884 {+-} 0.064) and 80.0% sensitivity at 85.7% specificity. The results demonstrated the feasibility of applying the CAD scheme to automatically detect early ILD using low-dose CT examinations.

  15. The Assessment of Health-Related Quality of Life in Scleroderma-Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Shahrzad M Lari

    2014-05-01

    Full Text Available Introduction: Pulmonary involvement is the most common cause of mortality and disability in patients with systemic sclerosis and it significantly affects the quality of life in these patients. Therefore, early diagnosis and treatment of pulmonary involvement seems necessary in patients with SSc. In this study, we aimed to assess the health-related quality of life (HRQoL in patients with Scleroderma-Interstitial Lung Disease (SSc-ILD and its relationship with pulmonary function parameters. Materials and Methods: Considering the inclusion and exclusion criteria, 25 patients with SSc-ILD were enrolled in this cross-sectional study from April 2012 to June 2013. Full tests of lung function, including body plethysmography and diffusing capacity of the lungs for carbon monoxide (DLCO, 6-minute walk distance (6MWD, and pulse oximetry were performed. The HRQoL was assessed using St. George’s and CAT questionnaires; also, dyspnea was evaluated for all the patients, using modified medical research council (MMRC scale. Afterwards, the relationship between the total scores of HRQoL questionnaires and the severity of lung disease was analyzed, based on the recorded variables. Results: The mean age of the patients was 40.36±9.50 years and the mean duration of the disease was 7.16±4.50 years. A statistically significant inverse correlation was observed between 6MWD (r=-0.50, P=0.01, DLCO (r=-0.67, P

  16. Doença pulmonar intersticial crônica na criança Chronic interstitial lung disease in children

    Directory of Open Access Journals (Sweden)

    Maria Aparecida S. S. Paiva

    2007-06-01

    conduct in a group of pediatric patients with chronic interstitial lung disease. METHODS: A retrospective study of 25 immunocompetent patients, aged 2 months to 17 years, with chronic interstitial lung disease, admitted to the Pediatric Pulmonary Section, Department of Pediatrics, Hospital dos Servidores do Estado, over a 20-year period (1984-2004. A routine protocol for persistent chronic pneumonias was used and the patients with interstitial lung disease were selected. Clinical, laboratory and imaging data were analyzed. RESULTS: Twenty-five patients were diagnosed with chronic interstitial lung disease, 13 were aged less than 2 years and 17 were male. Diagnoses were made based on history, physical examination and routine tests in one case, based on more complex tests in three cases and based on the results of invasive tests in 21 cases (20 by lung biopsy and one by bronchoalveolar lavage. Except for one patient with pulmonary lymphangiectasia, the long-term treatment (1 to 7 years consisted of corticosteroid, in six cases associated with hydroxychloroquine. Four patients required home oxygen therapy. The authors followed the patients in the outpatient department (6 a 8 visits/year. Patient outcome was: good (15; regular, with mild sequelae (4; and poor, with severe sequelae (3. One patient was lost in the follow-up period and two died. CONCLUSIONS: Chronic interstitial lung diseases in children are a group of rare pulmonary disorders, but a relevant one because of the possible progression to pulmonary fibrosis. Early diagnosis and a long-term, specialized treatment and follow-up are important for the patient outcome. Pediatricians should be aware of these diseases because in many cases diagnosis and treatment are overlooked.

  17. Erectile dysfunction is a common problem in interstitial lung diseases

    DEFF Research Database (Denmark)

    Fløe, Andreas; Hilberg, Ole; Wijsenbeek, Marlies

    2017-01-01

    Introduction: Erectile dysfunction (ED) is related to chronic diseases, including COPD. The patho- genesis may involve chronic hypoxia, which is common in interstitial lung disease (ILD). We aimed to study the relationship between ILD and ED. Method: Male patients with ILD detected by high...... degree of ED, thirty (56.6%) had moderate to severe ED, and 23 (43.4%) had severe ED. Low diffusion capacity and high body mass index showed a trend of increasing risk of moderate to severe ED. The risk increased with age (OR per 5-year increase=2.63 (1.25; 5.53)) and decreased with 6MWT distance (OR per...... 50 m increase=0.60 (0.41; 0.89). Only two patients (6.7%) received specific treatment with phosphodiesterase-5 inhibitors. Conclusion: Severe ED is a common problem in men with ILD, and is associated with poor walking distance and high age. Treatment coverage is low, and physicians should ad- dress...

  18. Interstitial lung disease in gefitinib-treated Japanese patients with non-small cell lung cancer – a retrospective analysis: JMTO LC03-02

    Directory of Open Access Journals (Sweden)

    Tada Harue

    2009-08-01

    Full Text Available Abstract Background In Japan, high incidences of interstitial lung disease (ILD and ILD-related deaths have been reported among gefitinib-treated patients with non-small cell lung cancer (NSCLC. We investigated the efficacy of gefitinib, the incidence of ILD and risk factors for ILD in these patients. Findings We obtained patient data retrospectively using questionnaires sent to 22 institutions. We asked for demographic and clinical data on NSCLC patients for whom gefitinib treatment had begun between July 2002 and February 2003. Data from a total of 526 patients were analyzed. The patient characteristics were as follows: 64% male, 69% with adenocarcinoma, 61% with a performance score of 0–1, and 5% with concurrent interstitial pneumonitis. The objective response proportion was 80/439 (18.2%; 95% CI: 14.7–22.0. ILD developed in 17 patients (3.2%; 95% CI 1.9–5.1%, of whom 7 died. According to multivariate analysis, female sex, history of prior chemotherapy, low absolute neutrophil count before gefitinib treatment, and adenocarcinoma histology were associated with response to gefitinib treatment. None of the factors we evaluated were associated with the development of ILD. Conclusion The results of this study are consistent with previously published values for treatment response proportions and incidence of ILD during gefitinib treatment in Japanese patients. Future studies should be aimed at identifying factors indicating that a patient has a high probability of receiving benefit from gefitinib and a low risk of developing ILD.

  19. Exploring the role of CHI3L1 in pre-metastatic lungs of mammary tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Stephania eLibreros

    2013-12-01

    Full Text Available Elevated levels of chitinase-3-like-1 (CHI3L1 are associated with poor prognosis, shorter recurrence-free intervals and low survival in breast cancer patients. Breast cancer often metastasizes to the lung. We hypothesized that molecules expressed in the pre-metastatic lung microenvironment could support the newly immigrant tumor cells by providing growth and angiogenic factors. Macrophages are known to play an important role in tumor growth by releasing pro-angiogenic molecules. Using mouse mammary tumor models, we have previously shown that during neoplastic progression both the mammary tumor cells and splenic macrophages from tumor-bearing mice express higher levels of CHI3L1 compared to normal control mice. However, the role of CHI3L1 in inducing angiogenesis by macrophages at the pulmonary microenvironment to support newly arriving breast cancer cells is not yet known. In this study, we determined the expression of CHI3L1 in bronchoalveolar lavage macrophages and interstitial macrophages in regulating angiogenesis that could support the growth of newly immigrant mammary tumor cells into the lung. Here we show that in vitro treatment of pulmonary macrophages with recombinant murine CHI3L1 resulted in enhanced expression of pro-angiogenic molecules including CCL2, CXCL2 and MMP-9. We and others have previously shown that inhibition of CHI3L1 decreases the production of angiogenic molecules. In this study, we explored if in vivo administration of chitin microparticles has an effect on the expression of CHI3L1 and pro-angiogenic molecules in the lungs of mammary tumor-bearing mice. We show that treatment with chitin microparticles decreases the expression of CHI3L1 and pro-angiogenic molecules in the metastatic lung. These studies suggest that targeting CHI3L1 may serve as a potential therapeutic agent to inhibit angiogenesis and thus possibly tumor growth and metastasis.

  20. Interstitial lung disease secondary to Cetuximab in bladder cancer: an Oncologist's perspective.

    Science.gov (United States)

    Price, Louise; Glynn, Patricia; Zarkar, Anjali

    2017-12-20

    A wide variety of cytotoxic medications cause interstitial lung disease (ILD). For the first time, we describe ILD in an 82-year-old woman with muscle invasive bladder cancer 10 days after receiving cetuximab as part of a novel trial. She had no significant medical history or drug allergies, had good exercise tolerance and a 5 pack-year smoking history. She received neoadjuvant chemotherapy (gemcitabine, cisplatin) with a good response on MRI. She was eligible for a phase 2 trial of cetuximab with chemotherapy and radiotherapy for muscle invasive bladder cancer (TUXEDO), in which the trial arm used cetuximab plus standard chemoradiotherapy to the bladder (64 grey in 32 fractions plus mitomycinandfluorouracil). Ten days after her third infusion of cetuximab, she was presented with type 1 respiratory failure. Thoracic CT scan demonstrated new widespread ground glass change in the lungs. She received high-dose steroids (prednisolone 1 mg/kg), broad spectrum antibacterial cover and non-invasive ventilation. She survived to be discharged with residual respiratory failure. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Chronic intersticial lung disease in the horse- Findings in arterial bloodgas analysis, tracheobronchial mucus cytology and radiological examination of the thorax; Chronisch interstitielle Lungenerkrankung beim Pferd - Blutgasanalytische, sekretzytolytische und röntgenologische Befunde

    Energy Technology Data Exchange (ETDEWEB)

    Dieckmann, M. [Klinik fuer Pferde, Tieraerztliche Hochschule Hannover (Germany); Klein, H. J.; Deegen, E.

    1990-07-01

    In 12 horses chronic interstitial lung disease was diagnosed. All horses were referrred because of unexplained loss of performance. In general there was no history of respiratory problems; 4 horses showed nasal discharge and 2 horses coughed. Results of arterial bloodgas analysis, tracheobronchial mucus cytology and radiological examination of the lungs were found in a typical combination, and they were different from results found generally in horses suffering from chronic obstructive pulmonary disease. Mean value of arterial partial pressure of oxygen was 100,6 mm Hg, arterial partial pressure of carbon dioxide was 45,1 mm Hg and alveolo-arterial difference in oxygen 5,1 mm Hg, respectively. In tracheobronchial aspirates pulmonary alveolar macrophages and neutrophil granulocytes were found in a relation of 2,6 : 1. Chest radiographs of all horses showed diffuse interstitial pattern throughout the lung.

  2. Study the level of sputum matrix metalloproteinase-9 and tissue inhibitor metaloprotienase-1 in patients with interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Sherif A. Esa

    2016-01-01

    Results: In this study, we have demonstrated that levels of sputum MMP-9 and TIMP-1 were significantly increased in patients with interstitial lung diseases than normal persons with highly significant statistical differences (p = 0.001. MMP-9 was positively correlated with number of neutrophils in the airway with highly significant statistical difference (p = 0.001.

  3. Rituximab in the Treatment of Interstitial Lung Disease Associated with Antisynthetase Syndrome: A Multicenter Retrospective Case Review.

    Science.gov (United States)

    Doyle, Tracy J; Dhillon, Namrata; Madan, Rachna; Cabral, Fernanda; Fletcher, Elaine A; Koontz, Diane C; Aggarwal, Rohit; Osorio, Juan C; Rosas, Ivan O; Oddis, Chester V; Dellaripa, Paul F

    2018-06-01

    To assess clinical outcomes including imaging findings on computed tomography (CT), pulmonary function testing (PFT), and glucocorticoid (GC) use in patients with the antisynthetase syndrome (AS) and interstitial lung disease (ILD) treated with rituximab (RTX). We retrospectively identified all patients at 2 institutions with AS-ILD who were treated with RTX. Baseline demographics, PFT, and chest CT were assessed before and after RTX. Two radiologists independently evaluated CT using a standardized scoring system. Twenty-five subjects at the Brigham and Women's Hospital (n = 13) and University of Pittsburgh Medical Center (n = 12) were included. Antisynthetase antibodies were identified in all patients (16 Jo1, 6 PL-12, 3 PL-7). In 21 cases (84%), the principal indication for RTX use was recurrent or progressive ILD, owing to failure of other agents. Comparing pre- and post-RTX pulmonary variables at 12 months, CT score and forced vital capacity were stable or improved in 88% and 79% of subjects, respectively. Total lung capacity (%) increased from 56 ± 13 to 64 ± 13 and GC dose decreased from 18 ± 9 to 12 ± 12 mg/day. Although DLCO (%) declined slightly at 1 year, it increased from 42 ± 17 to 70 ± 20 at 3 years. The most common imaging patterns on CT were nonspecific interstitial pneumonia (NSIP; n = 13) and usual interstitial pneumonia/fibrotic NSIP (n = 5), of which 5 had concurrent elements of cryptogenic organizing pneumonia. Stability or improvement in pulmonary function or severity of ILD on CT was seen in most patients. Use of RTX was well tolerated in the majority of patients. RTX may play a therapeutic role in patients with AS-ILD, and further clinical investigation is warranted.

  4. The evaluation of clinical usefulness of transbrochoscopic lung biopsy in undefined interstitial lung diseases: a retrospective study.

    Science.gov (United States)

    Han, Qian; Luo, Qun; Chen, Xiaobo; Xie, Jiaxing; Wu, Lulu; Chen, Rongchang

    2017-03-01

    Previous studies mostly focused on the diagnostic accuracy of transbronchoscopic lung biopsy (TBLB) in the diagnosis of interstitial lung diseases (ILDs). We aimed to explore the clinical usefulness of TBLB results in the diagnostic procedure of undefined ILDs. The retrospective analysis included patients undergoing TBLB for the diagnosis of undefined ILDs from January 2007 to December 2010. The clinically useful TBLB was defined as that lead to a specific histopathological diagnosis or that was consistent with the working diagnosis based on existing clinical and radiological data. A total of 664 patients were included in the study. TBLB failed to obtain lung parenchyma in 155 cases (23.3%). TBLB was considered clinically helpful in 202 procedures (30.4%), including 114 cases that provided definitive histopathological diagnoses and 88 cases that were consistent with working diagnoses. Among 202 cases of clinically useful TBLBs, the majority were diagnosed as pulmonary alveolar proteinosis (PAP) (67 cases, 33.2%), connective tissue disease-related ILDs (CTD-ILDs) (65, 32.2%) and idiopathic pulmonary fibrosis (IPF) (33, 16.3%). Although TBLB could provide definitive histopathological diagnoses in all cases diagnosed as PAP, only few cases of IPF (7, 21.2% of IPF diagnoses) and CTD-ILDs (9, 13.8% of CTD-ILD diagnoses) could be identified by TBLBs. The clinical usefulness of TBLB, in conjunction with thorough clinical and radiological data, in the diagnosis of ILDs may be varied depending on different subtypes. The use of histopathological analysis and the type of biopsy employed should therefore be considered on a case-by-case basis. © 2015 John Wiley & Sons Ltd.

  5. Quantitative GPCR and ion channel transcriptomics in primary alveolar macrophages and macrophage surrogates

    Directory of Open Access Journals (Sweden)

    Groot-Kormelink Paul J

    2012-10-01

    Full Text Available Abstract Background Alveolar macrophages are one of the first lines of defence against invading pathogens and play a central role in modulating both the innate and acquired immune systems. By responding to endogenous stimuli within the lung, alveolar macrophages contribute towards the regulation of the local inflammatory microenvironment, the initiation of wound healing and the pathogenesis of viral and bacterial infections. Despite the availability of protocols for isolating primary alveolar macrophages from the lung these cells remain recalcitrant to expansion in-vitro and therefore surrogate cell types, such as monocyte derived macrophages and phorbol ester-differentiated cell lines (e.g. U937, THP-1, HL60 are frequently used to model macrophage function. Methods The availability of high throughput gene expression technologies for accurate quantification of transcript levels enables the re-evaluation of these surrogate cell types for use as cellular models of the alveolar macrophage. Utilising high-throughput TaqMan arrays and focussing on dynamically regulated families of integral membrane proteins, we explore the similarities and differences in G-protein coupled receptor (GPCR and ion channel expression in alveolar macrophages and their widely used surrogates. Results The complete non-sensory GPCR and ion channel transcriptome is described for primary alveolar macrophages and macrophage surrogates. The expression of numerous GPCRs and ion channels whose expression were hitherto not described in human alveolar macrophages are compared across primary macrophages and commonly used macrophage cell models. Several membrane proteins known to have critical roles in regulating macrophage function, including CXCR6, CCR8 and TRPV4, were found to be highly expressed in macrophages but not expressed in PMA-differentiated surrogates. Conclusions The data described in this report provides insight into the appropriate choice of cell models for

  6. Analysis of acute exacerbation of interstitial lung disease associated with chemotherapy in patients with lung cancer: A feasibility of S-1.

    Science.gov (United States)

    Kakiuchi, Soji; Hanibuchi, Masaki; Tezuka, Toshifumi; Saijo, Atsuro; Otsuka, Kenji; Sakaguchi, Satoshi; Toyoda, Yuko; Goto, Hisatsugu; Kawano, Hiroshi; Azuma, Masahiko; Ogushi, Fumitaka; Nishioka, Yasuhiko

    2017-03-01

    Interstitial lung disease (ILD) is commonly concomitant with lung cancer, and its acute exacerbation (AE) is the most serious complication in patients receiving treatment for lung cancer. To investigate the incidence and characteristic features of AE of ILD, we conducted a retrospective study of 665 consecutive patients with lung cancer who were treated at our institute between 2008 and 2014. Among the 665 patients, 74 (11.1%) had preexisting ILD, and 64 of them received chemotherapy. Four of the 64 patients (6.3%) had experienced AE of ILD, and two (3.1%) died of respiratory failure during first-line chemotherapy. The use of a combination of carboplatin with tegafur-gimeracil-oteracil potassium (S-1) or paclitaxel as a first-line chemotherapy for non-small cell lung cancer led to a lower frequency of AE, at 8.3% (1/12) and 9.1% (1/11), respectively. The incidence of AE rose to 12.8% (5/39) during second-line treatment, and 14 (total: 15 times) of the 64 patients (21.9%) experienced AE from the time of diagnosis to the end of treatment. The incidence of AE was 17.7% (6/34), 15.8% (3/19), 5.0% (2/40), and 4.2% (1/24) in the paclitaxel-, vinorelbine-, etoposide-, and S-1-containing regimens, respectively. No difference in clinical features and laboratory data was detected between the AE and non-AE groups. Although this was a small retrospective study, its findings showed that S-1 and etoposide may be relatively safe options for the treatment of patients with lung cancer and concomitant ILD. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  7. Small cell lung cancer: Recruitment of macrophages by circulating tumor cells.

    Science.gov (United States)

    Hamilton, Gerhard; Rath, Barbara; Klameth, Lukas; Hochmair, Maximilan J

    2016-03-01

    Tumor-associated macrophages (TAMs) play an important role in tumor progression, suppression of antitumor immunity and dissemination. Blood monocytes infiltrate the tumor region and are primed by local microenvironmental conditions to promote tumor growth and invasion. Although many of the interacting cytokines and factors are known for the tumor-macrophage interactions, the putative contribution of circulating tumor cells (CTCs) is not known so far. These specialized cells are characterized by increased mobility, ability to degrade the extracellular matrix (ECM) and to enter the blood stream and generate secondary lesions which is a leading cause of death for the majority of tumor patients. The first establishment of two permanent CTC lines, namely BHGc7 and 10, from blood samples of advanced stage small cell lung cancer (SCLC) patients allowed us to investigate the CTC-immune cell interaction. Cocultures of peripheral blood mononuclear cells (PBMNCs) with CTCs or addition of CTC-conditioned medium (CTC-CM) in vitro resulted in monocyte-macrophage differentiation and appearance of CD14 + , CD163 weak and CD68 + macrophages expressing markers of TAMs. Furthermore, we screened the supernatants of CTC-primed macrophages for presence of approximately 100 cytokines and compared the expression with those induced by the local metastatic SCLC26A cell line. Macrophages recruited by SCLC26A-CM showed expression of osteopontin (OPN), monocyte chemoattractant protein-1 (MCP-1), IL-8, chitinase3-like 1 (CHI3L1), platelet factor (Pf4), IL-1ra and matrix metalloproteinase-9 (MMP-9) among other minor cytokines/chemokines. In contrast, BHGc7-CM induced marked overexpression of complement factor D (CFD)/adipsin and vitamin D-BP (VDBP), as well as increased secretion of OPN, lipocalin-2 (LCN2), CHI3L1, uPAR, MIP-1 and GDF-15/MIC-1. BHGc10, derived independently from relapsed SCLC, revealed an almost identical pattern with added expression of ENA-78/CXCL5. CMs of the non-tumor HEK293

  8. HRCT of diffuse interstitial pneumonia during treatment

    International Nuclear Information System (INIS)

    Takahashi, Masashi; Sano, Akira; Imanaka, Kazufumi

    1989-01-01

    HRCT was carried out in twenty patients with diffuse interstitial pneumonia: 13 cases of IIP, 3 of BOOP, 2 of drug-induced pneumonia, 1 of rheumatoid lung and acute interstitial pneumonia of unknown origin. With special attention to inflammatory activity, the patients underwent HRCT periodically during the treatment. Correlative investigation between HRCT image and grade of accumulation in 67 Ga scintigraphy was also performed. Response to steroid therapy was clearly reflected on HRCT image, that was shown as decreasing pulmonary density or thinning of honeycomb wall. HRCT is considered to be useful in assessing the activity of diffuse interstitial pneumonia. (author)

  9. Interstitial lung disease pattern turned out to be a predominantly lepidic lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Irena Hammen, Dr. Med

    2017-01-01

    Full Text Available We report a case of a 46-year-old woman without any medical history who presented to our Respiratory Department with exertional dyspnoea for the last 6 weeks associated with non-productive cough. Chest radiography showed bilateral diffuse interstitial opacity. Bronchoalveolar lavage and transbronchial biopsies performed during flexible bronchoscopy as a step in the diagnostic workup of idiopathic interstitial pneumonia showed cells of pulmonary adenocarcinoma.

  10. The diagnosis efficacy and safety of video-assisted thoracoscopy surgery (VATS) in undefined interstitial lung diseases: a retrospective study.

    Science.gov (United States)

    Luo, Qun; Han, Qian; Chen, Xiaobo; Xie, Jiaxing; Wu, Lulu; Chen, Rongchang

    2013-06-01

    To evaluate the efficacy and safety of lung biopsies by video-assisted thoracoscopy surgery (VATS) in the diagnosis of undefined interstitial lung disease (ILD). The retrospective analysis was performed in 32 who patients underwent VATS for the diagnosed with ILD from Jan 2007 to Dec 2011. The main reason for VATS for all the patients was due to no specific diagnosis could be obtained after non-invasive methods, transbronchial lung biopsy (TBLB) examination and the consultation with pulmonologist, radiologist and pathologist. The clinical profiles, chest high resolution computerized tomography (HRCT), laboratory profile, TBLB as well as the diagnosis of before and after the VATS were analyzed. The surgery site, biopsy number, duration of the thoracic drain, post-operative complications were also recorded. The 30- and 90-day post-operative mortality rates were calculated. The risk factors associated with the incidence of post-operative complications were assessed. The specific diagnosis could be established in all patients after VATS lung biopsies, with change from previous ones in 27 (84.4%). Among 20 cases (62.5%) diagnosed as unclassified ILD before the surgery, 14 (70.0%) were diagnosed as nonspecific interstitial pneumonia (NSIP), 3 (15.0%) as idiopathic pulmonary fibrosis (IPF) and 3 (15.0%) as connective tissue disease-related ILD (CTD-ILD). Among the 7 cases with complete change of diagnosis after VATS, 4 (57.1%) were cryptogenic organizing pneumonia (COP). The number of site of biopsy had no significant impact on the diagnostic efficacy. There were no significant change of vital sign and lung function after the VATS. 21 (65.6%) patients had post-operative complications, including pulmonary infection (56.3%), pulmonary atelectasis (28.1%) and pneumothorax (25.0%). The 30- and 90-day mortality rates were 0 and 5.2% respectively. Patients were divided into 2 groups based on the incidence of post-operative complications, and no significant difference was found

  11. Longitudinal micro-CT as an outcome measure of interstitial lung disease in TNF-transgenic mice.

    Directory of Open Access Journals (Sweden)

    Richard D Bell

    Full Text Available Rheumatoid arthritis associated interstitial lung disease (RA-ILD is a debilitating condition with poor survival prognosis. High resolution computed tomography (CT is a common clinical tool to diagnose RA-ILD, and is increasingly being adopted in pre-clinical studies. However, murine models recapitulating RA-ILD are lacking, and CT outcomes for inflammatory lung disease have yet to be formally validated. To address this, we validate μCT outcomes for ILD in the tumor necrosis factor transgenic (TNF-Tg mouse model of RA.Cross sectional μCT was performed on cohorts of male TNF-Tg mice and their WT littermates at 3, 4, 5.5 and 12 months of age (n = 4-6. Lung μCT outcomes measures were determined by segmentation of the μCT datasets to generate Aerated and Tissue volumes. After each scan, lungs were obtained for histopathology and 3 sections stained with hematoxylin and eosin. Automated histomorphometry was performed to quantify the tissue area (nuclei, cytoplasm, and extracellular matrix and aerated area (white space within the tissue sections. Spearman's correlation coefficients were used to evaluate the extent of association between μCT imaging and histopathology endpoints.TNF-Tg mice had significantly greater tissue volume, total lung volume and mean intensity at all timepoints compared to age matched WT littermates. Histomorphometry also demonstrated a significant increase in tissue area at 3, 4, and 5.5 months of age in TNF-Tg mice. Lung tissue volume was correlated with lung tissue area (ρ = 0.81, p<0.0001, and normalize lung aerated volume was correlated with normalized lung air area (ρ = 0.73, p<0.0001.We have validated in vivo μCT as a quantitative biomarker of ILD in mice. Further, development of longitudinal measures is critical for dissecting pathologic progression of ILD, and μCT is a useful non-invasive method to study lung inflammation in the TNF-Tg mouse model.

  12. Idiopathic interstitial pneumonias: radiologic-pathologic correlation

    International Nuclear Information System (INIS)

    Yoon, Young Cheol; Suh, Gee Young; Han, Joung Ho; Lee, Kyung Soo

    2002-01-01

    Idiopathic interstitial pneumonias are at present classified as one of four types: usual, nonspecific, acute, or desquamative. The acute form has the worst prognosis, followed by the usual and the nonspecific form; it is in desquamative cases that prognosis is best. At high-resolution CT, usual interstitial pneumonia, the most frequent type, manifests as patchy subpleural areas of ground-glass attenuation, irregular linear opacity, and honeycombing, which the nonspecific type, the second most frequent, appears as subpleural patchy areas of ground-glass attenuation with associated areas of irregular linear opacity. Acute interstitial pneumonia demonstrates extensive bilateral airspace consolidation and patchy or diffuse bilateral areas of ground-glass attenuation in middle and lower lung zones

  13. Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis.

    Science.gov (United States)

    Juge, Pierre-Antoine; Borie, Raphaël; Kannengiesser, Caroline; Gazal, Steven; Revy, Patrick; Wemeau-Stervinou, Lidwine; Debray, Marie-Pierre; Ottaviani, Sébastien; Marchand-Adam, Sylvain; Nathan, Nadia; Thabut, Gabriel; Richez, Christophe; Nunes, Hilario; Callebaut, Isabelle; Justet, Aurélien; Leulliot, Nicolas; Bonnefond, Amélie; Salgado, David; Richette, Pascal; Desvignes, Jean-Pierre; Lioté, Huguette; Froguel, Philippe; Allanore, Yannick; Sand, Olivier; Dromer, Claire; Flipo, René-Marc; Clément, Annick; Béroud, Christophe; Sibilia, Jean; Coustet, Baptiste; Cottin, Vincent; Boissier, Marie-Christophe; Wallaert, Benoit; Schaeverbeke, Thierry; Dastot le Moal, Florence; Frazier, Aline; Ménard, Christelle; Soubrier, Martin; Saidenberg, Nathalie; Valeyre, Dominique; Amselem, Serge; Boileau, Catherine; Crestani, Bruno; Dieudé, Philippe

    2017-05-01

    Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT , RTEL1 , PARN or SFTPC coding regions . The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT , RTEL1 , PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53-6.12; p=9.45×10 -4 ). Telomeres were shorter in RA-ILD patients with a TERT , RTEL1 or PARN mutation than in controls (p=2.87×10 -2 ).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility. Copyright ©ERS 2017.

  14. Cyclophosphamide-refractory scleroderma-associated interstitial lung disease: remarkable clinical and radiological response to a single course of rituximab combined with high-dose corticosteroids.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2011-10-01

    We would like to report our experience of using rituximab in cyclophosphamide refractory, rapidly progressive interstitial lung disease (ILD) in a patient with limited scleroderma. A 40-year-old man presented with 10-week history of inflammatory polyarthritis, which responded to a short course of oral corticosteroids. However, 3 weeks later, he developed new onset of exertional dyspnoea. High-resolution CT of the thorax was suggestive of early ILD. Surgical lung biopsy showed features of fibrotic non-specific interstitial pneumonia. He was diagnosed with scleroderma on the basis of: presence of anticentromere antibodies, Raynaud\\'s phenomenon, pulmonary fibrosis, digital oedema and hypomotility along with a dilated oesophagus. He was treated aggressively with pulse doses of corticosteroids and cyclophosphamide; however, his ILD continued to deteriorate. At this stage, he received rituximab (two pulses of 1 g each), which led to a gradual clinical improvement. Now, 12 months since his rituximab infusion, he walks 2 miles daily without any exertional dyspnoea.

  15. High-resolution CT of lymphoid interstitial pneumonia

    International Nuclear Information System (INIS)

    Vilgrain, V.; Frija, J.; Yana, C.; Couderc, L.J.; David, M.; Clauvel, J.P.; Laval-Jeantet, M.

    1989-01-01

    Three patients with lymphoid interstitial pneumonia (two HIV 1+ patients with chronic lymphadenopathic syndromes and one with a not-characterized autoimmune disease) have been studied with high-resolution computed tomography (HR-CT). This technique reveals septal lines, small reticulonodular opacities, polyhedral micronodular opacities, 'ground-glass' opacities and a dense, subpleural, curved broken line in one patient. The lesions dominate in the bases of the lungs. They are not characteristic for lymphoid interstitial pneumonia. If a patient presents with a chronic lymphadenopathic syndrome, the diagnosis of an opportunistic infection should not be automatically made, since the syndrome can be caused by lymphoid interstitial pneumonia [fr

  16. Characterization of interstitial lung disease in chest radiographs using SOM artificial neural network

    International Nuclear Information System (INIS)

    Azevedo-Marques, P.M. de; Ambrosio, P.E.; Pereira, R.R. Jr.; Valini, R. de A.; Salomao, S.C.

    2007-01-01

    This paper presents an automated approach to apply a self-organizing map (SOM) artificial neural network (ANN) as a tool for feature extraction and dimensionality reduction to recognize and characterize radiologic patterns of interstitial lung diseases in chest radiography. After feature extraction and dimensionality reduction a multilayer perceptron (MLP) ANN is applied for radiologic patterns classification in normal, linear, nodular or mixed. A leave-one-out methodology was applied for training and test over a database containing 17 samples of linear pattern, 9 samples of nodular pattern, 9 samples of mixed pattern and 18 samples of normal pattern. The MLP network provided an average result of 88.7% of right classification, with 100% of right classification for linear pattern, 55.5% for nodular pattern, 77.7% for mixed pattern and 100% for normal pattern. (orig.)

  17. Chronic interstitial pneumonia with honeycombing in coal workers

    Energy Technology Data Exchange (ETDEWEB)

    Brichet, A.; Tonnel, A.B.; Brambilla, E.; Devouassoux, G.; Remy-Jardin, M.; Copin, M.C.; Wallaert, B. [A. Calmette Hospital, Lille (France)

    2002-10-01

    Coal worker's pneumoconiosis (CWP) results from coal mine dust inhalation. The paper reports the presence of a chronic interstitial pneumonia (CIP) with honeycombing in 38 cases of coal miners, with or without CWP. The 38 patients were selected on the basis of clinical criteria which are unusual in CWP, i.e. fine inspiratory crackles and severe dyspnea. There were 37 men and one woman; mean age was 67.5 {+-} 9.1 years. Thirty-two were smokers. Duration of exposure was 26.7 {+-} 9.9 years. All the patients had clinical examination, chest radiography, computed tomography (CT), lung function, laboratory investigations, wedged fiberoptic bronchoscopy with bronchoalveolar lavage (BAL). In eight cases, lung specimens were obtained. Seventeen out of 38 had finger clubbing. 17 had radiological signs of CWP limited to the upper lobes or diffusely distributed. CT showed honeycombing (36 cases), and/or ground glass opacities (30 cases) with traction bronchiectasis (8 cases) predominant in the lower lobes. BAL analysis demonstrated an increased percentage of neutrophils (9.4% {+-} 6). Lung function showed a restrictive pattern associated with a decreased DLCO and hypoxemia. Lung specimens demonstrated in 2 cases a homogenous interstitial fibrosis of intra-alveolar septum with an accumulation of immune and inflammatory cells without temporal variation and with obvious honeycombing. The 6 other cases showed features of usual interstitial pneumonia. These cases, should alert other clinicians to a possible association between CIP with honeycombing and coal dust exposure, with or without associated CWP.

  18. “Marker of Self” CD47 on lentiviral vectors decreases macrophage-mediated clearance and increases delivery to SIRPA-expressing lung carcinoma tumors

    Directory of Open Access Journals (Sweden)

    Nisha G Sosale

    2016-01-01

    Full Text Available Lentiviruses infect many cell types and are now widely used for gene delivery in vitro, but in vivo uptake of these foreign vectors by macrophages is a limitation. Lentivectors are produced here from packaging cells that overexpress “Marker of Self” CD47, which inhibits macrophage uptake of cells when prophagocytic factors are also displayed. Single particle analyses show “hCD47-Lenti” display properly oriented human-CD47 for interactions with the macrophage's inhibitory receptor SIRPA. Macrophages derived from human and NOD/SCID/Il2rg−/− (NSG mice show a SIRPA-dependent decrease in transduction, i.e., transgene expression, by hCD47-Lenti compared to control Lenti. Consistent with known “Self” signaling pathways, macrophage transduction by control Lenti is decreased by drug inhibition of Myosin-II to the same levels as hCD47-Lenti. In contrast, human lung carcinoma cells express SIRPA and use it to enhance transduction by hCD47-Lenti- as illustrated by more efficient gene deletion using CRISPR/Cas9. Intravenous injection of hCD47-Lenti into NSG mice shows hCD47 prolongs circulation, unless a blocking anti-SIRPA is preinjected. In vivo transduction of spleen and liver macrophages also decreases for hCD47-Lenti while transduction of lung carcinoma xenografts increases. hCD47 could be useful when macrophage uptake is limiting on other viral vectors that are emerging in cancer treatments (e.g., Measles glycoprotein-pseudotyped lentivectors and also in targeting various SIRPA-expressing tumors such as glioblastomas.

  19. Functionalized synchrotron in-line phase-contrast computed tomography: a novel approach for simultaneous quantification of structural alterations and localization of barium-labelled alveolar macrophages within mouse lung samples

    Energy Technology Data Exchange (ETDEWEB)

    Dullin, Christian, E-mail: christian.dullin@med.uni-goettingen.de [University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Monego, Simeone dal [Cluster in Biomedicine, AREA Science Park Basovizza, Trieste (Italy); Larsson, Emanuel [Elettra Sincrotrone Trieste, Strada Statale 14, km 163.5 in AREA Science Park, 34149 Basovizza (Trieste) (Italy); University of Trieste, Trieste (Italy); Linköping University, SE-581 83 Linkoeping (Sweden); Mohammadi, Sara [Elettra Sincrotrone Trieste, Strada Statale 14, km 163.5 in AREA Science Park, 34149 Basovizza (Trieste) (Italy); Krenkel, Martin [University of Göttingen, Göttingen (Germany); Garrovo, Chiara; Biffi, Stefania [IRCCS Burlo Garofolo, Trieste (Italy); Lorenzon, Andrea [Cluster in Biomedicine, AREA Science Park Basovizza, Trieste (Italy); Markus, Andrea [University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Napp, Joanna [University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Max Planck Institute for Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen (Germany); University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Salditt, Tim [University of Göttingen, Göttingen (Germany); Accardo, Agostino [University of Trieste, Trieste (Italy); Alves, Frauke [University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Max Planck Institute for Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen (Germany); University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Tromba, Giuliana [Elettra Sincrotrone Trieste, Strada Statale 14, km 163.5 in AREA Science Park, 34149 Basovizza (Trieste) (Italy)

    2015-01-01

    This study presents an approach to increase the sensitivity of lung computed tomography (CT) imaging by utilizing in-line phase contrast CT in combination with single-distance phase-retrieval algorithms and a dedicated image-processing regime. As demonstrated here, functional CT imaging can be achieved for the assessment of both structural alterations in asthmatic mouse lung tissue and the accumulation pattern of instilled barium-sulfate-labelled macrophages in comparison with healthy controls. Functionalized computed tomography (CT) in combination with labelled cells is virtually non-existent due to the limited sensitivity of X-ray-absorption-based imaging, but would be highly desirable to realise cell tracking studies in entire organisms. In this study we applied in-line free propagation X-ray phase-contrast CT (XPCT) in an allergic asthma mouse model to assess structural changes as well as the biodistribution of barium-labelled macrophages in lung tissue. Alveolar macrophages that were barium-sulfate-loaded and fluorescent-labelled were instilled intratracheally into asthmatic and control mice. Mice were sacrificed after 24 h, lungs were kept in situ, inflated with air and scanned utilizing XPCT at the SYRMEP beamline (Elettra Synchrotron Light Source, Italy). Single-distance phase retrieval was used to generate data sets with ten times greater contrast-to-noise ratio than absorption-based CT (in our setup), thus allowing to depict and quantify structural hallmarks of asthmatic lungs such as reduced air volume, obstruction of airways and increased soft-tissue content. Furthermore, we found a higher concentration as well as a specific accumulation of the barium-labelled macrophages in asthmatic lung tissue. It is believe that XPCT will be beneficial in preclinical asthma research for both the assessment of therapeutic response as well as the analysis of the role of the recruitment of macrophages to inflammatory sites.

  20. β-thymosins and interstitial lung disease: study of a scleroderma cohort with a one-year follow-up

    Directory of Open Access Journals (Sweden)

    Messana Irene

    2011-02-01

    Full Text Available Abstract Background β-thymosins play roles in cytoskeleton rearrangement, angiogenesis, fibrosis and reparative process, thus suggesting a possible involvement in the pathogenesis of systemic sclerosis. The aim of the study was to investigate the presence of thymosins β4, β4 sulfoxide, and β10 in bronchoalveolar lavage fluid of scleroderma patients with interstitial lung disease and the relation of these factors with pulmonary functional and radiological parameters. Methods β-thymosins concentrations were determined by Reverse Phase-High Performance Liquid Chromatography-Electrospray-Mass Spectrometry in the bronchoalveolar lavage fluid of 46 scleroderma patients with lung involvement and of 15 controls. Results Thymosin β4, β4 sulfoxide, and β10 were detectable in bronchoalveolar lavage fluid of patients and controls. Thymosin β4 levels were significantly higher in scleroderma patients than in controls. In addition, analyzing the progression of scleroderma lung disease at one-year follow-up, we have found that higher thymosin β4 levels seem to have a protective role against lung tissue damage. Thymosin β4 sulfoxide levels were higher in the smokers and in the scleroderma patients with alveolitis. Conclusions We describe for the first time β-thymosins in bronchoalveolar lavage fluid and their possible involvement in the pathogenesis of scleroderma lung disease. Thymosin β4 seems to have a protective role against lung tissue damage, while its oxidation product mirrors an alveolar inflammatory status.

  1. Interstitial pulmonary alterations in visceral leishmaniasis: evaluation with high-resolution computed tomography; Alteracoes pulmonares intersticiais na leishmaniose visceral: avaliacao pela tomografia computadorizada de alta resolucao

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Norma Selma Santos; Cerri, Giovanni Guido [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina. Dept. de Radiologia

    1999-08-01

    Visceral leishmaniasis, also called kala-azar, is a disease caused by a protozoan, the Leishmania donovani chagasi, that comprises reticuloendothelial system with involvement of the liver, spleen and bone marrow. It is endemic in some areas of northeastern Brazil and other countries of Latin America and Africa. The pathogenesis is related to the immunologic system of patients that present with the inability to activate the phagocytosis of the macrophages. As occurs in the liver and kidneys, the lungs are also involved with interstitial abnormalities caused by Leishmania that are not dependent upon the presence of the parasite. The histopathologic changes described are the involvement of inter alveolar septal in three different phases, irregularly and diffusely throughout the whole pulmonary parenchyma. This work analyzed high-resolution computed tomography (HRCT) of the thorax in 17 patients with visceral leishmaniasis in order to detect and characterize the abnormalities described in the anatomo pathologic findings reported in the literature. The HRCT is being used to evaluate chronic interstitial lung disease in a good correlation with histologic findings. The most common findings detected by HRCT were the reticular opacities that include peribronchovascular interstitial thickening and interlobular septal thickening an ground-glass opacity. The HRCT suggests that similar changes to that found in alveolar structures may occur in the secondary pulmonary lobule and that the involvement in the parenchymal interstitium represents the findings reported by pathological studies in visceral leishmaniasis. (author)

  2. Regional distribution of ventilation-perfusion ratio in patients with interstitial pneumonia using Kr-81m

    International Nuclear Information System (INIS)

    Sekine, Hiroshi; Kawakami, Kenji; Shimada, Takao

    1983-01-01

    In order to know the pathophysiological change of interstitial pneumonia, it is important to detect the morphological change of vascular and air way systems in the lung. The study group consisted of 12 patients of interstitial pneumonia including IIP, PSS, RA, sarcoidosis, and hypersensitive pneumonia. The Kr-81m bolus inhalation from 3 different lung volumes were analyzed to detect regional ventilation abnormalities. The regional distribution of ventilation-perfusion ratio (V/Q) in the lung was obtained from the continuous inhalation and infusion Kr-81 m. In 7 patients, regional distribution of V/Q was also measured at rest and during exercise. In advanced stage of interstitial pneumonia, radioactivity in lower lung fields was decreased in bolus inhalation from TLC-400 ml lung volume, and present in lower lung in bolus inhalation from RV level. These findings are representing air way rigidity especially in lower lung fields. However, in early stage or reversible cases, it is difficult to detect the abnormal distribution of radioactivity in lung, in spite of decreased PO 2 . So it seems impossible to screen early stage or reversible cases of interstitial pneumonia by bolus inhalation method alone. At rest for normal subjects in the upright position, the apical zone had a high V/Q, but in the lower parts two third of V/Q distribution was relatively homogeneous. During exercise at 50W, the distribution became more uniform. In most cases of the disease, weak exercise (less than 40W) produced the same uniform V/Q distribution. It should be noted that in the disease not only was perfusion in upper lung fields increased, but that perfusion of lower lung fields was reduced. So late in the cource of extension of the disease, pulmonary vascular bed in the lower lung fields is restricted.(J.P.N.)

  3. Cell Origin Dictates Programming of Resident versus Recruited Macrophages during Acute Lung Injury.

    Science.gov (United States)

    Mould, Kara J; Barthel, Lea; Mohning, Michael P; Thomas, Stacey M; McCubbrey, Alexandra L; Danhorn, Thomas; Leach, Sonia M; Fingerlin, Tasha E; O'Connor, Brian P; Reisz, Julie A; D'Alessandro, Angelo; Bratton, Donna L; Jakubzick, Claudia V; Janssen, William J

    2017-09-01

    Two populations of alveolar macrophages (AMs) coexist in the inflamed lung: resident AMs that arise during embryogenesis, and recruited AMs that originate postnatally from circulating monocytes. The objective of this study was to determine whether origin or environment dictates the transcriptional, metabolic, and functional programming of these two ontologically distinct populations over the time course of acute inflammation. RNA sequencing demonstrated marked transcriptional differences between resident and recruited AMs affecting three main areas: proliferation, inflammatory signaling, and metabolism. Functional assays and metabolomic studies confirmed these differences and demonstrated that resident AMs proliferate locally and are governed by increased tricarboxylic acid cycle and amino acid metabolism. Conversely, recruited AMs produce inflammatory cytokines in association with increased glycolytic and arginine metabolism. Collectively, the data show that even though they coexist in the same environment, inflammatory macrophage subsets have distinct immunometabolic programs and perform specialized functions during inflammation that are associated with their cellular origin.

  4. Mycobacterium tuberculosis Infection and Innate Responses in a New Model of Lung Alveolar Macrophages.

    Science.gov (United States)

    Woo, Minjeong; Wood, Connor; Kwon, Doyoon; Park, Kyu-Ho Paul; Fejer, György; Delorme, Vincent

    2018-01-01

    Lung alveolar macrophages (AMs) are in the first line of immune defense against respiratory pathogens and play key roles in the pathogenesis of Mycobacterium tuberculosis ( Mtb ) in humans. Nevertheless, AMs are available only in limited amounts for in vitro studies, which hamper the detailed molecular understanding of host- Mtb interactions in these macrophages. The recent establishment of the self-renewing and primary Max Planck Institute (MPI) cells, functionally very close to lung AMs, opens unique opportunities for in vitro studies of host-pathogen interactions in respiratory diseases. Here, we investigated the suitability of MPI cells as a host cell system for Mtb infection. Bacterial, cellular, and innate immune features of MPI cells infected with Mtb were characterized. Live bacteria were readily internalized and efficiently replicated in MPI cells, similarly to primary murine macrophages and other cell lines. MPI cells were also suitable for the determination of anti-tuberculosis (TB) drug activity. The primary innate immune response of MPI cells to live Mtb showed significantly higher and earlier induction of the pro-inflammatory cytokines TNFα, interleukin 6 (IL-6), IL-1α, and IL-1β, as compared to stimulation with heat-killed (HK) bacteria. MPI cells previously showed a lack of induction of the anti-inflammatory cytokine IL-10 to a wide range of stimuli, including HK Mtb . By contrast, we show here that live Mtb is able to induce significant amounts of IL-10 in MPI cells. Autophagy experiments using light chain 3B immunostaining, as well as LysoTracker labeling of acidic vacuoles, demonstrated that MPI cells efficiently control killed Mtb by elimination through phagolysosomes. MPI cells were also able to accumulate lipid droplets in their cytoplasm following exposure to lipoproteins. Collectively, this study establishes the MPI cells as a relevant, versatile host cell model for TB research, allowing a deeper understanding of AMs functions in this

  5. Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats

    DEFF Research Database (Denmark)

    Schmal, H; Shanley, T P; Jones, M L

    1996-01-01

    Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that possesses chemotactic activity for neutrophils. Rat MIP-2 was cloned and expressed as a 7.9-kDa peptide that exhibited dose-dependent neutrophil chemotactic activity at concentrations from 10 to 250 nM. Rabbit polyclonal Ab to th...... instillation of LPS was found to be MIP-2-dependent. These data indicate that MIP-2 plays a significant role in LPS-induced inflammatory response in rat lungs and is required for the full recruitment of neutrophils....

  6. Adalimumab-induced acute interstitial lung disease in a patient with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Olivia Meira Dias

    2014-01-01

    Full Text Available The use of immunobiological agents for the treatment of autoimmune diseases is increasing in medical practice. Anti-TNF therapies have been increasingly used in refractory autoimmune diseases, especially rheumatoid arthritis, with promising results. However, the use of such therapies has been associated with an increased risk of developing other autoimmune diseases. In addition, the use of anti-TNF agents can cause pulmonary complications, such as reactivation of mycobacterial and fungal infections, as well as sarcoidosis and other interstitial lung diseases (ILDs. There is evidence of an association between ILD and the use of anti-TNF agents, etanercept and infliximab in particular. Adalimumab is the newest drug in this class, and some authors have suggested that its use might induce or exacerbate preexisting ILDs. In this study, we report the first case of acute ILD secondary to the use of adalimumab in Brazil, in a patient with rheumatoid arthritis and without a history of ILD.

  7. Genetic basis for childhood interstitial lung disease among Japanese infants and children.

    Science.gov (United States)

    Hayasaka, Itaru; Cho, Kazutoshi; Akimoto, Takuma; Ikeda, Masahiko; Uzuki, Yutaka; Yamada, Masafumi; Nakata, Koh; Furuta, Itsuko; Ariga, Tadashi; Minakami, Hisanori

    2018-02-01

    BackgroundGenetic variants responsible for childhood interstitial lung disease (chILD) have not been studied extensively in Japanese patients.MethodsThe study population consisted of 62 Japanese chILD patients. Twenty-one and four patients had pulmonary hypertension resistant to treatment (PH) and hypothyroidism, respectively. Analyses of genetic variants were performed in all 62 patients for SFTPC and ABCA3, in all 21 PH patients for FOXF1, and in a limited number of patients for NKX2.1.ResultsCausative genetic variants for chILD were identified in 11 (18%) patients: SFTPC variants in six, NKX2.1 variants in three, and FOXF1 variants in two patients. No patients had ABCA3 variants. All three and two patients with NKX2.1 variants had hypothyroidism and developmental delay, respectively. We found six novel variants in this study.ConclusionMutations in SFTPC, NKX2.1, and FOXF1 were identified among Japanese infants and children with chILD, whereas ABCA3 mutations were rare.

  8. Burden, resilience and coping in caregivers of patients with interstitial lung disease.

    Science.gov (United States)

    Shah, R J; Collard, H R; Morisset, J

    Prior work has described the experience of caregiving in idiopathic pulmonary fibrosis, but the effect on caregivers in interstitial lung disease (ILD) has not been explored. Describe the burden, resilience, and health related quality of life (HRQoL) of caregivers of people with ILD. In a mixed methods study, ILD caregivers completed questionnaires and participated in focus groups. A qualitative thematic analysis of the focus group transcripts was conducted. Thirty seven caregivers completed the survey, and 15 participated in the focus groups. 65% were female; the average age was 66 (SD = 13). The mean Short Form-36 role emotional and mental health scores were 18 (SD = 4) and 46 (SD = 7). The focus groups identified 4 major themes: emotional burden, changes in relationship, coping strategies, and unmet needs of caregivers. Caregiving for patients with ILD significantly impairs HRQoL, particularly, emotional health. Increasing resources could improve the caregiving experience in ILD. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Interstitial lung disease caused by TS-1: a case of long-term drug retention as a fatal adverse reaction.

    Science.gov (United States)

    Park, Joong-Min; Hwang, In Gyu; Suh, Suk-Won; Chi, Kyong-Choun

    2011-12-01

    TS-1 is an oral anti-cancer agent for gastric cancer with a high response rate and low toxicity. We report a case of long-term drug retention of TS-1 causing interstitial lung disease (ILD) as a fatal adverse reaction. A 65-year-old woman underwent a total gastrectomy with pathologic confirmation of gastric adenocarcinoma. She received 6 cycles of TS-1 and low-dose cisplatin for post-operative adjuvant chemotherapy followed by single-agent maintenance therapy with TS-1. After 8 months, the patient complained of a productive cough with sputum and mild dyspnea. A pulmonary evaluation revealed diffuse ILD in the lung fields, bilaterally. In spite of discontinuing chemotherapy and the administration of corticosteroids, the pulmonary symptoms did not improve, and the patient died of pulmonary failure. TS-1-induced ILD can be caused by long-term drug retention that alters the lung parenchyma irreversibly, the outcome of which can be life-threatening. Pulmonary evaluation for early detection of disease is recommended.

  10. Significance of myositis autoantibody in patients with idiopathic interstitial lung disease.

    Science.gov (United States)

    Song, Ju Sun; Hwang, Jiwon; Cha, Hoon-Suk; Jeong, Byeong-Ho; Suh, Gee Young; Chung, Man Pyo; Kang, Eun-Suk

    2015-05-01

    Some patients with interstitial lung disease (ILD) related to connective tissue disease (CTD) have a delayed diagnosis of the underlying CTD when the ILD is categorized as idiopathic. In this study, we evaluated the frequency of myositis autoantibodies in patients diagnosed with idiopathic ILD and investigated the clinical significance stemming from the presence of the antibodies. A total 32 patients diagnosed with idiopathic ILD were enrolled in this study. We analyzed a panel of 11 myositis autoantibody specificities in the patients using a line blot immunoassay. Then, we divided them into myositis autoantibody-positive and -negative groups and compared the clinical features and laboratory data between the two groups. Of the 32 idiopathic ILD patients, 12 patients had myositis autoantibodies encompassing 9 specificities, except for anti-Mi-2 and anti-PM-Scl 100 (12/32, 38%). Anti-synthetase autoantibodies including Jo-1, EJ, OJ, PL-7, and PL-12 were present in 7 patients (7/32, 22%). The group with myositis autoantibodies presented more frequently with the symptom of mechanic's hand and showed abnormal pulmonary function test results with low forced vital capacity, diffusing capacity for carbon monoxide, total lung capacity, and high lactate dehydrogenase values in blood when compared with the group without myositis antibodies. We strongly suggest that patients undergo an evaluation of myositis autoantibodies, if they are diagnosed with idiopathic ILD in the presence of clinical characteristics including mechanic's hand, arthralgia, and autoantibodies which are insufficient to make a diagnosis of a specific CTD category.

  11. Diffuse interstitial lung disease as a first manifestation of Waldenström's macroglobulinemia: case report and review of the literature.

    Science.gov (United States)

    Consuegra, Angélica; Marcos, Pedro J; Vázquez, Rubén; Pombo, Jorge; Debén, Guillermo; Verea-Hernando, Héctor

    2014-04-01

    Waldenström's macroglobulinemia (WM) is a lymphoid malignancy characterized by infiltration, mainly of the bone marrow and lymph nodes, by small mature lymphocytes showing plasmacytoid differentiation, associated with an IgM monoclonal band, and, in general, a low degree of aggressiveness. We present the first case reported in the Spanish literature of interstitial lung disease presenting as MW and we review the literature. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  12. Persistent pulmonary interstitial emphysema in a case of Langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    Abbey, Pooja; Narula, Mahender K.; Anand, Rama; Chandra, Jagdish

    2014-01-01

    We present the case of a 10-month-old boy with multisystem Langerhans cell histiocytosis showing thin-walled lung cysts along with computed tomography (CT) evidence of persistent pulmonary interstitial emphysema (PPIE), in the absence of pneumothorax or pneumomediastinum. Follow-up CT performed after 6 months demonstrated complete resolution of interstitial emphysema

  13. Postmortem changes in lungs in severe closed traumatic brain injury complicated by acute respiratory failure

    Directory of Open Access Journals (Sweden)

    V. A. Tumanskiy

    2013-08-01

    Full Text Available V.А. Tumanskіy, S.І. Ternishniy, L.M. Tumanskaya Pathological changes in the lungs were studied in the work of 42 patiens who died from severe closed intracranial injury (SCII. It was complicated with acute respiratory insufficient (ARI. The most modified subpleural areas were selected from every lobe of the lungs for pathological studies. Prepared histological sections were stained by means of hemotoxylin and eosin and by Van Giеson for light microscopy. The results of the investigation have shown absence of the significant difference of pathological changes in the lungs of patients who died from ARI because of severe brain injury and traumatic intracranial hemorrhage. Pathognomic pathological changes in the lungs as a result of acute lung injury syndrome (ALIS were found in deceased patients on the third day since the SCII (n=8. There was a significant bilateral interstitial edema and mild alveolar edema with the presence of red and blood cells in the alveoli, vascular plethora of the septum interalveolar and stasis of blood in the capillaries, the slight pericapillary leukocyte infiltration, subpleural hemorrhage and laminar pulmonary atelectasis. In deceased patients on 4-6 days after SCII that was complicated with ARI (n=14, morphological changes had been detected in the lungs. It was pathognomic for acute respiratory distress syndrome (ARDS with local pneumonic to be layered. A significant interstitial pulmonary edema was observed in the respiratory part of the lungs. The edema has spread from the walls of the alveoli into the interstitial spaces of the bronchioles and blood vessels, and also less marked serous-hemorrhagic alveolar edema with presence of the fibrin in the alveoli and macrophages. The ways of intrapleural lymphatic drainage were dilatated. Histopathological changes in the lungs of those who died on the 7-15th days after severe closed craniocerebral injury with ARI to be complicated (n=12 have been indicative of two

  14. Unusual progression and subsequent improvement in cystic lung disease in a child with radiation-induced lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, Michael S. [Monroe Carell Jr. Children' s Hospital at Vanderbilt, Department of Pediatrics, Nashville, TN (United States); Chadha, Ashley D. [Vanderbilt University School of Medicine, Division of Pulmonary Medicine, Department of Pediatrics, Nashville, TN (United States); Carroll, Clinton M.; Borinstein, Scott C. [Vanderbilt University School of Medicine, Division of Hematology and Oncology, Department of Pediatrics, Nashville, TN (United States); Young, Lisa R. [Vanderbilt University School of Medicine, Division of Pulmonary Medicine, Department of Pediatrics, Nashville, TN (United States); Vanderbilt University School of Medicine, Division of Allergy, Pulmonary and Critical Care, Department of Medicine, Nashville, TN (United States); Vanderbilt University School of Medicine, Division of Pulmonary Medicine, Nashville, TN (United States)

    2015-07-15

    Radiation-induced lung disease is a known complication of therapeutic lung irradiation, but the features have not been well described in children. We report the clinical, radiologic and histologic features of interstitial lung disease (ILD) in a 4-year-old child who had previously received lung irradiation as part of successful treatment for metastatic Wilms tumor. Her radiologic abnormalities and clinical symptoms developed in an indolent manner. Clinical improvement gradually occurred with corticosteroid therapy. However, the observed radiologic progression from interstitial and reticulonodular opacities to diffuse cystic lung disease, with subsequent improvement, is striking and has not been previously described in children. (orig.)

  15. Chronic pulmonary interstitial fibrosis in a blue-fronted Amazon parrot (Amazona aestiva aestiva).

    Science.gov (United States)

    Amann, Olga; Kik, Marja J L; Passon-Vastenburg, Maartje H A C; Westerhof, Ineke; Lumeij, Johannes T; Schoemaker, Nico J

    2007-03-01

    A 30-yr-old blue-fronted Amazon parrot (Amazon aestiva aestiva) was presented to the clinic with a history of sneezing more often during the last 2 mo. Physical examination revealed only a mild nasal discharge. Complete hematologic and plasma biochemical examination showed no abnormalities. Computerized tomography (CT) of the complete bird showed generalized lung alterations consistent with lung fibrosis. Two lung biopsies were taken. The results of the histologic examination of the biopsies confirmed the tentative CT diagnosis of pulmonary interstitial fibrosis. To our knowledge this is the first reported case of chronic pulmonary interstitial fibrosis diagnosed by means of a lung biopsy in an avian species. The histologic characteristics are discussed and compared with those of human idiopathic pulmonary fibrosis.

  16. The idiopathic interstitial pneumonias: understanding key radiological features

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, S. [Department of Radiology, Churchill Hospital, Old Road, Oxford OX3 7LJ (United Kingdom); Benamore, R., E-mail: Rachel.Benamore@orh.nhs.u [Department of Radiology, Churchill Hospital, Old Road, Oxford OX3 7LJ (United Kingdom)

    2010-10-15

    Many radiologists find it challenging to distinguish between the different interstitial idiopathic pneumonias (IIPs). The British Thoracic Society guidelines on interstitial lung disease (2008) recommend the formation of multidisciplinary meetings, with diagnoses made by combined radiological, pathological, and clinical findings. This review focuses on understanding typical and atypical radiological features on high-resolution computed tomography between the different IIPs, to help the radiologist determine when a confident diagnosis can be made and how to deal with uncertainty.

  17. The idiopathic interstitial pneumonias: understanding key radiological features

    International Nuclear Information System (INIS)

    Dixon, S.; Benamore, R.

    2010-01-01

    Many radiologists find it challenging to distinguish between the different interstitial idiopathic pneumonias (IIPs). The British Thoracic Society guidelines on interstitial lung disease (2008) recommend the formation of multidisciplinary meetings, with diagnoses made by combined radiological, pathological, and clinical findings. This review focuses on understanding typical and atypical radiological features on high-resolution computed tomography between the different IIPs, to help the radiologist determine when a confident diagnosis can be made and how to deal with uncertainty.

  18. Perfusion- and pattern-based quantitative CT indexes using contrast-enhanced dual-energy computed tomography in diffuse interstitial lung disease: relationships with physiologic impairment and prediction of prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Jung Won [Sungkyunkwan University School of Medicine, Department of Radiology, Kangbuk Samsung Hospital, Seoul (Korea, Republic of); Bae, Jang Pyo; Kim, Namkug; Chang, Yongjun; Seo, Joon Beom [University of Ulsan College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Lee, Ho Yun; Lee, Kyung Soo [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Chung, Man Pyo; Park, Hye Yun [Sungkyunkwan University School of Medicine, Department of Pulmonology, Samsung Medical Center, Seoul (Korea, Republic of)

    2016-05-15

    To evaluate automated texture-based segmentation of dual-energy CT (DECT) images in diffuse interstitial lung disease (DILD) patients and prognostic stratification by overlapping morphologic and perfusion information of total lung. Suspected DILD patients scheduled for surgical biopsy were prospectively included. Texture patterns included ground-glass opacity (GGO), reticulation and consolidation. Pattern- and perfusion-based CT measurements were assessed to extract quantitative parameters. Accuracy of texture-based segmentation was analysed. Correlations between CT measurements and pulmonary function test or 6-minute walk test (6MWT) were calculated. Parameters of idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP) and non-IPF/UIP were compared. Survival analysis was performed. Overall accuracy was 90.47 % for whole lung segmentation. Correlations between mean iodine values of total lung, 50-97.5th (%) attenuation and forced vital capacity or 6MWT were significant. Volume of GGO, reticulation and consolidation had significant correlation with DLco or SpO{sub 2} on 6MWT. Significant differences were noted between IPF/UIP and non-IPF/UIP in 6MWT distance, mean iodine value of total lung, 25-75th (%) attenuation and entropy. IPF/UIP diagnosis, GGO ratio, DILD extent, 25-75th (%) attenuation and SpO{sub 2} on 6MWT showed significant correlations with survival. DECT combined with pattern analysis is useful for analysing DILD and predicting survival by provision of morphology and enhancement. (orig.)

  19. Oxygen therapy for interstitial lung disease: a systematic review

    Directory of Open Access Journals (Sweden)

    Emily C. Bell

    2017-02-01

    Full Text Available This review aims to establish the impact of oxygen therapy on dyspnoea, health-related quality of life (HRQoL, exercise capacity and mortality in interstitial lung disease (ILD. We included studies that compared oxygen therapy to no oxygen therapy in adults with ILD. No limitations were placed on study design or intervention type. Two reviewers independently evaluated studies for inclusion, assessed risk of bias and extracted data. The primary outcome was dyspnoea. Eight studies evaluated the acute effects of oxygen (n=1509. There was no effect of oxygen therapy on modified Borg dyspnoea score at end exercise (mean difference (MD −0.06 units, 95% CI −0.24–0.13; two studies, n=27. However, effects on exercise outcomes consistently favoured oxygen therapy. One study showed reduction in dyspnoea at rest with oxygen in patients who were acutely unwell (MD visual analogue scale 30 mm versus 48 mm, p<0.05; n=10. Four studies of long-term oxygen therapy (n=2670 had high risk of bias and no inferences could be drawn. This systematic review showed no effects of oxygen therapy on dyspnoea during exercise in ILD, although exercise capacity was increased. Future trials should evaluate whether acute improvements in exercise capacity with oxygen can be translated into improved physical activity and HRQoL.

  20. The interplay of lung surfactant proteins and lipids assimilates the macrophage clearance of nanoparticles.

    Directory of Open Access Journals (Sweden)

    Christian A Ruge

    Full Text Available The peripheral lungs are a potential entrance portal for nanoparticles into the human body due to their large surface area. The fact that nanoparticles can be deposited in the alveolar region of the lungs is of interest for pulmonary drug delivery strategies and is of equal importance for toxicological considerations. Therefore, a detailed understanding of nanoparticle interaction with the structures of this largest and most sensitive part of the lungs is important for both nanomedicine and nanotoxicology. Astonishingly, there is still little known about the bio-nano interactions that occur after nanoparticle deposition in the alveoli. In this study, we compared the effects of surfactant-associated protein A (SP-A and D (SP-D on the clearance of magnetite nanoparticles (mNP with either more hydrophilic (starch or hydrophobic (phosphatidylcholine surface modification by an alveolar macrophage (AM cell line (MH-S using flow cytometry and confocal microscopy. Both proteins enhanced the AM uptake of mNP compared with pristine nanoparticles; for the hydrophilic ST-mNP, this effect was strongest with SP-D, whereas for the hydrophobic PL-mNP it was most pronounced with SP-A. Using gel electrophoretic and dynamic light scattering methods, we were able to demonstrate that the observed cellular effects were related to protein adsorption and to protein-mediated interference with the colloidal stability. Next, we investigated the influence of various surfactant lipids on nanoparticle uptake by AM because lipids are the major surfactant component. Synthetic surfactant lipid and isolated native surfactant preparations significantly modulated the effects exerted by SP-A and SP-D, respectively, resulting in comparable levels of macrophage interaction for both hydrophilic and hydrophobic nanoparticles. Our findings suggest that because of the interplay of both surfactant lipids and proteins, the AM clearance of nanoparticles is essentially the same, regardless

  1. Functionalized synchrotron in-line phase-contrast computed tomography: a novel approach for simultaneous quantification of structural alterations and localization of barium-labelled alveolar macrophages within mouse lung samples.

    Science.gov (United States)

    Dullin, Christian; dal Monego, Simeone; Larsson, Emanuel; Mohammadi, Sara; Krenkel, Martin; Garrovo, Chiara; Biffi, Stefania; Lorenzon, Andrea; Markus, Andrea; Napp, Joanna; Salditt, Tim; Accardo, Agostino; Alves, Frauke; Tromba, Giuliana

    2015-01-01

    Functionalized computed tomography (CT) in combination with labelled cells is virtually non-existent due to the limited sensitivity of X-ray-absorption-based imaging, but would be highly desirable to realise cell tracking studies in entire organisms. In this study we applied in-line free propagation X-ray phase-contrast CT (XPCT) in an allergic asthma mouse model to assess structural changes as well as the biodistribution of barium-labelled macrophages in lung tissue. Alveolar macrophages that were barium-sulfate-loaded and fluorescent-labelled were instilled intratracheally into asthmatic and control mice. Mice were sacrificed after 24 h, lungs were kept in situ, inflated with air and scanned utilizing XPCT at the SYRMEP beamline (Elettra Synchrotron Light Source, Italy). Single-distance phase retrieval was used to generate data sets with ten times greater contrast-to-noise ratio than absorption-based CT (in our setup), thus allowing to depict and quantify structural hallmarks of asthmatic lungs such as reduced air volume, obstruction of airways and increased soft-tissue content. Furthermore, we found a higher concentration as well as a specific accumulation of the barium-labelled macrophages in asthmatic lung tissue. It is believe that XPCT will be beneficial in preclinical asthma research for both the assessment of therapeutic response as well as the analysis of the role of the recruitment of macrophages to inflammatory sites.

  2. Studies on the binding and transport processes of americium-241 hydroxide polymers in rat lung and bovine alveolar macrophages

    International Nuclear Information System (INIS)

    Taya, A.

    1986-03-01

    The binding of Am-241 hydroxide polymers to the cell components of rat lung was investigated using differential centrifugation, density gradient centrifugation with different media, gel chromatography, free flow electrophoresis and electron microscopic autoradiography with Pu-241. The bovine alveolar macrophage cultures were introduced as an in vitro test system for Am-241 uptake. Form the biochemical and electron microscopic studies it can be concluded that Am-241 is taken up by pulmonary macrophages, where its first storage site is probably the lysosome. Then the Am-241 seems to be solubilized in the lysosomes and to be bound to the cytosolic ferritin of macrophages. Am-241 might be released from the cells and crosses the alveolar membranes as bound to transferrin or as low molecular weight form. (orig.) [de

  3. The classification, natural history and radiological/histological appearance of idiopathic pulmonary fibrosis and the other idiopathic interstitial pneumonias

    Directory of Open Access Journals (Sweden)

    G. Raghu

    2008-12-01

    Full Text Available The idiopathic interstitial pneumonias (IIPs are a heterogeneous group of rare interstitial lung diseases (ILDs or diffuse parenchymal lung diseases, which, as their name implies, are of unknown aetiology. The past 10 yrs have seen important advances in the classification of the IIPs into idiopathic pulmonary fibrosis (IPF and its corresponding histopathological pattern of usual interstitial pneumonia (UIP, plus six non-IPF IIP subtypes. The present article will look at the current classification of IIPs, arising from the Consensus Statement of the American Thoracic Society and European Respiratory Society, and discusses the importance of differential diagnosis of IPF from the non-IPF IIP subtypes, especially nonspecific interstitial pneumonia. Diagnosis of IIPs is a dynamic process involving close collaboration between pulmonologists, radiologists and pathologists. Increasingly accurate diagnosis of IPF has been made possible by the use of high-resolution computed tomography (HRCT and refinements in surgical lung biopsy. In IPF, a lung HRCT will typically reveal irregular reticular opacities, traction bronchiestasis and, most importantly, peripheral honeycombing. In contrast, histological examination shows evidence of UIP manifesting as typically subpleural and paraseptal established fibrosis, often with honeycomb changes, associated with mild chronic inflammation and varying numbers of fibroblastic foci in continuity with the edges of areas of established fibrosis. Despite these advances, obtaining a consistent and uniform diagnosis of idiopathic interstitial pneumonias is difficult, with studies showing significant disagreement in the diagnosis of interstitial lung diseases between academic centres of expertise and community-based clinicians. Greater interaction between academic and community clinicians, together with improved education, is needed to bridge this gap.

  4. CFTR-dependent defect in alternatively-activated macrophages in cystic fibrosis.

    Science.gov (United States)

    Tarique, Abdullah A; Sly, Peter D; Holt, Patrick G; Bosco, Anthony; Ware, Robert S; Logan, Jayden; Bell, Scott C; Wainwright, Claire E; Fantino, Emmanuelle

    2017-07-01

    The role of the macrophages in cystic fibrosis (CF) lung disease has been poorly studied. We hypothesized that alternatively activated M2 macrophages are abnormal in CF lung disease. Blood samples were collected from adults (n=13) children (n=27) with CF on admission for acute pulmonary exacerbation and when clinically stable. Monocytes were differentiated into macrophages and polarized into classical (M1) and alternatively-activated (M2) phenotypes, function determined ex-vivo and compared with healthy controls. In the absence of functional cystic fibrosis trans-membrane conductance regulator (CFTR), either naturally in patients with CF or induced with CFTR inhibitors, monocyte-derived macrophages do not respond to IL-13/IL-4, fail to polarize into M2s associated with a post-transcriptional failure to produce and express IL-13Rα1 on the macrophage surface Polarization to the M1 phenotype was unaffected. CFTR-dependent imbalance of macrophage phenotypes and functions could contribute to the exaggerated inflammatory response seen in CF lung disease. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  5. PD-L1 Expression of Tumor Cells, Macrophages, and Immune Cells in Non-Small Cell Lung Cancer Patients with Malignant Pleural Effusion.

    Science.gov (United States)

    Tseng, Yen-Han; Ho, Hsiang-Ling; Lai, Chiung-Ru; Luo, Yung-Hung; Tseng, Yen-Chiang; Whang-Peng, Jacqueline; Lin, Yi-Hsuan; Chou, Teh-Ying; Chen, Yuh-Min

    2018-03-01

    Whether immunohistochemical staining of programmed death ligand 1 (PD-L1) on cells of pleural effusion could be used to predict response to immunotherapy treatment has not been reported. We retrospectively enrolled patients who had undergone malignant pleural effusion drainage and had effusion cell block specimens from 2014 to 2016. Immunohistochemical staining for PD-L1 was performed with tumor cells, immune cells, and macrophages of all cell block specimens. Immunoactivity was scored as 0 for absence of staining and 1+ for faint, 2+ for moderate, and 3+ for intense membranous staining. Patients' clinicopathological characteristics were also collected. PD-L1 expression of pleural effusion tumor cells was associated with the PD-L1 expression of macrophages (p = 0.003) and immune cells (p pleural effusion tumor cells and macrophages. The low intensity of PD-L1 expression in immune cells is associated with the poor survival of patients with lung cancer with malignant pleural effusion. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  6. Clinical Management of Acute Interstitial Pneumonia: A Case Report

    Directory of Open Access Journals (Sweden)

    Yang Xia

    2012-01-01

    Full Text Available We describe a 51-year-old woman who was admitted to hospital because of cough and expectoration accompanied with general fatigue and progressive dyspnea. Chest HRCT scan showed areas of ground glass attenuation, consolidation, and traction bronchiectasis in bilateral bases of lungs. BAL fluid test and transbronchial lung biopsy failed to offer insightful evidence for diagnosis. She was clinically diagnosed with acute interstitial pneumonia (AIP. Treatment with mechanical ventilation and intravenous application of methylprednisolone (80 mg/day showed poor clinical response and thus was followed by steroid pulse therapy (500 mg/day, 3 days. However, she died of respiratory dysfunction eventually. Autopsy showed diffuse alveolar damage associated with hyaline membrane formation, pulmonary interstitial, immature collagen edema, and focal type II pneumocyte hyperplasia.

  7. Interstitial lung disease in anti-synthetase syndrome: Initial and follow-up CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Debray, Marie-Pierre, E-mail: marie-pierre.debray@bch.aphp.fr [AP-HP, Bichat-Claude Bernard Hospital, Department of Radiology, 46, rue Henri Huchard, 75877 Paris Cedex 18 (France); Borie, Raphael, E-mail: raphael.borie@bch.aphp.fr [AP-HP, Bichat-Claude Bernard Hospital, Department of Pneumology A and Centre de Compétence Maladies Pulmonaires rares, DHU Fire 46, rue Henri Huchard, 75877 Paris Cedex 18 (France); Inserm, U1152, Paris (France); Revel, Marie-Pierre, E-mail: marie-pierre.revel@htd.aphp.fr [AP-HP, Cochin Hospital, Department of Radiology, 27, Rue du Fg Saint Jacques, 75679 Paris Cedex 14 (France); Naccache, Jean-Marc, E-mail: jean-marc.naccache@tnn.aphp.fr [AP-HP, Avicenne Hospital, Department of Pneumology and Centre de Compétence Maladies Pulmonaires rares, Bobigny (France); AP-HP, Tenon Hospital, Department of Pneumology and Centre de Compétence Maladies Pulmonaires rares, 4, rue de la Chine, 75020 Paris (France); Khalil, Antoine, E-mail: antoine.khalil@tnn.aphp.fr [AP-HP, Tenon Hospital, Department of Radiology, 4, rue de la Chine, 75020 Paris (France); Toper, Cécile, E-mail: cecile.toper@gmail.com [AP-HP, Tenon Hospital, Department of Pneumology and Centre de Compétence Maladies Pulmonaires rares, 4, rue de la Chine, 75020 Paris (France); Israel-Biet, Dominique, E-mail: dominique.israel-biet@egp.aphp.fr [Université Paris Descartes and AP-HP, Department of Pneumology, Georges Pompidou European Hospital, 20, rue Leblanc, 75015 Paris (France); and others

    2015-03-15

    Purpose: To describe the initial and follow-up CT features of interstitial lung disease associated with anti-synthetase syndrome (AS-ILD). Materials and methods: Two independent thoracic radiologists retrospectively analysed thin-section CT images obtained at diagnosis of AS-ILD in 33 patients (17 positive for anti-Jo1, 13 for anti-PL12, and three for anti-PL7 antibodies). They evaluated the pattern, distribution and extent of the CT abnormalities. They also evaluated the change in findings during follow-up (median 27 months; range 13–167 months) in 26 patients. Results: At diagnosis, ground-glass opacities (100%), reticulations (87%) and traction bronchiectasis (76%) were the most common CT findings. Consolidations were present in 45% of patients. A non-specific interstitial pneumonia (NSIP), organizing pneumonia (OP) or mixed NSIP-OP CT pattern were observed in 15 out of 33 (45%), seven out of 33 (21%) and eight out of 33 (24%) patients, respectively, whereas the CT pattern was indeterminate in three patients. During follow-up, consolidations decreased or disappeared in 11 out of 12 patients (92%), among which seven within the first 6 months, but honeycombing progressed or appeared in ten out of 26 patients (38%) and overall disease extent increased in nine out of 26 patients (35%). Conclusion: CT features at diagnosis of AS-ILD mainly suggest NSIP and OP, isolated or in combination. Consolidations decrease or disappear in most cases but the disease may progress to fibrosis in more than one third of patients.

  8. Understanding the Determinants of Health-Related Quality of Life in Rheumatoid Arthritis-Associated Interstitial Lung Disease

    Science.gov (United States)

    Natalini, Jake G.; Swigris, Jeff J.; Morisset, Julie; Elicker, Brett M.; Jones, Kirk D.; Fischer, Aryeh; Collard, Harold R.; Lee, Joyce S.

    2017-01-01

    Rationale Health-related quality of life (HRQL) is impaired among patients with interstitial lung disease (ILD). Little is understood about HRQL in specific subtypes of ILD. Objectives The aim of this study was to characterize and identify clinical determinants of HRQL among patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and compare them to patients with idiopathic pulmonary fibrosis (IPF). Methods We identified patients with a diagnosis of RA-ILD and IPF from an ongoing longitudinal cohort of ILD patients. HRQL was measured at their baseline visit using the Short Form Health Survey (SF-36), versions 1 and 2. Regression models were used to characterize and understand the relationship between selected baseline clinical covariates, the physical component score (PCS) and mental component score (MCS) of the SF-36. Measurements and Main Results RA-ILD patients (n=50) were more likely to be younger and female compared to IPF patients (n=50). After controlling for age and pulmonary function, RA-ILD patients had a lower HRQL compared to IPF patients, as measured by the PCS (P=0.03), with significant differences in two of four PCS domains – bodily pain (P<0.01) and general health (P=0.01). Clinical covariates most strongly associated with a lower PCS in RA-ILD patients compared to IPF patients were the presence of joint pain or stiffness and dyspnea severity (P<0.01). Mental and emotional health, as measured by the MCS, was similar between RA-ILD and IPF patients. Conclusion The physical components of HRQL appear worse in RA-ILD patients compared to IPF patients as measured by the PCS of the SF-36. Differences in the PCS of the SF-36 can be explained in part by dyspnea severity and joint symptoms among patients with RA-ILD. PMID:28502413

  9. Computed tomography in opportunistic lung infections

    International Nuclear Information System (INIS)

    Hartelius, H.

    1988-01-01

    Chest radiography in two teenage boys, one with Wiscott-Aldrich's syndrome and one with acute lymphatic leucemia in remission showed increased interstitial pattern. In both computed tomography (CT) of the lungs showed heavy interstitial pneumonia, rather different in appearance but in both cases equal to the CT findings in opportunistic lung infections known from immunoincompetent patients with for instance pneumocystis carinii and/or cytomegalo virus infections. In both patients the CT findings led to lung biopsy establishing the etiologic agent. (orig.)

  10. Microbiology specimens obtained at the time of surgical lung biopsy for interstitial lung disease: clinical yield and cost analysis.

    Science.gov (United States)

    Fibla, Juan J; Brunelli, Alessandro; Allen, Mark S; Wigle, Dennis; Shen, Robert; Nichols, Francis; Deschamps, Claude; Cassivi, Stephen D

    2012-01-01

    In efforts to obtain complete results, current practice in surgical lung biopsy (LB) for interstitial lung disease (ILD) recommends sending lung tissue samples for bacterial, mycobacterial, fungal, and viral cultures. This study assesses the value of this practice by evaluating the microbiology findings obtained from LB for ILD and their associated costs. A total of 296 consecutive patients (140 women, 156 men, median age=61 years) underwent LB for ILD from 2002 to 2009. All had lung tissue sent for microbiology examination. Microbiology results and resultant changes in patient management were analyzed retrospectively. A cost analysis was performed based upon nominal hospital charges adjusted on current inflation rates. Cost data included cultures, stains, smears, direct fluorescent antibody studies, and microbiologist consulting fees. As many as 25 patients (8.4%) underwent open LB and 271 (91.6%) underwent thoracoscopic LB. A total of 592 specimens were assessed (range 1-4 per patient). The most common pathologic diagnoses were idiopathic pulmonary fibrosis in 122 (41.2%), cryptogenic organizing pneumonia in 31 (10.5%), and respiratory bronchiolitis ILD in 16 (5.4%). Microbiology testing was negative in 174 patients (58.8%). A total of 118 of 122 (96.7%) positive results were clinically considered to be contaminants and resulted in no change in clinical management. The most common contaminants were Propionibacterium acnes (38 patients; 31%) and Penicillium fungus (16 patients; 13%). In only four patients (1.4%), the organism cultured (Nocardia one, Histoplasma one, and Aspergillus fumigatus two) resulted in a change in clinical management. The cost of microbiology studies per specimen was $984 (€709), with a total cost for the study cohort being $582,000 (€420,000). The yield and impact on clinical management of microbiology specimens from LB for ILD is very low. Its routine use in LB is questionable. We suggest it should be limited to those cases of ILD with

  11. Idiopathic interstitial pneumonias: imaging-pathology correlation

    International Nuclear Information System (INIS)

    Ellis, Stephen M.; Hansell, David M.

    2002-01-01

    The terminology related to idiopathic interstitial pneumonia (IIP) remains confusing and in some cases wholly inaccurate. In addition, a greater understanding of the correlation between high-resolution computed tomography (HRCT) appearances and the corresponding histopathological changes found in the interstitial pneumonias has resulted in a crucial role for HRCT in the investigation of IIPs. The role of the radiologist is becoming increasingly important with a strong emphasis on establishing a diagnosis without resorting to lung biopsy. We aim to clarify the current classification of the IIPs highlighting their clinical, pathological and imaging characteristics in order to assist the radiologist in performing their increasingly important diagnostic role. (orig.)

  12. Interstitial lung disease in systemic autoimmune rheumatic diseases: a comprehensive review.

    Science.gov (United States)

    Atzeni, Fabiola; Gerardi, Maria Chiara; Barilaro, Giuseppe; Masala, Ignazio Francesco; Benucci, Maurizio; Sarzi-Puttini, Piercarlo

    2018-01-01

    Interstitial lung diseases (ILDs) are among the most serious complications associated with systemic rheumatic diseases, and lead to significant morbidity and mortality; they may also be the first manifestation of connective tissue diseases (CTDs). The aim of this narrative review is to summarise the data concerning the pathogenesis of CTD/ILD and its distinguishing features in different rheumatic diseseas. Areas covered: The pathogenesis, clinical aspects and treatment of ILD associated with rheumatic systemic diseases and CTDs were reviewed by searching the PubMed, Medline, and Cochrane Library databases for papers published between 1995 and February 2017 using combinations of words or terms. Articles not written in English were excluded. Expert commentary: The management of CTD-ILD is challenging because of the lack of robust data regarding the treatments used, the heterogeneity of the diseases themselves, and the scarcity of well-defined outcome measures. Treatment decisions are often made clinically on the basis of functional, radiographic progression, and exacerbating factors such as age and the burden of comorbidities. Given the complexities of diagnosis and the paucity of treatment trials, the management of CTD patients with ILD requires multidisciplinary collaboration between rheumatologists and pulmonologists in CTD-ILD clinics.

  13. Mycobacterium tuberculosis Infection and Innate Responses in a New Model of Lung Alveolar Macrophages

    Directory of Open Access Journals (Sweden)

    Minjeong Woo

    2018-03-01

    Full Text Available Lung alveolar macrophages (AMs are in the first line of immune defense against respiratory pathogens and play key roles in the pathogenesis of Mycobacterium tuberculosis (Mtb in humans. Nevertheless, AMs are available only in limited amounts for in vitro studies, which hamper the detailed molecular understanding of host-Mtb interactions in these macrophages. The recent establishment of the self-renewing and primary Max Planck Institute (MPI cells, functionally very close to lung AMs, opens unique opportunities for in vitro studies of host-pathogen interactions in respiratory diseases. Here, we investigated the suitability of MPI cells as a host cell system for Mtb infection. Bacterial, cellular, and innate immune features of MPI cells infected with Mtb were characterized. Live bacteria were readily internalized and efficiently replicated in MPI cells, similarly to primary murine macrophages and other cell lines. MPI cells were also suitable for the determination of anti-tuberculosis (TB drug activity. The primary innate immune response of MPI cells to live Mtb showed significantly higher and earlier induction of the pro-inflammatory cytokines TNFα, interleukin 6 (IL-6, IL-1α, and IL-1β, as compared to stimulation with heat-killed (HK bacteria. MPI cells previously showed a lack of induction of the anti-inflammatory cytokine IL-10 to a wide range of stimuli, including HK Mtb. By contrast, we show here that live Mtb is able to induce significant amounts of IL-10 in MPI cells. Autophagy experiments using light chain 3B immunostaining, as well as LysoTracker labeling of acidic vacuoles, demonstrated that MPI cells efficiently control killed Mtb by elimination through phagolysosomes. MPI cells were also able to accumulate lipid droplets in their cytoplasm following exposure to lipoproteins. Collectively, this study establishes the MPI cells as a relevant, versatile host cell model for TB research, allowing a deeper understanding of AMs functions

  14. Mucin 5B promoter polymorphism is associated with susceptibility to interstitial lung diseases in Chinese males.

    Directory of Open Access Journals (Sweden)

    Chunli Wang

    Full Text Available The variation of G>T in the MUC5B promoter (rs35705950 has been associated with idiopathic pulmonary fibrosis (IPF and familial interstitial pneumonia (FIP in Caucasians, but no information is available regarding this variant in the Chinese population. We recruited 405 patients with interstitial lung diseases (ILD, including 165 IPF patients and 2043 healthy controls, for genotyping the MUC5B gene in the Chinese population. One hundred three patients with pneumonia and 360 patients with autoimmune diseases (ADs were recruited as disease controls. Our results indicated that the prevalence of the minor allele (T of the polymorphism rs35705950 in healthy Chinese subjects was approximately 0.66%, which was lower than that described in the Caucasian population. The frequencies of the T allele were 3.33% and 2.22% in IPF and ILD patients, respectively, and these values were significantly higher than those of healthy controls (P = 0.001, OR = 4.332 for IPF, and P = 0.002, OR = 2.855 for ILD. A stratified analysis showed that this variant in MUC5B associated with the risk for ILD mainly in older male Chinese subjects. No difference was observed between patients with pneumonia, AD patients, and healthy controls.

  15. Comorbidities in interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    George A. Margaritopoulos

    2017-01-01

    Full Text Available Fibrosing lung disorders include a large number of diseases with diverse behaviour. Patients can die because of the progression of their illness, remain stable or even improve after appropriate treatment has been instituted. Comorbidities, such as acute and chronic infection, gastro-oesophageal reflux, pulmonary hypertension, lung cancer, cardiovascular diseases, and obstructive sleep apnoea, can pre-exist or develop at any time during the course of the disease and, if unidentified and untreated, may impair quality of life, impact upon the respiratory status of the patients, and ultimately lead to disease progression and death. Therefore, early identification and accurate treatment of comorbidities is essential.

  16. Granulocyte-macrophage colony stimulatory factor enhances the pro-inflammatory response of interferon-γ-treated macrophages to Pseudomonas aeruginosa infection.

    Directory of Open Access Journals (Sweden)

    Sonali Singh

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe infections at compromised epithelial surfaces, such those found in burns, wounds, and in lungs damaged by mechanical ventilation or recurrent infections, particularly in cystic fibrosis (CF patients. CF patients have been proposed to have a Th2 and Th17-biased immune response suggesting that the lack of Th1 and/or over exuberant Th17 responses could contribute to the establishment of chronic P. aeruginosa infection and deterioration of lung function. Accordingly, we have observed that interferon (IFN-γ production by peripheral blood mononuclear cells from CF patients positively correlated with lung function, particularly in patients chronically infected with P. aeruginosa. In contrast, IL-17A levels tended to correlate negatively with lung function with this trend becoming significant in patients chronically infected with P. aeruginosa. These results are in agreement with IFN-γ and IL-17A playing protective and detrimental roles, respectively, in CF. In order to explore the protective effect of IFN-γ in CF, the effect of IFN-γ alone or in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF, on the ability of human macrophages to control P. aeruginosa growth, resist the cytotoxicity induced by this bacterium or promote inflammation was investigated. Treatment of macrophages with IFN-γ, in the presence and absence of GM-CSF, failed to alter bacterial growth or macrophage survival upon P. aeruginosa infection, but changed the inflammatory potential of macrophages. IFN-γ caused up-regulation of monocyte chemoattractant protein-1 (MCP-1 and TNF-α and down-regulation of IL-10 expression by infected macrophages. GM-CSF in combination with IFN-γ promoted IL-6 production and further reduction of IL-10 synthesis. Comparison of TNF-α vs. IL-10 and IL-6 vs. IL-10 ratios revealed the following hierarchy in regard to the pro-inflammatory potential of human

  17. Granulocyte-macrophage colony stimulatory factor enhances the pro-inflammatory response of interferon-γ-treated macrophages to Pseudomonas aeruginosa infection.

    Science.gov (United States)

    Singh, Sonali; Barr, Helen; Liu, Yi-Chia; Robins, Adrian; Heeb, Stephan; Williams, Paul; Fogarty, Andrew; Cámara, Miguel; Martínez-Pomares, Luisa

    2015-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe infections at compromised epithelial surfaces, such those found in burns, wounds, and in lungs damaged by mechanical ventilation or recurrent infections, particularly in cystic fibrosis (CF) patients. CF patients have been proposed to have a Th2 and Th17-biased immune response suggesting that the lack of Th1 and/or over exuberant Th17 responses could contribute to the establishment of chronic P. aeruginosa infection and deterioration of lung function. Accordingly, we have observed that interferon (IFN)-γ production by peripheral blood mononuclear cells from CF patients positively correlated with lung function, particularly in patients chronically infected with P. aeruginosa. In contrast, IL-17A levels tended to correlate negatively with lung function with this trend becoming significant in patients chronically infected with P. aeruginosa. These results are in agreement with IFN-γ and IL-17A playing protective and detrimental roles, respectively, in CF. In order to explore the protective effect of IFN-γ in CF, the effect of IFN-γ alone or in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), on the ability of human macrophages to control P. aeruginosa growth, resist the cytotoxicity induced by this bacterium or promote inflammation was investigated. Treatment of macrophages with IFN-γ, in the presence and absence of GM-CSF, failed to alter bacterial growth or macrophage survival upon P. aeruginosa infection, but changed the inflammatory potential of macrophages. IFN-γ caused up-regulation of monocyte chemoattractant protein-1 (MCP-1) and TNF-α and down-regulation of IL-10 expression by infected macrophages. GM-CSF in combination with IFN-γ promoted IL-6 production and further reduction of IL-10 synthesis. Comparison of TNF-α vs. IL-10 and IL-6 vs. IL-10 ratios revealed the following hierarchy in regard to the pro-inflammatory potential of human macrophages

  18. The role of inducible nitric oxide synthase for interstitial remodeling of alveolar septa in surfactant protein D-deficient mice

    Science.gov (United States)

    Atochina-Vasserman, Elena N.; Massa, Christopher B.; Birkelbach, Bastian; Guo, Chang-Jiang; Scott, Pamela; Haenni, Beat; Beers, Michael F.; Ochs, Matthias; Gow, Andrew J.

    2015-01-01

    Surfactant protein D (SP-D) modulates the lung's immune system. Its absence leads to NOS2-independent alveolar lipoproteinosis and NOS2-dependent chronic inflammation, which is critical for early emphysematous remodeling. With aging, SP-D knockout mice develop an additional interstitial fibrotic component. We hypothesize that this age-related interstitial septal wall remodeling is mediated by NOS2. Using invasive pulmonary function testing such as the forced oscillation technique and quasistatic pressure-volume perturbation and design-based stereology, we compared 29-wk-old SP-D knockout (Sftpd−/−) mice, SP-D/NOS2 double-knockout (DiNOS) mice, and wild-type mice (WT). Structural changes, including alveolar epithelial surface area, distribution of septal wall thickness, and volumes of septal wall components (alveolar epithelium, interstitial tissue, and endothelium) were quantified. Twenty-nine-week-old Sftpd−/− mice had preserved lung mechanics at the organ level, whereas elastance was increased in DiNOS. Airspace enlargement and loss of surface area of alveolar epithelium coexist with increased septal wall thickness in Sftpd−/− mice. These changes were reduced in DiNOS, and compared with Sftpd−/− mice a decrease in volumes of interstitial tissue and alveolar epithelium was found. To understand the effects of lung pathology on measured lung mechanics, structural data were used to inform a computational model, simulating lung mechanics as a function of airspace derecruitment, septal wall destruction (loss of surface area), and septal wall thickening. In conclusion, NOS2 mediates remodeling of septal walls, resulting in deposition of interstitial tissue in Sftpd−/−. Forward modeling linking structure and lung mechanics describes the complex mechanical properties by parenchymatous destruction (emphysema), interstitial remodeling (septal wall thickening), and altered recruitability of acinar airspaces. PMID:26320150

  19. Carbon Particles in Airway Macrophage as a Surrogate Marker in the Early Detection of Lung Diseases

    Directory of Open Access Journals (Sweden)

    NK Kalappanavar

    2012-03-01

    Full Text Available Background: It has been shown that inhalation of carbonaceous particulate matter may impair lung function in children. Objective: Using the carbon content of airway macrophages as a marker of individual exposure to particulate matter derived from fossil fuel, we sought direct evidence for this association. Methods: 300 children from puffed rice industrial areas and 300 children from population living in green zone were selected randomly. Airway macrophages were obtained from healthy children through sputum induction, and the grading of ultrafine carbon particles in airway macrophages was measured. Pulmonary function was also measured by spirometry. Results: Pulmonary function tests showed that in industrial area 42.6% and 20.3% of children had moderate obstructive airway disease and restrictive airway disease, respectively. In the green zone area, 7% of children had obstructive airway disease and 6% had restrictive airway disease. Evaluation of airway macrophages for ultrafine carbon particles revealed that in industrial area there were ultrafine carbon particles of grade 2 in 23% of subjects and grade 3 in 8.33% of individuals with obstructive airway disease. In the green zone area, the rates were 1.67% and 0.7%, respectively. Conclusion: The study provides a first evidence of the strong association between air pollution and development of airway diseases. Carbon particles in the sputum can be used as a marker for air pollution.

  20. Disseminated dendriform pulmonary ossification associated with usual interstitial pneumonia: incidence and thin-section CT-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Sung; Chung, Myung Jin [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea); Han, Joungho [Sungkyunkwan University School of Medicine, Department of Pathology, Seoul (Korea); Chung, Man Pyo [Sungkyunkwan University School of Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Seoul (Korea); Choi, Yong Soo [Sungkyunkwan University School of Medicine, Division of Thoracic Surgery, Seoul (Korea)

    2005-08-01

    The aim of this work was to assess the incidence of disseminated pulmonary dendriform ossification in usual interstitial pneumonia and nonspecific interstitial pneumonia, and to correlate thin-section computed tomography (CT) and histopathologic findings. We retrospectively reviewed thin-section CT and pathologic specimens of biopsy-proven usual interstitial pneumonia (75 patients, 57 men and 18 women, mean age 60 years, range 29-83 years) and nonspecific interstitial pneumonia (44 patients, 9 men and 35 women, mean age 55 years, range 20-73 years). On review of CT and histopathologic specimens, diffuse dendriform ossification was identified in five (four men and one woman, age range 41-68 years, mean 58 years) of 75 patients (6.7%) with usual interstitial pneumonia. It was not seen in any of 44 patients with nonspecific interstitial pneumonia. With thin-section CT (osteoporosis window; window width 818, level 273), disseminated dendriform pulmonary ossification was detected as multiple tiny calcifications in bibasilar subpleural lungs (100% sensitive and 100% specific when compared with histopathologic findings as the gold standard). The thin-section CT finding of multiple tiny calcifications in bibasilar subpleural lungs might be of some help in the differential diagnosis between usual interstitial pneumonia and nonspecific interstitial pneumonia, considering they were not seen in any patients with nonspecific interstitial pneumonia (0%, 0/44) in our series. (orig.)

  1. Disseminated dendriform pulmonary ossification associated with usual interstitial pneumonia: incidence and thin-section CT-pathologic correlation

    International Nuclear Information System (INIS)

    Kim, Tae Sung; Chung, Myung Jin; Han, Joungho; Chung, Man Pyo; Choi, Yong Soo

    2005-01-01

    The aim of this work was to assess the incidence of disseminated pulmonary dendriform ossification in usual interstitial pneumonia and nonspecific interstitial pneumonia, and to correlate thin-section computed tomography (CT) and histopathologic findings. We retrospectively reviewed thin-section CT and pathologic specimens of biopsy-proven usual interstitial pneumonia (75 patients, 57 men and 18 women, mean age 60 years, range 29-83 years) and nonspecific interstitial pneumonia (44 patients, 9 men and 35 women, mean age 55 years, range 20-73 years). On review of CT and histopathologic specimens, diffuse dendriform ossification was identified in five (four men and one woman, age range 41-68 years, mean 58 years) of 75 patients (6.7%) with usual interstitial pneumonia. It was not seen in any of 44 patients with nonspecific interstitial pneumonia. With thin-section CT (osteoporosis window; window width 818, level 273), disseminated dendriform pulmonary ossification was detected as multiple tiny calcifications in bibasilar subpleural lungs (100% sensitive and 100% specific when compared with histopathologic findings as the gold standard). The thin-section CT finding of multiple tiny calcifications in bibasilar subpleural lungs might be of some help in the differential diagnosis between usual interstitial pneumonia and nonspecific interstitial pneumonia, considering they were not seen in any patients with nonspecific interstitial pneumonia (0%, 0/44) in our series. (orig.)

  2. Nonrespiratory lung function

    Energy Technology Data Exchange (ETDEWEB)

    Isawa, Toyoharu [Tohoku University Research Institute for Chest Disease and Cancer, Sendai (Japan)

    1994-07-01

    The function of the lungs is primarily the function as a gas exchanger: the venous blood returning to the lungs is arterialized with oxygen in the lungs and the arterialized blood is sent back again to the peripheral tissues of the whole body to be utilized for metabolic oxygenation. Besides the gas exchanging function which we call ''respiratory lung function'' the lungs have functions that have little to do with gas exchange itself. We categorically call the latter function of the lungs as ''nonrespiratory lung function''. The lungs consist of the conductive airways, the gas exchanging units like the alveoli, and the interstitial space that surrounds the former two compartments. The interstitial space contains the blood and lymphatic capillaries, collagen and elastic fibers and cement substances. The conductive airways and the gas exchanging units are directly exposed to the atmosphere that contains various toxic and nontoxic gases, fume and biological or nonbiological particles. Because the conductive airways are equipped with defense mechanisms like mucociliary clearance or coughs to get rid of these toxic gases, particles or locally produced biological debris, we are usually free from being succumbed to ill effects of inhaled materials. By use of nuclear medicine techniques, we can now evaluate mucociliary clearance function, and other nonrespiratory lung functions as well in vivo.

  3. Nonrespiratory lung function

    International Nuclear Information System (INIS)

    Isawa, Toyoharu

    1994-01-01

    The function of the lungs is primarily the function as a gas exchanger: the venous blood returning to the lungs is arterialized with oxygen in the lungs and the arterialized blood is sent back again to the peripheral tissues of the whole body to be utilized for metabolic oxygenation. Besides the gas exchanging function which we call ''respiratory lung function'' the lungs have functions that have little to do with gas exchange itself. We categorically call the latter function of the lungs as ''nonrespiratory lung function''. The lungs consist of the conductive airways, the gas exchanging units like the alveoli, and the interstitial space that surrounds the former two compartments. The interstitial space contains the blood and lymphatic capillaries, collagen and elastic fibers and cement substances. The conductive airways and the gas exchanging units are directly exposed to the atmosphere that contains various toxic and nontoxic gases, fume and biological or nonbiological particles. Because the conductive airways are equipped with defense mechanisms like mucociliary clearance or coughs to get rid of these toxic gases, particles or locally produced biological debris, we are usually free from being succumbed to ill effects of inhaled materials. By use of nuclear medicine techniques, we can now evaluate mucociliary clearance function, and other nonrespiratory lung functions as well in vivo

  4. Mortality Risk Prediction in Scleroderma-Related Interstitial Lung Disease: The SADL Model.

    Science.gov (United States)

    Morisset, Julie; Vittinghoff, Eric; Elicker, Brett M; Hu, Xiaowen; Le, Stephanie; Ryu, Jay H; Jones, Kirk D; Haemel, Anna; Golden, Jeffrey A; Boin, Francesco; Ley, Brett; Wolters, Paul J; King, Talmadge E; Collard, Harold R; Lee, Joyce S

    2017-11-01

    Interstitial lung disease (ILD) is an important cause of morbidity and mortality in patients with scleroderma (Scl). Risk prediction and prognostication in patients with Scl-ILD are challenging because of heterogeneity in the disease course. We aimed to develop a clinical mortality risk prediction model for Scl-ILD. Patients with Scl-ILD were identified from two ongoing longitudinal cohorts: 135 patients at the University of California, San Francisco (derivation cohort) and 90 patients at the Mayo Clinic (validation cohort). Using these two separate cohorts, a mortality risk prediction model was developed and validated by testing every potential candidate Cox model, each including three or four variables of a possible 19 clinical predictors, for time to death. Model discrimination was assessed using the C-index. Three variables were included in the final risk prediction model (SADL): ever smoking history, age, and diffusing capacity of the lung for carbon monoxide (% predicted). This continuous model had similar performance in the derivation (C-index, 0.88) and validation (C-index, 0.84) cohorts. We created a point scoring system using the combined cohort (C-index, 0.82) and used it to identify a classification with low, moderate, and high mortality risk at 3 years. The SADL model uses simple, readily accessible clinical variables to predict all-cause mortality in Scl-ILD. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  5. Synthesized interstitial lung texture for use in anthropomorphic computational phantoms

    Science.gov (United States)

    Becchetti, Marc F.; Solomon, Justin B.; Segars, W. Paul; Samei, Ehsan

    2016-04-01

    A realistic model of the anatomical texture from the pulmonary interstitium was developed with the goal of extending the capability of anthropomorphic computational phantoms (e.g., XCAT, Duke University), allowing for more accurate image quality assessment. Contrast-enhanced, high dose, thorax images for a healthy patient from a clinical CT system (Discovery CT750HD, GE healthcare) with thin (0.625 mm) slices and filtered back- projection (FBP) were used to inform the model. The interstitium which gives rise to the texture was defined using 24 volumes of interest (VOIs). These VOIs were selected manually to avoid vasculature, bronchi, and bronchioles. A small scale Hessian-based line filter was applied to minimize the amount of partial-volumed supernumerary vessels and bronchioles within the VOIs. The texture in the VOIs was characterized using 8 Haralick and 13 gray-level run length features. A clustered lumpy background (CLB) model with added noise and blurring to match CT system was optimized to resemble the texture in the VOIs using a genetic algorithm with the Mahalanobis distance as a similarity metric between the texture features. The most similar CLB model was then used to generate the interstitial texture to fill the lung. The optimization improved the similarity by 45%. This will substantially enhance the capabilities of anthropomorphic computational phantoms, allowing for more realistic CT simulations.

  6. Persistence of ventilatory defect after resolution of pulmonary interstitial emphysema in a preterm baby.

    Science.gov (United States)

    Filho, Luiz Vicente Ferreira da Silva; Rossi, Felipe De Souza; Deutsch, Alice d'Agostini; Yagui, Ana Cristina Zanon; Timenetsky, Karina; Rebello, Celso de Moura

    2010-07-01

    Pulmonary interstitial emphysema is a common complication of mechanical ventilation in preterm babies. We report a case of severe unilateral pulmonary interstitial emphysema in a premature newborn, treated with high-frequency oscillatory ventilation, lateral decubitus positioning and selective intubation. After complete radiological resolution of the pulmonary emphysema in the left lung, the patient was studied by electrical impedance tomography and a marked reduction of ventilation was identified in the left lung despite radiological resolution of the cysts. This finding indicates that functional abnormalities may persist for longer periods after radiologic resolution of such lesions.

  7. Airway-centered interstitial fibrosis: etiology, clinical findings and prognosis.

    Science.gov (United States)

    Kuranishi, Lilian Tiemi; Leslie, Kevin O; Ferreira, Rimarcs Gomes; Coletta, Ester Aparecida Ney; Storrer, Karin Mueller; Soares, Maria Raquel; de Castro Pereira, Carlos Alberto

    2015-05-09

    Airway-centered Interstitial Fibrosis (ACIF) is a common pathologic pattern observed in our practice. The objectives of this study are to describe the causes associated with ACIF in a large sample of patients and its effect on survival. A retrospective study in three centers of interstitial lung disease in São Paulo, between January of 1995 and December of 2012. The surgical lung biopsy specimens were reviewed by three pathologists. The clinical, functional and tomographic findings were analyzed by a standardized protocol. There were 68 cases of ACIF, most of them women. The mean age was 57 ± 12 yr. Dyspnea, cough, restrictive pattern at spirometry and oxygen desaturation at exercise were common. A reticular pattern with peribronchovascular infiltrates was found in 79% of the cases. The etiologies of ACIF were hypersensitivity pneumonitis in 29 (42.6%), gastroesophageal reflux disease in 17 (25.0%), collagen vascular disease in 4 (5.9%), a combination of them in 15 cases and idiopathic in 3 (4.4%). The median survival was 116 months (95% CI = 58.5 - 173.5). Lower values of oxygen saturation at rest, presence of cough and some histological findings--organizing tissue in the airways, fibroblastic foci and microscopic honeycombing--were predictors of worse survival. ACIF is an interstitial lung disease with a better survival when compared with IPF. The main etiologies are HP and GERD. The oxygen saturation at rest, the presence of cough and some histological findings are predictors of survival.

  8. Diagnostic accuracy for X-ray chest in interstitial lung disease as confirmed by high resolution computed tomography (HRCT) chest

    International Nuclear Information System (INIS)

    Afzal, F.; Raza, S.; Shafique, M.

    2017-01-01

    Objective: To determine the diagnostic accuracy of x-ray chest in interstitial lung disease as confirmed by high resolution computed tomography (HRCT) chest. Study Design: A cross-sectional validational study. Place and Duration of Study: Department of Diagnostic Radiology, Combined Military Hospital Rawalpindi, from Oct 2013 to Apr 2014. Material and Method: A total of 137 patients with clinical suspicion of interstitial lung disease (ILD) aged 20-50 years of both genders were included in the study. Patients with h/o previous histopathological diagnosis, already taking treatment and pregnant females were excluded. All the patients had chest x-ray and then HRCT. The x-ray and HRCT findings were recorded as presence or absence of the ILD. Results: Mean age was 40.21 ± 4.29 years. Out of 137 patients, 79 (57.66 percent) were males and 58 (42.34 percent) were females with male to female ratio of 1.36:1. Chest x-ray detected ILD in 80 (58.39 percent) patients, out of which, 72 (true positive) had ILD and 8 (false positive) had no ILD on HRCT. Overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of chest x-ray in diagnosing ILD was 80.0 percent, 82.98 percent, 90.0 percent, 68.42 percent and 81.02 percent respectively. Conclusion: This study concluded that chest x-ray is simple, non-invasive, economical and readily available alternative to HRCT with an acceptable diagnostic accuracy of 81 percent in the diagnosis of ILD. (author)

  9. Management of a patient undergoing sitting position craniotomy for acoustic neuroma with co-existing interstitial lung disease

    Directory of Open Access Journals (Sweden)

    Deepa Suvarna

    2015-01-01

    Full Text Available A 38-year-old woman with acoustic neuroma associated with occupational interstitial lung disease (ILD was successfully managed for sitting position craniotomy using carefully titrated desflurane-based anaesthesia. The anaesthetic challenges included maintenance an adequate depth of anaesthesia, reducing perioperative airway events and ensuring smooth recovery. While dealing with ILD patient in sitting position, careful risk assessment is important because it will help us predict the course of the perioperative events. Balanced general anaesthesia using desflurane fulfilled the requirement of good depth and smooth recovery in this patient. Though there are reports of maintenance of anaesthesia with other inhalational agents, there are scanty reports of using desflurane in these cases.

  10. CD1d-restricted IFN-γ-secreting NKT cells promote immune complex-induced acute lung injury by regulating macrophage-inflammatory protein-1α production and activation of macrophages and dendritic cells.

    Science.gov (United States)

    Kim, Ji Hyung; Chung, Doo Hyun

    2011-02-01

    Immune complex-induced acute lung injury (IC-ALI) has been implicated in various pulmonary disease states. However, the role of NKT cells in IC-ALI remains unknown. Therefore, we explored NKT cell functions in IC-ALI using chicken egg albumin and anti-chicken egg albumin IgG. The bronchoalveolar lavage fluid of CD1d(-/-) and Jα18(-/-) mice contained few Ly6G(+)CD11b(+) granulocytes, whereas levels in B6 mice were greater and were increased further by α-galactosyl ceramide. IFN-γ and MIP-1α production in the lungs was greater in B6 than CD1d(-/-) mice. Adoptive transfer of wild type (WT) but not IFN-γ-, MIP-1α-, or FcγR-deficient NKT cells into CD1d(-/-) mice caused recruitment of inflammatory cells to the lungs. Moreover, adoptive transfer of IFN-γR-deficient NKT cells enhanced MIP-1α production and cell recruitment in the lungs of CD1d(-/-) or CD1d(-/-)IFN-γ(-/-) mice, but to a lesser extent than WT NKT cells. This suggests that IFN-γ-producing NKT cells enhance MIP-1α production in both an autocrine and a paracrine manner. IFN-γ-deficient NKT cells induced less IL-1β and TNF-α production by alveolar macrophages and dendritic cells in CD1d(-/-) mice than did WT NKT cells. Taken together, these data suggest that CD1d-restricted IFN-γ-producing NKT cells promote IC-ALI by producing MIP-1α and enhancing proinflammatory cytokine production by alveolar macrophages and dendritic cells.

  11. The relationship between ventilatory lung motion and pulmonary perfusion shown by ventilatory lung motion imaging

    International Nuclear Information System (INIS)

    Fujii, Tadashige; Tanaka, Masao; Nakatsuka, Tatsuya; Yoshimura, Kazuhiko; Hirose, Yoshiki; Hirayama, Jiro; Kobayashi, Toshio; Handa, Kenjiro

    1991-01-01

    Using ventilatory lung motion imaging, which was obtained from two perfusion lung scintigrams with 99m Tc-macroaggregated albumin taken in maximal inspiration and maximal expiration, the lung motion (E-I/I) of the each unilateral lung was studied in various cardiopulmonary diseases. The sum of (E-I)/I(+) of the unilateral lung was decreased in the diseased lung for localized pleuropulmonary diseases, including primary lung cancer and pleural thickening, and in both lungs for heart diseases, and diffuse pulmonary diseases including diffuse interstitial pneumonia and diffuse panbronchiolitis. The sum of (E-I)/I(+) of the both lungs, which correlated with vital capacity and PaO 2 , was decreased in diffuse interstitial pneumonia, pulmonary emphysema, diffuse panbronchiolitis, primary lung cancer, pleural diseases and so on. (E-I)/I(+), correlated with pulmonary perfusion (n=49, r=0.51, p 81m Kr or 133 Xe (n=49, r=0.61, p<0.001) than pulmonary perfusion. The ventilatory lung motion imaging, which demonstrates the motion of the intra-pulmonary areas and lung edges, appears useful for estimating pulmonary ventilation of the perfused area as well as pulmonary perfusion. (author)

  12. Usual interstitial pneumonia and nonspecific interstitial pneumonia: Correlation between CT findings at the site of biopsy with pathological diagnoses

    Energy Technology Data Exchange (ETDEWEB)

    Sumikawa, Hiromitsu, E-mail: h-sumikawa@radiol.med.osaka-u.ac.jp [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0825 (Japan); Johkoh, Takeshi [Department of Radiology, Kinki Central Hospital of Mutual Aid Association of Public Health Teachers, 3-1 Kurumazuka, Itami, Hyougo 664-8533 (Japan); Fujimoto, Kiminori [Department of Radiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011 (Japan); Ichikado, Kazuya [Division of Respiratory Medicine, Saiseikai Kumamoto Hospital, 5-3-1 Tikami, Kumamoto, 861-4193 (Japan); Colby, Thomas V. [Department of Pathology, Mayo Clinic, Scottsdale, AZ (United States); Fukuoka, Junya [Laboratory of Pathology, Toyama University Hospital, Toyama (Japan); Taniguchi, Hiroyuki; Kondoh, Yasuhiro; Kataoka, Kensuke [Department of Respiratory Medicine, Tosei General Hospital, 160 Nishioiwake-cho, Seto City, Aichi (Japan); Yanagawa, Masahiro; Koyama, Mitsuhiro; Honda, Osamu; Tomiyama, Noriyuki [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0825 (Japan)

    2012-10-15

    Objectives: The aim of this study was to correlate high-resolution CT (HRCT) findings at the site of biopsy with the whole lung CT and pathologic diagnoses in usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). Methods: The study included 35 patients (25 UIP and 10 NSIP) diagnosed both pathologically and clinically. 81 surgical biopsy specimens (54 UIP, and 27 NSIP) and extracted areas corresponding to biopsy sites on HRCT were analyzed. CT interpretations were compared with pathological diagnoses in both extracted images and the whole lung. Concordant and discordant cases in multiple extracted images were divided and analyzed. Then the whole cases were categorized by including or not at least one UIP diagnosis of extracted images and evaluated. Results: The diagnoses in extracted sites significantly correlated with pathological diagnoses (p = 0.047). There were significant differences in the concordances of extracted images compared with the diagnosis of whole lung and pathology (p = 0.008, 0.003, respectively). All 7 cases that were not concordant were diagnosed as radiological UIP with whole lung CT. The cases with at least one UIP diagnosis of extracted CT images were diagnosed as UIP in pathology more frequently (18 in 25) (p = 0.007). Conclusions: Radiological UIP in whole CT had more frequently discordant diagnoses from multiple extracted images than NSIP. And there were more cases in pathological UIP that included at least one UIP diagnosis of extracted images compared with pathological NSIP.

  13. Identification of early-stage usual interstitial pneumonia from low-dose chest CT scans using fractional high-density lung distribution

    Science.gov (United States)

    Xie, Yiting; Salvatore, Mary; Liu, Shuang; Jirapatnakul, Artit; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

    2017-03-01

    A fully-automated computer algorithm has been developed to identify early-stage Usual Interstitial Pneumonia (UIP) using features computed from low-dose CT scans. In each scan, the pre-segmented lung region is divided into N subsections (N = 1, 8, 27, 64) by separating the lung from anterior/posterior, left/right and superior/inferior in 3D space. Each subsection has approximately the same volume. In each subsection, a classic density measurement (fractional high-density volume h) is evaluated to characterize the disease severity in that subsection, resulting in a feature vector of length N for each lung. Features are then combined in two different ways: concatenation (2*N features) and taking the maximum in each of the two corresponding subsections in the two lungs (N features). The algorithm was evaluated on a dataset consisting of 51 UIP and 56 normal cases, a combined feature vector was computed for each case and an SVM classifier (RBF kernel) was used to classify them into UIP or normal using ten-fold cross validation. A receiver operating characteristic (ROC) area under the curve (AUC) was used for evaluation. The highest AUC of 0.95 was achieved by using concatenated features and an N of 27. Using lung partition (N = 27, 64) with concatenated features had significantly better result over not using partitions (N = 1) (p-value < 0.05). Therefore this equal-volume partition fractional high-density volume method is useful in distinguishing early-stage UIP from normal cases.

  14. MyD88 mediates in vivo effector functions of alveolar macrophages in acute lung inflammatory responses to carbon nanotube exposure

    Energy Technology Data Exchange (ETDEWEB)

    Frank, Evan A. [Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267 (United States); Birch, M. Eileen [National Institute for Occupational Safety and Health, Cincinnati, OH 45213 (United States); Yadav, Jagjit S., E-mail: Jagjit.Yadav@uc.edu [Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267 (United States)

    2015-11-01

    Carbon nanotubes (CNTs) are rapidly emerging as high-priority occupational toxicants. CNT powders contain fibrous particles that aerosolize readily in places of manufacture and handling, posing an inhalation risk for workers. Studies using animal models indicate that lung exposure to CNTs causes prolonged inflammatory responses and diffuse alveolar injury. The mechanisms governing CNT-induced lung inflammation are not fully understood but have been suggested to involve alveolar macrophages (AMs). In the current study, we sought to systematically assess the effector role of AMs in vivo in the induction of lung inflammatory responses to CNT exposures and investigate their cell type-specific mechanisms. Multi-wall CNTs characterized for various physicochemical attributes were used as the CNT type. Using an AM-specific depletion and repopulation approach in a mouse model, we unambiguously demonstrated that AMs are major effector cells necessary for the in vivo elaboration of CNT-induced lung inflammation. We further investigated in vitro AM responses and identified molecular targets which proved critical to pro-inflammatory responses in this model, namely MyD88 as well as MAPKs and Ca{sup 2} {sup +}/CamKII. We further demonstrated that MyD88 inhibition in donor AMs abrogated their capacity to reconstitute CNT-induced inflammation when adoptively transferred into AM-depleted mice. Taken together, this is the first in vivo demonstration that AMs act as critical effector cell types in CNT-induced lung inflammation and that MyD88 is required for this in vivo effector function. AMs and their cell type-specific mechanisms may therefore represent potential targets for future therapeutic intervention of CNT-related lung injury. - Highlights: • Demonstrated in vivo effector role of alveolar macrophages (AMs) in CNT toxicity • MyD88, MAPKs, and Ca{sup 2} {sup +}/CamKII are required for AM inflammatory responses in vitro. • MyD88 signaling is required for in vivo effector

  15. Early detection of interstitial pneumonia by 67Ga-citrate scintigraphy

    International Nuclear Information System (INIS)

    Ito, Shinsaku; Mikami, Riichiro; Ryujin, Yoshitada

    1985-01-01

    In this paper we report our recent experience indicating usefulness of 67 Ga-citrate scintigraphy in 4 cases with inflammatory pulmonary diseases. These cases showed abnormal pulmonary 67 Ga uptake with normal chest radiographs. The first case with malignant lymphoma and the second one with lung cancer suffered from pulmonary infection following secondary immuno-insufficiency due to radiotherapy and chemotherapy. Pneumocystis carinii was suspected as causative agent in the first case, and gram negative bacilli in the second case. The third case with lung cancer developed radiation pneumonia after radiotherapy. The fourth case with acute bronchitis developed drug induced interstitial pneumonia presumably due to minocycline administration. It is concluded that 67 Ga-citrate scintigraphy is more sensitive for early detection of interstitial pneumonia than routine chest radiography. (author)

  16. CCR8 signaling influences Toll-like receptor 4 responses in human macrophages in inflammatory diseases.

    Science.gov (United States)

    Reimer, Martina Kvist; Brange, Charlotte; Rosendahl, Alexander

    2011-12-01

    CCR8 immunity is generally associated with Th2 responses in allergic diseases. In this study, we demonstrate for the first time a pronounced attenuated influx of macrophages in ovalbumin (OVA)-challenged CCR8 knockout mice. To explore whether macrophages in human inflamed lung tissue also were CCR8 positive, human lung tissue from patients with chronic obstructive pulmonary disease (COPD) was evaluated. Indeed, CCR8 expression was pronounced in invading monocytes/macrophages from lungs of patients with Global Initiative for Obstructive Lung Disease (GOLD) stage IV COPD. Given this expression pattern, the functional role of CCR8 on human macrophages was evaluated in vitro. Human peripheral blood monocytes expressed low levels of CCR8, while macrophage colony-stimulating factor (M-CSF)-derived human macrophages expressed significantly elevated surface levels of CCR8. Importantly, CCL1 directly regulated the expression of CD18 and CD49b and hence influenced the adhesion capacity of human macrophages. CCL1 drives chemotaxis in M-CSF-derived macrophages, and this could be completely inhibited by lipopolysaccharide (LPS). Whereas both CCL1 and LPS monotreatment inhibited spontaneous superoxide release in macrophages, CCL1 significantly induced superoxide release in the presence of LPS in a dose-dependent manner. Finally, CCL1 induced production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and could inhibit LPS-induced cytokine production in a dose-dependent manner. Our data demonstrate, for the first time, the presence of CCR8 on inflammatory macrophages in human COPD lung tissue. Importantly, the functional data from human macrophages suggest a potential cross talk between the CCR8 and the Toll-like receptor 4 (TLR4) pathways, both of which are present in COPD patients.

  17. Macrophage immunoregulatory pathways in tuberculosis.

    Science.gov (United States)

    Rajaram, Murugesan V S; Ni, Bin; Dodd, Claire E; Schlesinger, Larry S

    2014-12-01

    Macrophages, the major host cells harboring Mycobacterium tuberculosis (M.tb), are a heterogeneous cell type depending on their tissue of origin and host they are derived from. Significant discord in macrophage responses to M.tb exists due to differences in M.tb strains and the various types of macrophages used to study tuberculosis (TB). This review will summarize current concepts regarding macrophage responses to M.tb infection, while pointing out relevant differences in experimental outcomes due to the use of divergent model systems. A brief description of the lung environment is included since there is increasing evidence that the alveolar macrophage (AM) has immunoregulatory properties that can delay optimal protective host immune responses. In this context, this review focuses on selected macrophage immunoregulatory pattern recognition receptors (PRRs), cytokines, negative regulators of inflammation, lipid mediators and microRNAs (miRNAs). Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Lung injury, inflammation and Akt signaling following inhalation of particulate hexavalent chromium

    International Nuclear Information System (INIS)

    Beaver, Laura M.; Stemmy, Erik J.; Constant, Stephanie L.; Schwartz, Arnold; Little, Laura G.; Gigley, Jason P.; Chun, Gina; Sugden, Kent D.

    2009-01-01

    Certain particulate hexavalent chromium [Cr(VI)] compounds are human respiratory carcinogens that release genotoxic soluble chromate, and are associated with fibrosis, fibrosarcomas, adenocarcinomas and squamous cell carcinomas of the lung. We postulate that inflammatory processes and mediators may contribute to the etiology of Cr(VI) carcinogenesis, however the immediate (0-24 h) pathologic injury and immune responses after exposure to particulate chromates have not been adequately investigated. Our aim was to determine the nature of the lung injury, inflammatory response, and survival signaling responses following intranasal exposure of BALB/c mice to particulate basic zinc chromate. Factors associated with lung injury, inflammation and survival signaling were measured in airway lavage fluid and in lung tissue. A single chromate exposure induced an acute immune response in the lung, characterized by a rapid and significant increase in IL-6 and GRO-α levels, an influx of neutrophils, and a decline in macrophages in lung airways. Histological examination of lung tissue in animals challenged with a single chromate exposure revealed an increase in bronchiolar cell apoptosis and mucosal injury. Furthermore, chromate exposure induced injury and inflammation that progressed to alveolar and interstitial pneumonitis. Finally, a single Cr(VI) challenge resulted in a rapid and persistent increase in the number of airways immunoreactive for phosphorylation of the survival signaling protein Akt, on serine 473. These data illustrate that chromate induces both survival signaling and an inflammatory response in the lung, which we postulate may contribute to early oncogenesis

  19. Exhaled ethane: an in vivo biomarker of lipid peroxidation in interstitial lung diseases.

    Science.gov (United States)

    Kanoh, Soichiro; Kobayashi, Hideo; Motoyoshi, Kazuo

    2005-10-01

    Oxidative stress plays a role in the pathogenesis and progression of interstitial lung disease (ILD). Exhaled ethane is a product of lipid peroxidation that has been proposed as a biomarker of oxidative stress in vivo. To determine whether the exhaled ethane level is elevated in patients with ILD and to compare it with other clinical parameters. Breath samples were collected from 34 patients with ILD, including 13 with idiopathic pulmonary fibrosis (IPF), 9 patients with cryptogenic organizing pneumonia, 6 patients with collagen vascular disease-associated interstitial pneumonia, and 6 patients with pulmonary sarcoidosis. Gas samples were obtained at hospital admission and after 3 weeks. After each expired sample was concentrated using a trap-and-purge procedure, the ethane level was analyzed by gas chromatography. Exhaled ethane levels were elevated in ILD patients (n = 34, mean +/- SD, 8.5 +/- 8.0 pmol/dL) compared with healthy volunteers (n = 16, 2.9 +/- 1.0 pmol/dL; p ethane levels were largely consistent with the clinical course. Four patients with IPF who had persistently high ethane levels died or deteriorated, whereas those with ethane levels ethane concentrations were positively correlated with levels of lactate dehydrogenase (Spearman rank correlation coefficient [rs], 0.28, p = 0.026) and C-reactive protein (rs, 0.38, p = 0.025) and were inversely correlated with Pa(O2) (rs, - 0.40, p = 0.0026). Patients showing increased uptake on (67)Ga scintigraphy demonstrated higher ethane levels (n = 19, 7.5 +/- 5.7 pmol/dL) compared with those who did not show increased uptake on scintigraphy (n = 10, 3.0 +/- 2.4 pmol/dL; p ethane is elevated in patients with ILD and is correlated with the clinical outcome, suggesting that it provides useful information about ongoing oxidative stress, and thereby disease activity and severity in ILD.

  20. Zbtb7a induction in alveolar macrophages is implicated in anti-HLA-mediated lung allograft rejection.

    Science.gov (United States)

    Nayak, Deepak K; Zhou, Fangyu; Xu, Min; Huang, Jing; Tsuji, Moriya; Yu, Jinsheng; Hachem, Ramsey; Gelman, Andrew E; Bremner, Ross M; Smith, Michael A; Mohanakumar, Thalachallour

    2017-07-12

    Chronic rejection significantly limits long-term success of solid organ transplantation. De novo donor-specific antibodies (DSAs) to mismatched donor human leukocyte antigen after human lung transplantation predispose lung grafts to chronic rejection. We sought to delineate mediators and mechanisms of DSA pathogenesis and to define early inflammatory events that trigger chronic rejection in lung transplant recipients and obliterative airway disease, a correlate of human chronic rejection, in mouse. Induction of transcription factor zinc finger and BTB domain containing protein 7a (Zbtb7a) was an early response critical in the DSA-induced chronic rejection. A cohort of human lung transplant recipients who developed DSA and chronic rejection demonstrated greater Zbtb7a expression long before clinical diagnosis of chronic rejection compared to nonrejecting lung transplant recipients with stable pulmonary function. Expression of DSA-induced Zbtb7a was restricted to alveolar macrophages (AMs), and selective disruption of Zbtb7a in AMs resulted in less bronchiolar occlusion, low immune responses to lung-restricted self-antigens, and high protection from chronic rejection in mice. Additionally, in an allogeneic cell transfer protocol, antigen presentation by AMs was Zbtb7a-dependent where AMs deficient in Zbtb7a failed to induce antibody and T cell responses. Collectively, we demonstrate that AMs play an essential role in antibody-induced pathogenesis of chronic rejection by regulating early inflammation and lung-restricted humoral and cellular autoimmunity. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  1. Clinical algorithms for the diagnosis and prognosis of interstitial lung disease in systemic sclerosis.

    Science.gov (United States)

    Hax, Vanessa; Bredemeier, Markus; Didonet Moro, Ana Laura; Pavan, Thaís Rohde; Vieira, Marcelo Vasconcellos; Pitrez, Eduardo Hennemann; da Silva Chakr, Rafael Mendonça; Xavier, Ricardo Machado

    2017-10-01

    Interstitial lung disease (ILD) is currently the primary cause of death in systemic sclerosis (SSc). Thoracic high-resolution computed tomography (HRCT) is considered the gold standard for diagnosis. Recent studies have proposed several clinical algorithms to predict the diagnosis and prognosis of SSc-ILD. To test the clinical algorithms to predict the presence and prognosis of SSc-ILD and to evaluate the association of extent of ILD with mortality in a cohort of SSc patients. Retrospective cohort study, including 177 SSc patients assessed by clinical evaluation, laboratory tests, pulmonary function tests, and HRCT. Three clinical algorithms, combining lung auscultation, chest radiography, and percentage predicted forced vital capacity (FVC), were applied for the diagnosis of different extents of ILD on HRCT. Univariate and multivariate Cox proportional models were used to analyze the association of algorithms and the extent of ILD on HRCT with the risk of death using hazard ratios (HR). The prevalence of ILD on HRCT was 57.1% and 79 patients died (44.6%) in a median follow-up of 11.1 years. For identification of ILD with extent ≥10% and ≥20% on HRCT, all algorithms presented a high sensitivity (>89%) and a very low negative likelihood ratio (algorithms, especially the algorithm C (HR = 3.47, 95% CI: 1.62-7.42), which identified the presence of ILD based on crackles on lung auscultation, findings on chest X-ray, or FVC 20% on HRCT or, in indeterminate cases, FVC algorithms had a good diagnostic performance for extents of SSc-ILD on HRCT with clinical and prognostic relevance (≥10% and ≥20%), and were also strongly related to mortality. Non-HRCT-based algorithms could be useful when HRCT is not available. This is the first study to replicate the prognostic algorithm proposed by Goh et al. in a developing country. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Idiopathic interstitial pneumonias. From classification to diagnostic work-up

    International Nuclear Information System (INIS)

    Mueller-Mang, C.; Bankier, A.; Stiebellehner, L.; Schmid, K.

    2007-01-01

    Idiopathic interstitial pneumonias (IIP) comprise seven entities with distinct histologic patterns. In their idiopathic form IIP are rare diseases. They are, nevertheless, considered prototypes of the much more common secondary interstitial pneumonias. The advent of high-resolution computed tomography (HRCT) has had a profound impact on the imaging of IIP, because the detailed delineation of the lung anatomy allows a close correlation between the histologic patterns of IIP and the CT features. On the basis of CT morphology and in the correct clinical context, the radiologist can achieve an accurate diagnosis in many cases. However, due to overlap between the various entities, complementary lung biopsy is recommended in virtually all cases. This article reviews the CT pattern of IIP and offers relevant clinical and histological information for the purpose of enabling the radiologist to understand and participate in the multidisciplinary concept of IIP. (orig.) [de

  3. AhR-dependent secretion of PDGF-BB by human classically activated macrophages exposed to DEP extracts stimulates lung fibroblast proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Jaguin, Marie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes Cedex (France); Lecureur, Valérie, E-mail: valerie.lecureur@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France)

    2015-06-15

    Lung diseases are aggravated by exposure to diesel exhaust particles (DEPs) found in air pollution. Macrophages are thought to play a crucial role in lung immune response to these pollutants, even if the mechanisms involved remain incompletely characterized. In the present study, we demonstrated that classically and alternative human macrophages (MΦ) exhibited increased secretion of PDGF-B in response to DEP extract (DEPe). This occurred via aryl hydrocarbon receptor (AhR)-activation because DEPe-induced PDGF-B overexpression was abrogated after AhR expression knock-down by RNA interference, in both M1 and M2 polarizing MΦ. In addition, TCDD and benzo(a)pyrene, two potent AhR ligands, also significantly increased mRNA expression of PDGF-B in M1 MΦ, whereas some weak ligands of AhR did not. We next evaluated the impact of conditioned media (CM) from MΦ culture exposed to DEPe or of recombinant PDGF-B onto lung fibroblast proliferation. The tyrosine kinase inhibitor, AG-1295, prevents phosphorylations of PDGF-Rβ, AKT and ERK1/2 and the proliferation of MRC-5 fibroblasts induced by recombinant PDGF-B and by CM from M1 polarizing MΦ, strongly suggesting that the PDGF-BB secreted by DEPe-exposed MΦ is sufficient to activate the PDGF-Rβ pathway of human lung fibroblasts. In conclusion, we demonstrated that human MΦ, whatever their polarization status, secrete PDGF-B in response to DEPe and that PDGF-B is a target gene of AhR. Therefore, induction of PDGF-B by DEP may participate in the deleterious effects towards human health triggered by such environmental urban contaminants. - Highlights: • PDGF-B expression and secretion are increased by DEPe exposure in human M1 and M2 MΦ. • DEPe-induced PDGF-B expression is aryl-hydrocarbon-dependent. • DEPe-exposed M1 MΦ secrete sufficient PDGF-B to increase lung fibroblast proliferation.

  4. CCR8 Signaling Influences Toll-Like Receptor 4 Responses in Human Macrophages in Inflammatory Diseases ▿

    Science.gov (United States)

    Kvist Reimer, Martina; Brange, Charlotte; Rosendahl, Alexander

    2011-01-01

    CCR8 immunity is generally associated with Th2 responses in allergic diseases. In this study, we demonstrate for the first time a pronounced attenuated influx of macrophages in ovalbumin (OVA)-challenged CCR8 knockout mice. To explore whether macrophages in human inflamed lung tissue also were CCR8 positive, human lung tissue from patients with chronic obstructive pulmonary disease (COPD) was evaluated. Indeed, CCR8 expression was pronounced in invading monocytes/macrophages from lungs of patients with Global Initiative for Obstructive Lung Disease (GOLD) stage IV COPD. Given this expression pattern, the functional role of CCR8 on human macrophages was evaluated in vitro. Human peripheral blood monocytes expressed low levels of CCR8, while macrophage colony-stimulating factor (M-CSF)-derived human macrophages expressed significantly elevated surface levels of CCR8. Importantly, CCL1 directly regulated the expression of CD18 and CD49b and hence influenced the adhesion capacity of human macrophages. CCL1 drives chemotaxis in M-CSF-derived macrophages, and this could be completely inhibited by lipopolysaccharide (LPS). Whereas both CCL1 and LPS monotreatment inhibited spontaneous superoxide release in macrophages, CCL1 significantly induced superoxide release in the presence of LPS in a dose-dependent manner. Finally, CCL1 induced production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and could inhibit LPS-induced cytokine production in a dose-dependent manner. Our data demonstrate, for the first time, the presence of CCR8 on inflammatory macrophages in human COPD lung tissue. Importantly, the functional data from human macrophages suggest a potential cross talk between the CCR8 and the Toll-like receptor 4 (TLR4) pathways, both of which are present in COPD patients. PMID:21976223

  5. The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time

    International Nuclear Information System (INIS)

    Ma, Junliang; Liu, Lunxu; Che, Guowei; Yu, Nanbin; Dai, Fuqiang; You, Zongbing

    2010-01-01

    Tumor-associated macrophages (TAMs) play an important role in growth, progression and metastasis of tumors. In non-small cell lung cancer (NSCLC), TAMs' anti-tumor or pro-tumor role is not determined. Macrophages are polarized into M1 (with anti-tumor function) and M2 (with pro-tumor function) forms. This study was conducted to determine whether the M1 and M2 macrophage densities in NSCLC are associated with patient's survival time. Fifty patients with an average of 1-year survival (short survival group) and 50 patients with an average of 5-year survival (long survival group) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical double-staining of CD68/HLA-DR (markers for M1 macrophages) and CD68/CD163 (markers for M2 macrophages) was performed and evaluated in a blinded fashion. The M1 and M2 macrophage densities in the tumor islets, stroma, or islets and stroma were determined using computer-aided microscopy. Correlation of the macrophage densities and patient's survival time was analyzed using the Statistical Package for the Social Sciences. Approximately 70% of TAMs were M2 macrophages and the remaining 30% were M1 macrophages in NSCLC. The M2 macrophage densities (approximately 78 to 113 per mm 2 ) in the tumor islets, stroma, or islets and stroma were not significantly different between the long survival and short survival groups. The M1 macrophage densities in the tumor islets (approximately 70/mm 2 ) and stroma (approximately 34/mm 2 ) of the long survival group were significantly higher than the M1 macrophage densities in the tumor islets (approximately 7/mm 2 ) and stroma (13/mm 2 ) of the short survival group (P < 0.001 and P < 0.05, respectively). The M2 macrophage densities were not associated with patient's survival time. The M1 macrophage densities in the tumor islets, stroma, or islets and stroma

  6. Macrophages Contribute to the Spermatogonial Niche in the Adult Testis

    Directory of Open Access Journals (Sweden)

    Tony DeFalco

    2015-08-01

    Full Text Available The testis produces sperm throughout the male reproductive lifespan by balancing self-renewal and differentiation of spermatogonial stem cells (SSCs. Part of the SSC niche is thought to lie outside the seminiferous tubules of the testis; however, specific interstitial components of the niche that regulate spermatogonial divisions and differentiation remain undefined. We identified distinct populations of testicular macrophages, one of which lies on the surface of seminiferous tubules, in close apposition to areas of tubules enriched for undifferentiated spermatogonia. These macrophages express spermatogonial proliferation- and differentiation-inducing factors, such as colony-stimulating factor 1 (CSF1 and enzymes involved in retinoic acid (RA biosynthesis. We show that transient depletion of macrophages leads to a disruption in spermatogonial differentiation. These findings reveal an unexpected role for macrophages in the spermatogonial niche in the testis and raise the possibility that macrophages play previously unappreciated roles in stem/progenitor cell regulation in other tissues.

  7. Chitinase 1 Is a Biomarker for and Therapeutic Target in Scleroderma-Associated Interstitial Lung Disease That Augments TGF-β1 Signaling

    Science.gov (United States)

    Lee, Chun Geun; Herzog, Erica L.; Ahangari, Farida; Zhou, Yang; Gulati, Mridu; Lee, Chang-Min; Peng, Xueyan; Feghali-Bostwick, Carol; Jimenez, Sergio A.; Varga, John; Elias, Jack A.

    2014-01-01

    Interstitial lung disease (ILD) with pulmonary fibrosis is an important manifestation in systemic sclerosis (SSc, scleroderma) where it portends a poor prognosis. However, biomarkers that predict the development and or severity of SSc-ILD have not been validated, and the pathogenetic mechanisms that engender this pulmonary response are poorly understood. In this study, we demonstrate in two different patient cohorts that the levels of chitotriosidase (Chit1) bioactivity and protein are significantly increased in the circulation and lungs of SSc patients compared with demographically matched controls. We also demonstrate that, compared with patients without lung involvement, patients with ILD show high levels of circulating Chit1 activity that correlate with disease severity. Murine modeling shows that in comparison with wild-type mice, bleomycin-induced pulmonary fibrosis was significantly reduced in Chit1−/− mice and significantly enhanced in lungs from Chit1 overexpressing transgenic animals. In vitro studies also demonstrated that Chit1 interacts with TGF-β1 to augment fibroblast TGF-β receptors 1 and 2 expression and TGF-β–induced Smad and MAPK/ERK activation. These studies indicate that Chit1 is potential biomarker for ILD in SSc and a therapeutic target in SSc-associated lung fibrosis and demonstrate that Chit1 augments TGF-β1 effects by increasing receptor expression and canonical and noncanonical TGF-β1 signaling. PMID:22826322

  8. Spectrum of interstitial lung diseases at a tertiary center in a developing country: A study of 803 subjects.

    Directory of Open Access Journals (Sweden)

    Sahajal Dhooria

    Full Text Available The spectrum of interstitial lung diseases (ILDs have mainly been reported from the developed countries; data from developing countries is sparse and conflicting. The aim of this study is to describe the distribution of various ILDs from a developing country.This is an analysis of prospectively collected clinical, radiological and histological data of consecutive subjects (age >12 years with ILDs from a single tertiary care medical center. The diagnosis of the specific subtype of ILD was made according to standard criteria for various ILDs.A total of 803 subjects (mean age, 50.6 years; 50.2% women were enrolled between March 2015 to February 2017 of which 566 (70.5% were diagnosed during the study period (incident cases. Sarcoidosis (42.2%, idiopathic pulmonary fibrosis (IPF, 21.2%, connective tissue disease (CTD-related ILDs (12.7%, hypersensitivity pneumonitis (10.7%, and non-IPF idiopathic interstitial pneumonias (9.2% were the most common ILDs. The spectrum of ILDs was not significantly different (p = 0.87 between incident and prevalent cases. A histopathological specimen was obtained in 49.9% of the subjects yielding a histologically confirmed diagnosis in 40.6%. A diagnostic procedure was not performed in 402 subjects; the most common reasons were presence of definite usual interstitial pneumonia pattern on high resolution computed tomography and patients' unwillingness to undergo the procedure.Sarcoidosis, IPF and CTD-ILDs were the most common ILDs seen at a tertiary center in northern India similar to the spectrum reported from developed countries. More studies are required from developing countries to ascertain the spectrum of ILDs in different geographic locales.

  9. Effect of macrophage and matrix metalloproteinase-9 on proliferation of pulmonary fibroblast and synthesis of collagen IV

    International Nuclear Information System (INIS)

    Song Liangwen; Sun Li; Diao Ruiying; Li Yang; Zhang Yong; Yin Jiye

    2006-01-01

    Objective: To explore pathogenetic mechanism in initiation of radiation-induced pulmonary fibrosis. Methods: Alveolar macrophages in Wistar rats irradiated by 60 Co γ-ray were collected by alveolar lavage; condition medium was prepared for stimulating human lung fibroblast (HLF) proliferation; HLF proliferation activity was determined by MTT method; collagen IV (Col IV) in HLF was determined by Western blot; the activity of matrix metalloproteinase-9 (MMP-9) was determined by zymography. Results: HLF proliferation activity was significantly increased after stimulation of condition medium, and the increase was most evident within 48-72 hs. Col IV synthesis in HLF was increased and reached a peak at 12 h after stimulation and then began to decrease. MMP-9 activity began to increase at 12 h and reached a peak at 48 h and then decreased after 72 h. Conclusions: Cobalt-60 gamma ray irradiation of 20 Gy can stimulate secretion of some cytokines in alveolar macrophage to promote pulmonary interstitial fibroblast proliferation and synthesis of Col IV . Col IV can stimulate MMP-9 increase; MMP-9 can degrade excess Col IV. Such changes are involved in remodeling process of early pulmonary injury. (authors)

  10. Macrophage and tumor cell responses to repetitive pulsed X-ray radiation

    Science.gov (United States)

    Buldakov, M. A.; Tretyakova, M. S.; Ryabov, V. B.; Klimov, I. A.; Kutenkov, O. P.; Kzhyshkowska, J.; Bol'shakov, M. A.; Rostov, V. V.; Cherdyntseva, N. V.

    2017-05-01

    To study a response of tumor cells and macrophages to the repetitive pulsed low-dose X-ray radiation. Methods. Tumor growth and lung metastasis of mice with an injected Lewis lung carcinoma were analysed, using C57Bl6. Monocytes were isolated from a human blood, using CD14+ magnetic beads. IL6, IL1-betta, and TNF-alpha were determined by ELISA. For macrophage phenotyping, a confocal microscopy was applied. “Sinus-150” was used for the generation of pulsed X-ray radiation (the absorbed dose was below 0.1 Gy, the pulse repetition frequency was 10 pulse/sec). The irradiation of mice by 0.1 Gy pulsed X-rays significantly inhibited the growth of primary tumor and reduced the number of metastatic colonies in the lung. Furthermore, the changes in macrophage phenotype and cytokine secretion were observed after repetitive pulsed X-ray radiation. Conclusion. Macrophages and tumor cells had a different response to a low-dose pulsed X-ray radiation. An activation of the immune system through changes of a macrophage phenotype can result in a significant antitumor effect of the low-dose repetitive pulsed X-ray radiation.

  11. Psycho-Physiological Associates of Dyspnea in Hospitalized Patients with Interstitial Lung Diseases: A Cross-Sectional Study.

    Science.gov (United States)

    Zhou, Yan Hua; Mak, Yim Wah

    2017-10-24

    Dyspnea has been found to be an independent predictor of mortality among patients with respiratory diseases and is often regarded as a difficult symptom to control in patients with interstitial lung diseases (ILDs). Previous studies have found an association of psychological and physiological factors with dyspnea among patients with chronic obstructive airway diseases. However, symptom management of hospitalized patients with ILDs has been hampered by difficulty in priority, since they are often admitted with multiple psycho-physiological needs. This study examined the prevalence of dyspnea and the psycho-physiological factors associated with it among hospitalized Chinese patients with ILDs. We studied 165 hospitalized patients with ILDs recruited consecutively over three months in a public hospital in Guangzhou, China. Dyspnea and common psycho-physiological factors, including cough symptoms, activity capacity, lung function, physical and mental health status, and anxiety and depression symptoms, were measured. By ordered logistic regression, level of dyspnea statistically significantly affected performance in a six-minute walk test and physical functioning in work or other regular daily activities in hospitalized patients with ILDs. Respiratory rehabilitation with an appropriate intensity of exercise training or other strategies for enhancing the physical functioning of this population with moderate and severe levels of dyspnea should be prioritized.

  12. Identifying decreased diaphragmatic mobility and diaphragm thickening in interstitial lung disease: the utility of ultrasound imaging

    Science.gov (United States)

    Santana, Pauliane Vieira; Prina, Elena; Albuquerque, André Luis Pereira; Carvalho, Carlos Roberto Ribeiro; Caruso, Pedro

    2016-01-01

    Objective: To investigate the applicability of ultrasound imaging of the diaphragm in interstitial lung disease (ILD). Methods: Using ultrasound, we compared ILD patients and healthy volunteers (controls) in terms of diaphragmatic mobility during quiet and deep breathing; diaphragm thickness at functional residual capacity (FRC) and at total lung capacity (TLC); and the thickening fraction (TF, proportional diaphragm thickening from FRC to TLC). We also evaluated correlations between diaphragmatic dysfunction and lung function variables. Results: Between the ILD patients (n = 40) and the controls (n = 16), mean diaphragmatic mobility was comparable during quiet breathing, although it was significantly lower in the patients during deep breathing (4.5 ± 1.7 cm vs. 7.6 ± 1.4 cm; p < 0.01). The patients showed greater diaphragm thickness at FRC (p = 0.05), although, due to lower diaphragm thickness at TLC, they also showed a lower TF (p < 0.01). The FVC as a percentage of the predicted value (FVC%) correlated with diaphragmatic mobility (r = 0.73; p < 0.01), and an FVC% cut-off value of < 60% presented high sensitivity (92%) and specificity (81%) for indentifying decreased diaphragmatic mobility. Conclusions: Using ultrasound, we were able to show that diaphragmatic mobility and the TF were lower in ILD patients than in healthy controls, despite the greater diaphragm thickness at FRC in the former. Diaphragmatic mobility correlated with ILD functional severity, and an FVC% cut-off value of < 60% was found to be highly accurate for indentifying diaphragmatic dysfunction on ultrasound. PMID:27167428

  13. Nonantibiotic macrolides restore airway macrophage phagocytic function with potential anti-inflammatory effects in chronic lung diseases.

    Science.gov (United States)

    Hodge, Sandra; Tran, Hai B; Hamon, Rhys; Roscioli, Eugene; Hodge, Greg; Jersmann, Hubertus; Ween, Miranda; Reynolds, Paul N; Yeung, Arthur; Treiberg, Jennifer; Wilbert, Sibylle

    2017-05-01

    We reported defective efferocytosis associated with cigarette smoking and/or airway inflammation in chronic lung diseases, including chronic obstructive pulmonary disease, severe asthma, and childhood bronchiectasis. We also showed defects in phagocytosis of nontypeable Haemophilus influenzae (NTHi), a common colonizer of the lower airway in these diseases. These defects could be substantially overcome with low-dose azithromycin; however, chronic use may induce bacterial resistance. The aim of the present study was therefore to investigate two novel macrolides-2'-desoxy-9-(S)-erythromycylamine (GS-459755) and azithromycin-based 2'-desoxy molecule (GS-560660)-with significantly diminished antibiotic activity against Staphylococcus aureus , Streptococcus pneumonia , Moraxella catarrhalis , and H. influenzae We tested their effects on efferocytosis, phagocytosis of NTHi, cell viability, receptors involved in recognition of apoptotic cells and/or NTHi (flow cytometry), secreted and cleaved intracellular IL-1β (cytometric bead array, immunofluorescence/confocal microscopy), and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) using primary alveolar macrophages and THP-1 macrophages ± 10% cigarette smoke extract. Dose-response experiments showed optimal prophagocytic effects of GS-459755 and GS-560660 at concentrations of 0.5-1 µg/ml compared with our findings with azithromycin. Both macrolides significantly improved phagocytosis of apoptotic cells and NTHi (e.g., increases in efferocytosis and phagocytosis of NTHi: GS-459755, 23 and 22.5%, P = 0.043; GS-560660, 23.5 and 22%, P = 0.043, respectively). Macrophage viability remained >85% following 24 h exposure to either macrolide at concentrations up to 20 µg/ml. Secreted and intracellular-cleaved IL-1β was decreased with both macrolides with no significant changes in recognition molecules c-mer proto-oncogene tyrosine kinase; scavenger receptor class A, member 1; Toll

  14. Evaluation of the alveolar macrophage role in the pulmonary distribution of actinide oxides

    International Nuclear Information System (INIS)

    Guezingar-Liebard, Florence

    1999-01-01

    Actinide oxide inhalation is potentially a risk during the fuel fabrication process in the electronuclear industry. These particles can induce pulmonary lesions. The alveolar macrophage play an important role in the particle sequestration and transport but the actinide toxicity towards these cells is not well known. The aim of this work was to characterize the evolution of particle localisation in lungs after inhalation and to evaluate the role of macrophages in the lesion histo-genesis. We have used of a solid track detector to visualise alpha dose distribution within lung tissue. After 237 NpO 2 , MOX or PuO 2 inhalation by rats, different kinetics of clearance were observed for the sub-pleural and peri-bronchial areas compared to the others alveolar areas. For initial lung burdens that alter the lung clearance, particle aggregates were observed. Their kinetic and localisation vary depending on the aerosol, for a same global dose delivered to the lungs. This could be due to the different specific alpha activities of the particles and to the particle number deposited in the lung to obtain a similar burden but it could be also due to a chemical toxicity of neptunium higher than that of the others actinides. The flow cytometry methods developed allow us to measure apoptosis, phagocytosis and free radicals generation. After addition of soluble uranium to the culture medium, similar results were obtained using either alveolar macrophages extracted from rats or a macrophage cell line. This work confirms that alveolar macrophages are involved in the aggregate formation which induces heterogeneous dose distribution within the different lung tissues. (author) [fr

  15. Idiopathic pleuroparenchymal fibroelastosis, a rare entity of interstitial pneumonia: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Chun; Chae, Eun Jin; Song, Joon Seon [University of Ulsan College of Medicine, Asan Medical Center, Seou (Korea, Republic of)

    2014-04-15

    Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a recently described, very rare type of fibrotic interstitial lung disease predominantly involving subpleural areas of both upper lungs. IPPFE has distinctive radiologic and pathologic features: progressive subpleural opacity with fibrotic changes, predominantly in upper lungs, and dense elastic component on histology. We experienced one case of surgically confirmed IPPFE, with progression of radiologic findings on the serial CT examinations. We herein report the characteristic radiologic features of IPPFE with pathologic and clinical manifestations.

  16. Unilateral lung transplantation for pulmonary fibrosis.

    Science.gov (United States)

    1986-05-01

    Improvements in immunosuppression and surgical techniques have made unilateral lung transplantation feasible in selected patients with end-stage interstitial lung disease. We report two cases of successful unilateral lung transplantation for end-stage respiratory failure due to pulmonary fibrosis. The patients, both oxygen-dependent, had progressive disease refractory to all treatment, with an anticipated life expectancy of less than one year on the basis of the rate of progression of the disease. Both patients were discharged six weeks after transplantation and returned to normal life. They are alive and well at 26 months and 14 months after the procedure. Pulmonary-function studies have shown substantial improvement in their lung volumes and diffusing capacities. For both patients, arterial oxygen tension is now normal and there is no arterial oxygen desaturation with exercise. This experience shows that unilateral lung transplantation, for selected patients with end-stage interstitial lung disease, provides a good functional result. Moreover, it avoids the necessity for cardiac transplantation, as required by the combined heart-lung procedure, and permits the use of the donor heart for another recipient.

  17. Activation of Alveolar Macrophages after Plutonium Oxide Inhalation in Rats: Involvement in the Early Inflammatory Response

    Energy Technology Data Exchange (ETDEWEB)

    Van der Meeren, A.; Tourdes, F.; Gremy, O.; Grillon, G.; Abram, M.C.; Poncy, J.L.; Griffiths, N. [CEA, DSV, DRR, SRCA, Centre DAM Ile de France, F-91297 Bruyeres Le Chatel, Arpajon (France)

    2008-07-01

    Alveolar macrophages play an important role in the distribution, clearance and inflammatory reactions after particle inhalation, which may influence long-term events such as fibrosis and tumorigenesis. The objectives of the present study were to investigate the early inflammatory events after plutonium oxide inhalation in rats and involvement of alveolar macrophages. Lung changes were studied from 3 days to 3 months after inhalation of PuO{sub 2} or different isotopic compositions (70% or 97% {sup 239}Pu) and initial lung deposits (range 2.1 to 43.4 kBq/rat). Analyses of bronchoalveolar lavages showed early increases in the numbers of granulocytes, lymphocytes and multi-nucleated macrophages. The activation of macrophages was evaluated ex vivo by measurement of inflammatory mediator levels in culture supernatants. TNF-alpha and chemokine MCP-1, MIP-2 and CINC-1 production was elevated from 7 days after inhalation and remained so up to 3 months. In contrast, IL-1 beta, IL-6 and IL-10 production was unchanged. At 6 weeks, pulmonary macrophage numbers and activation state were increased as observed from an immunohistochemistry study of lung sections with anti-ED1. Similarly, histological analyses of lung sections also showed evidence of inflammatory responses. In conclusion, our results indicate early inflammatory changes in the lungs of PuO{sub 2}-contaminated animals and the involvement of macrophages in this process. A dose-effect relationship was observed between the amount of radionuclide inhaled or retained at the time of analysis and inflammatory mediator production by alveolar macrophages 14 days after exposure. For similar initial lung deposits, the inflammatory manifestation appears higher for 97% {sup 239}Pu than for 70% {sup 239}Pu. (authors)

  18. Role of bronchoscopy in evaluation of cases with sputum smear negative pulmonary tuberculosis, interstitial lung disease and lung malignancy: A retrospective study of 712 cases.

    Science.gov (United States)

    Kumar, Raj; Gupta, Nitesh

    2015-01-01

    The introduction of flexible bronchoscope has revolutionized the field of pulmonary medicine and is a standard instrument used for diagnostic purpose. A retrospective analysis of the clinico-radiological profile, indication, biopsy procedure and complications, for patients undergoing bronchoscopy at one of the respiratory unit at a tertiary care center in India. Retrospective analysis of 712 bronchoscopies was done in regard to demographic profile, clinical and radiological presentation and diagnostic indication. The results were analyzed on basis of bronchoscopy inspection and histopathological specimen obtained from transbronchial (TBLB), endobronchial biopsy (EBLB) and cytology specimen by transbronchial needle aspiration (TBNA). Furthermore, diagnostic yield of each biopsy procedure and their combination was evaluated. Of 712 patients undergoing bronchoscopy, the pathological diagnosis was achieved in 384 (53.93%). Of 384 diagnosed cases, the clinic-radio-pathological diagnosis of pulmonary tuberculosis in 88 (22.19%), interstitial lung disease (ILDs) in 226 (58.85%), and lung cancer in 70 (18.22%) cases. Of 116 sputum smear negative tuberculosis patients, 88 (75.86%) were diagnosed to be pulmonary tuberculosis; the contribution of BAL being 71.59%. Of 226 ILDs, sarcoidosis was most common 148/226 (65.48%). Among 70 lung cancer diagnosed cases, squamous cell carcinoma was most common (54.28%). The results from current study reemphasizes on the diagnostic utility as well as safety of the bronchoscopy procedure. Copyright © 2015 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

  19. Cyclophosphamide for connective tissue disease-associated interstitial lung disease.

    Science.gov (United States)

    Barnes, Hayley; Holland, Anne E; Westall, Glen P; Goh, Nicole Sl; Glaspole, Ian N

    2018-01-03

    Approximately one-third of individuals with interstitial lung disease (ILD) have associated connective tissue disease (CTD). The connective tissue disorders most commonly associated with ILD include scleroderma/systemic sclerosis (SSc), rheumatoid arthritis, polymyositis/dermatomyositis, and Sjögren's syndrome. Although many people with CTD-ILD do not develop progressive lung disease, a significant proportion do progress, leading to reduced physical function, decreased quality of life, and death. ILD is now the major cause of death amongst individuals with systemic sclerosis.Cyclophosphamide is a highly potent immunosuppressant that has demonstrated efficacy in inducing and maintaining remission in autoimmune and inflammatory illnesses. However this comes with potential toxicities, including nausea, haemorrhagic cystitis, bladder cancer, bone marrow suppression, increased risk of opportunistic infections, and haematological and solid organ malignancies.Decision-making in the treatment of individuals with CTD-ILD is difficult; the clinician needs to identify those who will develop progressive disease, and to weigh up the balance between a high level of need for therapy in a severely unwell patient population against the potential for adverse effects from highly toxic therapy, for which only relatively limited data on efficacy can be found. Similarly, it is not clear whether histological subtype, disease duration, or disease extent can be used to predict treatment responsiveness. To assess the efficacy and adverse effects of cyclophosphamide in the treatment of individuals with CTD-ILD. We performed searches on CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to May 2017. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. We included randomised controlled parallel-group trials that compared cyclophosphamide in any form, used individually or concomitantly with other immunomodulating therapies, versus non

  20. Contemporary challenges for specialist nursing in interstitial lung disease.

    Science.gov (United States)

    Russell, Anne Marie; Olive, Sandra; Lines, Sarah; Murphy, Anna; Hocking, Julie; Newell, Karen; Morris, Helen; Harris, Emma; Dixon, Catherine; Agnew, Sarah; Burge, Geraldine

    2018-03-01

    The role of clinical nurse specialists (CNSs) in interstitial lung disease (ILD) is evolving in response to clinical guidelines and the growth of clinical research. The role is well established in the UK, although more ILD posts are needed to ensure supply meets clinical demand. This phenomenon is also happening across Europe. An appreciation of the similarities and differences between CNS and advanced nurse practitioners is important given the challenges in defining, developing and supporting this nursing specialisation. Globally, different models exist. In some countries charitable organisations take a leading role in supporting patients. Many European centres look to the National Institute for Health and Care Excellence guidelines and quality standards as a template to develop and evaluate the role of the ILD CNS. We present a UK perspective in the context of a government subsidised healthcare system to promote professional discussion and debate regarding the future of nursing practice in the ILD specialty. ILDs are often complex and associated with significant mortality, morbidity and co-morbid conditions that require a technical healthcare skill setThere is worldwide shortage of nurses, low retention rates and retirement of many skilled nursesCollaboration across the ILD interdisciplinary community is needed to safeguard the future of our professions and high-quality patient careThe ILD interdisciplinary and nurse network has identified key priorities to help secure the future of the ILD clinical and academic nurse specialism. To explain the similarities and differences between clinical nurse specialists (CNSs) and advanced nurse practitioners (ANPs) in the context of ILD specialismTo review contemporary nursing specialism in the UK's government subsidised healthcare systemTo stimulate discussion and debate across the European/international respiratory community regarding the clinical and academic development of the ILD CNSTo identify key priorities that will

  1. Computer-assisted quantification of interstitial lung disease associated with rheumatoid arthritis: Preliminary technical validation

    International Nuclear Information System (INIS)

    Marten, K.; Dicken, V.; Kneitz, C.; Hoehmann, M.; Kenn, W.; Hahn, D.; Engelke, C.

    2009-01-01

    Purpose: To validate a threshold-based prototype software application (MeVis PULMO 3D) for quantification of chronic interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) using variable threshold settings for segmentation of diseased lung areas. Methods: Twenty-two patients with rheumatoid arthritis were included and underwent thin-section CT (4 x 1.25 mm collimation). CT scans were assessed by two observers for extent of ILD (EoILD), and twice by MeVis PULMO 3D for each protocol. MeVis PULMO 3D used four segmentation threshold (ST) settings (ST = -740, -780, -800 and -840 HU). Pulmonary function tests were obtained in all patients. Statistical evaluation used 95% limits of agreement (LoA) and linear regression analysis. Results: There was total concordance between the software measurements. Interobserver agreement was good (LoA = -28.36 to 17.58%). EoILD by readers correlated strongly with DL CO (r = -0.702, p CO at ST of -800 HU (r = -0.44, -0.49, -0.58 and -0.57 for ST = -740, -780, -800 and -840, respectively; p = 0.007-0.05) and moderately with FVC (r = -0.44, -0.51, -0.59 and -0.45 for ST = -740, -780, -800 and -840), respectively; p = 0.007-0.05). Conclusion: The MeVis PULMO 3D system used holds promise to become a valuable instrument for quantification of chronic ILD in patients with RA when using the threshold value of -800 HU, with evidence of the closest correlations, both with human observers and physiologic impairment.

  2. IMPORTANCE OF CYCLOPHOSPHANUM IN THE TREATMENT OF INTERSTITIAL LUNG LESION IN PATIENTS WITH SCLERODERMA SYSTEMATICA (A REVIEW OF LITERATURE

    Directory of Open Access Journals (Sweden)

    Olga Aleksandrova Koneva

    2010-01-01

    Full Text Available Interstitial lung diseases (ILD are a common manifestation of scleroderma systematica (SSD that along with pulmonary arterial hypertension remains the leading cause of death in this nosological entity. As of now, cyclophosphanum remains the only immunosuppressant recommended by the European League against Rheumatism for the treatment of ILD in SSD. The paper analyzes the papers providing evidence for the efficacy of cyclophosphanum in ILD in patients with SSD. It also considers the regimens and duration of treatment with cyclophosphanum, ways of evaluating its efficacy and effects on extrapulmonary manifestations of SSD. It is concluded that cyclophosphanum has a positive, predominantly stabilizing, effect on the course of ILD in SSD.

  3. Preliminary studies on the spatial-temporal microdistribution of inhaled soluble plutonium in the lungs of dogs

    International Nuclear Information System (INIS)

    Cho, M.W.; Dagle, G.E.

    1987-01-01

    The pulmonary microdistribution of inhaled soluble plutonium in four beagle dogs was studied in autoradiographs of histologic sections and transmission electron micrographs of lungs. Dogs were exposed to a single nose-only aerosol of 239 Pu nitrate with a post-exposure time ranging from 1 month to 42 months. At one month after the exposure, the plutonium was dispersed throughout the lung section, with a higher percentage of the activity found on alveolar macrophages and alveolar septa. However, a nonrandom localization of the plutonium was observed as time passed. The focal concentrations were primarily in nodular or diffuse interstitial fibrotic tissues typically contiguous with subpleural, peribronchial, or perivascular areas. More than 50% of the total activity was in the form of single-tracks at one month exposure, and this percentage increased with time. In summary, this preliminary study suggests an initial random dispersion of soluble plutonium with increased concentration of activity to nonrandom focal locations with time

  4. Interstitial lung disease associated with collagen vascular disorders: disease quantification using a computer-aided diagnosis tool

    International Nuclear Information System (INIS)

    Marten, K.; Engelke, C.; Dicken, V.; Kneitz, C.; Hoehmann, M.; Kenn, W.; Hahn, D.

    2009-01-01

    The purpose of this study was to evaluate a computer-aided diagnosis (CAD) tool compared to human observers in quantification of interstitial lung disease (ILD) in patients with collagen-vascular disorders. A total of 52 patients with rheumatoid arthritis (n=24), scleroderma (n=14) and systemic lupus erythematosus (n=14) underwent thin-section CT. Two independent observers assessed the extent of ILD (EoILD), reticulation (EoRet) and ground-glass opacity (EoGGO). CAD assessed EoILD twice. Pulmonary function tests were obtained. Statistical evaluation used 95% limits of agreement and linear regression analysis. CAD correlated well with diffusing capacity (DL CO ) (R=-0.531, P CO (R=-0.705, P CO and moderately with FVC (DL CO : R=-0.663; FVC: R=-0.436; P≤0.005). The CAD system is a promising tool for ILD quantification, showing close correlation with human observers and physiologic impairment. (orig.)

  5. Lung cancer development in patients with connective tissue disease-related interstitial lung disease: A retrospective observational study.

    Science.gov (United States)

    Enomoto, Yasunori; Inui, Naoki; Yoshimura, Katsuhiro; Nishimoto, Koji; Mori, Kazutaka; Kono, Masato; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Iwashita, Toshihide; Suda, Takafumi

    2016-12-01

    Previous studies have reported that patients with idiopathic pulmonary fibrosis occasionally develop lung cancer (LC). However, in connective tissue disease (CTD)-related interstitial lung disease (ILD), there are few data regarding the LC development. The aim of the present study was to evaluate the clinical significance of LC development in patients with CTD-ILD. A retrospective review of our database of 562 patients with ILD between 2000 and 2014 identified 127 patients diagnosed with CTD-ILD. The overall and cumulative incidences of LC were calculated. In addition, the risk factors and prognostic impact of LC development were evaluated. The median age at the ILD diagnosis was 63 years (range 37-84 years), and 73 patients (57.5%) were female. The median follow-up period from the ILD diagnosis was 67.4 months (range 10.4-322.1 months). During the period, 7 out of the 127 patients developed LC (overall incidence 5.5%). The cumulative incidences at 1, 3, and 5 years were 0.0%, 1.8%, and 2.9%, respectively. The risk of LC development was significantly higher in patients with higher smoking pack-year (odds ratio [OR] 1.028; 95% confidence interval [CI] 1.008-1.049; P = 0.007) and emphysema on chest high-resolution computed tomography (OR 14.667; 95% CI 2.871-74.926; P = 0.001). The median overall survival time after developing LC was 7.0 months (95% CI 4.9-9.1 months), and the most common cause of death was LC, not ILD. According to the Cox proportional hazard model analysis with time-dependent covariates, patients who developed LC showed significantly poorer prognosis than those who did not (hazard ratio 87.86; 95% CI 19.56-394.67; P < 0.001). In CTD-ILD, clinicians should be careful with the risk of LC development in patients with a heavy smoking history and subsequent emphysema. Although not so frequent, the complication could be a poor prognostic determinant.

  6. Characteristics and potential role of M2 macrophages in COPD

    Directory of Open Access Journals (Sweden)

    He S

    2017-10-01

    Full Text Available Shengyang He, Lihua Xie, Junjuan Lu, Shenghua SunDepartment of Respiratory Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China Background: COPD is a multi-pathogenesis disease mainly caused by smoking. A further understanding of the mechanism of smoking-related COPD might contribute to preventions and treatments of this disease in the early stages. This study was designed to identify the characteristics of M2 macrophages in COPD for a better understanding about their potential role.Materials and methods: COPD models were built in the C57BL/6 mouse by cigarette smoke (CS exposure combined with intraperitoneal injection of cigarette smoke extract (CSE. The modeling efficiency was evaluated by lung function and hematoxylin and eosin (H&E staining. The number of different macrophage phenotypes was detected by immunohistochemical staining (IHS of CD206, CD86 and CD68 on the lung tissue paraffin section. The RAW264.7 cells were polarized toward the M2 phenotype by interleukin IL-4 and confirmed by a flow cytometer. The gene expression levels of TGF-βRII, Smad2, Smad3 and Smad7 in CSE-treated M2 macrophages were detected by real-time reverse transcription polymerase chain reaction (RT-PCR. The expression levels of TGF-β/Smad pathway-related makers (TGF-βRII, p-Smad2, p-Smad3, Smad7 and TGF-β in alveolar M2 macrophages were detected by two consecutive paraffin section IHS.Results: The COPD model is well established, which is confirmed by the lung function test and lung H&E staining. The whole number of macrophages and the ratio of M2/M1 phenotype are both increased (p<0.05. The level of CD206+ cells in IL-4-stimulated RAW264.7 cells is up to 93.4%, which is confirmed by a flow cytometer. The gene expression of TGF-βRII, Smad2, Smad3 and Smad7 are all enhanced (p<0.05 in CES-treated M2 macrophages, which is detected by RT-PCR. The protein levels of TGF-β/Smad pathway-related markers are

  7. Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice.

    Science.gov (United States)

    Xu, J; Xu, F; Barrett, E

    2008-07-01

    Metalloelastase (MMP-12), mainly produced by macrophages, has been shown to play a key role in the pathogenesis of emphysema in animal models. Chronic cigarette smoke increases pulmonary MMP-12, which is closely correlated with an elevation of pulmonary substance P (SP). Because alveolar macrophages (AMs) contain the neurokinin-1 receptor (NK1R), we tested whether SP was able to trigger the upregulation of MMP-12 synthesis in AMs by acting on the NK1R. AMs isolated from bronchoalveolar lavage cells in C3H/HeN mice were cultured with control medium or SP that was coupled without or with NK1R antagonists (CP-99,994 or aprepitant) for 24 h. We found that SP significantly increased the mRNA of MMP-12 and NK1R by 11-fold and 82%, respectively, in AMs (PNCAP) to degenerate PCFs, respectively. Our results show that NCAP treatment significantly decreased mRNA and protein levels of SP associated with a reduction NK1R and MMP-12 in the lungs and AMs. These findings suggest that SP has a modulatory effect on pulmonary MMP-12 by acting on NK1R to trigger MMP-12 syntheses in the AMs.

  8. Incidence of interstitial pneumonia after hyperfractionated total body irradiation before autologous bone marrow/stem cell transplantation

    International Nuclear Information System (INIS)

    Lohr, F.; Schraube, P.; Wenz, F.; Flentje, M.; Kalle, K. von; Haas, R.; Hunstein, W.; Wannenmacher, M.

    1995-01-01

    Purpose/Objectives Interstitial pneumonia (IP) is a severe complication after allogenic bone marrow transplantation (BMT) with incidence rates between 10 % and 40 % in different series. It is a polyetiologic disease that occurs depending on age, graft vs. host disease (GvHD), CMV-status, total body irradiation (TBI) and immunosuppressive therapy after BMT. The effects of fractionation and dose rate are not entirely clear. This study evaluates the incidence of lethal IP after hyperfractionated TBI for autologous BMT or stem cell transplantation. Materials and Methods Between 1982 and 1992, 182 patients (60 % male, 40 % female) were treated with hyperfractionated total body irradiation (TBI) before autologous bone marrow transplantation. Main indications were leukemias and lymphomas (53 % AML, 21 % ALL, 22 % NHL, 4 % others) Median age was 30 ys (15 - 55 ys). A total dose of 14.4 Gy was applied using lung blocks (12 fractions of 1.2 Gy in 4 days, dose rate 7-18 cGy/min, lung dose 9 - 9.5 Gy). TBI was followed by cyclophosphamide (200 mg/kg). 72 % were treated with bone marrow transplantation, 28 % were treated with stem cell transplantation. Interstitial pneumonia was diagnosed clinically, radiologically and by autopsy. Results 4 patients died most likely of interstitial pneumonia. For another 12 patients interstitial pneumonia was not the most likely cause of death but could not be excluded. Thus, the incidence of lethal IP was at least 2.2 % but certainly below 8.8 %. Conclusion Lethal interstitial pneumonia is a rare complication after total body irradiation before autologous bone marrow transplantation in this large, homogeously treated series. In the autologous setting, total doses of 14.4 Gy can be applied with a low risk for developing interstitial pneumonia if hyperfractionation and lung blocks are used. This falls in line with data from series with identical twins or t-cell depleted marrow and smaller, less homogeneous autologous transplant studies. Thus

  9. GSK3β-dependent inhibition of AMPK potentiates activation of neutrophils and macrophages and enhances severity of acute lung injury

    Science.gov (United States)

    Park, Dae Won; Jiang, Shaoning; Liu, Yanping; Siegal, Gene P.; Inoki, Ken; Abraham, Edward

    2014-01-01

    Although AMP-activated protein kinase (AMPK) is involved in regulating carbohydrate and lipid metabolism, activated AMPK also plays an anti-inflammatory role in many cell populations. However, despite the ability of AMPK activation to diminish the severity of inflammatory responses, previous studies have found that AMPK activity is diminished in LPS-treated neutrophils and also in lungs of mice with LPS-induced acute lung injury (ALI). Since GSK3β participates in regulating AMPK activity, we examined potential roles for GSK3β in modulating LPS-induced activation of neutrophils and macrophages and in influencing severity of ALI. We found that GSK3β-dependent phosphorylation of T479-AMPK was associated with pT172 dephosphorylation and inactivation of AMPK following TLR4 engagement. GSK3β inhibitors BIO (6-bromoindirubin-3′-oxime), SB216763, or siRNA knockdown of GSK3β, but not the PI3K/AKT inhibitor LY294002, prevented Thr172-AMPK dephosphorylation. Exposure to LPS resulted in rapid binding between IKKβ and AMPKα, and phosphorylation of S485-AMPK by IKKβ. These results suggest that IKKβ-dependent phosphorylation of S485-AMPK was an essential step in subsequent phosphorylation and inactivation AMPK by GSK3β. Inhibition of GSK3β activity delayed IκBα degradation and diminished expression of the proinflammatory TNF-α in LPS-stimulated neutrophils and macrophages. In vivo, inhibition of GSK3β decreased the severity of LPS-induced lung injury as assessed by development of pulmonary edema, production of TNF-α and MIP-2, and release of the alarmins HMGB1 and histone 3 in the lungs. These results show that inhibition of AMPK by GSK3β plays an important contributory role in enhancing LPS-induced inflammatory responses, including worsening the severity of ALI. PMID:25239914

  10. Usual interstitial pneumonia in adult-onset still's disease

    International Nuclear Information System (INIS)

    Rodelo, Joaquin; Gonzalez, Luis Alonso; Velasquez, Monica Patricia; Vasquez, Gloria; Uribe, Oscar; Perez, Maria del Pilar; Ramirez, Luis Alberto

    2005-01-01

    Adult-onset still's disease (AOSD) is a multi-system inflammatory disorder of unknown origin, characterized by high spiking fevers, evanescent salmon colored rash, arthralgias or arthritis, hepatospleno-megaly, Iymphadenopathy and sore throat. It is not uncommon for AOSD to involve other organs, such as the liver, the kidney; the bone marrow and less often the lungs. Pulmonary involvement ranges from 30 to 40 % (0 to 53 %), the pulmonary manifestations of AOSD include pleurisy, acute pneumonitis and even the acute respiratory distress syndrome. We present a case of a patient with AOSD who developed an interstitial lung disease and reviewed the literature on it

  11. British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders.

    Science.gov (United States)

    Hurst, John R; Verma, Nisha; Lowe, David; Baxendale, Helen E; Jolles, Stephen; Kelleher, Peter; Longhurst, Hilary J; Patel, Smita Y; Renzoni, Elisabetta A; Sander, Clare R; Avery, Gerard R; Babar, Judith L; Buckland, Matthew S; Burns, Siobhan; Egner, William; Gompels, Mark M; Gordins, Pavels; Haddock, Jamanda A; Hart, Simon P; Hayman, Grant R; Herriot, Richard; Hoyles, Rachel K; Huissoon, Aarnoud P; Jacob, Joseph; Nicholson, Andrew G; Rassl, Doris M; Sargur, Ravishankar B; Savic, Sinisa; Seneviratne, Suranjith L; Sheaff, Michael; Vaitla, Prashantha M; Walters, Gareth I; Whitehouse, Joanna L; Wright, Penny A; Condliffe, Alison M

    A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, -0.5, and -1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: "GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded." There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Characterization of rat lung ICAM-1

    DEFF Research Database (Denmark)

    Beck-Schimmer, B; Schimmer, R C; Schmal, H

    1998-01-01

    studies, rat pulmonary artery endothelial cells (RPAEC), rat alveolar macrophages and aortic rings were stimulated (as described below) and evaluated for ICAM-1 expression. TREATMENT: RPAEC and macrophages were stimulated with lipopolysaccharide (LPS) and recombinant murine tumour necrosis factor alpha...... peaked at 4 h, while lung ICAM- I protein peaked at 6 h. CONCLUSIONS: Quantitation of ICAM-1 expression in vitro and in vivo suggests that ICAM-1 plays a central role in two lung inflammatory models. Furthermore, lung ICAM-1 upregulation involves at least two cell types: vascular endothelial cells...

  13. Lung ultrasound for the diagnosis of post-operative complications after lung transplantation

    DEFF Research Database (Denmark)

    Rømhild Davidsen, Jesper; Lawaetz Schultz, Hans Henrik; Henriksen, Daniel Pilsgaard

    2017-01-01

    Lung ultrasound (LUS) has a high diagnostic accuracy for the identification of pleural effusion, pneumonia, and interstitial syndrome (IS), all of which are common complications in the early phase after lung transplantation (LTx), and may be associated with primary graft dysfunction, bleeding, or...... after LTx, and could be an alternative to conventional and more time-consuming thoracic imaging....

  14. Protein kinase D is increased and activated in lung epithelial cells and macrophages in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Gan, Huachen; McKenzie, Raymond; Hao, Qin; Idell, Steven; Tang, Hua

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and usually fatal lung disease of unknown etiology for which no effective treatments currently exist. Hence, there is a profound need for the identification of novel drugable targets to develop more specific and efficacious therapeutic intervention in IPF. In this study, we performed immunohistochemical analyses to assess the cell type-specific expression and activation of protein kinase D (PKD) family kinases in normal and IPF lung tissue sections. We also analyzed PKD activation and function in human lung epithelial cells. We found that PKD family kinases (PKD1, PKD2 and PKD3) were increased and activated in the hyperplastic and regenerative alveolar epithelial cells lining remodeled fibrotic alveolar septa and/or fibroblast foci in IPF lungs compared with normal controls. We also found that PKD family kinases were increased and activated in alveolar macrophages, bronchiolar epithelium, and honeycomb cysts in IPF lungs. Interestingly, PKD1 was highly expressed and activated in the cilia of IPF bronchiolar epithelial cells, while PKD2 and PKD3 were expressed in the cell cytoplasm and nuclei. In contrast, PKD family kinases were not apparently increased and activated in IPF fibroblasts or myofibroblasts. We lastly found that PKD was predominantly activated by poly-L-arginine, lysophosphatidic acid and thrombin in human lung epithelial cells and that PKD promoted epithelial barrier dysfunction. These findings suggest that PKD may participate in the pathogenesis of IPF and may be a novel target for therapeutic intervention in this disease.

  15. A case of idiopathic interstitial pneumonia

    OpenAIRE

    豊見山, 寛; 兼島, 洋; 下地, 克佳; 金城, 勇徳; 中富, 昌夫; 小張, 一峰; 松井, 克明; Tomiyama, Hiroshi; Kaneshima, Hiroshi; Shimoji, Katsuyoshi; Kinjo, Yutoku; Nakatomi, Masao; Kobari, Kazumine; Matsui, Katsuaki; 琉球大学医学部第一内科

    1982-01-01

    A case of idiopathic interstitial pneumonia was reported. A 53-year-old man was admitted to our hospital with his complaint of shortness of breath. On physical examination clubbing of the fingers was noticed and velcro rales was heard on the bilateral lower back. On laboratory data no remarkable finding was revealed. Chest roentgenogram showed diffuse reticulonodular shadow and small ring shadow of the bilateral lower lung fields. On pulmonary function test decline of VC and DLco was revealed...

  16. Regulation of ozone-induced lung inflammation and injury by the β-galactoside-binding lectin galectin-3

    International Nuclear Information System (INIS)

    Sunil, Vasanthi R.; Francis, Mary; Vayas, Kinal N.; Cervelli, Jessica A.; Choi, Hyejeong; Laskin, Jeffrey D.; Laskin, Debra L.

    2015-01-01

    Macrophages play a dual role in ozone toxicity, contributing to both pro- and anti-inflammatory processes. Galectin-3 (Gal-3) is a lectin known to regulate macrophage activity. Herein, we analyzed the role of Gal-3 in the response of lung macrophages to ozone. Bronchoalveolar lavage (BAL) and lung tissue were collected 24–72 h after exposure (3 h) of WT and Gal-3 -/- mice to air or 0.8 ppm ozone. In WT mice, ozone inhalation resulted in increased numbers of proinflammatory (Gal-3 + , iNOS + ) and anti-inflammatory (MR-1 + ) macrophages in the lungs. While accumulation of iNOS + macrophages was attenuated in Gal-3 -/- mice, increased numbers of enlarged MR-1 + macrophages were noted. This correlated with increased numbers of macrophages in BAL. Flow cytometric analysis showed that these cells were CD11b + and consisted mainly (> 97%) of mature (F4/80 + CD11c + ) proinflammatory (Ly6GLy6C hi ) and anti-inflammatory (Ly6GLy6C lo ) macrophages. Increases in both macrophage subpopulations were observed following ozone inhalation. Loss of Gal-3 resulted in a decrease in Ly6C hi macrophages, with no effect on Ly6C lo macrophages. CD11b + Ly6G + Ly6C + granulocytic (G) and monocytic (M) myeloid derived suppressor cells (MDSC) were also identified in the lung after ozone. In Gal-3 -/- mice, the response of G-MDSC to ozone was attenuated, while the response of M-MDSC was heightened. Changes in inflammatory cell populations in the lung of ozone treated Gal-3 -/- mice were correlated with reduced tissue injury as measured by cytochrome b5 expression. These data demonstrate that Gal-3 plays a role in promoting proinflammatory macrophage accumulation and toxicity in the lung following ozone exposure. - Highlights: • Multiple monocytic-macrophage subpopulations accumulate in the lung after ozone inhalation. • Galectin-3 plays a proinflammatory role in ozone-induced lung injury. • In the absence of gal-3, inflammatory cells with a myeloid derived suppressor cell phenotype

  17. Neutrophil elastase-induced elastin degradation mediates macrophage influx and lung injury in 60% O2-exposed neonatal rats.

    Science.gov (United States)

    Masood, Azhar; Yi, Man; Belcastro, Rosetta; Li, Jun; Lopez, Lianet; Kantores, Crystal; Jankov, Robert P; Tanswell, A Keith

    2015-07-01

    Neutrophil (PMNL) influx precedes lung macrophage (LM) influx into the lung following exposure of newborn pups to 60% O2. We hypothesized that PMNL were responsible for the signals leading to LM influx. This was confirmed when inhibition of PMNL influx with a CXC chemokine receptor-2 antagonist, SB-265610, also prevented the 60% O2-dependent LM influx, LM-derived nitrotyrosine formation, and pruning of small arterioles. Exposure to 60% O2 was associated with increased lung contents of neutrophil elastase and α-elastin, a marker of denatured elastin, and a decrease in elastin fiber density. This led us to speculate that neutrophil elastase-induced elastin fragments were the chemokines that led to a LM influx into the 60% O2-exposed lung. Inhibition of neutrophil elastase with sivelestat or elafin attenuated the LM influx. Sivelestat also attenuated the 60% O2-induced decrease in elastin fiber density. Daily injections of pups with an antibody to α-elastin prevented the 60% O2-dependent LM influx, impaired alveologenesis, and impaired small vessel formation. This suggests that neutrophil elastase inhibitors may protect against neonatal lung injury not only by preventing structural elastin degradation, but also by blocking elastin fragment-induced LM influx, thus preventing tissue injury from LM-derived peroxynitrite formation. Copyright © 2015 the American Physiological Society.

  18. Severe respiratory failure as a presenting feature of an interstitial lung disease associated with anti-synthetase syndrome (ASS).

    Science.gov (United States)

    Piroddi, Ines Maria Grazia; Ferraioli, Gianluca; Barlascini, Cornelius; Castagneto, Corrado; Nicolini, Antonello

    2016-07-01

    Anti-synthetase syndrome (ASS) is defined as a heterogeneous connective tissue disorder characterized by the association of an interstitial lung disease (ILD) with or without inflammatory myositis with the presence of anti-aminoacyl-tRNA-synthetase antibodies. ILD is one of the major extra-muscular manifestations of polymyositis and dermatomyositis. We report a case of a patient with dyspnea, cough, and intermittent fever as well as ILD associated ASS in the absence of muscular involvement. This patient was admitted to the emergency department with severe respiratory failure requiring non-invasive ventilation. Our patient's case demonstrates that the diagnosis of ASS may not be obvious. However, its diagnosis leads to appropriate and potentially life-saving treatment. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  19. M2 polarization enhances silica nanoparticle uptake by macrophages

    Directory of Open Access Journals (Sweden)

    Jessica eHoppstädter

    2015-03-01

    Full Text Available While silica nanoparticles have enabled numerous industrial and medical applications, their toxicological safety requires further evaluation. Macrophages are the major cell population responsible for nanoparticle clearance in vivo. The prevailing macrophage phenotype largely depends on the local immune status of the host. Whereas M1-polarized macrophages are considered as pro-inflammatory macrophages involved in host defense, M2 macrophages exhibit anti-inflammatory and wound-healing properties, but also promote tumor growth.We employed different models of M1 and M2 polarization: GM-CSF/LPS/IFN-gamma was used to generate primary human M1 cells and M-CSF/IL-10 to differentiate M2 monocyte-derived macrophages. PMA-differentiated THP-1 cells were polarized towards an M1 type by LPS/IFN-gamma and towards M2 by IL-10. Uptake of fluorescent silica nanoparticles (Ø 26 and 41 nm and microparticles (Ø 1.75 µm was quantified. At the concentration used (50 µg/ml, silica nanoparticles did not influence cell viability as assessed by MTT assay. Nanoparticle uptake was enhanced in M2-polarized primary human monocyte-derived macrophages compared with M1 cells, as shown by flow cytometric and microscopic approaches. In contrast, the uptake of microparticles did not differ between M1 and M2 phenotypes. M2 polarization was also associated with increased nanoparticle uptake in the macrophage-like THP-1 cell line. In accordance, in vivo polarized M2-like primary human tumor-associated macrophages (TAM obtained from lung tumors took up more nanoparticles than M1-like alveolar macrophages isolated from the surrounding lung tissue.In summary, our data indicate that the M2 polarization of macrophages promotes nanoparticle internalization. Therefore, the phenotypical differences between macrophage subsets should be taken into consideration in future investigations on nanosafety, but might also open up therapeutic perspectives allowing to specifically target M2

  20. The relationship of SSRI and SNRI usage with interstitial lung disease and bronchiectasis in an elderly population: a case–control study

    Directory of Open Access Journals (Sweden)

    Rosenberg T

    2017-11-01

    Full Text Available Ted Rosenberg,1 Rory Lattimer,2 Patrick Montgomery,3 Christian Wiens,4 Liran Levy5 1Department of Family Medicine, University of British Columbia and Island Medical Program, Victoria, BC, 2Home Team Medical Services, Victoria, BC, 3Division of Geriatric Medicine, University of British Columbia, Victoria, BC, 4Geriatric Psychiatry, University of British Columbia, Victoria, BC, 5Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada Background: The association between interstitial lung disease (ILD and selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors (SSRI/SNRI has been previously described in published case reports. However, its prevalence may be more common than expected. We examined the association between SSRI/SNRI usage and presence of ILD and or bronchiectasis (ILD/B in an elderly population.Methods: We conducted a retrospective case series and case–control study involving all 296 eligible elderly patients in one primary care geriatric practice in Victoria, BC, Canada. Cases required the presence of ILD/B on computed tomography (CT or chest X-ray (CXR. Cases were excluded if they had other causes for ILD/B on CXR or CT such as exposure to known pneumotoxic drugs, metastatic cancer, rheumatoid lung disease, sarcoidosis, previous pulmonary tuberculosis, or pneumoconiosis. Data were abstracted from the patients’ medical record. The exposure variable was standardized cumulative person-month (p-m dose of SSRI/SNRI. The study was approved by the Clinical Research Ethics Board of University of British Columbia with a waiver of informed consent.Results: A total of 12 cases and 273 controls were identified. Their mean ages were 89.0 and 88.7 years, respectively (p=0.862. A total of 10/12 cases and 99/273 controls were exposed to SSRI/SNRI. The odds ratio was 8.79, 95% confidence interval 2.40–32.23 (p=0.001. The median p-m exposure to SSRI/SNRI was 110.0 months for cases and 29.5 for

  1. Nontypeable Haemophilus influenzae induces sustained lung oxidative stress and protease expression.

    Directory of Open Access Journals (Sweden)

    Paul T King

    Full Text Available Nontypeable Haemophilus influenzae (NTHi is a prevalent bacterium found in a variety of chronic respiratory diseases. The role of this bacterium in the pathogenesis of lung inflammation is not well defined. In this study we examined the effect of NTHi on two important lung inflammatory processes 1, oxidative stress and 2, protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils from 15 subjects, and human-lung fibroblast and epithelial cell lines from 16 subjects. Cells were stimulated with NTHi to measure the effect on reactive oxygen species (ROS production and extracellular trap formation. We also measured the production of the oxidant, 3-nitrotyrosine (3-NT in the lungs of mice infected with this bacterium. NTHi induced widespread production of 3-NT in mouse lungs. This bacterium induced significantly increased ROS production in human fibroblasts, epithelial cells, macrophages and neutrophils; with the highest levels in the phagocytic cells. In human macrophages NTHi caused a sustained, extracellular production of ROS that increased over time. The production of ROS was associated with the formation of macrophage extracellular trap-like structures which co-expressed the protease metalloproteinase-12. The formation of the macrophage extracellular trap-like structures was markedly inhibited by the addition of DNase. In this study we have demonstrated that NTHi induces lung oxidative stress with macrophage extracellular trap formation and associated protease expression. DNase inhibited the formation of extracellular traps.

  2. KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts

    International Nuclear Information System (INIS)

    Ohshimo, Shinichiro; Yokoyama, Akihito; Hattori, Noboru; Ishikawa, Nobuhisa; Hirasawa, Yutaka; Kohno, Nobuoki

    2005-01-01

    The serum level of KL-6, a MUC1 mucin, is a clinically useful marker for various interstitial lung diseases. Previous studies demonstrated that KL-6 promotes chemotaxis of human fibroblasts. However, the pathophysiological role of KL-6 remains poorly understood. Here, we further investigate the functional aspects of KL-6 in proliferation and apoptosis of lung fibroblasts. KL-6 accelerated the proliferation and inhibited the apoptosis of all human lung fibroblasts examined. An anti-KL-6 monoclonal antibody counteracted both of these effects induced by KL-6 on human lung fibroblasts. The pro-fibroproliferative and anti-apoptotic effects of KL-6 are greater than and additive to those of the maximum effective concentrations of platelet-derived growth factor, basic fibroblast growth factor, and transforming growth factor-β. These findings indicate that increased levels of KL-6 in the epithelial lining fluid may stimulate fibrotic processes in interstitial lung diseases and raise the possibility of applying an anti-KL-6 antibody to treat interstitial lung diseases

  3. Impaired clearance of influenza A virus in obese, leptin receptor deficient mice is independent of leptin signaling in the lung epithelium and macrophages.

    Directory of Open Access Journals (Sweden)

    Kathryn A Radigan

    Full Text Available During the recent H1N1 outbreak, obese patients had worsened lung injury and increased mortality. We used a murine model of influenza A pneumonia to test the hypothesis that leptin receptor deficiency might explain the enhanced mortality in obese patients.We infected wild-type, obese mice globally deficient in the leptin receptor (db/db and non-obese mice with tissue specific deletion of the leptin receptor in the lung epithelium (SPC-Cre/LepR fl/fl or macrophages and alveolar type II cells (LysM-Cre/Lepr fl/fl with influenza A virus (A/WSN/33 [H1N1] (500 and 1500 pfu/mouse and measured mortality, viral clearance and several markers of lung injury severity.The clearance of influenza A virus from the lungs of mice was impaired in obese mice globally deficient in the leptin receptor (db/db compared to normal weight wild-type mice. In contrast, non-obese, SP-C-Cre+/+/LepR fl/fl and LysM-Cre+/+/LepR fl/fl had improved viral clearance after influenza A infection. In obese mice, mortality was increased compared with wild-type mice, while the SP-C-Cre+/+/LepR fl/fl and LysM-Cre+/+/LepR fl/fl mice exhibited improved survival.Global loss of the leptin receptor results in reduced viral clearance and worse outcomes following influenza A infection. These findings are not the result of the loss of leptin signaling in lung epithelial cells or macrophages. Our results suggest that factors associated with obesity or with leptin signaling in non-myeloid populations such as natural killer and T cells may be associated with worsened outcomes following influenza A infection.

  4. The elusive antifibrotic macrophage

    Directory of Open Access Journals (Sweden)

    Adhyatmika eAdhyatmika

    2015-11-01

    Full Text Available Fibrotic diseases, especially of the liver, the cardiovascular system, the kidneys, and the lungs account for approximately 45% of deaths in Western societies. Fibrosis is a serious complication associated with aging and/or chronic inflammation or injury and cannot be treated effectively yet. It is characterized by excessive deposition of extracellular matrix (ECM proteins by myofibroblasts and impaired degradation by macrophages. This ultimately destroys the normal structure of an organ, which leads to loss of function. Most efforts to develop drugs have focused on inhibiting ECM production by myofibroblasts and have not yielded many effective drugs yet. Another option is to stimulate the cells that are responsible for degradation and uptake of excess ECM, i.e. antifibrotic macrophages. However, macrophages are plastic cells that have many faces in fibrosis, including profibrotic behaviour stimulating ECM production. This can be dependent on their origin, as the different organs have tissue-resident macrophages with different origins and a various influx of incoming monocytes in steady-state conditions and during fibrosis. To be able to pharmacologically stimulate the right kind of behaviour in fibrosis, a thorough characterization of antifibrotic macrophages is necessary, as well as an understanding of the signals they need to degrade ECM. In this review we will summarize the current state of the art regarding the antifibrotic macrophage phenotype and the signals that stimulate its behaviour.

  5. Early detection of drug-induced pneumonitis by gallium-67 lung scan in six patients with normal chest radiographs

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, H; Sawa, H; Takashima, S [Osaka City Univ. (Japan). Hospital

    1981-06-01

    Increased pulmonary accumulation of Gallium-67-citrate was observed in 6 patients (4 with malignant lymphoma, 1 with uterine cancer and 1 with acute myelocytic leukemia) preceding the appearance of any abnormal findings in both chest X-ray and blood gas data. All of them had received multiple courses of chemotherapy. In these patients, the anticancer drugs were administered for 13 to 22 weeks (mean 15 weeks). One patient with malignant lymphoma showed abnormal /sup 67/Ga lung uptake greater than hepatic activity, 3 patients (malignant lymphoma, 2 and uterine cancer, 1) visualized abnormal /sup 67/Ga lung uptake equal to hepatic activity and 2 cases (malignant lymphoma, 1 and acute myelocytic leukemia, 1) demonstrated abnormal accumulation of /sup 67/Ga in the lung greater than background activity. In 4 patients (3 with malignant lymphoma and 1 with uterine cancer) out of 6, transbronchial lung biopsy obtained after the /sup 67/Ga scans showed non-specific interstitial pneumonitis with infiltration of lymphocytes and macrophages compatible with drug-induced pneumonitis. In the other 2 patients, cytology and cultures were negative and follow up /sup 67/Ga lung scans revealed a reduction in intensity of uptake after treatment with corticosteroid. Therefore, we considered that the /sup 67/Ga lung scan was useful for early detection of drug-induced pneumonitis.

  6. Anti-Cyclic Citrullinated Peptide Antibodies and Severity of Interstitial Lung Disease in Women with Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Alberto Daniel Rocha-Muñoz

    2015-01-01

    Full Text Available Objective. To evaluate whether serum titers of second-generation anticyclic citrullinated peptide antibodies (anti-CCP2 are associated with the severity and extent of interstitial lung disease in rheumatoid arthritis (RA-ILD. Methods. In across-sectional study, 39 RA-ILD patients confirmed by high-resolution computed tomography (HRCT were compared with 42 RA without lung involvement (RA only. Characteristics related to RA-ILD were assessed in all of the patients and serum anti-CCP2 titers quantified. Results. Higher anti-CCP2 titers were found in RA-ILD compared with RA only (medians 77.9 versus 30.2 U/mL, P<0.001. In the logistic regression analysis after adjustment for age, disease duration (DD, smoke exposure, disease activity, functioning, erythrocyte sedimentation rate, and methotrexate (MTX treatment duration, the characteristics associated with RA-ILD were higher anti-CCP2 titers (P=0.003 and + RF (P=0.002. In multivariate linear regression, the variables associated with severity of ground-glass score were anti-CCP2 titers (P=0.02 and with fibrosis score DD (P=0.01, anti-CCP2 titers (P<0.001, and MTX treatment duration (P<0.001. Conclusions. Anti-CCP2 antibodies are markers of severity and extent of RA-ILD in HRCT. Further longitudinal studies are required to identify if higher anti-CCP2 titers are associated with worst prognosis in RA-ILD.

  7. Regulation of ozone-induced lung inflammation and injury by the β-galactoside-binding lectin galectin-3

    Energy Technology Data Exchange (ETDEWEB)

    Sunil, Vasanthi R., E-mail: sunilva@pharmacy.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Francis, Mary, E-mail: maryfranrutgers@gmail.com [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Vayas, Kinal N., E-mail: kinalv5@gmail.com [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Cervelli, Jessica A., E-mail: j.cervelli@pharmacy.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Choi, Hyejeong, E-mail: choi@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Department of Environmental and Occupational Medicine, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ (United States)

    2015-04-15

    Macrophages play a dual role in ozone toxicity, contributing to both pro- and anti-inflammatory processes. Galectin-3 (Gal-3) is a lectin known to regulate macrophage activity. Herein, we analyzed the role of Gal-3 in the response of lung macrophages to ozone. Bronchoalveolar lavage (BAL) and lung tissue were collected 24–72 h after exposure (3 h) of WT and Gal-3{sup -/-} mice to air or 0.8 ppm ozone. In WT mice, ozone inhalation resulted in increased numbers of proinflammatory (Gal-3{sup +}, iNOS{sup +}) and anti-inflammatory (MR-1{sup +}) macrophages in the lungs. While accumulation of iNOS{sup +} macrophages was attenuated in Gal-3{sup -/-} mice, increased numbers of enlarged MR-1{sup +} macrophages were noted. This correlated with increased numbers of macrophages in BAL. Flow cytometric analysis showed that these cells were CD11b{sup +} and consisted mainly (> 97%) of mature (F4/80{sup +}CD11c{sup +}) proinflammatory (Ly6GLy6C{sup hi}) and anti-inflammatory (Ly6GLy6C{sup lo}) macrophages. Increases in both macrophage subpopulations were observed following ozone inhalation. Loss of Gal-3 resulted in a decrease in Ly6C{sup hi} macrophages, with no effect on Ly6C{sup lo} macrophages. CD11b{sup +}Ly6G{sup +}Ly6C{sup +} granulocytic (G) and monocytic (M) myeloid derived suppressor cells (MDSC) were also identified in the lung after ozone. In Gal-3{sup -/-} mice, the response of G-MDSC to ozone was attenuated, while the response of M-MDSC was heightened. Changes in inflammatory cell populations in the lung of ozone treated Gal-3{sup -/-} mice were correlated with reduced tissue injury as measured by cytochrome b5 expression. These data demonstrate that Gal-3 plays a role in promoting proinflammatory macrophage accumulation and toxicity in the lung following ozone exposure. - Highlights: • Multiple monocytic-macrophage subpopulations accumulate in the lung after ozone inhalation. • Galectin-3 plays a proinflammatory role in ozone-induced lung injury. • In the

  8. Chromate Dissociation from Primer Paint in Simulated Lung Fluid.

    Science.gov (United States)

    2000-03-01

    and simulated interstitial lung fluid is surface active component (dipalmitoyl lecithin : DPL) in simulated surfactant lung fluid (Dennis, 1982:470...Biology in Health and Disease Vol 84: Surfactant Therapy for Lung Disease. Ed. Bengt Robertson and H. William Taeusch. New York, NY: Mrecel Dekker inc

  9. Progressive multiple cystic changes in both lungs in a patient treated with gefitinib for lung adenocarcinoma with multiple lung metastases

    International Nuclear Information System (INIS)

    Ryu, Yon Ju; Chun, Eun Mi; Lee, Soon Nam; Shim, Sung Shin

    2014-01-01

    Gefitinib is regarded as a relatively safe agent for the treatment of an advanced non-small cell lung cancer (NSCLC). Pulmonary toxicity such as interstitial lung disease associated with gefitinib is uncommon with an estimated all time incidence around 1% worldwide. Moreover, a case of gefitinib associated with pulmonary cystic changes has not been reported yet. In this report we present a case of progressive multiple air cystic changes in both lungs in a patient with NSCLC and intrapulmonary metastases who underwent a gefitinib therapy.

  10. Low Levels of IGF-1 Contribute to Alveolar Macrophage Dysfunction in Cystic Fibrosis1

    OpenAIRE

    Bessich, Jamie L.; Nymon, Amanda B.; Moulton, Lisa A; Dorman, Dana; Ashare, Alix

    2013-01-01

    Alveolar macrophages are major contributors to lung innate immunity. Although alveolar macrophages from CFTR−/− mice have impaired function, no study has investigated primary alveolar macrophages in adults with cystic fibrosis (CF). CF patients have low levels of insulin-like growth factor 1 (IGF-1), and our prior studies demonstrate a relationship between IGF-1 and macrophage function. We hypothesize that reduced IGF-1 in CF leads to impaired alveolar macrophage function and chronic infectio...

  11. Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function.

    Science.gov (United States)

    Takata, Kazuyuki; Kozaki, Tatsuya; Lee, Christopher Zhe Wei; Thion, Morgane Sonia; Otsuka, Masayuki; Lim, Shawn; Utami, Kagistia Hana; Fidan, Kerem; Park, Dong Shin; Malleret, Benoit; Chakarov, Svetoslav; See, Peter; Low, Donovan; Low, Gillian; Garcia-Miralles, Marta; Zeng, Ruizhu; Zhang, Jinqiu; Goh, Chi Ching; Gul, Ahmet; Hubert, Sandra; Lee, Bernett; Chen, Jinmiao; Low, Ivy; Shadan, Nurhidaya Binte; Lum, Josephine; Wei, Tay Seok; Mok, Esther; Kawanishi, Shohei; Kitamura, Yoshihisa; Larbi, Anis; Poidinger, Michael; Renia, Laurent; Ng, Lai Guan; Wolf, Yochai; Jung, Steffen; Önder, Tamer; Newell, Evan; Huber, Tara; Ashihara, Eishi; Garel, Sonia; Pouladi, Mahmoud A; Ginhoux, Florent

    2017-07-18

    Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues. Co-culturing human or murine iMacs with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMacs differentiated in vivo into microglia after injection into the brain and into functional alveolar macrophages after engraftment in the lung. Finally, iPSCs from a patient with familial Mediterranean fever differentiated into iMacs with pro-inflammatory characteristics, mimicking the disease phenotype. Altogether, iMacs constitute a source of tissue-resident macrophage precursors that can be used for biological, pathophysiological, and therapeutic studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Evaluation of amniotic mesenchymal cell derivatives on cytokine production in equine alveolar macrophages: an in vitro approach to lung inflammation.

    Science.gov (United States)

    Zucca, Enrica; Corsini, Emanuela; Galbiati, Valentina; Lange-Consiglio, Anna; Ferrucci, Francesco

    2016-09-20

    Data obtained in both animal models and clinical trials suggest that cell-based therapies represent a potential therapeutic strategy for lung repair and remodeling. Recently, new therapeutic approaches based on the use of stem cell derivatives (e.g., conditioned medium (CM) and microvesicles (MVs)) to regenerate tissues and improve their functions were proposed. The aim of this study was to investigate the immunomodulatory effects of equine amniotic mesenchymal cell derivatives on lipopolysaccharide (LPS)-induced cytokine production in equine alveolar macrophages, which may be beneficial in lung inflammatory disorders such as recurrent airway obstruction (RAO) in horses. RAO shares many features with human asthma, including an increased number of cells expressing mRNA for interleukin (IL)-4 and IL-5 and a decreased expression of IFN-γ in bronchoalveolar lavage fluid (BALF) of affected horses. The release of TNF-α, IL-6, and TGF-β1 at different time points (1, 24, 48, and 72 h) was measured in equine alveolar macrophages stimulated or not with LPS (10 and 100 ng/mL) in the presence or absence of 10 % CM or 50 × 10(6) MVs/mL. Cytokines were measured using commercially available ELISA kits. For multiple comparisons, analysis of variance was used with Tukey post-hoc test. Differences were considered significant at p ≤ 0.05. Significant modulatory effects of CM on LPS-induced TNF-α release at 24 h, and of both CM and MVs on TNF-α release at 48 h were observed. A trend toward a modulatory effect of both CM and MVs on the release of TGF-β and possibly IL-6 was visible over time. Results support the potential use of CM and MVs in lung regenerative medicine, especially in situations in which TGF-β may be detrimental, such as respiratory allergy. Further studies should evaluate the potential clinical applications of CM and MVs in equine lung diseases, such as RAO and other inflammatory disorders.

  13. Chlamydia pneumoniae hides inside apoptotic neutrophils to silently infect and propagate in macrophages.

    Directory of Open Access Journals (Sweden)

    Jan Rupp

    Full Text Available BACKGROUND: Intracellular pathogens have developed elaborate strategies for silent infection of preferred host cells. Chlamydia pneumoniae is a common pathogen in acute infections of the respiratory tract (e.g. pneumonia and associated with chronic lung sequelae in adults and children. Within the lung, alveolar macrophages and polymorph nuclear neutrophils (PMN are the first line of defense against bacteria, but also preferred host phagocytes of chlamydiae. METHODOLOGY/PRINCIPAL FINDINGS: We could show that C. pneumoniae easily infect and hide inside neutrophil granulocytes until these cells become apoptotic and are subsequently taken up by macrophages. C. pneumoniae infection of macrophages via apoptotic PMN results in enhanced replicative activity of chlamydiae when compared to direct infection of macrophages, which results in persistence of the pathogen. Inhibition of the apoptotic recognition of C. pneumoniae infected PMN using PS- masking Annexin A5 significantly lowered the transmission of chlamydial infection to macrophages. Transfer of apoptotic C. pneumoniae infected PMN to macrophages resulted in an increased TGF-ss production, whereas direct infection of macrophages with chlamydiae was characterized by an enhanced TNF-alpha response. CONCLUSIONS/SIGNIFICANCE: Taken together, our data suggest that C. pneumoniae uses neutrophil granulocytes to be silently taken up by long-lived macrophages, which allows for efficient propagation and immune protection within the human host.

  14. p38 mitogen-activated protein kinase up-regulates LPS-induced NF-κB activation in the development of lung injury and RAW 264.7 macrophages

    International Nuclear Information System (INIS)

    Kim, Hee J.; Lee, Hui S.; Chong, Young H.; Kang, Jihee Lee

    2006-01-01

    Clarification of the key regulatory steps that lead to nuclear factor-kappa B (NF-κB) under cellular and pathological conditions is very important. The action of p38 mitogen-activated protein kinase (MAPK) on the upstream of NF-κB activation remains controversial. To examine this issue using an in vivo lung injury model, SB203580, a p38 MAPK inhibitor was given intraorally 1 h prior to lipopolysaccharide (LPS) treatment (intratracheally). The mice were sacrificed 4 h after LPS treatment. SB203580 substantially suppressed LPS-induced rises in p38 MAPK phosphorylation, neutrophil recruitment, total protein content in bronchoalveolar lavage fluid, and apoptosis of bronchoalveolar cells. Furthermore, SB203580 blocked LPS-induced NF-κB activation in lung tissue through down-regulation of serine phosphorylation, degradation of IκB-α, and consequent translocation of the p65 subunit of NF-κB to the nucleus. It is likely that, in cultured RAW 264.7 macrophages, SB203580 also blocked LPS-induced NF-κB activation in a dose-dependent manner. SB203580 inhibited LPS-induced serine phosphorylation, degradation of IκB-α, and tyrosine phosphorylation of p65 NF-κB. These data indicate that p38 MAPK acts upstream of LPS-induced NF-κB activation by modulating the phosphorylation of IκB-α and p65 NF-κB during acute lung injury. Because LPS-stimulated macrophages may contribute to inflammatory lung injury, the inhibition of the p38 MAPK-mediated intracellular signaling pathway leading to NF-κB activation represents a target for the attenuation of lung inflammation and parenchymal damage

  15. Estrogen Signaling Contributes to Sex Differences in Macrophage Polarization during Asthma.

    Science.gov (United States)

    Keselman, Aleksander; Fang, Xi; White, Preston B; Heller, Nicola M

    2017-09-01

    Allergic asthma is a chronic Th2 inflammation in the lungs that constricts the airways and presents as coughing and wheezing. Asthma mostly affects boys in childhood and women in adulthood, suggesting that shifts in sex hormones alter the course of the disease. Alveolar macrophages have emerged as major mediators of allergic lung inflammation in animal models as well as humans. Whether sex differences exist in macrophage polarization and the molecular mechanism(s) that drive differential responses are not well understood. We found that IL-4-stimulated bone marrow-derived and alveolar macrophages from female mice exhibited greater expression of M2 genes in vitro and after allergen challenge in vivo. Alveolar macrophages from female mice exhibited greater expression of the IL-4Rα and estrogen receptor (ER) α compared with macrophages from male mice following allergen challenge. An ERα-specific agonist enhanced IL-4-induced M2 gene expression in macrophages from both sexes, but more so in macrophages from female mice. Furthermore, IL-4-stimulated macrophages from female mice exhibited more transcriptionally active histone modifications at M2 gene promoters than did macrophages from male mice. We found that supplementation of estrogen into ovariectomized female mice enhanced M2 polarization in vivo upon challenge with allergen and that macrophage-specific deletion of ERα impaired this M2 polarization. The effects of estrogen are long-lasting; bone marrow-derived macrophages from ovariectomized mice implanted with estrogen exhibited enhanced IL-4-induced M2 gene expression compared with macrophages from placebo-implanted littermates. Taken together, our findings suggest that estrogen enhances IL-4-induced M2 gene expression and thereby contributes to sex differences observed in asthma. Copyright © 2017 by The American Association of Immunologists, Inc.

  16. NFAT5-Regulated Macrophage Polarization Supports the Proinflammatory Function of Macrophages and T Lymphocytes.

    Science.gov (United States)

    Tellechea, Mónica; Buxadé, Maria; Tejedor, Sonia; Aramburu, Jose; López-Rodríguez, Cristina

    2018-01-01

    Macrophages are exquisite sensors of tissue homeostasis that can rapidly switch between pro- and anti-inflammatory or regulatory modes to respond to perturbations in their microenvironment. This functional plasticity involves a precise orchestration of gene expression patterns whose transcriptional regulators have not been fully characterized. We had previously identified the transcription factor NFAT5 as an activator of TLR-induced responses, and in this study we explore its contribution to macrophage functions in different polarization settings. We found that both in classically and alternatively polarized macrophages, NFAT5 enhanced functions associated with a proinflammatory profile such as bactericidal capacity and the ability to promote Th1 polarization over Th2 responses. In this regard, NFAT5 upregulated the Th1-stimulatory cytokine IL-12 in classically activated macrophages, whereas in alternatively polarized ones it enhanced the expression of the pro-Th1 mediators Fizz-1 and arginase 1, indicating that it could promote proinflammatory readiness by regulating independent genes in differently polarized macrophages. Finally, adoptive transfer assays in vivo revealed a reduced antitumor capacity in NFAT5-deficient macrophages against syngeneic Lewis lung carcinoma and ID8 ovarian carcinoma cells, a defect that in the ID8 model was associated with a reduced accumulation of effector CD8 T cells at the tumor site. Altogether, detailed analysis of the effect of NFAT5 in pro- and anti-inflammatory macrophages uncovered its ability to regulate distinct genes under both polarization modes and revealed its predominant role in promoting proinflammatory macrophage functions. Copyright © 2017 by The American Association of Immunologists, Inc.

  17. Interstitial nephritis.

    Science.gov (United States)

    Papper, S

    1980-01-01

    There are many causes of interstitial nephritis other than pyelonephritis. The term interstitial nephritis does not connote a single etiologic or pathogenetic mechanism; it rather arbitrarily places together a wider variety of renal diseases that have a predilection for early and major involvement of the renal interstitium. The prototype of acute interstitial nephritis is acute pyelonephritis. In addition, there is a drug-related acute interstitial disease that is probably of immunological nature and usually reverses with discontinuance of the offending drug. Chronic interstitial nephritis includes many diverse illnesses. Nonobstructive pyelonephritis occurs but its prevalence is debated. Analgesic abuse nephropathy is not rare and is potentially reversible. Papillary necrosis has many causes and a wide spectrum of clinical presentations. Heavy metals, such as lead, cause interstitial nephritis. Balkan nephropathy occurs in an endemic area and although not bacterial in origin is of unknown cause.

  18. Role of Alveolar Macrophages in Chronic Obstructive Pulmonary Disease

    Science.gov (United States)

    Vlahos, Ross; Bozinovski, Steven

    2014-01-01

    Alveolar macrophages (AMs) represent a unique leukocyte population that responds to airborne irritants and microbes. This distinct microenvironment coordinates the maturation of long-lived AMs, which originate from fetal blood monocytes and self-renew through mechanisms dependent on GM-CSF and CSF-1 signaling. Peripheral blood monocytes can also replenish lung macrophages; however, this appears to occur in a stimuli specific manner. In addition to mounting an appropriate immune response during infection and injury, AMs actively coordinate the resolution of inflammation through efferocytosis of apoptotic cells. Any perturbation of this process can lead to deleterious responses. In chronic obstructive pulmonary disease (COPD), there is an accumulation of airway macrophages that do not conform to the classic M1/M2 dichotomy. There is also a skewed transcriptome profile that favors expression of wound-healing M2 markers, which is reflective of a deficiency to resolve inflammation. Endogenous mediators that can promote an imbalance in inhibitory M1 vs. healing M2 macrophages are discussed, as they are the plausible mechanisms underlying why AMs fail to effectively resolve inflammation and restore normal lung homeostasis in COPD. PMID:25309536

  19. Pulmonary interstitial emphysema presenting in a woman on the intensive care unit: case report and review of literature

    Directory of Open Access Journals (Sweden)

    Jovaisa Tomas

    2011-06-01

    Full Text Available Abstract Introduction Pulmonary interstitial emphysema is a life-threatening form of ventilator-induced lung injury. We present one of the few reported adult cases of pulmonary interstitial emphysema in a woman with respiratory failure admitted to our intensive care unit. Case presentation An 87-year-old Caucasian woman with a diagnosis of community-acquired pneumonia was admitted to our intensive care unit requiring invasive ventilation. The combination of a poor oxygenation index and bilateral alveolar/interstitial infiltrates on a chest radiograph fulfilled the criteria for adult respiratory distress syndrome; the cause was thought to be a combination of the direct pneumonic pulmonary injury and extrapulmonary severe sepsis. By day seven, the fraction of inspired oxygen, peak airway and positive end expiratory pressures weaned sufficiently to allow an uncomplicated percutaneous tracheostomy. On day 10, problems with ventilation necessitated recruitment maneuvers with a Mapleson C circuit, after which dramatic surgical emphysema was noted. An upper airway bronchoscopy showed no obvious tracheal wall injury, and computed tomography of her chest showed extensive surgical emphysema, perivascular emphysema and peribronchial emphysema, which were consistent with a diagnosis of pulmonary interstitial emphysema. Over the following days, despite protective ventilatory strategies and intercostal tube thoracostomy, lung compliance along with oxygenation deteriorated and our patient died on day 14. Conclusion The development of pulmonary interstitial emphysema is a rare but real risk when caring for patients with worsening lung compliance on the intensive care unit. Improved awareness of the condition, early protective ventilation strategies and timely treatment of any of the lethal complications will hopefully result in improved survival from the condition in adults.

  20. Auscultation of Velcro Crackles is Associated With Usual Interstitial Pneumonia.

    Science.gov (United States)

    Sellarés, Jacobo; Hernández-González, Fernanda; Lucena, Carmen M; Paradela, Marina; Brito-Zerón, Pilar; Prieto-González, Sergio; Benegas, Mariana; Cuerpo, Sandra; Espinosa, Gerard; Ramírez, José; Sánchez, Marcelo; Xaubet, Antoni

    2016-02-01

    Auscultation of Velcro crackles has been proposed as a key finding in physical lung examination in patients with interstitial lung diseases (ILDs), especially in idiopathic pulmonary fibrosis (IPF). However, no studies have been carried out to assess the association of Velcro crackles with other clinical variables.We evaluated a cohort of 132 patients, prospectively and consecutively included in our ILD diagnostic program at a tertiary referral center. All patients were auscultated during the physical examination. The patients were divided into 2 groups: "presence" or "nonpresence" of bilateral Velcro crackles.Of all patients assessed, 83 (63%) presented Velcro crackles in the respiratory auscultation. Patients with Velcro crackles usually had more frequently cough and dyspnea at the moment of diagnosis. Forced vital capacity (P = 0.002) and lung diffusion capacity for carbon monoxide (P = 0.04) was lower in these patients. The ILD-GAP index was higher in the group with Velcro crackles (P = 0.01). All patients with usual interstitial pneumonia (UIP) in high-resolution computed tomography and all patients with final IPF diagnosis presented Velcro crackles. In multivariate analysis, the presence of Velcro crackles was independently associated with an UIP pattern.In patients suspected of having ILD, the auscultation of Velcro crackles was associated with UIP, a possibility which must be taken into consideration in early ILD detection in primary care.

  1. CT and conventional radiographic techniques in interstitial pulmonary disease

    International Nuclear Information System (INIS)

    Leipner, N.; Schueller, H.; Uexkuell-Gueldenband, V. v.; Schlolaut, K.H.; Overlack, A.; Bonn Univ.

    1988-01-01

    One hundred and sixty-four patients with pulmonary fibrosis were examined by CT and by conventional radiological methods. Sixty patients had asbestosis, thirty-nine silicosis, forty sarcoidosis and twenty-five had idiopathic pulmonary fibrosis. CT is superior to conventional radiography in evaluating interstitial pulmonary changes, particularly of the pleura and the lung parenchyma. In sixty-nine patients there were some findings which could only be demonstrated by CT. In asbestosis, silicosis and sarcoidosis the CT classification of the lung parenchyma which we have suggested produces significantly better correlation with vital capacity than can be achieved from conventional chest films, according to the guidelines of the I.L.O. (orig./GDG) [de

  2. Humidifier disinfectant-associated children's interstitial lung disease: Computed tomographic features, histopathologic correlation and comparison between survivors and non-survivors

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hee Mang; Lee, Jin Seong; Do, Kyung-Hyun; Jung, Ah Young; Yoon, Chong Hyun; Cho, Young Ah [Asan Medical Center, University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Songpa-gu, Seoul (Korea, Republic of); Lee, Eun; Hong, Soo-Jong [Asan Medical Center, University of Ulsan College of Medicine, Department of Pediatrics, Songpa-gu, Seoul (Korea, Republic of); Kim, Seon-Ok [Asan Medical Center, University of Ulsan College of Medicine, Department of Clinical Epidemiology and Biostatistics, Songpa-gu, Seoul (Korea, Republic of); Jang, Se-Jin [Asan Medical Center, University of Ulsan College of Medicine, Departments of Pathology, Songpa-gu, Seoul (Korea, Republic of)

    2016-01-15

    To report radiologic findings with histopathologic correlations of humidifier disinfectant-associated children's interstitial lung disease (HD-chILD) and to compare computed tomography (CT) findings between survivors and non-survivors. Forty-seven children with HD-chILD (27.4 ± 12.4 months old) were categorized as survivors (n = 25) and non-survivors (n = 22). The patterns, distributions, and chronological changes in lung lesions at follow-up CT were investigated. Histopathologic correlations were performed in 23 patients. CT features were characterized by chronological changes, from consolidation to centrilobular opacities, and lesions eventually became faint centrilobular nodules. Histopathologic features were bronchocentric-distributed fibro-inflammatory lesions, which were more profound in the advanced stage than the early stage. Consolidation ≥30 % [hazard ratio (HR), 2.932], centrilobular opacities ≥60 % of the total lung volume (TLV; HR, 0.206) and spontaneous air leaks (HR, 3.457) were significant factors associated with patient survival, as per univariate analysis. Consolidation ≥30 % (HR, 3.519), centrilobular opacities ≥60 % (HR, 0.205) and diffuse ground glass opacity (GGO) ≥70 % of the TLV (HR, 3.521) were significant factors associated with patient survival, as determined via multivariate analysis. Distinctive chronological CT features were observed in the HD-chILD images. Spontaneous air leaks, consolidation, GGO, and centrilobular opacities were prognostic factors. (orig.)

  3. Measurement of lung fluid volumes and albumin exclusion in sheep

    International Nuclear Information System (INIS)

    Pou, N.A.; Roselli, R.J.; Parker, R.E.; Clanton, J.A.; Harris, T.R.

    1989-01-01

    A radioactive tracer technique was used to determine interstitial diethylenetriaminepentaacetic acid (DTPA) and albumin distribution volume in sheep lungs. 125 I- and/or 131 I-labeled albumin were injected intravenously and allowed to equilibrate for 24 h. 99m Tc-labeled DTPA and 51 Cr-labeled erythrocytes were injected and allowed to equilibrate (2 h and 15 min, respectively) before a lethal dose of thiamylal sodium. Two biopsies (1-3 g) were taken from each lung and the remaining tissue was homogenized for wet-to-dry lung weight and volume calculations. Estimates of distribution volumes from whole lung homogenized samples were statistically smaller than biopsy samples for extravascular water, interstitial 99m Tc-DTPA, and interstitial albumin. The mean fraction of the interstitium (Fe), which excludes albumin, was 0.68 +/- 0.04 for whole lung samples compared with 0.62 +/- 0.03 for biopsy samples. Hematocrit may explain the consistent difference. To make the Fe for biopsy samples match that for homogenized samples, a mean hematocrit, which was 82% of large vessel hematocrit, was required. Excluded volume fraction for exogenous sheep albumin was compared with that of exogenous human albumin in two sheep, and no difference was found at 24 h

  4. Debilitating lung disease among surface coal miners with no underground mining tenure.

    Science.gov (United States)

    Halldin, Cara N; Reed, William R; Joy, Gerald J; Colinet, Jay F; Rider, James P; Petsonk, Edward L; Abraham, Jerrold L; Wolfe, Anita L; Storey, Eileen; Laney, A Scott

    2015-01-01

    To characterize exposure histories and respiratory disease among surface coal miners identified with progressive massive fibrosis from a 2010 to 2011 pneumoconiosis survey. Job history, tenure, and radiograph interpretations were verified. Previous radiographs were reviewed when available. Telephone follow-up sought additional work and medical history information. Among eight miners who worked as drill operators or blasters for most of their tenure (median, 35.5 years), two reported poor dust control practices, working in visible dust clouds as recently as 2012. Chest radiographs progressed to progressive massive fibrosis in as few as 11 years. One miner's lung biopsy demonstrated fibrosis and interstitial accumulation of macrophages containing abundant silica, aluminum silicate, and titanium dust particles. Overexposure to respirable silica resulted in progressive massive fibrosis among current surface coal miners with no underground mining tenure. Inadequate dust control during drilling/blasting is likely an important etiologic factor.

  5. Positron emission tomography of the lung

    International Nuclear Information System (INIS)

    Wollmer, P.

    1984-01-01

    Positron emission tomography enables the distribution of positron emitting isotopes to be imaged in a transverse plane through the body and the regional concentration of the isotope to be measured quantitatively. This thesis reports some applications of positron emission tomography to studies of pulmonary pathophysiology. Measurements in lung phantoms showed that regional lung density could be measured from a transmission tomogram obtained with an external source of positron emitting isotope. The regional, fractional blood volume was measured after labelling the blood with carbon-11-monoxide. Regional extravascular lung density (lung tissue and interstitial water per unit thoracic volume) was obtained by subtracting fractional blood volume from lung density. Measurements in normal subjects revealed large regional variations in lung density and fractional blood volume in the supine posture. Extravascular lung density showed a more uniform distribution. The technique has been used to study patients with chronic interstitial pulmonary oedema, pulmonary sarcoidosis and fibrosis, pulmonary arterial hypertension and patients with intracardiac, left-to-right shunt. Tomographic measurements of pulmonary tissue concentration of radionuclides are difficult, since corrections for the blood content and the inflation of the lung must be applied. A simultaneous measurement of lung density and fractional blood volume allows such corrections to be made and the extravascular tracer concentration to be calculated. This has been applied to measurements of the tissue penetration of carbon-11-labelled erythromycin in patients with lobar pneumonia. (author)

  6. Pulmonary hypertension in chronic obstructive and interstitial lung diseases

    DEFF Research Database (Denmark)

    Andersen, Charlotte U; Mellemkjær, Søren; Nielsen-Kudsk, Jens Erik

    2013-01-01

    , and is considered one of the most frequent types of PH. However, the prevalence of PH among patients with COPD and ILD is not clear. The diagnosis of PH in chronic lung disease is often established by echocardiographic screening, but definitive diagnosis requires right heart catheterization, which...... is not systematically performed in clinical practice. Given the large number of patients with chronic lung disease, biomarkers to preclude or increase suspicion of PH are needed. NT-proBNP may be used as a rule-out test, but biomarkers with a high specificity for PH are still required. It is not known whether specific...... treatment with existent drugs effective in pulmonary arterial hypertension (PAH) is beneficial in lung disease related PH. Studies investigating existing PAH drugs in animal models of lung disease related PH have indicated a positive effect, and so have case reports and open label studies. However...

  7. Influence of chest background on pulmonary 99m Tc-DTPA clearance in interstitial lung disease

    International Nuclear Information System (INIS)

    Ishizaka, Akitoshi; Kanazawa, Minoru; Suzuki, Yukio; Hasegawa, Naoki; Kubo, Atsushi; Kawashiro, Takeo

    1992-01-01

    The authors examined the effect of chest extracellular 99m T c -diethylenetriamine pentaacetate (DTPA) as a background in the measurement of pulmonary 99m T c -DTPA clearance in patients with interstitial lung disease (ILD). Eight healthy nonsmokers (HN) and eight patients with ILD were studied. They monitored changes in gamma counts after the inhalation of 99m T c -DTPA aerosol by using a gamma camera placed over the anterior chest. The rate constant of pulmonary 99m T c -DTPA clearance (k; %/min) was assessed by calculating the slope of the decrease in the gamma counts. The chest background, estimated by 99m T c -DTPA intravenous injection, was subtracted from the original data to obtain the corrected DTPA clearance (k c ; %/min). In patients with ILD, k was significantly greater [2.19 ± 1.03 (SD) %/min; n = 8] compared with HN (0.86 ± 0.17%/min; n = 8; P c was also greater (2.80 ± 1.15%/min; n = 8; P c among all subjects (r = 0.987, P 99m T c -DTPA clearance. 16 refs., 2 figs., 2 tabs

  8. Bronchoalveolar lavage in patients with interstitial lung diseases: side effects and factors affecting fluid recovery.

    Science.gov (United States)

    Dhillon, D P; Haslam, P L; Townsend, P J; Primett, Z; Collins, J V; Turner-Warwick, M

    1986-05-01

    One hundred and seventy patients with interstitial lung diseases undergoing bronchoalveolar lavage (BAL), were contrasted with 51 patients undergoing fibreoptic bronchoscopy alone to define the factors which predispose to post-lavage side-effects. Transient post-bronchoscopy fall in the peak expired flow (PEF) greater than or equal to 20% occurred in both groups (24% and 23% respectively), and thus was probably related to the bronchoscopy procedure. Post-lavage pyrexia (greater than or equal to 1 degree C) occurred only in the patients undergoing BAL (26%), p less than 0.001. Only 4% with pyrexia required antibiotics, and only 2% with falls in PEF needed bronchodilator therapy. The only significant clinical association was more frequent pyrexia in patients on treatment with prednisolone, particularly in women (p less than 0.01). Pyrexia was also associated with higher lavage fluid introduction volumes (greater than 240 ml). Side effects did not relate to the percentages of lavage fluid recovered, although smokers had lower recoveries and, recoveries tended to be higher in sarcoidosis than cryptogenic fibrosing alveolitis. Serial lavages in 25 patients caused no significant increase in side effects.

  9. Pathology of radiation induced lung damage

    International Nuclear Information System (INIS)

    Kawabata, Yoshinori; Murata, Yoshihiko; Ogata, Hideo; Katagiri, Shiro; Sugita, Hironobu; Iwai, Kazuo; Sakurai, Isamu.

    1985-01-01

    We examined pathological findings of radiation induced lung damage. Twenty-three cases are chosen from our hospital autopsy cases for 9 years, which fulfil strict criteria of radiation lung damage. Lung damage could be classified into 3 groups : 1) interstitial pneumonia type (9 cases), 2) intermediate pneumonia type (8 cases), and 3) alveolar pneumonia type (6 cases), according to the degree of intra-luminal exudation. These classification is well correlated with clinical findings. Pathological alveolar pneumonia type corresponds to symptomatic, radiologic ground glass pneumonic shadow. And pathologic interstitial type corresponds to clinical asymptomatic, radiologic reticulo-nodular shadow. From the clinico-pathological view point these classification is reasonable one. Radiation affects many lung structures and showed characteristic feature of repair. Elastofibrosis of the alveolar wall is observed in every cases, obstructive bronchiolitis are observed in 5 cases, and obstructive bronchiolitis in 9 cases. They are remarkable additional findings. Thickening of the interlobular septum, broncho-vascular connective tissue, and pleural layer are observed in every cases together with vascular lesions. (author)

  10. Diffuse parenchymal lung disease

    Directory of Open Access Journals (Sweden)

    Sara Tomassetti

    2017-04-01

    Full Text Available Between September 2015 and August 2016 there were >1500 publications in the field of diffuse parenchymal lung diseases (DPLDs. For the Clinical Year in Review session at the European Respiratory Society Congress that was held in London, UK, in September 2016, we selected only five articles. This selection, made from the enormous number of published papers, does not include all the relevant studies that will significantly impact our knowledge in the field of DPLDs in the near future. This review article provides our personal view on the following topics: early diagnosis of idiopathic pulmonary fibrosis, current knowledge on the multidisciplinary team diagnosis of DPLDs and the diagnostic role of transbronchial cryobiopsy in this diagnostic setting, insights on the new entity of interstitial pneumonia with autoimmune features, and new therapeutic approaches for scleroderma-related interstitial lung disease.

  11. Acrolein induced both pulmonary inflammation and the death of lung epithelial cells.

    Science.gov (United States)

    Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Isobe, Ken-Ichi

    2014-09-02

    Acrolein, a compound found in cigarette smoke, is a major risk factor for respiratory diseases. Previous research determined that both acrolein and cigarette smoke produced reactive oxygen species (ROS). As many types of pulmonary injuries are associated with inflammation, this study sought to ascertain the extent to which exposure to acrolein advanced inflammatory state in the lungs. Our results showed that intranasal exposure of mice to acrolein increased CD11c(+)F4/80(high) macrophages in the lungs and increased ROS formation via induction of NF-κB signaling. Treatment with acrolein activated macrophages and led to their increased production of ROS and expression of several key pro-inflammatory cytokines. In in vitro studies, acrolein treatment of bone marrow-derived GM-CSF-dependent immature macrophages (GM-IMs), activated the cells and led to their increased production of ROS and expression of several key pro-inflammatory cytokines. Acrolein treatment of macrophages induced apoptosis of lung epithelial cells. Inclusion of an inhibitor of ROS formation markedly decreased acrolein-mediated macrophage activation and reduced the extent of epithelial cell death. These results indicate that acrolein can cause lung damage, in great part by mediating the increased release of pro-inflammatory cytokines/factors by macrophages. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Lung structure and function relation in systemic sclerosis: Application of lung densitometry

    Energy Technology Data Exchange (ETDEWEB)

    Ninaber, Maarten K., E-mail: m.k.ninaber@lumc.nl [Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Stolk, Jan; Smit, Jasper; Le Roy, Ernest J. [Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Kroft, Lucia J.M. [Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Els Bakker, M. [Division of Image Processing, Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Vries Bouwstra, Jeska K. de; Schouffoer, Anne A. [Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Staring, Marius; Stoel, Berend C. [Division of Image Processing, Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands)

    2015-05-15

    Highlights: • A quantitative CT parameter of lung parenchyma in systemic sclerosis is presented. • We examine the optimal percentage threshold for the percentile density. • The 85th percentile density threshold correlated significantly with lung function. • A lung structure–function relation is confirmed. • We report applicability of Perc85 in progression mapping of interstitial lung disease. - Abstract: Introduction: Interstitial lung disease occurs frequently in patients with systemic sclerosis (SSc). Quantitative computed tomography (CT) densitometry using the percentile density method may provide a sensitive assessment of lung structure for monitoring parenchymal damage. Therefore, we aimed to evaluate the optimal percentile density score in SSc by quantitative CT densitometry, against pulmonary function. Material and methods: We investigated 41 SSc patients by chest CT scan, spirometry and gas transfer tests. Lung volumes and the nth percentile density (between 1 and 99%) of the entire lungs were calculated from CT histograms. The nth percentile density is defined as the threshold value of densities expressed in Hounsfield units. A prerequisite for an optimal percentage was its correlation with baseline DLCO %predicted. Two patients showed distinct changes in lung function 2 years after baseline. We obtained CT scans from these patients and performed progression analysis. Results: Regression analysis for the relation between DLCO %predicted and the nth percentile density was optimal at 85% (Perc85). There was significant agreement between Perc85 and DLCO %predicted (R = −0.49, P = 0.001) and FVC %predicted (R = −0.64, P < 0.001). Two patients showed a marked change in Perc85 over a 2 year period, but the localization of change differed clearly. Conclusions: We identified Perc85 as optimal lung density parameter, which correlated significantly with DLCO and FVC, confirming a lung parenchymal structure–function relation in SSc. This provides

  13. Lung structure and function relation in systemic sclerosis: Application of lung densitometry

    International Nuclear Information System (INIS)

    Ninaber, Maarten K.; Stolk, Jan; Smit, Jasper; Le Roy, Ernest J.; Kroft, Lucia J.M.; Els Bakker, M.; Vries Bouwstra, Jeska K. de; Schouffoer, Anne A.; Staring, Marius; Stoel, Berend C.

    2015-01-01

    Highlights: • A quantitative CT parameter of lung parenchyma in systemic sclerosis is presented. • We examine the optimal percentage threshold for the percentile density. • The 85th percentile density threshold correlated significantly with lung function. • A lung structure–function relation is confirmed. • We report applicability of Perc85 in progression mapping of interstitial lung disease. - Abstract: Introduction: Interstitial lung disease occurs frequently in patients with systemic sclerosis (SSc). Quantitative computed tomography (CT) densitometry using the percentile density method may provide a sensitive assessment of lung structure for monitoring parenchymal damage. Therefore, we aimed to evaluate the optimal percentile density score in SSc by quantitative CT densitometry, against pulmonary function. Material and methods: We investigated 41 SSc patients by chest CT scan, spirometry and gas transfer tests. Lung volumes and the nth percentile density (between 1 and 99%) of the entire lungs were calculated from CT histograms. The nth percentile density is defined as the threshold value of densities expressed in Hounsfield units. A prerequisite for an optimal percentage was its correlation with baseline DLCO %predicted. Two patients showed distinct changes in lung function 2 years after baseline. We obtained CT scans from these patients and performed progression analysis. Results: Regression analysis for the relation between DLCO %predicted and the nth percentile density was optimal at 85% (Perc85). There was significant agreement between Perc85 and DLCO %predicted (R = −0.49, P = 0.001) and FVC %predicted (R = −0.64, P < 0.001). Two patients showed a marked change in Perc85 over a 2 year period, but the localization of change differed clearly. Conclusions: We identified Perc85 as optimal lung density parameter, which correlated significantly with DLCO and FVC, confirming a lung parenchymal structure–function relation in SSc. This provides

  14. Function of macrophage scavenger receptor 1 gene polymorphisms in chronic obstructive pulmonary disease with and without lung cancer in China.

    Science.gov (United States)

    Xie, Liang; Chen, Wei; Dong, Ran; He, Bin; Zhao, Kaishun; Zhang, Li; Zhou, Min; He, Ping

    2018-05-01

    The present study assessed the association between the variants of macrophage scavenger receptor (MSR)1 and chronic obstructive pulmonary disease (COPD), with or without lung cancer in China. COPD and lung cancer were previously regarded as two separate diseases. However, it has since been reported that there are close associations between COPD and lung cancer. Lung cancer may be an outcome of COPD. COPD may also coexist with lung cancer, and patients with COPD with lung cancer tend to have increased mortality. It is important to have a better understanding of the pathogenesis of COPD and the reason why it develops into lung cancer. MSR1 serves a crucial function in phagocytosis, which may be associated with the pathogenesis of COPD and lung cancer in patients with COPD. From 1 July 2015 to 20 February 2016, 100 patients with COPD and lung cancer, 100 patients with COPD without lung cancer and 100 healthy smokers were enrolled at the Shanghai Ruijin Hospital (Shanghai, China) for the genotyping of eight single-nucleotide polymorphisms (SNPs; ex3P36A_C>G, ex3S41Y_C>A, ex4V113A_T>C, ex4P174Y_G>T, ex6P275A_C>G, ex6R293×_C>T, ex10G369S_G>A and ex11H441R_A>G) via gene sequencing. The genotype frequencies of these SNPs did not significantly differ between patients with COPD with and without lung cancer, and the healthy controls. However, during DNA sequencing, the SNP rs13306550 (IVS4+3A>G) was identified in the splice donor site and was significantly associated with an increased risk of COPD compared with the healthy smokers (P=0.0053). The present study demonstrated that the variant rs13306550 was a risk factor for COPD susceptibility, but that did not influence lung cancer pathogenesis in patients with COPD. However, the mechanisms underlying the influence of rs13306550 on COPD development and progression remain to be elucidated and require further study.

  15. Role of Alveolar Macrophages in Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Vlahos, Ross; Bozinovski, Steven

    2014-01-01

    Alveolar macrophages (AMs) represent a unique leukocyte population that responds to airborne irritants and microbes. This distinct microenvironment coordinates the maturation of long-lived AMs, which originate from fetal blood monocytes and self-renew through mechanisms dependent on GM-CSF and CSF-1 signaling. Peripheral blood monocytes can also replenish lung macrophages; however, this appears to occur in a stimuli specific manner. In addition to mounting an appropriate immune response durin...

  16. Phagocytosis-induced 51Cr release from activated macrophages and blood mononuclears. Effect of colchicine and antioxidants

    International Nuclear Information System (INIS)

    McGee, M.P.; Hale, A.H.

    1981-01-01

    The chromium-release test was adapted to the measurement of the cellular injury induced when activated macrophages phagocytose particulates. Macrophages obtained from rabbit lungs undergoing BCG-induced chronic inflammation released more chromium when incubated in the presence of phagocytosable particles than when incubated under resting conditions. Blood mononuclear cells, 40-60% monocytes, procured from the same BCG-injected animals, were less susceptible to phagocytosis-induced injury than the macrophages obtained from the lungs. The amount of chromium released by the activated macrophages was proportional to the number of particles present during incubation. In the presence of catalase, the amounts of chromium released by phagocytosing and resting macrophages were similar; in the presence of superoxide dismutase and cytochrome c, the amount of chromium released by phagocytosing macrophages was 13-35% less than the amount of chromium released by macrophages incubated without the antioxidants. In addition, colchicine, an inhibitor of degranulation also exerted partial inhibition of the chromium release. These results suggest that oxygen radicals and lysosomal contents contribute to the cellular injury that results from phagocytosis

  17. Current Concept and Update of the Macrophage Plasticity Concept: Intracellular Mechanisms of Reprogramming and M3 Macrophage “Switch” Phenotype

    Science.gov (United States)

    Malyshev, Igor; Malyshev, Yuri

    2015-01-01

    Macrophages play a key role in immunity. In this review, we consider the traditional notion of macrophage plasticity, data that do not fit into existing concepts, and a hypothesis for existence of a new switch macrophage phenotype. Depending on the microenvironment, macrophages can reprogram their phenotype toward the proinflammatory M1 phenotype or toward the anti-inflammatory M2 phenotype. Macrophage reprogramming involves well-coordinated changes in activities of signalling and posttranslational mechanisms. Macrophage reprogramming is provided by JNK-, PI3K/Akt-, Notch-, JAK/STAT-, TGF-β-, TLR/NF-κB-, and hypoxia-dependent pathways. Posttranscriptional regulation is based on micro-mRNA. We have hypothesized that, in addition to the M1 and M2 phenotypes, an M3 switch phenotype exists. This switch phenotype responds to proinflammatory stimuli with reprogramming towards the anti-inflammatory M2 phenotype or, contrarily, it responds to anti-inflammatory stimuli with reprogramming towards the proinflammatory M1 phenotype. We have found signs of such a switch phenotype in lung diseases. Understanding the mechanisms of macrophage reprogramming will assist in the selection of new therapeutic targets for correction of impaired immunity. PMID:26366410

  18. Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.

    Science.gov (United States)

    Newton, Chad A; Batra, Kiran; Torrealba, Jose; Kozlitina, Julia; Glazer, Craig S; Aravena, Carlos; Meyer, Keith; Raghu, Ganesh; Collard, Harold R; Garcia, Christine Kim

    2016-12-01

    Heterozygous mutations in four telomere-related genes have been linked to pulmonary fibrosis, but little is known about similarities or differences of affected individuals.115 patients with mutations in telomerase reverse transcriptase (TERT) (n=75), telomerase RNA component (TERC) (n=7), regulator of telomere elongation helicase 1 (RTEL1) (n=14) and poly(A)-specific ribonuclease (PARN) (n=19) were identified and clinical data were analysed.Approximately one-half (46%) had a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF); others had unclassifiable lung fibrosis (20%), chronic hypersensitivity pneumonitis (12%), pleuroparenchymal fibroelastosis (10%), interstitial pneumonia with autoimmune features (7%), an idiopathic interstitial pneumonia (4%) and connective tissue disease-related interstitial fibrosis (3%). Discordant interstitial lung disease diagnoses were found in affected individuals from 80% of families. Patients with TERC mutations were diagnosed at an earlier age than those with PARN mutations (51±11 years versus 64±8 years; p=0.03) and had a higher incidence of haematological comorbidities. The mean rate of forced vital capacity decline was 300 mL·year -1 and the median time to death or transplant was 2.87 years. There was no significant difference in time to death or transplant for patients across gene mutation groups or for patients with a diagnosis of IPF versus a non-IPF diagnosis.Genetic mutations in telomere related genes lead to a variety of interstitial lung disease (ILD) diagnoses that are universally progressive. Copyright ©ERS 2016.

  19. Alternative activation of macrophages and pulmonary fibrosis are modulated by scavenger receptor, macrophage receptor with collagenous structure.

    Science.gov (United States)

    Murthy, Shubha; Larson-Casey, Jennifer L; Ryan, Alan J; He, Chao; Kobzik, Lester; Carter, A Brent

    2015-08-01

    Alternative activation of alveolar macrophages is linked to fibrosis following exposure to asbestos. The scavenger receptor, macrophage receptor with collagenous structure (MARCO), provides innate immune defense against inhaled particles and pathogens; however, a receptor for asbestos has not been identified. We hypothesized that MARCO acts as an initial signaling receptor for asbestos, polarizes macrophages to a profibrotic M2 phenotype, and is required for the development of asbestos-induced fibrosis. Compared with normal subjects, alveolar macrophages isolated from patients with asbestosis express higher amounts of MARCO and have greater profibrotic polarization. Arginase 1 (40-fold) and IL-10 (265-fold) were higher in patients. In vivo, the genetic deletion of MARCO attenuated the profibrotic environment and pulmonary fibrosis in mice exposed to chrysotile. Moreover, alveolar macrophages from MARCO(-/-) mice polarize to an M1 phenotype, whereas wild-type mice have higher Ym1 (>3.0-fold) and nearly 7-fold more active TGF-β1 in bronchoalveolar lavage (BAL) fluid (BALF). Arg(432) and Arg(434) in domain V of MARCO are required for the polarization of macrophages to a profibrotic phenotype as mutation of these residues reduced FIZZ1 expression (17-fold) compared with cells expressing MARCO. These observations demonstrate that a macrophage membrane protein regulates the fibrotic response to lung injury and suggest a novel target for therapeutic intervention. © FASEB.

  20. Nicotine Impairs Macrophage Control of Mycobacterium tuberculosis.

    Science.gov (United States)

    Bai, Xiyuan; Stitzel, Jerry A; Bai, An; Zambrano, Cristian A; Phillips, Matthew; Marrack, Philippa; Chan, Edward D

    2017-09-01

    Pure nicotine impairs macrophage killing of Mycobacterium tuberculosis (MTB), but it is not known whether the nicotine component in cigarette smoke (CS) plays a role. Moreover, the mechanisms by which nicotine impairs macrophage immunity against MTB have not been explored. To neutralize the effects of nicotine in CS extract, we used a competitive inhibitor to the nicotinic acetylcholine receptor (nAChR)-mecamylamine-as well as macrophages derived from mice with genetic disruption of specific subunits of nAChR. We also determined whether nicotine impaired macrophage autophagy and whether nicotine-exposed T regulatory cells (Tregs) could subvert macrophage anti-MTB immunity. Mecamylamine reduced the CS extract increase in MTB burden by 43%. CS extract increase in MTB was also significantly attenuated in macrophages from mice with genetic disruption of either the α7, β2, or β4 subunit of nAChR. Nicotine inhibited autophagosome formation in MTB-infected THP-1 cells and primary murine alveolar macrophages, as well as increased the intracellular MTB burden. Nicotine increased migration of THP-1 cells, consistent with the increased number of macrophages found in the lungs of smokers. Nicotine induced Tregs to produce transforming growth factor-β. Naive mouse macrophages co-cultured with nicotine-exposed Tregs had significantly greater numbers of viable MTB recovered with increased IL-10 production and urea production, but no difference in secreted nitric oxide as compared with macrophages cocultured with unexposed Tregs. We conclude that nicotine in CS plays an important role in subverting macrophage control of MTB infection.

  1. Pulmonary Hypertension in Parenchymal Lung Disease

    Science.gov (United States)

    Tsangaris, Iraklis; Tsaknis, Georgios; Anthi, Anastasia; Orfanos, Stylianos E.

    2012-01-01

    Idiopathic pulmonary arterial hypertension (IPAH) has been extensively investigated, although it represents a less common form of the pulmonary hypertension (PH) family, as shown by international registries. Interestingly, in types of PH that are encountered in parenchymal lung diseases such as interstitial lung diseases (ILDs), chronic obstructive pulmonary disease (COPD), and many other diffuse parenchymal lung diseases, some of which are very common, the available data is limited. In this paper, we try to browse in the latest available data regarding the occurrence, pathogenesis, and treatment of PH in chronic parenchymal lung diseases. PMID:23094153

  2. The evidence of benefits of exercise training in interstitial lung disease: a randomised controlled trial.

    Science.gov (United States)

    Dowman, Leona M; McDonald, Christine F; Hill, Catherine J; Lee, Annemarie L; Barker, Kathryn; Boote, Claire; Glaspole, Ian; Goh, Nicole S L; Southcott, Anne M; Burge, Angela T; Gillies, Rebecca; Martin, Alicia; Holland, Anne E

    2017-07-01

    Uncertainty exists regarding the clinical relevance of exercise training across the range of interstitial lung diseases (ILDs). To establish the impact of exercise training in patients with ILDs of differing aetiology and severity. 142 participants with ILD (61 idiopathic pulmonary fibrosis (IPF), 22 asbestosis, 23 connective tissue disease-related ILD (CTD-ILD) and 36 with other aetiologies) were randomised to either 8 weeks of supervised exercise training or usual care. Six-minute walk distance (6MWD), Chronic Respiratory Disease Questionnaire (CRDQ), St George Respiratory Questionnaire IPF-specific version (SGRQ-I) and modified Medical Research Council dyspnoea score were measured at baseline, 9 weeks and 6 months. Exercise training significantly increased 6MWD (25 m, 95% CI 2 to 47 m) and health-related quality of life (CRDQ and SGRQ-I) in people with ILD. Larger improvements in 6MWD, CRDQ, SGRQ-I and dyspnoea occurred in asbestosis and IPF compared with CTD-ILD, but with few significant differences between subgroups. Benefits declined at 6 months except in CTD-ILD. Lower baseline 6MWD and worse baseline symptoms were associated with greater benefit in 6MWD and symptoms following training. Greater gains were seen in those whose exercise prescription was successfully progressed according to the protocol. At 6 months, sustained improvements in 6MWD and symptoms were associated with better baseline lung function and less pulmonary hypertension. Exercise training is effective in patients across the range of ILDs, with clinically meaningful benefits in asbestosis and IPF. Successful exercise progression maximises improvements and sustained treatment effects favour those with milder disease. Results, ACTRN12611000416998. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Arterial Carboxyhemoglobin Measurement Is Useful for Evaluating Pulmonary Inflammation in Subjects with Interstitial Lung Disease.

    Science.gov (United States)

    Hara, Yu; Shinkai, Masaharu; Kanoh, Soichiro; Fujikura, Yuji; K Rubin, Bruce; Kawana, Akihiko; Kaneko, Takeshi

    2017-01-01

    Objective The arterial concentration of carboxyhemoglobin (CO-Hb) in subjects with inflammatory pulmonary disease is higher than that in healthy individuals. We retrospectively analyzed the relationship between the CO-Hb concentration and established markers of disease severity in subjects with interstitial lung disease (ILD). Methods The CO-Hb concentration was measured in subjects with newly diagnosed or untreated ILD and the relationships between the CO-Hb concentration and the serum biomarker levels, lung function, high-resolution CT (HRCT) findings, and the uptake in gallium-67 ( 67 Ga) scintigraphy were evaluated. Results Eighty-one non-smoking subjects were studied (mean age, 67 years). Among these subjects, (A) 17 had stable idiopathic pulmonary fibrosis (IPF), (B) 9 had an acute exacerbation of IPF, (C) 44 had stable non-IPF, and (D) 11 had an exacerbation of non-IPF. The CO-Hb concentrations of these subjects were (A) 1.5±0.5%, (B) 2.1±0.5%, (C) 1.2±0.4%, and (D) 1.7±0.5%. The CO-Hb concentration was positively correlated with the serum levels of surfactant protein (SP)-A (r=0.38), SP-D (r=0.39), and the inflammation index (calculated from HRCT; r=0.57) and was negatively correlated with the partial pressure of oxygen in the arterial blood (r=-0.56) and the predicted diffusion capacity of carbon monoxide (r=-0.61). The CO-Hb concentrations in subjects with a negative heart sign on 67 Ga scintigraphy were higher than those in subjects without a negative heart sign (1.4±0.5% vs. 1.1±0.3%, p=0.018). Conclusion The CO-Hb levels of subjects with ILD were increased, particularly during an exacerbation, and were correlated with the parameters that reflect pulmonary inflammation.

  4. The Role of Inflammasome in Inflammatory Macrophage in Mycobacterium Avium Complex-lung Disease and Mycobacterium Abscessus-lung Disease

    Science.gov (United States)

    2014-06-27

    To Investigate the Inflammasome Response of Inflammatory and Resting Macrophage; To Compare the Difference of Inflammasome Response of Inflammatory Macrophage; To Study the Diagnostic Aid From Immunological Markers in Inflammasome Response

  5. Peptide secreted by human alveolar macrophages releases neutrophil granule contents

    International Nuclear Information System (INIS)

    MacArthur, C.K.; Miller, E.J.; Cohen, A.B.

    1987-01-01

    A monoclonal antibody was developed against an 8000-kDa enzyme-releasing peptide (ERP) released from human alveolar macrophages. ERP was isolated on an immunoaffinity column containing the antibody bound to staphylococcal protein A-Sepharose, and by autoradiography. Release of ERP from the macrophages is not changed by plastic adherence, phagocytosis, calcium ionophore, or phorbol esters. The peptide was not antigenically similar to interferon-γ, tumor necrosis factor, or interleukin lα or 1β. The release of constituents from azurophilic and specific granules was the main identified biologic function of ERP. ERP was a more effective secretagogue in the untreated neutrophils and f-met-leu-phe was more effective in the cytochalasin B-treated neutrophils. Absorption of ERP from macrophage-conditioned medium removed a small amount of the chemotactic activity; however, the immunopurified peptide was not chemotactic or chemokinetic for neutrophils, and at high concentrations, it suppressed base line chemokinesis. Treatment of washed macrophages with trypsin released active ERP of approximately the same m.w. of spontaneously secreted ERP. These studies showed that human alveolar macrophages release a peptide which is a secretagogue for human neutrophils under conditions which may be encountered in the lungs during certain disease states. Proteolytic enzymes which are free in the lungs may release the peptide and lead to the secretion of neutrophil enzymes

  6. Dysregulation of Macrophage Activation Profiles by Engineered Nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Kodali, Vamsi; Littke, Matthew H.; Tilton, Susan C.; Teeguarden, Justin G.; Shi, Liang; Frevert, Charles W.; Wang, Wei; Pounds, Joel G.; Thrall, Brian D.

    2013-08-27

    Although the potential human health impacts from exposure to engineered nanoparticles (ENPs) are uncertain, past epidemiological studies have established correlations between exposure to ambient air pollution particulates and the incidence of pneumonia and lung infections. Using amorphous silica and superparamagnetic iron oxide (SPIO) as model high production volume ENPs, we examined how macrophage activation by bacterial lipopolysaccharide (LPS) or the lung pathogen Streptococcus pneumoniae is altered by ENP pretreatment. Neither silica nor SPIO treatment elicited direct cytotoxic or pro-inflammatory effects in bone marrow-derived macrophages. However, pretreatment of macrophages with SPIO caused extensive reprogramming of nearly 500 genes regulated in response to LPS challenge, hallmarked by exaggerated activation of oxidative stress response pathways and suppressed activation of both pro- and anti-inflammatory pathways. Silica pretreatment altered regulation of only 67 genes, but there was strong correlation with gene sets affected by SPIO. Macrophages exposed to SPIO displayed a phenotype suggesting an impaired ability to transition from an M1 to M2-like activation state, characterized by suppressed IL-10 induction, enhanced TNFα production, and diminished phagocytic activity toward S. pneumoniae. Studies in macrophages deficient in scavenger receptor A (SR-A) showed SR-A participates in cell uptake of both the ENPs and S. pneumonia and co-regulates the anti-inflammatory IL-10 pathway. Thus, mechanisms for dysregulation of innate immunity exist by virtue that common receptor recognition pathways are used by some ENPs and pathogenic bacteria, although the extent of transcriptional reprogramming of macrophage function depends on the physicochemical properties of the ENP after internalization. Our results also illustrate that biological effects of ENPs may be indirectly manifested only after challenging normal cell function. Finally, nanotoxicology screening

  7. Diagnostic accuracy of computed tomography and histopathology in the diagnosis of usual interstitial pneumonia

    International Nuclear Information System (INIS)

    Aaloekken, Trond Mogens; Mynarek, Georg; Kolbenstvedt, Alf; Naalsund, Anne; Elnaes Berstad, Audun; Solberg, Steinar; Stroem, Erik H.; Scott, Helge; Soeyseth, Vidar

    2012-01-01

    Background: The relative clinical benefit of histopathology and computed tomography (CT) in patients with idiopathic interstitial pneumonia (IIP) is under debate. Purpose: To analyze thin-section CT features and histopathologic findings in patients with usual interstitial pneumonia (UIP) in the clinical context of idiopathic pulmonary fibrosis (IPF), and to evaluate and compare diagnostic accuracy of the two methods among patients with an appropriate spectrum of IIP. Material and Methods: The study included 91 patients (49 men; mean age 53.2 years; median follow-up 7.2 years) with clinically suspected interstitial lung disease. All underwent surgical lung biopsy and thin-section CT. Two independent readers retrospectively assessed the CT images for the extent and pattern of abnormality and made a first-choice diagnosis. Two pathologists retrospectively assessed the histopathologic slides. In 64 patients with IIP, a retrospective composite reference standard identified 41 patients with UIP. CT characteristics of UIP and IIPs other than UIP were compared with univariate and multivariate analyses. Results: There was good agreement between the readers for the correct first-choice CT diagnosis of UIP (κ = 0.79). The sensitivity, specificity, and positive predictive value of the CT diagnosis of UIP were 63%, 96%, and 96%, respectively. The sensitivity, specificity, and positive predictive value of the histological diagnosis of UIP were 73%, 74%, and 83%, respectively. The CT feature that best differentiated UIP from IIPs other than UIP was the extent of reticular pattern (odds ratio, 5.1). Conclusion: Surgical lung biopsy may not be warranted in patients with thin-section CT diagnosis of UIP

  8. Diagnostic accuracy of computed tomography and histopathology in the diagnosis of usual interstitial pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Aaloekken, Trond Mogens; Mynarek, Georg; Kolbenstvedt, Alf (Dept. of Radiology, Oslo Univ. Hospital Rikshospitalet, Oslo (Norway)), Email: trond.mogens.aalokken@rikshospitalet.no; Naalsund, Anne (Dept. of Pulmonology, Oslo Univ. Hospital Rikshospitalet (Norway)); Elnaes Berstad, Audun (Dept. of Radiology, Oslo Univ. Hospital Rikshospitalet, Oslo (Norway); Univ. of Oslo (Norway)); Solberg, Steinar (Dept. of Thoracic Surgery, Oslo Univ. Hospital Rikshospitalet (Norway)); Stroem, Erik H.; Scott, Helge (Dept. of Pathology, Oslo Univ. Hospital Rikshospitalet (Norway)); Soeyseth, Vidar (Univ. of Oslo (Norway); Depts. of Pulmonology, Akershus Univ. Hospital, Loerenskog (Norway))

    2012-04-15

    Background: The relative clinical benefit of histopathology and computed tomography (CT) in patients with idiopathic interstitial pneumonia (IIP) is under debate. Purpose: To analyze thin-section CT features and histopathologic findings in patients with usual interstitial pneumonia (UIP) in the clinical context of idiopathic pulmonary fibrosis (IPF), and to evaluate and compare diagnostic accuracy of the two methods among patients with an appropriate spectrum of IIP. Material and Methods: The study included 91 patients (49 men; mean age 53.2 years; median follow-up 7.2 years) with clinically suspected interstitial lung disease. All underwent surgical lung biopsy and thin-section CT. Two independent readers retrospectively assessed the CT images for the extent and pattern of abnormality and made a first-choice diagnosis. Two pathologists retrospectively assessed the histopathologic slides. In 64 patients with IIP, a retrospective composite reference standard identified 41 patients with UIP. CT characteristics of UIP and IIPs other than UIP were compared with univariate and multivariate analyses. Results: There was good agreement between the readers for the correct first-choice CT diagnosis of UIP (kappa = 0.79). The sensitivity, specificity, and positive predictive value of the CT diagnosis of UIP were 63%, 96%, and 96%, respectively. The sensitivity, specificity, and positive predictive value of the histological diagnosis of UIP were 73%, 74%, and 83%, respectively. The CT feature that best differentiated UIP from IIPs other than UIP was the extent of reticular pattern (odds ratio, 5.1). Conclusion: Surgical lung biopsy may not be warranted in patients with thin-section CT diagnosis of UIP

  9. Pulmonary hypertension in interstitial lung disease: Limitations of echocardiography compared to cardiac catheterization.

    Science.gov (United States)

    Keir, Gregory J; Wort, S John; Kokosi, Maria; George, Peter M; Walsh, Simon L F; Jacob, Joseph; Price, Laura; Bax, Simon; Renzoni, Elisabetta A; Maher, Toby M; MacDonald, Peter; Hansell, David M; Wells, Athol U

    2018-01-12

    In interstitial lung disease (ILD), pulmonary hypertension (PH) is a major adverse prognostic determinant. Transthoracic echocardiography (TTE) is the most widely used tool when screening for PH, although discordance between TTE and right heart catheter (RHC) measured pulmonary haemodynamics is increasingly recognized. We evaluated the predictive utility of the updated European Society of Cardiology/European Respiratory Society (ESC/ERS) TTE screening recommendations against RHC testing in a large, well-characterized ILD cohort. Two hundred and sixty-five consecutive patients with ILD and suspected PH underwent comprehensive assessment, including RHC, between 2006 and 2012. ESC/ERS recommended tricuspid regurgitation (TR) velocity thresholds for assigning high (>3.4 m/s), intermediate (2.9-3.4 m/s) and low (3.4 m/s, and excluded PH in 60% of ILD subjects with a TR velocity <2.8 m/s. Thus, the ESC/ERS guidelines misclassified 40% of subjects as 'low probability' of PH, when PH was confirmed on subsequent RHC. Evaluating alternative TR velocity thresholds for assigning a low probability of PH did not significantly improve the ability of TR velocity to exclude a diagnosis of PH. In patients with ILD and suspected PH, currently recommended ESC/ERS TR velocity screening thresholds were associated with a high positive predictive value (86%) for confirming PH, but were of limited value in excluding PH, with 40% of patients misclassified as low probability when PH was confirmed at subsequent RHC. © 2018 Asian Pacific Society of Respirology.

  10. Biopsia en enfermedad intersticial pulmonar Lung biopsy for the diagnosis of interstitial lung disease

    Directory of Open Access Journals (Sweden)

    Silvia Quadrelli

    2007-12-01

    Full Text Available El objetivo del presente estudio fue determinar el rédito diagnóstico y los factores asociados a mayor morbimortalidad en la biopsia quirúrgica de pulmón en pacientes con enfermedad intersticial difusa. Se analizaron en forma retrospectiva los registros clínicos de 71 pacientes. Se registraron complicaciones en 16 pacientes (22.5%. La mortalidad operatoria fue 11.2%. Los pacientes en quienes la biopsia se realizó por videotoracoscopia (n = 52 y por toracotomía (n = 17 tuvieron la misma duración de estadía en terapia intensiva y de estadía hospitalaria. La tasa de complicaciones (22.2% vs. 21.0%, p = 1.0000 y la mortalidad (9.2 vs. 15.7%, p = 0.2738 no fueron diferentes. Ocho pacientes murieron dentro de los 30 días. La prevalencia de inmunosupresión (4/8 vs. 9/63, p = 0.0325 fue significativamente superior en el grupo de pacientes fallecidos. Estos pacientes tuvieron valores preoperatorios más elevados de urea (50 ± 20.1 mg/dl vs. 31.2 ± 10.3 mg/ dl, p = 0.0013 y menores valores de saturación de O2: 82.7 ± 14.8% vs. 92.8 ± 3.4%, p = 0.0009. En los 11 pacientes con iniciación aguda la mortalidad fue significativamente más elevada (36.3% vs. 7.1%, p = 0.0223. La biopsia aportó un diagnóstico específico en 100% de los pacientes y cambió la estrategia terapéutica en 66.7%. En conclusión, la biopsia de pulmón por vía toracoscópica es un procedimiento útil y seguro en los pacientes con enfermedad intersticial difusa del pulmón. Sin embargo, en el grupo de pacientes inmunocomprometidos, con cuadros de presentación aguda y con insuficiencia respiratoria preoperatoria, la mortalidad es elevada y deben balancearse muy críticamente los riesgos contra los beneficios en ese grupo de enfermos.The objective of this study was to determine the morbidity, mortality and diagnostic yield of video assisted thoracoscopy (VATS and thoracotomy lung biopsy in interstitial lung disease (ILD. Clinical records of 71 patients were

  11. The effect of CSF-1 administration on lung maturation in a mouse model of neonatal hyperoxia exposure.

    Science.gov (United States)

    Jones, Christina V; Alikhan, Maliha A; O'Reilly, Megan; Sozo, Foula; Williams, Timothy M; Harding, Richard; Jenkin, Graham; Ricardo, Sharon D

    2014-09-06

    Lung immaturity due to preterm birth is a significant complication affecting neonatal health. Despite the detrimental effects of supplemental oxygen on alveolar formation, it remains an important treatment for infants with respiratory distress. Macrophages are traditionally associated with the propagation of inflammatory insults, however increased appreciation of their diversity has revealed essential functions in development and regeneration. Macrophage regulatory cytokine Colony-Stimulating Factor-1 (CSF-1) was investigated in a model of neonatal hyperoxia exposure, with the aim of promoting macrophages associated with alveologenesis to protect/rescue lung development and function. Neonatal mice were exposed to normoxia (21% oxygen) or hyperoxia (Hyp; 65% oxygen); and administered CSF-1 (0.5 μg/g, daily × 5) or vehicle (PBS) in two treatment regimes; 1) after hyperoxia from postnatal day (P)7-11, or 2) concurrently with five days of hyperoxia from P1-5. Lung structure, function and macrophages were assessed using alveolar morphometry, barometric whole-body plethysmography and flow cytometry. Seven days of hyperoxia resulted in an 18% decrease in body weight and perturbation of lung structure and function. In regime 1, growth restriction persisted in the Hyp + PBS and Hyp + CSF-1 groups, although perturbations in respiratory function were resolved by P35. CSF-1 increased CSF-1R+/F4/80+ macrophage number by 34% at P11 compared to Hyp + PBS, but was not associated with growth or lung structural rescue. In regime 2, five days of hyperoxia did not cause initial growth restriction in the Hyp + PBS and Hyp + CSF-1 groups, although body weight was decreased at P35 with CSF-1. CSF-1 was not associated with increased macrophages, or with functional perturbation in the adult. Overall, CSF-1 did not rescue the growth and lung defects associated with hyperoxia in this model; however, an increase in CSF-1R+ macrophages was not associated with an

  12. The value of the abnormalities of bronchovascular bundles in the diagnosis of diffused lung diseases

    International Nuclear Information System (INIS)

    Li Tieyi; Ji Jingling

    1997-01-01

    To evaluate the abnormalities of bronchovascular bundles in the differential diagnosis of the diffuse lung disease, seventy-two patients with diffuse lung diseases were evaluated, 15 of 72 patients were pathologically proven and the others clinically proven. Of these 72 patients, there were 33 patients with diffuse pulmonary interstitial disease, 5 patients with pulmonary parenchymal disease, 14 patients with bronchial disease, and 20 patients with disseminated disease. All patients had conventional CT scan of the chest, some also had HRCT scan. All CT images were jointly reviewed by two radiologists. The features of the abnormalities of bronchovascular bundles included: (1) Thinning of bronchovascular bundles, predominantly seen in diffuse interstitial disease of lung and chronic bronchitis; (2) thickening of bronchovascular bundles, predominantly seen in interstitial diseases and disseminated lung diseases such as sarcoidosis and lymphangitis carcinomatosis with beaded appearance of bronchovascular bundles; (3) Increased visibility of bronchovascular bundles, predominantly seen in bronchiolitis and disseminated lung diseases. CT features of the abnormalities of bronchovascular bundles are present in 80% of diffuse lung diseases. The features are not specific, but the beaded bronchovascular bundles are always seen in sarcoidosis and lymphangitis carcinomatosis. In making a distinction between idiopathic pulmonary fibrosis and chronic bronchitis complicated with interstitial fibrosis, the position of diaphragm is of value in differential diagnosis, normal or elevated diaphragm is usually seen in the former, while low and flattened diaphragm in the latter. Change of the appearance of bronchovascular bundles from normality to abnormality reflects the process of development of the lung disease

  13. Risk of acute exacerbation of interstitial pneumonia after pulmonary resection for lung cancer in patients with idiopathic pulmonary fibrosis based on preoperative high-resolution computed tomography

    International Nuclear Information System (INIS)

    Suzuki, Hidemi; Sekine, Yasuo; Yoshida, Shigetoshi

    2011-01-01

    In patients with lung cancer accompanied by idiopathic pulmonary fibrosis (IPF), acute exacerbation of the IPF often occurs after pulmonary resection; however, few studies have been done to identify its preexisting risk factors. We analyzed the high-resolution computed tomography (HRCT) findings of IPF to identify the radiological characteristics of IPF susceptible to acute exacerbation after lung cancer surgery. We reviewed retrospectively 28 lung cancer patients with IPF who underwent pulmonary resection. Clinical data, respiratory function, HRCT findings, and historical features were compared between the acute exacerbation (n=9) and nonexacerbation (n=19) groups. The classification of radiological findings of IPF on HRCT was done using a scoring system of seven factors related to the interstitial shadow, including fibrosis, ground-glass opacity, and low-attenuation area. There were no significant differences in clinical background, respiratory function, composite physiologic index, or pathological features between the groups; however, the degree of fibrosis on preoperative HRCT was significantly higher in the exacerbation group (P<0.003). The fibrosis score was higher on the opposite side to the lung cancer in the exacerbation group (P<0.05). Although it is difficult to predict postoperative acute IPF exacerbation, the degree and laterality of co-existing fibrosis seem to be predictors. (author)

  14. Role of CC chemokines (macrophage inflammatory protein-1 beta, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Bless, N M; Huber-Lang, M; Guo, R F

    2000-01-01

    The role of the CC chemokines, macrophage inflammatory protein-1 beta (MIP-1 beta), monocyte chemotactic peptide-1 (MCP-1), and RANTES, in acute lung inflammatory injury induced by intrapulmonary deposition of IgG immune complexes injury in rats was determined. Rat MIP-1 beta, MCP-1, and RANTES...... were cloned, the proteins were expressed, and neutralizing Abs were developed. mRNA and protein expression for MIP-1 beta and MCP-1 were up-regulated during the inflammatory response, while mRNA and protein expression for RANTES were constitutive and unchanged during the inflammatory response....... Treatment of rats with anti-MIP-1 beta Ab significantly decreased vascular permeability by 37% (p = 0.012), reduced neutrophil recruitment into lung by 65% (p = 0.047), and suppressed levels of TNF-alpha in bronchoalveolar lavage fluids by 61% (p = 0.008). Treatment of rats with anti-rat MCP-1 or anti...

  15. Pulmonary epithelial permeability in normal subjects and patients with idiopathic interstitial pneumonia

    International Nuclear Information System (INIS)

    Anazawa, Yoshiki; Isawa, Toyoharu; Teshima, Takeo; Miki, Makoto; Motomiya, Masakichi

    1991-01-01

    99m Tc-DTPA is a low molecular weight substance, which is believed to pass through the pulmonary epithelium when it is inhaled as an aerosol. We performed 99m Tc-DTPA inhalation studies in 10 nonsmoking normal subjects and 10 patients with biopsy proven idiopathic interstitial pneumonia prior to therapy. 99m Tc-DTPA aerosol was inhaled for 3 min with the subject in the supine position and radioactivity was measured anteriorly with a gamma camera and recorded on computer. Measurements were performed for 3 min with the subject inhaling aerosol and for the subsequent 30 min with the subject in the same position. Time activity curves from the five regions of interest (ROIs) including the entire left lung, the entire right lung, and the upper, middle and lower third of the right lung were separately fitted to a single exponential function for the initial 7 min following cessation of inhalation, and the respective clearance half life (t1/2) in min was calculated. Lung function data, arterial blood gas tensions and blood chemistry were also obtained for comparison with the t1/2 values. The t1/2 values were significantly smaller in all ROIs in patients with idiopathic interstitial pneumonia than in normal subjects, indicating an increased pulmonary epithelial permeability in these patients. There was no relationship between t1/2 and %DL co , %DL co /V A , PaO 2 , or LDH. Although the true pathophysiologic significance of t1/2 measured using 99m Tc-DTPA aerosol is still not known, we consider that this measurement may be an important indicator of nonrespiratory lung function, in particular the degree of alveolar epithelial damage. (author)

  16. OSCAR Is a Receptor for Surfactant Protein D That Activates TNF-α Release from Human CCR2+ Inflammatory Monocytes

    DEFF Research Database (Denmark)

    Barrow, Alexander D; Palarasah, Yaseelan; Bugatti, Mattia

    2015-01-01

    of recombinant SP-D and captured native SP-D from human bronchoalveolar lavage. OSCAR localized in an intracellular compartment of alveolar macrophages together with SP-D. Moreover, we found OSCAR on the surface of interstitial lung and blood CCR2(+) inflammatory monocytes, which secreted TNF-α when exposed...

  17. Tomography patterns of lung disease in systemic sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Bastos, Andrea de Lima; Correa, Ricardo de Amorim; Ferreira, Gilda Aparecida, E-mail: andrealb@ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina

    2016-09-15

    Currently, lung impairment is the leading factor responsible for the morbidity and mortality associated with systemic sclerosis. Therefore, the recognition of the various tomography patterns becomes decisive in the clinical management of these patients. In high-resolution computed tomography studies, the most common pattern is that of nonspecific interstitial pneumonia. However, there are other forms of lung involvement that must also be recognized. The aim of this study was to review the literature on the main changes resulting from pulmonary involvement in systemic sclerosis and the corresponding radiological findings, considering the current classification of interstitial diseases. We searched the Medline (PubMed), Lilacs, and SciELO databases in order to select articles related to pulmonary changes in systemic sclerosis and published in English between 2000 and 2015. The pulmonary changes seen on computed tomography in systemic sclerosis are varied and are divided into three main categories: interstitial, alveolar, and vascular. Interstitial changes constitute the most common type of pulmonary involvement in systemic sclerosis. However, alveolar and vascular manifestations must also be recognized and considered in the presence of atypical clinical presentations and inadequate treatment responses. (author)

  18. Tomography patterns of lung disease in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Andréa de Lima Bastos

    Full Text Available Abstract Currently, lung impairment is the leading factor responsible for the morbidity and mortality associated with systemic sclerosis. Therefore, the recognition of the various tomography patterns becomes decisive in the clinical management of these patients. In high-resolution computed tomography studies, the most common pattern is that of nonspecific interstitial pneumonia. However, there are other forms of lung involvement that must also be recognized. The aim of this study was to review the literature on the main changes resulting from pulmonary involvement in systemic sclerosis and the corresponding radiological findings, considering the current classification of interstitial diseases. We searched the Medline (PubMed, Lilacs, and SciELO databases in order to select articles related to pulmonary changes in systemic sclerosis and published in English between 2000 and 2015. The pulmonary changes seen on computed tomography in systemic sclerosis are varied and are divided into three main categories: interstitial, alveolar, and vascular. Interstitial changes constitute the most common type of pulmonary involvement in systemic sclerosis. However, alveolar and vascular manifestations must also be recognized and considered in the presence of atypical clinical presentations and inadequate treatment responses.

  19. Tomography patterns of lung disease in systemic sclerosis

    International Nuclear Information System (INIS)

    Bastos, Andrea de Lima; Correa, Ricardo de Amorim; Ferreira, Gilda Aparecida

    2016-01-01

    Currently, lung impairment is the leading factor responsible for the morbidity and mortality associated with systemic sclerosis. Therefore, the recognition of the various tomography patterns becomes decisive in the clinical management of these patients. In high-resolution computed tomography studies, the most common pattern is that of nonspecific interstitial pneumonia. However, there are other forms of lung involvement that must also be recognized. The aim of this study was to review the literature on the main changes resulting from pulmonary involvement in systemic sclerosis and the corresponding radiological findings, considering the current classification of interstitial diseases. We searched the Medline (PubMed), Lilacs, and SciELO databases in order to select articles related to pulmonary changes in systemic sclerosis and published in English between 2000 and 2015. The pulmonary changes seen on computed tomography in systemic sclerosis are varied and are divided into three main categories: interstitial, alveolar, and vascular. Interstitial changes constitute the most common type of pulmonary involvement in systemic sclerosis. However, alveolar and vascular manifestations must also be recognized and considered in the presence of atypical clinical presentations and inadequate treatment responses. (author)

  20. The unresolved issue of oxygen therapy in lung fibrosis: Some clues from a Spanish cohort

    Directory of Open Access Journals (Sweden)

    Irene Martin-Robles

    2014-01-01

    Full Text Available Indication of oxygen therapy in fibrotic interstitial lung diseases is not standardized and its specific requirements are not well defined. The objective of this study was to evaluate ambulatory oxygen therapy features in lung fibrotic patients. Clinical and exploratory data, including 6-minute walking test and pulmonary hypertension, from one hundred and seven patients with fibrotic interstitial lung disease that received ambulatory oxygen treatment were studied. In up to 40% of cases the prescription of oxygen therapy was made after performing a 6-minute walking test. Patients who required ambulatory oxygen only during exercise presented a mild to moderate reduction of the predicted % FVC (62.1 ± 19 and DLCO (49 ± 14.4 while patients who had respiratory failure at rest (mean PaO2 51.9 ± 6.7 presented a moderate reduction of %FVC (56.8 ± 15.6 but a severe decrease of %DLCO (31.67 ± 12. Pulmonary hypertension (PH was evaluated in 47.7% of patients and occurred in 60.8% of them. In conclusion, there is no pulmonary functional predictor of oxyhaemoglobin desaturation during exercise. PH is frequently associated with interstitial lung diseases, mainly when respiratory failure at rest appears. The heterogeneity of the patients and limitation of retrospective studies could be the cause of the tributes for potential benefits of oxygen treatment in interstitial lung diseases.

  1. What Are Asbestos-Related Lung Diseases?

    Science.gov (United States)

    ... asbestosis include: Fibrotic lung disease Pneumoconiosis (NOO-mo-ko-ne-O-sis) Interstitial (in-ter-STISH-al) ... tissue samples. One way is through bronchoscopy (bron-KOS-ko-pee). For this procedure, your doctor will ...

  2. Retention of inhaled plutonium oxide. Elimination procedures by pulmonary lavage and effect of the alveolar macrophage

    International Nuclear Information System (INIS)

    Nolibe, Daniel.

    1977-03-01

    A large fraction of the plutonium particles, reaching the deeper lung are retained in the alveolar macrophages during several months. Cell function changes were measured in vivo and in vitro. Stimulation of macrophage mobility and phagocytosis or natural clearance processes were uneffective on PuO 2 excretion. In vivo pulmonary lavage was the only effective therapy. The procedures of in toto pulmonary lavage in order to obtain the highest number of macrophages are described. A study of the physiological and histological consequences showed no long-term pathology, lesions observed during 48 h after lavage were restored quickly. A single lavage eliminated 12-25% only of the lung burden. A procedure of ten repeated lavages (1 per week) eliminated 60-90% of the lung burden. The action of lavage seemed twofold: direct elimination in the rinsing liquid and faster pulmonary clearance with low lymph node overload. Survivals in treated animals kept for long-term observations were compatible with the lung burdens remaining after treatment. Demontration of an inhibiting effect on pulmonary fibrosis should indicate a larger utilization [fr

  3. The Evaluation of Interstitial Abnormalities in Group B of the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Classification of Chronic Obstructive Pulmonary Disease (COPD).

    Science.gov (United States)

    Ohgiya, Masahiro; Matsui, Hirotoshi; Tamura, Atsuhisa; Kato, Takafumi; Akagawa, Shinobu; Ohta, Ken

    2017-10-15

    Objective In 2011, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification categorized chronic obstructive pulmonary disease (COPD) patients into 4 groups. A report demonstrated that the mortality in Group B was higher than that in Group C. Ischemic heart disease and cancer were suggested to be the cause. The aim of the present study was to test the hypothesis that interstitial lung abnormalities (ILAs) are more prevalent in Group B than Group C and that they may be responsible for the higher mortality in Group B. Methods Patients were selected based on their pulmonary function test results. The inclusion criterion was a forced expiratory volume in 1 second (FEV 1 )/forced vital capacity (FVC) of COPD patients, ILAs were detected in 10.3% of the patients in Group A, 22.5% of the patients in Group B, 5.6% of the patients in Group C, and 23.1% of the patients in Group D. In Group B, the frequency of ILAs was significantly higher and the area affected by the ILAs was significantly greater in comparison to Group C. Among the patterns of interstitial abnormalities, the area of honeycombing in Group B was significantly greater than that in Group C. Furthermore, among the patients in Group B, the LAA in the ILA-positive patients was significantly greater than that in the ILA-negative patients. Conclusion In Group B, the area occupied by ILAs-especially honeycombing-was greater than that in Group C. This contributed to the preserved %FEV 1 and possibly to the poorer prognosis of the patients in Group B.

  4. Increased iron sequestration in alveolar macrophages in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Quentin Philippot

    Full Text Available Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease (COPD pathogenesis. Iron accumulation has been implicated in oxidative stress in other diseases, such as Alzheimer's and Parkinson's diseases, but little is known about iron accumulation in COPD. We sought to determine if iron content and the expression of iron transport and/or storage genes in lung differ between controls and COPD subjects, and whether changes in these correlate with airway obstruction. Explanted lung tissue was obtained from transplant donors, GOLD 2-3 COPD subjects, and GOLD 4 lung transplant recipients, and bronchoalveolar lavage (BAL cells were obtained from non-smokers, healthy smokers, and GOLD 1-3 COPD subjects. Iron-positive cells were quantified histologically, and the expression of iron uptake (transferrin and transferrin receptor, storage (ferritin and export (ferroportin genes was examined by real-time RT-PCR assay. Percentage of iron-positive cells and expression levels of iron metabolism genes were examined for correlations with airflow limitation indices (forced expiratory volume in the first second (FEV1 and the ratio between FEV1 and forced vital capacity (FEV1/FVC. The alveolar macrophage was identified as the predominant iron-positive cell type in lung tissues. Furthermore, the quantity of iron deposit and the percentage of iron positive macrophages were increased with COPD and emphysema severity. The mRNA expression of iron uptake and storage genes transferrin and ferritin were significantly increased in GOLD 4 COPD lungs compared to donors (6.9 and 3.22 fold increase, respectively. In BAL cells, the mRNA expression of transferrin, transferrin receptor and ferritin correlated with airway obstruction. These results support activation of an iron sequestration mechanism by alveolar macrophages in COPD, which we postulate is a protective mechanism against iron induced oxidative

  5. [The efficacy of phlebotomy with a low iron diet in the management of pulmonary iron overload].

    Science.gov (United States)

    Fukuda, Tomoko; Kimura, Fumiaki; Watanabe, Yoichi; Yoshino, Tadasi; Kimura, Ikuro

    2003-05-01

    Numerous studies have shown that workers in ferriferous industries have an elevated risk of respiratory tract neoplasia and other airway diseases. Evidence is presented that iron is a carcinogenic and tissue toxic hazard as regarding the inhalation of ferriferous substances. Elimination of the inhaled iron and prevention from accumulation of iron in the lung seems to be very important. A 26-year-old man was admitted to our hospital complaining of right chest pain. He had worked as an arc welder for two years without a mask. A chest CT showed diffuse ground glass opacity in the bilateral lung fields. A transbronchial lung biopsy specimen showed numerous alveolar and interstitial iron-laden macrophages. A 200 ml phlebotomy was carried out biweekly in combination with a low iron diet (8 mg/day). When serum ferritin reached 20 ng/ml, phlebotomy was stopped. After that, serum ferritin level was kept at around 20 ng/ml with the low iron diet alone. A transbronchial lung biopsy was carried out again 7 months later and the specimen showed remarkable reduction in the number of iron-laden alveolar and interstitial macrophages. Phlebotomy in combination with a low iron diet might become a useful strategy in the management of pulmonary conditions associated with iron loading.

  6. Nephron progenitor cell death elicits a limited compensatory response associated with interstitial expansion in the neonatal kidney

    Directory of Open Access Journals (Sweden)

    Sree Deepthi Muthukrishnan

    2018-01-01

    Full Text Available The final nephron number in an adult kidney is regulated by nephron progenitor cell availability and collecting duct branching in the fetal period. Fetal environmental perturbations that cause reductions in cell numbers in these two compartments result in low nephron endowment. Previous work has shown that maternal dietary factors influence nephron progenitor cell availability, with both caloric restriction and protein deprivation leading to reduced cell numbers through apoptosis. In this study, we evaluate the consequences of inducing nephron progenitor cell death on progenitor niche dynamics and on nephron endowment. Depletion of approximately 40% of nephron progenitor cells by expression of diphtheria toxin A at embryonic day 15 in the mouse results in 10-20% nephron reduction in the neonatal period. Analysis of cell numbers within the progenitor cell pool following induction of apoptosis reveals a compensatory response in which surviving progenitor cells increase their proliferation and replenish the niche. The proliferative response is temporally associated with infiltration of macrophages into the nephrogenic zone. Colony stimulating factor 1 (CSF1 has a mitogenic effect on nephron progenitor cells, providing a potential explanation for the compensatory proliferation. However, CSF1 also promotes interstitial cell proliferation, and the compensatory response is associated with interstitial expansion in recovering kidneys which can be pharmacologically inhibited by treatment with clodronate liposomes. Our findings suggest that the fetal kidney employs a macrophage-dependent compensatory regenerative mechanism to respond to acute injury caused by death of nephron progenitor cells, but that this regenerative response is associated with neonatal interstitial expansion.

  7. Critical Role of Airway Macrophages in Modulating Disease Severity during Influenza Virus Infection of Mice ▿

    Science.gov (United States)

    Tate, Michelle D.; Pickett, Danielle L.; van Rooijen, Nico; Brooks, Andrew G.; Reading, Patrick C.

    2010-01-01

    Airway macrophages provide a first line of host defense against a range of airborne pathogens, including influenza virus. In this study, we show that influenza viruses differ markedly in their abilities to infect murine macrophages in vitro and that infection of macrophages is nonproductive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus strain PR8 (H1N1) was poor in its ability to infect macrophages and highly virulent for mice. Depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in BJx109-infected mice but did not modulate disease severity in PR8-infected mice. The severe disease observed in macrophage-depleted mice infected with BJx109 was associated with exacerbated virus replication in the airways, leading to severe airway inflammation, pulmonary edema, and vascular leakage, indicative of lung injury. Thymic atrophy, lymphopenia, and dysregulated cytokine and chemokine production were additional systemic manifestations associated with severe disease. Thus, airway macrophages play a critical role in limiting lung injury and associated disease caused by BJx109. Furthermore, the inability of PR8 to infect airway macrophages may be a critical factor contributing to its virulence for mice. PMID:20504924

  8. Vildagliptin-induced acute lung injury: a case report.

    Science.gov (United States)

    Ohara, Nobumasa; Kaneko, Masanori; Sato, Kazuhiro; Maruyama, Ryoko; Furukawa, Tomoyasu; Tanaka, Junta; Kaneko, Kenzo; Kamoi, Kyuzi

    2016-08-12

    Dipeptidyl peptidase-4 inhibitors are a class of oral hypoglycemic drugs and are used widely to treat type 2 diabetes mellitus in many countries. Adverse effects include nasopharyngitis, headache, elevated serum pancreatic enzymes, and gastrointestinal symptoms. In addition, a few cases of interstitial pneumonia associated with their use have been reported in the Japanese literature. Here we describe a patient who developed drug-induced acute lung injury shortly after the administration of the dipeptidyl peptidase-4 inhibitor vildagliptin. A 38-year-old Japanese woman with diabetes mellitus developed acute respiratory failure 1 day after administration of vildagliptin. Chest computed tomography revealed nonsegmental ground-glass opacities in her lungs. There was no evidence of bacterial pneumonia or any other cause of her respiratory manifestations. After discontinuation of vildagliptin, she recovered fully from her respiratory disorder. She received insulin therapy for her diabetes mellitus, and her subsequent clinical course has been uneventful. The period of drug exposure in previously reported cases of patients with drug-induced interstitial pneumonia caused by dipeptidyl peptidase-4 inhibitor varied from several days to over 6 months. In the present case, our patient developed interstitial pneumonia only 1 day after the administration of vildagliptin. The precise mechanism of her vildagliptin-induced lung injury remains uncertain, but physicians should consider that dipeptidyl peptidase-4 inhibitor-induced lung injury, although rare, may appear acutely, even within days after administration of this drug.

  9. 15-Lipoxygenases regulate the production of chemokines in human lung macrophages.

    Science.gov (United States)

    Abrial, C; Grassin-Delyle, S; Salvator, H; Brollo, M; Naline, E; Devillier, P

    2015-09-01

    15-Lipoxygenase (15-LOX) activity is associated with inflammation and immune regulation. The objectives of the present study were to investigate the expression of 15-LOX-1 and 15-LOX-2 and evaluate the enzymes' roles in the polarization of human lung macrophages (LMs) in response to LPS and Th2 cytokines (IL-4/-13). LMs were isolated from patients undergoing surgery for carcinoma. The cells were cultured with a 15-LOX inhibitor (PD146176 or ML351), a COX inhibitor (indomethacin), a 5-LOX inhibitor (MK886) or vehicle and then stimulated with LPS (10 ng · mL(-1)), IL-4 (10 ng · mL(-1)) or IL-13 (50 ng · mL(-1)) for 24 h. Levels of ALOX15 (15-LOX-1) and ALOX15B (15-LOX-2) transcripts were determined by real-time quantitative PCR. Immunoassays were used to measure levels of LPS-induced cytokines (TNF-α, CCL2, CCL3, CCL4, CXCL1, CXCL8 and CXCL10) and Th2 cytokine-induced chemokines (CCL13, CCL18 and CCL22) in the culture supernatant. Stimulation of LMs with LPS was associated with increased expression of ALOX15B, whereas stimulation with IL-4/IL-13 induced the expression of ALOX15. PD146176 and ML351 (10 μM) reduced the release of the chemokines induced by LPS and Th2 cytokines. The effects of these 15-LOX inhibitors were maintained in the presence of indomethacin and MK886. Furthermore, indomethacin revealed the inhibitory effect of PD146176 on TNF-α release. Inhibition of the 15-LOX pathways is involved in the down-regulation of the in vitro production of chemokines in LMs. Our results suggest that the 15-LOX pathways have a role in the pathogenesis of inflammatory lung disorders and may thus constitute a potential drug target. © 2015 The British Pharmacological Society.

  10. Dual role of YM1+ M2 macrophages in allergic lung inflammation

    NARCIS (Netherlands)

    Draijer, Christina; Robbe, Patricia; Boorsma, Carian E; Hylkema, Machteld N; Melgert, Barbro N

    2018-01-01

    Alternatively activated (M2 or YM1+) macrophages have been associated with the development of asthma but their contribution to disease initiation and progression remains unclear. To assess the therapeutic potential of modulating these M2 macrophages, we have studied inhibition of M2 polarisation

  11. Protective roles of free avian respiratory macrophages in captive birds

    Directory of Open Access Journals (Sweden)

    Mbuvi P. Mutua

    Full Text Available In the mammalian lung, respiratory macrophages provide front line defense against invading pathogens and particulate matter. In birds, respiratory macrophages are known as free avian respiratory macrophages (FARM and a dearth of the cells in the avian lung has been purported to foreordain a weak first line of pulmonary defense, a condition associated with high mortality of domestic birds occasioned by respiratory inflictions. Avian pulmonary mechanisms including a three tiered aerodynamic filtration system, tight epithelial junctions and an efficient mucociliary escalator system have been known to supplement FARM protective roles. Current studies, however, report FARM to exhibit an exceptionally efficient phagocytic capacity and are effective in elimination of invading pathogens. In this review, we also report on effects of selective synthetic peroxisome proliferator activated receptor gamma (PPAR γ agonists on non phlogistic phagocytic properties in the FARM. To develop effective therapeutic interventions targeting FARM in treatment and management of respiratory disease conditions in the poultry, further studies are required to fully understand the role of FARM in innate and adaptive immune responses.

  12. Pulmonary microRNA profiling: implications in upper lobe predominant lung disease.

    Science.gov (United States)

    Armstrong, David A; Nymon, Amanda B; Ringelberg, Carol S; Lesseur, Corina; Hazlett, Haley F; Howard, Louisa; Marsit, Carmen J; Ashare, Alix

    2017-01-01

    Numerous pulmonary diseases manifest with upper lobe predominance including cystic fibrosis, smoking-related chronic obstructive pulmonary disease, and tuberculosis. Zonal hypoxia, characteristic of these pulmonary maladies, and oxygen stress in general is known to exert profound effects on various important aspects of cell biology. Lung macrophages are major participants in the pulmonary innate immune response and regional differences in macrophage responsiveness to hypoxia may contribute in the development of lung disease. MicroRNAs are ubiquitous regulators of human biology and emerging evidence indicates altered microRNA expression modulates respiratory disease processes. The objective of this study is to gain insight into the epigenetic and cellular mechanisms influencing regional differences in lung disease by investigating effect of hypoxia on regional microRNA expression in the lung. All studies were performed using primary alveolar macrophages ( n  = 10) or bronchoalveolar lavage fluid ( n  = 16) isolated from human subjects. MicroRNA was assayed via the NanoString nCounter microRNA assay. Divergent molecular patterns of microRNA expression were observed in alternate lung lobes, specifically noted was disparate expression of miR-93 and miR-4454 in alveolar macrophages along with altered expression of miR-451a and miR-663a in bronchoalveolar lavage fluid. Gene ontology was used to identify potential downstream targets of divergent microRNAs. Targets include cytokines and matrix metalloproteinases, molecules that could have a significant impact on pulmonary inflammation and fibrosis. Our findings show variant regional microRNA expression associated with hypoxia in alveolar macrophages and BAL fluid in the lung-upper vs lower lobe. Future studies should address whether these specific microRNAs may act intracellularly, in a paracrine/endocrine manner to direct the innate immune response or may ultimately be involved in pulmonary host-to-pathogen trans

  13. Early detection of interstitial pneumonia by WXGa-citrate scintigraphy. Cases of abnormal pulmonary WXGa uptake with normal chest radiographs

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Shinsaku; Mikami, Riichiro; Ryujin, Yoshitada

    1985-04-01

    In this paper we report our recent experience indicating usefulness of WXGa-citrate scintigraphy in 4 cases with inflammatory pulmonary diseases. These cases showed abnormal pulmonary WXGa uptake with normal chest radiographs. The first case with malignant lymphoma and the second one with lung cancer suffered from pulmonary infection following secondary immuno-insufficiency due to radiotherapy and chemotherapy. Pneumocystis carinii was suspected as causative agent in the first case, and gram negative bacilli in the second case. The third case with lung cancer developed radiation pneumonia after radiotherapy. The fourth case with acute bronchitis developed drug induced interstitial pneumonia presumably due to minocycline administration. It is concluded that WXGa-citrate scintigraphy is more sensitive for early detection of interstitial pneumonia than routine chest radiography.

  14. Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS).

    Science.gov (United States)

    Mukhopadhyay, Sanjay; Parambil, Joseph G

    2012-10-01

    Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from "acute exacerbation of IPF," a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Correlation between HRCT findings, pulmonary function tests and bronchoalveolar lavage cytology in interstitial lung disease associated with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Biederer, J.; Muhle, C.; Heller, M.; Reuter, M.; Schnabel, A.; Gross, W.L.

    2004-01-01

    A prospective study correlating high-resolution computed tomography (HRCT), lung function tests (PFT) and bronchoalveolar lavage (BAL) cytology in patients with interstitial lung disease (ILD) associated with rheumatoid arthritis (RA). Fifty-three RA patients with suspected ILD (19 men, 34 women) underwent 71 HRCT (14 of 53 with sequential HRCT, mean follow-up 24.3 months). The HRCT evaluation by two observers on consensus included a semi-quantitative characterisation of lesion pattern and profusion on representative anatomical levels. Fifty-two HRCT were followed by PFT and BAL. Agreement or discordance of HRCT-, PFT- and BAL findings were analysed with Pearson's correlation, κ score and McNemar's test. Tobacco-fume exposure was estimated in pack years. Smoking/non-smoking groups were compared with Student's t test. In 49 of 53 patients, HRCT was suggestive of ILD associated with RA (66 of 71 HRCT). Reticular lesions were found in 40 of 53 patients, in 15 of 40 presenting as mixed pattern with ground-glass opacities (GGO). Pure reticular patterns predominated in patients with long duration of ILD (p>0.01). Pure GGO were not observed. Lesion profusion was highly variable and correlated moderately negative with diffusion capacity (mean 88.2% (SD±20.9%); r=-0.54; p 0.2), but not towards lymphocytosis (κ=0.10; p=0.23; McNemar test p>0.2). Differences in smoking history were not significant (p>0.1). The HRCT appears most appropriate for the detection and follow-up of ILD associated with RA. The PFT and BAL correlate only partially with lesion profusion or grading on HRCT, but they contribute valuable information about dynamic lung function and differential diagnoses (pneumonia, medication side effects). (orig.)

  16. HRCT findings in the lungs of non-smokers with neurofibromatosis

    International Nuclear Information System (INIS)

    Oikonomou, Anastasia; Vadikolias, Konstantinos; Birbilis, Theodosios; Bouros, Demosthenes; Prassopoulos, Panos

    2011-01-01

    Purpose: Interstitial lung disease in neurofibromatosis (NF) has been disputed and attributed to smoking-related changes. The aim of this study was to describe HRCT findings in the lungs of non-smokers with NF. Materials and methods: Six never-smokers with NF underwent lung HRCT. Two radiologists evaluated the HRCT scans and a final decision was reached by consensus. The HRCT scans were analyzed with regard to the number, size, location (upper, middle or lower lung zone) and distribution (peripheral and central) of lung cysts and the presence of ground-glass density centrilobular micronodules. Results: All patients with NF had small (2–18 mm) thin wall cysts and upper-lobe predominant patchy areas of ground-glass density centrilobular micronodules. In five cases, there were 3–17 cysts and in one there were numerous (>100). Lung cysts were central (1), subpleural (1) and in both locations (4). Conclusion: Interstitial lung disease in NF is not associated with smoking and may be entirely asymptomatic. HRCT may reveal small cysts, with barely perceptible walls therefore not representing emphysema and occasionally a minimal micronodular pattern of ground glass opacity. There was no radiologic evidence of lung fibrosis, honeycombing or severe bullous disease.

  17. Mechanisms controlling the volume of pleural fluid and extravascular lung water

    Directory of Open Access Journals (Sweden)

    G. Miserocchi

    2009-12-01

    Full Text Available Pleural and interstitial lung fluid volumes are strictly controlled and maintained at the minimum thanks to the ability of lymphatics to match the increase in filtration rate. In the pleural cavity, fluid accumulation is easily accommodated by retraction of lung and chest wall (high compliance of the pleural space; the increase of lymph flow per unit increase in pleural fluid volume is high due to the great extension of the parietal lymphatic. However, for the lung interstitium, the increase in lymph flow to match increased filtration does not need to be so great. In fact, increased filtration only causes a minor increase in extravascular water volume (<10% due to a marked increase in interstitial pulmonary pressure (low compliance of the extracellular matrix which, in turn, buffers further filtration. Accordingly, a less extended lymphatic network is needed. The efficiency of lymphatic control is achieved through a high lymphatic conductance in the pleural fluid and through a low interstitial compliance for the lung interstitium. Fluid volume in both compartments is so strictly controlled that it is difficult to detect initial deviations from the physiological state; thus, a great physiological advantage turns to be a disadvantage on a clinical basis as it prevents an early diagnosis of developing disease.

  18. Autopsy-proven causes of death in lungs of patients immunocompromised by secondary interstitial pneumonia Causas de óbito por pneumonia intersticial secundária em autópsias pulmonares de pacientes imunocomprometidos

    Directory of Open Access Journals (Sweden)

    Alberto Antonio Terrabuio Junior

    2007-02-01

    Full Text Available PURPOSE: To present the more frequent associations found in autopsies of immunocompromised patients who developed secondary interstitial pneumonia as well as the risk of death (odds ratio in having specific secondary interstitial pneumonia according to the cause of immunocompromise. METHOD: From January 1994 to March 2004, 17,000 autopsies were performed at Hospital das Clínicas, São Paulo University Medical School. After examining the pathology report review, we selected 558 of these autopsies (3.28% from patients aged 15 years or more with primary underlying diseases who developed radiologically diffuse infiltrates of the lung during their hospital course and died after secondary interstitial pneumonia (bronchopneumonia, lobar pneumonia, interstitial pneumonia, diffuse alveolar damage, pulmonary recurrence of underlying disease, drug-induced lung disease, cardiogenic pulmonary edema, or pulmonary embolism. Histology slides were reviewed by experienced pathologists to confirm or not the presence of secondary interstitial pneumonia. Statistical analysis included the Fisher exact test to verify any association between histopathology and the cause of immunocompromise; a logistic regression was used to predict the risk of death for specific histological findings for each of the independent variables in the model. RESULTS: Secondary interstitial pneumonia was histologically represented by diffuse interstitial pneumonitis ranging from mild nonspecific findings (n = 213 to a pattern of diffuse alveolar damage (n = 273. The principal causes of immunocompromise in patients with diffuse alveolar damage were sepsis (136 cases, neoplasia (113 cases, diabetes mellitus (37 cases, and transplantation (48 cases. A high risk of death by pulmonary edema was found for patients with carcinoma of colon. Similarly, in patients with lung cancer or cachexia, A high risk of death by bronchopneumonia (OR = 3.6; OR = 2.6, respectively was found. Pulmonary

  19. A Patient with Non-Hodgkin Lymphoma and Nonspecific Interstitial Pneumonia during Ibrutinib Therapy.

    Science.gov (United States)

    Jungmann, Sven; Ludwig, Wolf-Dieter; Schönfeld, Nicolas; Blum, Torsten-Gerriet; Großwendt, Claudia; Boch, Christian; Rehbock, Beate; Griff, Sergej; Schmittel, Alexander; Bauer, Torsten T

    2017-01-01

    We present a 74-year-old male with nonspecific interstitial pneumonia (NSIP) during treatment with ibrutinib for mantle cell lymphoma. Previously, the patient had received six cycles of bendamustine and rituximab and six cycles of R-CHOP, followed by rituximab maintenance therapy. Respiratory tract complications of ibrutinib other than infectious pneumonia have not been mentioned in larger trials, but individual case reports hinted to a possible association with the development of pneumonitis. In our patient, the onset of alveolitis that progressed towards NSIP together with the onset of ibrutinib treatment suggests causality. One week after ibrutinib was discontinued, nasal symptoms resolved first. A follow-up CT showed a reduction in the reticular hyperdensities and ground-glass opacities, suggestive of restitution of the lung disease. To our knowledge, this is the first case showing a strong link between ibrutinib and interstitial lung disease, strengthening a previous report on subacute pneumonitis. Our findings have clinical implications because pulmonary side effects were reversible at this early stage. We, therefore, suggest close monitoring for respiratory side effects in patients receiving ibrutinib.

  20. A Patient with Non-Hodgkin Lymphoma and Nonspecific Interstitial Pneumonia during Ibrutinib Therapy

    Directory of Open Access Journals (Sweden)

    Sven Jungmann

    2017-01-01

    Full Text Available We present a 74-year-old male with nonspecific interstitial pneumonia (NSIP during treatment with ibrutinib for mantle cell lymphoma. Previously, the patient had received six cycles of bendamustine and rituximab and six cycles of R-CHOP, followed by rituximab maintenance therapy. Respiratory tract complications of ibrutinib other than infectious pneumonia have not been mentioned in larger trials, but individual case reports hinted to a possible association with the development of pneumonitis. In our patient, the onset of alveolitis that progressed towards NSIP together with the onset of ibrutinib treatment suggests causality. One week after ibrutinib was discontinued, nasal symptoms resolved first. A follow-up CT showed a reduction in the reticular hyperdensities and ground-glass opacities, suggestive of restitution of the lung disease. To our knowledge, this is the first case showing a strong link between ibrutinib and interstitial lung disease, strengthening a previous report on subacute pneumonitis. Our findings have clinical implications because pulmonary side effects were reversible at this early stage. We, therefore, suggest close monitoring for respiratory side effects in patients receiving ibrutinib.

  1. Pathogenic TH17 inflammation is sustained in the lungs by conventional dendritic cells and Toll-like receptor 4 signaling.

    Science.gov (United States)

    Shalaby, Karim H; Lyons-Cohen, Miranda R; Whitehead, Gregory S; Thomas, Seddon Y; Prinz, Immo; Nakano, Hideki; Cook, Donald N

    2017-11-14

    Mechanisms that elicit mucosal T H 17 cell responses have been described, yet how these cells are sustained in chronically inflamed tissues remains unclear. We sought to understand whether maintenance of lung T H 17 inflammation requires environmental agents in addition to antigen and to identify the lung antigen-presenting cell (APC) types that sustain the self-renewal of T H 17 cells. Animals were exposed repeatedly to aspiration of ovalbumin alone or together with environmental adjuvants, including common house dust extract (HDE), to test their role in maintaining lung inflammation. Alternatively, antigen-specific effector/memory T H 17 cells, generated in culture with CD4 + T cells from Il17a fate-mapping mice, were adoptively transferred to assess their persistence in genetically modified animals lacking distinct lung APC subsets or cell-specific Toll-like receptor (TLR) 4 signaling. T H 17 cells were also cocultured with lung APC subsets to determine which of these could revive their expansion and activation. T H 17 cells and the consequent neutrophilic inflammation were poorly sustained by inhaled antigen alone but were augmented by inhalation of antigen together with HDE. This was associated with weight loss and changes in lung physiology consistent with interstitial lung disease. The effect of HDE required TLR4 signaling predominantly in lung hematopoietic cells, including CD11c + cells. CD103 + and CD11b + conventional dendritic cells interacted directly with T H 17 cells in situ and revived the clonal expansion of T H 17 cells both ex vivo and in vivo, whereas lung macrophages and B cells could not. T H 17-dependent inflammation in the lungs can be sustained by persistent TLR4-mediated activation of lung conventional dendritic cells. Published by Elsevier Inc.

  2. Assessment of carbon nanoparticle exposure on murine macrophage function

    Science.gov (United States)

    Suro-Maldonado, Raquel M.

    There is growing concern about the potential cytotoxicity of nanoparticles. Exposure to respirable ultrafine particles (2.5uM) can adversely affect human health and have been implicated with episodes of increased respiratory diseases such as asthma and allergies. Nanoparticles are of particular interest because of their ability to penetrate into the lung and potentially elicit health effects triggering immune responses. Nanoparticles are structures and devises with length scales in the 1 to 100-nanometer range. Black carbon (BC) nanoparticles have been observed to be products of combustion, especially flame combustion and multi-walled carbon nanotubes (MWCNT) have been shown to be found in both indoor and outdoor air. Furthermore, asbestos, which have been known to cause mesothelioma as well as lung cancer, have been shown to be structurally identical to MWCNTs. The aims of these studies were to examine the effects of carbon nanoparticles on murine macrophage function and clearance mechanisms. Macrophages are immune cells that function as the first line of defense against invading pathogens and are likely to be amongst the first cells affected by nanoparticles. Our research focused on two manufactured nanoparticles, MWCNT and BC. The two were tested against murine-derived macrophages in a chronic contact model. We hypothesized that long-term chronic exposure to carbon nanoparticles would decrease macrophages ability to effectively respond to immunological challenge. Production of nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), cell surface macrophage; activation markers, reactive oxygen species formation (ROS), and antigen processing and presentation were examined in response to lipopolysaccharide (LPS) following a 144hr exposure to the particulates. Data demonstrated an increase in TNF-alpha, and NO production; a decrease in phagocytosis and antigen processing and presentation; and a decrease in the expression levels of cell surface macrophage

  3. Selective macrophage inhibition abolishes warfarin-induced reduction of metastasis

    NARCIS (Netherlands)

    Maat, B.

    1980-01-01

    Warfarin administered to tumor-bearing mice reduces the number of spontaneous lung metastases. Both macrophage inhibitors silica and carrageenan abolish the warfarin-induced decrease in tumour metastasis, which strongly supports the concept that the antitumour effect of coumarin derivatives is

  4. Pro-inflammatory effects and oxidative stress in lung macrophages and epithelial cells induced by ambient particulate matter

    International Nuclear Information System (INIS)

    Michael, S.; Montag, M.; Dott, W.

    2013-01-01

    The objective of this study was to compare the toxicological effects of different source-related ambient PM10 samples in regard to their chemical composition. In this context we investigated airborne PM from different sites in Aachen, Germany. For the toxicological investigation human alveolar epithelial cells (A549) and murine macrophages (RAW264.7) were exposed from 0 to 96 h to increasing PM concentrations (0–100 μg/ml) followed by analyses of cell viability, pro-inflammatory and oxidative stress responses. The chemical analysis of these particles indicated the presence of 21 elements, water-soluble ions and PAHs. The toxicological investigations of the PM10 samples demonstrated a concentration- and time-dependent decrease in cell viability and an increase in pro-inflammatory and oxidative stress markers. -- Highlights: ► The study compares the toxicological effects of different source-related particles with regard to their chemical composition. ► The chemical characterization of the coarse particles revealed clear differences in elemental, TC and PAH composition. ► Equal mass concentrations of urban traffic and rural PM caused different toxicological responses. ► The observations confirm the hypothesis that particle composition, as well as origin, influence the PM-induced toxicity. -- The toxicological responses of lung epithelial cells and macrophages differ significantly after an exposure to equal mass concentrations of urban traffic and rural PM

  5. Biochemical and morphological changes in endothelial cells in response to hypoxic interstitial edema

    Directory of Open Access Journals (Sweden)

    Miserocchi Giuseppe

    2006-01-01

    Full Text Available Abstract Background A correlation between interstial pulmonary matrix disorganization and lung cellular response was recently documented in cardiogenic interstitial edema as changes in the signal-cellular transduction platforms (lipid microdomains: caveoale and lipid rafts. These findings led to hypothesize a specific "sensing" function by lung cells resulting from a perturbation in cell-matrix interaction. We reason that the cell-matrix interaction may differ between the cardiogenic and the hypoxic type of lung edema due to the observed difference in the sequential degradation of matrix proteoglycans (PGs family. In cardiogenic edema a major fragmentation of high molecular weight PGs of the interfibrillar matrix was found, while in hypoxia the fragmentation process mostly involved the PGs of the basement membrane controlling microvascular permeability. Based on these considerations, we aim to describe potential differences in the lung cellular response to the two types of edema. Methods We analysed the composition of plasma membrane and of lipid microdomains in lung tissue samples from anesthetized rabbits exposed to mild hypoxia (12 % O2 for 3–5 h causing interstitial lung edema. Lipid analysis was performed by chromatographic techniques, while protein analysis by electrophoresis and Western blotting. Lipid peroxidation was assessed on total plasma membranes by a colorimetric assay (Bioxytech LPO-586, OxisResearch. Plasma membrane fluidity was also assessed by fluorescence. Lipid microdomains were isolated by discontinuous sucrose gradient. We also performed a morphometric analysis on lung cell shape on TEM images from lung tissue specimen. Results After hypoxia, phospholipids content in plasma membranes remained unchanged while the cholesterol/phospholipids ratio increased significantly by about 9% causing a decrease in membrane fluidity. No significant increase in lipid peroxidation was detected. Analysis of lipid microdomains showed a

  6. Undifferentiated connective tissue disease and interstitial lung disease: Trying to define patterns.

    Science.gov (United States)

    Alberti, María Laura; Paulin, Francisco; Toledo, Heidegger Mateos; Fernández, Martín Eduardo; Caro, Fabián Matías; Rojas-Serrano, Jorge; Mejía, Mayra Edith

    To identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. Retrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: 'highly specific' connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1: 320), and 'specific' ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. Sixty-six patients were included. Twenty-nine (43.94%) showed at least one 'highly specific' CTD manifestation, 16 (28.57%) had a 'specific' ANA staining pattern and 29 (43.94%) high ANA titer. Patients with 'highly specific' CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [-1 to 10] vs -6% [-16 to -4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. The presence of 'highly specific' CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  7. Análise de 39 casos de pneumonia intersticial crônica idiopática Analysis of 39 cases of idiopathic chronic interstitial pneumonia

    Directory of Open Access Journals (Sweden)

    Rogério Rufino

    2006-12-01

    Full Text Available OBJETIVO: Analisar de forma retrospectiva fragmentos de biópsias pulmonares que receberam o diagnóstico de pneumonia intersticial crônica idiopática, à luz da classificação da American Thoracic Society e European Respiratory Society, de 2000. MÉTODOS: A partir da revisão de 252 fragmentos de biópsias pulmonares a céu aberto de pacientes com doença intersticial pulmonar, no período de 1977 a 1999, 39 casos de doença pulmonar intersticial idiopática foram selecionados e reavaliados por dois patologistas, segundo a classificação da American Thoracic Society e European Respiratory Society, de 2000. RESULTADOS: Vinte e oito dos 39 diagnósticos foram mantidos (71,8%. Uma nova entidade patológica, a pneumonia intersticial não específica, foi incluída na reclassificação e houve superposição de padrões em seis casos. Mantiveram o mesmo diagnóstico 28 casos, 4 casos apresentaram associação entre fibrose pulmonar idiopática e organização pneumônica criptogênica, 1 entre organização pneumônica criptogênica e pneumonia intersticial não específica, e 1 entre pneumonia intersticial descamativa e pneumonia intersticial não específica. Todos os casos de fibrose pulmonar idiopática foram confirmados, embora 3 deles estivessem associados a organização pneumônica criptogênica. Os diagnósticos anteriores foram quase todos mantidos na revisão dos espécimes (p > 0,05. CONCLUSÃO: A classificação das doenças pulmonares intersticiais da American Thoracic Society e European Respiratory Society é uma ferramenta útil aos patologistas que lidam com biópsias pulmonares.OBJECTIVE: To make a retrospective analysis of lung biopsy samples obtained from patients diagnosed with chronic idiopathic interstitial pneumonia, as defined in the American Thoracic Society/European Respiratory Society classification system made public in 2000. METHODS: Samples from 252 open-lung biopsies of patients with interstitial lung disease, all

  8. Acute lyme infection presenting with amyopathic dermatomyositis and rapidly fatal interstitial pulmonary fibrosis: a case report

    Directory of Open Access Journals (Sweden)

    Nguyen Hanh

    2010-06-01

    Full Text Available Abstract Introduction Dermatomyositis has been described in the setting of lyme infection in only nine previous case reports. Although lyme disease is known to induce typical clinical findings that are observed in various collagen vascular diseases, to our knowledge, we believe that our case is the first presentation of acute lyme disease associated with amyopathic dermatomyositis, which was then followed by severe and fatal interstitial pulmonary fibrosis only two months later. Case presentation We present a case of a 64-year-old African-American man with multiple medical problems who was diagnosed with acute lyme infection after presenting with the pathognomonic rash and confirmatory serology. In spite of appropriate antimicrobial therapy for lyme infection, he developed unexpected amyopathic dermatomyositis and then interstitial lung disease. Conclusions This case illustrates a potential for lyme disease to produce clinical syndromes that may be indistinguishable from primary connective tissue diseases. An atypical and sequential presentation (dermatomyositis and interstitial lung disease of a common disease (lyme infection is discussed. This case illustrates that in patients who are diagnosed with lyme infection who subsequently develop atypical muscular, respiratory or other systemic complaints, the possibility of severe rheumatological and pulmonary complications should be considered.

  9. A stepwise composite echocardiographic score predicts severe pulmonary hypertension in patients with interstitial lung disease.

    Science.gov (United States)

    Bax, Simon; Bredy, Charlene; Kempny, Aleksander; Dimopoulos, Konstantinos; Devaraj, Anand; Walsh, Simon; Jacob, Joseph; Nair, Arjun; Kokosi, Maria; Keir, Gregory; Kouranos, Vasileios; George, Peter M; McCabe, Colm; Wilde, Michael; Wells, Athol; Li, Wei; Wort, Stephen John; Price, Laura C

    2018-04-01

    European Respiratory Society (ERS) guidelines recommend the assessment of patients with interstitial lung disease (ILD) and severe pulmonary hypertension (PH), as defined by a mean pulmonary artery pressure (mPAP) ≥35 mmHg at right heart catheterisation (RHC). We developed and validated a stepwise echocardiographic score to detect severe PH using the tricuspid regurgitant velocity and right atrial pressure (right ventricular systolic pressure (RVSP)) and additional echocardiographic signs. Consecutive ILD patients with suspected PH underwent RHC between 2005 and 2015. Receiver operating curve analysis tested the ability of components of the score to predict mPAP ≥35 mmHg, and a score devised using a stepwise approach. The score was tested in a contemporaneous validation cohort. The score used "additional PH signs" where RVSP was unavailable, using a bootstrapping technique. Within the derivation cohort (n=210), a score ≥7 predicted severe PH with 89% sensitivity, 71% specificity, positive predictive value 68% and negative predictive value 90%, with similar performance in the validation cohort (n=61) (area under the curve (AUC) 84.8% versus 83.1%, p=0.8). Although RVSP could be estimated in 92% of studies, reducing this to 60% maintained a fair accuracy (AUC 74.4%). This simple stepwise echocardiographic PH score can predict severe PH in patients with ILD.

  10. The FGL2/fibroleukin prothrombinase is involved in alveolar macrophage activation in COPD through the MAPK pathway

    International Nuclear Information System (INIS)

    Liu, Yanling; Xu, Sanpeng; Xiao, Fei; Xiong, Yan; Wang, Xiaojin; Gao, Sui; Yan, Weiming; Ning, Qin

    2010-01-01

    Fibrinogen-like protein 2 (FGL2)/fibroleukin has been reported to play a vital role in the pathogenesis of some critical inflammatory diseases by possessing immunomodulatory activity through the mediation of 'immune coagulation' and the regulation of maturation and proliferation of immune cells. We observed upregulated FGL2 expression in alveolar macrophages from peripheral lungs of chronic obstructive pulmonary disease (COPD) patients and found a correlation between FGL2 expression and increased macrophage activation markers (CD11b and CD14). The role of FGL2 in the activation of macrophages was confirmed by the detection of significantly decreased macrophage activation marker (CD11b, CD11c, and CD71) expression as well as the inhibition of cell migration and inflammatory cytokine (IL-8 and MMP-9) production in an LPS-induced FGL2 knockdown human monocytic leukemia cell line (THP-1). Increased FGL2 expression co-localized with upregulated phosphorylated p38 mitogen-activated protein kinase (p38-MAPK) in the lung tissues from COPD patients. Moreover, FGL2 knockdown in THP-1 cells significantly downregulated LPS-induced phosphorylation of p38-MAPK while upregulating phosphorylation of c-Jun N-terminal kinase (JNK). Thus, we demonstrate that FGL2 plays an important role in macrophage activation in the lungs of COPD patients through MAPK pathway modulation.

  11. Zinc and zinc transporters in macrophages and their roles in efferocytosis in COPD.

    Directory of Open Access Journals (Sweden)

    Rhys Hamon

    Full Text Available Our previous studies have shown that nutritional zinc restriction exacerbates airway inflammation accompanied by an increase in caspase-3 activation and an accumulation of apoptotic epithelial cells in the bronchioles of the mice. Normally, apoptotic cells are rapidly cleared by macrophage efferocytosis, limiting any secondary necrosis and inflammation. We therefore hypothesized that zinc deficiency is not only pro-apoptotic but also impairs macrophage efferocytosis. Impaired efferocytic clearance of apoptotic epithelial cells by alveolar macrophages occurs in chronic obstructive pulmonary disease (COPD, cigarette-smoking and other lung inflammatory diseases. We now show that zinc is a factor in impaired macrophage efferocytosis in COPD. Concentrations of zinc were significantly reduced in the supernatant of bronchoalveolar lavage fluid of patients with COPD who were current smokers, compared to healthy controls, smokers or COPD patients not actively smoking. Lavage zinc was positively correlated with AM efferocytosis and there was decreased efferocytosis in macrophages depleted of Zn in vitro by treatment with the membrane-permeable zinc chelator TPEN. Organ and cell Zn homeostasis are mediated by two families of membrane ZIP and ZnT proteins. Macrophages of mice null for ZIP1 had significantly lower intracellular zinc and efferocytosis capability, suggesting ZIP1 may play an important role. We investigated further using the human THP-1 derived macrophage cell line, with and without zinc chelation by TPEN to mimic zinc deficiency. There was no change in ZIP1 mRNA levels by TPEN but a significant 3-fold increase in expression of another influx transporter ZIP2, consistent with a role for ZIP2 in maintaining macrophage Zn levels. Both ZIP1 and ZIP2 proteins were localized to the plasma membrane and cytoplasm in normal human lung alveolar macrophages. We propose that zinc homeostasis in macrophages involves the coordinated action of ZIP1 and ZIP2

  12. Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.

    Directory of Open Access Journals (Sweden)

    Katrin Högner

    2013-02-01

    Full Text Available Influenza viruses (IV cause pneumonia in humans with progression to lung failure and fatal outcome. Dysregulated release of cytokines including type I interferons (IFNs has been attributed a crucial role in immune-mediated pulmonary injury during severe IV infection. Using ex vivo and in vivo IV infection models, we demonstrate that alveolar macrophage (AM-expressed IFN-β significantly contributes to IV-induced alveolar epithelial cell (AEC injury by autocrine induction of the pro-apoptotic factor TNF-related apoptosis-inducing ligand (TRAIL. Of note, TRAIL was highly upregulated in and released from AM of patients with pandemic H1N1 IV-induced acute lung injury. Elucidating the cell-specific underlying signalling pathways revealed that IV infection induced IFN-β release in AM in a protein kinase R- (PKR- and NF-κB-dependent way. Bone marrow chimeric mice lacking these signalling mediators in resident and lung-recruited AM and mice subjected to alveolar neutralization of IFN-β and TRAIL displayed reduced alveolar epithelial cell apoptosis and attenuated lung injury during severe IV pneumonia. Together, we demonstrate that macrophage-released type I IFNs, apart from their well-known anti-viral properties, contribute to IV-induced AEC damage and lung injury by autocrine induction of the pro-apoptotic factor TRAIL. Our data suggest that therapeutic targeting of the macrophage IFN-β-TRAIL axis might represent a promising strategy to attenuate IV-induced acute lung injury.

  13. The reliability of lung ultrasound in assessment of idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Manolescu D

    2018-03-01

    Full Text Available Diana Manolescu,1 Lavinia Davidescu,2 Daniel Traila,3 Cristian Oancea,3 Voicu Tudorache3 1Radiology Department, University of Medicine and Pharmacy “Victor Babes”, Timişoara, Romania; 2Department of Pulmonology, University of Medicine and Pharmacy Oradea, Oradea, Romania; 3Department of Pulmonology, University of Medicine and Pharmacy “Victor Babes”, Timişoara, Romania Abstract: Idiopathic pulmonary fibrosis (IPF is the severest form of idiopathic interstitial pneumonia, with a median survival time estimated at 2–5 years from the time of diagnosis. It occurs mainly in elderly adults, suggesting a strong link between the fibrosis process and aging. Although chest high-resolution computed tomography (HRCT is currently the method of choice in IPF assessment, diagnostic imaging with typical usual interstitial pneumonia (UIP provides definitive results in only 55%, requiring an invasive surgical procedure such as lung biopsy or cryobiopsy for the final diagnostic analysis. Lung ultrasound (LUS as a noninvasive, non-radiating examination is very sensitive to detect subtle changes in the subpleural space. The evidence of diffuse, multiple B-lines defined as vertical, hyperechoic artifacts is the hallmark of interstitial syndrome. A thick, irregular, fragmented pleura line is associated with subpleural fibrotic scars. The total numbers of B-lines are correlated with the extension of pulmonary fibrosis on HRCT, being an LUS marker of severity. The average distance between two adjacent B-lines is an indicator of a particular pattern on HRCT. It is used to appreciate a pure reticular fibrotic pattern as in IPF compared with a predominant ground glass pattern seen in fibrotic nonspecific interstitial pattern. The distribution of the LUS artifacts has a diagnostic value. An upper predominance of multiple B-lines associated with the thickening of pleura line is an LUS feature of an inconsistent UIP pattern, excluding the IPF diagnosis. LUS is a

  14. Bronchoscopic Lung Cryobiopsy Increases Diagnostic Confidence in the Multidisciplinary Diagnosis of Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Tomassetti, Sara; Wells, Athol U; Costabel, Ulrich; Cavazza, Alberto; Colby, Thomas V; Rossi, Giulio; Sverzellati, Nicola; Carloni, Angelo; Carretta, Elisa; Buccioli, Matteo; Tantalocco, Paola; Ravaglia, Claudia; Gurioli, Christian; Dubini, Alessandra; Piciucchi, Sara; Ryu, Jay H; Poletti, Venerino

    2016-04-01

    Surgical lung biopsy is often required for a confident multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF). Alternative, less-invasive biopsy methods, such as bronchoscopic lung cryobiopsy (BLC), are highly desirable. To address the impact of BLC on diagnostic confidence in the multidisciplinary diagnosis of IPF. In this cross-sectional study we selected 117 patients with fibrotic interstitial lung disease without a typical usual interstitial pneumonia pattern on high-resolution computed tomography. All cases underwent lung biopsies: 58 were BLC, and 59 were surgical lung biopsy (SLB). Two clinicians, two radiologists, and two pathologists sequentially reviewed clinical-radiologic findings and biopsy results, recording at each step in the process their diagnostic impressions and confidence levels. We observed a major increase in diagnostic confidence after the addition of BLC, similar to SLB (from 29 to 63%, P = 0.0003 and from 30 to 65%, P = 0.0016 of high confidence IPF diagnosis, in the BLC group and SLB group, respectively). The overall interobserver agreement in IPF diagnosis was similar for both approaches (BLC overall kappa, 0.96; SLB overall kappa, 0.93). IPF was the most frequent diagnosis (50 and 39% in the BLC and SLB group, respectively; P = 0.23). After the addition of histopathologic information, 17% of cases in the BLC group and 19% of cases in the SLB group, mostly idiopathic nonspecific interstitial pneumonia and hypersensitivity pneumonitis, were reclassified as IPF. BLC is a new biopsy method that has a meaningful impact on diagnostic confidence in the multidisciplinary diagnosis of interstitial lung disease and may prove useful in the diagnosis of IPF. This study provides a robust rationale for future studies investigating the diagnostic accuracy of BLC compared with SLB.

  15. Selecting registration schemes in case of interstitial lung disease follow-up in CT

    International Nuclear Information System (INIS)

    Vlachopoulos, Georgios; Korfiatis, Panayiotis; Skiadopoulos, Spyros; Kazantzi, Alexandra; Kalogeropoulou, Christina; Pratikakis, Ioannis; Costaridou, Lena

    2015-01-01

    Purpose: Primary goal of this study is to select optimal registration schemes in the framework of interstitial lung disease (ILD) follow-up analysis in CT. Methods: A set of 128 multiresolution schemes composed of multiresolution nonrigid and combinations of rigid and nonrigid registration schemes are evaluated, utilizing ten artificially warped ILD follow-up volumes, originating from ten clinical volumetric CT scans of ILD affected patients, to select candidate optimal schemes. Specifically, all combinations of four transformation models (three rigid: rigid, similarity, affine and one nonrigid: third order B-spline), four cost functions (sum-of-square distances, normalized correlation coefficient, mutual information, and normalized mutual information), four gradient descent optimizers (standard, regular step, adaptive stochastic, and finite difference), and two types of pyramids (recursive and Gaussian-smoothing) were considered. The selection process involves two stages. The first stage involves identification of schemes with deformation field singularities, according to the determinant of the Jacobian matrix. In the second stage, evaluation methodology is based on distance between corresponding landmark points in both normal lung parenchyma (NLP) and ILD affected regions. Statistical analysis was performed in order to select near optimal registration schemes per evaluation metric. Performance of the candidate registration schemes was verified on a case sample of ten clinical follow-up CT scans to obtain the selected registration schemes. Results: By considering near optimal schemes common to all ranking lists, 16 out of 128 registration schemes were initially selected. These schemes obtained submillimeter registration accuracies in terms of average distance errors 0.18 ± 0.01 mm for NLP and 0.20 ± 0.01 mm for ILD, in case of artificially generated follow-up data. Registration accuracy in terms of average distance error in clinical follow-up data was in the

  16. Selecting registration schemes in case of interstitial lung disease follow-up in CT

    Energy Technology Data Exchange (ETDEWEB)

    Vlachopoulos, Georgios; Korfiatis, Panayiotis; Skiadopoulos, Spyros; Kazantzi, Alexandra [Department of Medical Physics, School of Medicine,University of Patras, Patras 26504 (Greece); Kalogeropoulou, Christina [Department of Radiology, School of Medicine, University of Patras, Patras 26504 (Greece); Pratikakis, Ioannis [Department of Electrical and Computer Engineering, Democritus University of Thrace, Xanthi 67100 (Greece); Costaridou, Lena, E-mail: costarid@upatras.gr [Department of Medical Physics, School of Medicine, University of Patras, Patras 26504 (Greece)

    2015-08-15

    Purpose: Primary goal of this study is to select optimal registration schemes in the framework of interstitial lung disease (ILD) follow-up analysis in CT. Methods: A set of 128 multiresolution schemes composed of multiresolution nonrigid and combinations of rigid and nonrigid registration schemes are evaluated, utilizing ten artificially warped ILD follow-up volumes, originating from ten clinical volumetric CT scans of ILD affected patients, to select candidate optimal schemes. Specifically, all combinations of four transformation models (three rigid: rigid, similarity, affine and one nonrigid: third order B-spline), four cost functions (sum-of-square distances, normalized correlation coefficient, mutual information, and normalized mutual information), four gradient descent optimizers (standard, regular step, adaptive stochastic, and finite difference), and two types of pyramids (recursive and Gaussian-smoothing) were considered. The selection process involves two stages. The first stage involves identification of schemes with deformation field singularities, according to the determinant of the Jacobian matrix. In the second stage, evaluation methodology is based on distance between corresponding landmark points in both normal lung parenchyma (NLP) and ILD affected regions. Statistical analysis was performed in order to select near optimal registration schemes per evaluation metric. Performance of the candidate registration schemes was verified on a case sample of ten clinical follow-up CT scans to obtain the selected registration schemes. Results: By considering near optimal schemes common to all ranking lists, 16 out of 128 registration schemes were initially selected. These schemes obtained submillimeter registration accuracies in terms of average distance errors 0.18 ± 0.01 mm for NLP and 0.20 ± 0.01 mm for ILD, in case of artificially generated follow-up data. Registration accuracy in terms of average distance error in clinical follow-up data was in the

  17. Mixed Herbal Medicine Induced Diffuse Infiltrative Lung Disease: The HRCT and Histopathologic Findings

    International Nuclear Information System (INIS)

    Kim, Tae Gyu; Shin, Eun A; Kim, Joung Sook

    2010-01-01

    The purpose of this study was to evaluate the high-resolution CT (HRCT) and pathologic findings of mixed herbal medicine-induced diffuse interstitial lung disease. Eight patients (6 women and 2 men, age range: 31 to 81 years, mean age: 51.4 years) who presented with cough or dyspnea after taking mixed herbal medicine were included in this study. All the patients underwent plain chest radiography and HRCT. We obtained pathologic specimens from 7 patients via fluoroscopy guided large bore cutting needle biopsy and transbronchial lung biopsy. All the patients were treated with steroid therapy. The most common HRCT finding was bilateral diffuse ground glass opacity (n=7), followed by peribronchial consolidation (n=5) and inter- or intralobular septal thickening (n=2). For the disease distribution, the lower lung zone was dominantly involved. The pathologic results of 7 patients were nonspecific interstitial pneumonia (n=3), bronchiolitis obliterans organizing pneumonia (n=2), hypersensitivity pneumonitis (n=1) and eosinophilic pneumonia (n=1). Irrespective of the pathologic results, all 8 patients improved clinically and radiologically after steroid treatment. The HRCT findings of mixed herbal medicine-induced diffuse infiltrative lung disease were mainly bilateral diffuse ground glass opacity, peribronchial consolidation and dominant involvement of the lower lung zone. Those pathologic findings were nonspecific and the differential diagnosis could include interstitial pneumonia, bronchiolitis obliterans organizing pneumonia, hypersensitivity pneumonitis and eosinophilic pneumonia

  18. Mixed Herbal Medicine Induced Diffuse Infiltrative Lung Disease: The HRCT and Histopathologic Findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Gyu; Shin, Eun A [Sanggye Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of); Kim, Joung Sook [Mokdong Hospital, Ewha Womans University College of Medicine, Seoul (Korea, Republic of)

    2010-12-15

    The purpose of this study was to evaluate the high-resolution CT (HRCT) and pathologic findings of mixed herbal medicine-induced diffuse interstitial lung disease. Eight patients (6 women and 2 men, age range: 31 to 81 years, mean age: 51.4 years) who presented with cough or dyspnea after taking mixed herbal medicine were included in this study. All the patients underwent plain chest radiography and HRCT. We obtained pathologic specimens from 7 patients via fluoroscopy guided large bore cutting needle biopsy and transbronchial lung biopsy. All the patients were treated with steroid therapy. The most common HRCT finding was bilateral diffuse ground glass opacity (n=7), followed by peribronchial consolidation (n=5) and inter- or intralobular septal thickening (n=2). For the disease distribution, the lower lung zone was dominantly involved. The pathologic results of 7 patients were nonspecific interstitial pneumonia (n=3), bronchiolitis obliterans organizing pneumonia (n=2), hypersensitivity pneumonitis (n=1) and eosinophilic pneumonia (n=1). Irrespective of the pathologic results, all 8 patients improved clinically and radiologically after steroid treatment. The HRCT findings of mixed herbal medicine-induced diffuse infiltrative lung disease were mainly bilateral diffuse ground glass opacity, peribronchial consolidation and dominant involvement of the lower lung zone. Those pathologic findings were nonspecific and the differential diagnosis could include interstitial pneumonia, bronchiolitis obliterans organizing pneumonia, hypersensitivity pneumonitis and eosinophilic pneumonia

  19. Effect of mixing scanner types and reconstruction kernels on the characterization of lung parenchymal pathologies: emphysema, interstitial pulmonary fibrosis and normal non-smokers

    Science.gov (United States)

    Xu, Ye; van Beek, Edwin J.; McLennan, Geoffrey; Guo, Junfeng; Sonka, Milan; Hoffman, Eric

    2006-03-01

    In this study we utilize our texture characterization software (3-D AMFM) to characterize interstitial lung diseases (including emphysema) based on MDCT generated volumetric data using 3-dimensional texture features. We have sought to test whether the scanner and reconstruction filter (kernel) type affect the classification of lung diseases using the 3-D AMFM. We collected MDCT images in three subject groups: emphysema (n=9), interstitial pulmonary fibrosis (IPF) (n=10), and normal non-smokers (n=9). In each group, images were scanned either on a Siemens Sensation 16 or 64-slice scanner, (B50f or B30 recon. kernel) or a Philips 4-slice scanner (B recon. kernel). A total of 1516 volumes of interest (VOIs; 21x21 pixels in plane) were marked by two chest imaging experts using the Iowa Pulmonary Analysis Software Suite (PASS). We calculated 24 volumetric features. Bayesian methods were used for classification. Images from different scanners/kernels were combined in all possible combinations to test how robust the tissue classification was relative to the differences in image characteristics. We used 10-fold cross validation for testing the result. Sensitivity, specificity and accuracy were calculated. One-way Analysis of Variances (ANOVA) was used to compare the classification result between the various combinations of scanner and reconstruction kernel types. This study yielded a sensitivity of 94%, 91%, 97%, and 93% for emphysema, ground-glass, honeycombing, and normal non-smoker patterns respectively using a mixture of all three subject groups. The specificity for these characterizations was 97%, 99%, 99%, and 98%, respectively. The F test result of ANOVA shows there is no significant difference (p <0.05) between different combinations of data with respect to scanner and convolution kernel type. Since different MDCT and reconstruction kernel types did not show significant differences in regards to the classification result, this study suggests that the 3-D AMFM can

  20. Mild pulmonary emphysema a risk factor for interstitial lung disease when using cetuximab for squamous cell carcinoma of the head and neck.

    Science.gov (United States)

    Okamoto, Isaku; Tsukahara, Kiyoaki; Sato, Hiroki; Motohashi, Ray; Yunaiyama, Daisuke; Shimizu, Akira

    2017-12-01

    Interstitial lung disease (ILD) is an occasionally fatal adverse event associated with cetuximab (Cmab) therapy. Our objective was to clarify to what degree pulmonary emphysema is a risk factor in the treatment of head and neck cancer with Cmab through a retrospective analysis. Subjects were 116 patients who were administered Cmab for head and neck squamous cell carcinoma. The degree of pulmonary emphysema before initiating treatment with Cmab was visually assessed retrospectively, with scoring according to the Goddard classification used in Japanese chronic obstructive pulmonary disease (COPD) guidelines for chest computed tomography (CT). Scoring was conducted by two diagnostic radiologists and mean scores were used. Cutoffs for the development and nondevelopment of ILD were examined by receiver operating characteristic (ROC) analysis and Fisher's exact test. Values of p pulmonary emphysema would represent a risk factor for ILD when using Cmab.

  1. Personalised medicine in interstitial lung diseases: Number 6 in the Series "Personalised medicine in respiratory diseases" Edited by Renaud Louis and Nicolas Roche.

    Science.gov (United States)

    Kokosi, Maria A; Margaritopoulos, George A; Wells, Athol U

    2018-06-30

    Interstitial lung diseases in general, and idiopathic pulmonary fibrosis in particular, are complex disorders with multiple pathogenetic pathways, various disease behaviour profiles and different responses to treatment, all facets that make personalised medicine a highly attractive concept. Personalised medicine is aimed at describing distinct disease subsets taking into account individual lifestyle, environmental exposures, genetic profiles and molecular pathways. The cornerstone of personalised medicine is the identification of biomarkers that can be used to inform diagnosis, prognosis and treatment stratification. At present, no data exist validating a personalised approach in individual diseases. However, the importance of the goal amply justifies the characterisation of genotype and pathway signatures with a view to refining prognostic evaluation and trial design, with the ultimate aim of selecting treatments according to profiles in individual patients. Copyright ©ERS 2018.

  2. Punica granatum L. Leaf Extract Attenuates Lung Inflammation in Mice with Acute Lung Injury.

    Science.gov (United States)

    Pinheiro, Aruanã Joaquim Matheus Costa Rodrigues; Gonçalves, Jaciara Sá; Dourado, Ádylla Wilenna Alves; de Sousa, Eduardo Martins; Brito, Natilene Mesquita; Silva, Lanna Karinny; Batista, Marisa Cristina Aranha; de Sá, Joicy Cortez; Monteiro, Cinara Regina Aragão Vieira; Fernandes, Elizabeth Soares; Monteiro-Neto, Valério; Campbell, Lee Ann; Zago, Patrícia Maria Wiziack; Lima-Neto, Lidio Gonçalves

    2018-01-01

    The hydroalcoholic extract of Punica granatum (pomegranate) leaves was previously demonstrated to be anti-inflammatory in a rat model of lipopolysaccharide- (LPS-) induced acute peritonitis. Here, we investigated the anti-inflammatory effects of the ethyl acetate fraction obtained from the pomegranate leaf hydroalcoholic extract (EAFPg) on the LPS-induced acute lung injury (ALI) mouse model. Male Swiss mice received either EAFPg at different doses or dexamethasone (per os) prior to LPS intranasal instillation. Vehicle-treated mice were used as controls. Animals were culled at 4 h after LPS challenge, and the bronchoalveolar lavage fluid (BALF) and lung samples were collected for analysis. EAFPg and kaempferol effects on NO and cytokine production by LPS-stimulated RAW 264.7 macrophages were also investigated. Pretreatment with EAFPg (100-300 mg/kg) markedly reduced cell accumulation (specially neutrophils) and collagen deposition in the lungs of ALI mice. The same animals presented with reduced lung and BALF TNF- α and IL-1 β expression in comparison with vehicle controls ( p < 0.05). Additionally, incubation with either EAFPg or kaempferol (100  μ g/ml) reduced NO production and cytokine gene expression in cultured LPS-treated RAW 264.7 macrophages. Overall, these results demonstrate that the prophylactic treatment with EAFPg attenuates acute lung inflammation. We suggest this fraction may be useful in treating ALI.

  3. Punica granatum L. Leaf Extract Attenuates Lung Inflammation in Mice with Acute Lung Injury

    Science.gov (United States)

    Pinheiro, Aruanã Joaquim Matheus Costa Rodrigues; Gonçalves, Jaciara Sá; Dourado, Ádylla Wilenna Alves; de Sousa, Eduardo Martins; Brito, Natilene Mesquita; Silva, Lanna Karinny; Batista, Marisa Cristina Aranha; de Sá, Joicy Cortez; Monteiro, Cinara Regina Aragão Vieira; Fernandes, Elizabeth Soares; Campbell, Lee Ann; Zago, Patrícia Maria Wiziack

    2018-01-01

    The hydroalcoholic extract of Punica granatum (pomegranate) leaves was previously demonstrated to be anti-inflammatory in a rat model of lipopolysaccharide- (LPS-) induced acute peritonitis. Here, we investigated the anti-inflammatory effects of the ethyl acetate fraction obtained from the pomegranate leaf hydroalcoholic extract (EAFPg) on the LPS-induced acute lung injury (ALI) mouse model. Male Swiss mice received either EAFPg at different doses or dexamethasone (per os) prior to LPS intranasal instillation. Vehicle-treated mice were used as controls. Animals were culled at 4 h after LPS challenge, and the bronchoalveolar lavage fluid (BALF) and lung samples were collected for analysis. EAFPg and kaempferol effects on NO and cytokine production by LPS-stimulated RAW 264.7 macrophages were also investigated. Pretreatment with EAFPg (100–300 mg/kg) markedly reduced cell accumulation (specially neutrophils) and collagen deposition in the lungs of ALI mice. The same animals presented with reduced lung and BALF TNF-α and IL-1β expression in comparison with vehicle controls (p < 0.05). Additionally, incubation with either EAFPg or kaempferol (100 μg/ml) reduced NO production and cytokine gene expression in cultured LPS-treated RAW 264.7 macrophages. Overall, these results demonstrate that the prophylactic treatment with EAFPg attenuates acute lung inflammation. We suggest this fraction may be useful in treating ALI. PMID:29675437

  4. Interstitial Features at Chest CT Enhance the Deleterious Effects of Emphysema in the COPDGene Cohort.

    Science.gov (United States)

    Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Rahaghi, Farbod N; Sanchez-Ferrero, Gonzalo Vegas; Putman, Rachel K; Hunninghake, Gary M; Onieva, Jorge Onieva; Martinez, Fernando J; Choi, Augustine M; Bowler, Russell P; Lynch, David A; Hatabu, Hiroto; Bhatt, Surya P; Dransfield, Mark T; Wells, J Michael; Rosas, Ivan O; San Jose Estepar, Raul; Washko, George R

    2018-06-05

    Purpose To determine if interstitial features at chest CT enhance the effect of emphysema on clinical disease severity in smokers without clinical pulmonary fibrosis. Materials and Methods In this retrospective cohort study, an objective CT analysis tool was used to measure interstitial features (reticular changes, honeycombing, centrilobular nodules, linear scar, nodular changes, subpleural lines, and ground-glass opacities) and emphysema in 8266 participants in a study of chronic obstructive pulmonary disease (COPD) called COPDGene (recruited between October 2006 and January 2011). Additive differences in patients with emphysema with interstitial features and in those without interstitial features were analyzed by using t tests, multivariable linear regression, and Kaplan-Meier analysis. Multivariable linear and Cox regression were used to determine if interstitial features modified the effect of continuously measured emphysema on clinical measures of disease severity and mortality. Results Compared with individuals with emphysema alone, those with emphysema and interstitial features had a higher percentage predicted forced expiratory volume in 1 second (absolute difference, 6.4%; P < .001), a lower percentage predicted diffusing capacity of lung for carbon monoxide (DLCO) (absolute difference, 7.4%; P = .034), a 0.019 higher right ventricular-to-left ventricular (RVLV) volume ratio (P = .029), a 43.2-m shorter 6-minute walk distance (6MWD) (P < .001), a 5.9-point higher St George's Respiratory Questionnaire (SGRQ) score (P < .001), and 82% higher mortality (P < .001). In addition, interstitial features modified the effect of emphysema on percentage predicted DLCO, RVLV volume ratio, 6WMD, SGRQ score, and mortality (P for interaction < .05 for all). Conclusion In smokers, the combined presence of interstitial features and emphysema was associated with worse clinical disease severity and higher mortality than was emphysema alone. In addition, interstitial features

  5. Pathophysiology of Pulmonary Hypertension in Chronic Parenchymal Lung Disease.

    Science.gov (United States)

    Singh, Inderjit; Ma, Kevin Cong; Berlin, David Adam

    2016-04-01

    Pulmonary hypertension commonly complicates chronic obstructive pulmonary disease and interstitial lung disease. The association of chronic lung disease and pulmonary hypertension portends a worse prognosis. The pathophysiology of pulmonary hypertension differs in the presence or absence of lung disease. We describe the physiological determinants of the normal pulmonary circulation to better understand the pathophysiological factors implicated in chronic parenchymal lung disease-associated pulmonary hypertension. This review will focus on the pathophysiology of 3 forms of chronic lung disease-associated pulmonary hypertension: idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and sarcoidosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. RNA interference targeting carbohydrate sulfotransferase 3 diminishes macrophage accumulation, inhibits MMP-9 expression and promotes lung recovery in murine pulmonary emphysema.

    Science.gov (United States)

    Kai, Yoshiro; Tomoda, Koichi; Yoneyama, Hiroyuki; Yoshikawa, Masanori; Kimura, Hiroshi

    2015-12-09

    Chondroitin sulfate proteoglycans are an important mediators in inflammation and leukocyte trafficking. However, their roles in pulmonary emphysema have not been explored. In a murine model of elastase-induced pulmonary emphysema, we found increased carbohydrate sulfotransferase 3 (CHST3), a specific enzyme that synthesizes chondroitin 6-sulfate proteoglycan (C6SPG). To elucidate the role of C6SPG, we investigated the effect of small interfering RNA (siRNA) targeting CHST3 that inhibits C6SPG-synthesis on the pathogenesis of pulmonary emphysema. Mice were intraperitoneally injected with CHST3 siRNA or negative control siRNA on day0 and 7 after intratracheal instillation of elastase. Histology, respiratory function, glycosaminoglycans (GAGs) content, bronchoalveolar lavage (BAL), elastin staining and gene expressions of tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-9 mRNA were evaluated on day7 and/or day21. CHST3 mRNA increased at day 7 and decreased thereafter in lung. CHST3 siRNA successfully inhibited the expression of CHST3 mRNA throughout the study and this was associated with significant reduction of GAGs and C6SPG. Airway destruction and respiratory function were improved by the treatment with CHST3 siRNA. CHST3 siRNA reduced the number of macrophages both in BAL and lung parenchyma and also suppressed the increased expressions of TNF-α and MMP-9 mRNA. Futhermore, CHST3 siRNA improved the reduction of the elastin in the alveolar walls. CHST3 siRNA diminishes accumulation of excessive macrophages and the mediators, leading to accelerate the functional recovery from airway damage by repair of the elastin network associated with pulmonary emphysema.

  7. Macrophages as key elements of Mixed-oxide [U-Pu(O2)] distribution and pulmonary damage after inhalation?

    Science.gov (United States)

    Van der Meeren, Anne; Moureau, Agnes; Griffiths, Nina M

    2014-11-01

    Abstract Purpose: To investigate the consequences of alveolar macrophage (AM) depletion on Mixed OXide fuel (MOX: U, Pu oxide) distribution and clearance, as well as lung damage following MOX inhalation. Rats were exposed to MOX by nose only inhalation. AM were depleted with intratracheal administration of liposomal clodronate at 6 weeks. Lung changes, macrophage activation, as well as local and systemic actinide distribution were studied up to 3 months post-inhalation. Clodronate administration modified excretion/retention patterns of α activity. At 3 months post-inhalation lung retention was higher in clodronate-treated rats compared to Phosphate Buffered Saline (PBS)-treated rats, and AM-associated α activity was also increased. Retention in liver was higher in clodronate-treated rats and fecal and urinary excretions were lower. Three months after inhalation, rats exhibited lung fibrotic lesions and alveolitis, with no marked differences between the two groups. Foamy macrophages of M2 subtype [inducible Nitric Oxide Synthase (iNOS) negative but galectin-3 positive] were frequently observed, in correlation with the accumulation of MOX particles. AM from all MOX-exposed rats showed increased chemokine levels as compared to sham controls. Despite the transient reduced AM numbers in clodronate-treated animals no major differences on lung damage were observed as compared to non-treated rats after MOX inhalation. The higher lung activity retention in rats receiving clodronate seems to be part of a general inflammatory response and needs further investigation.

  8. Effects of vitamin D supplementation on alveolar macrophage gene expression: preliminary results of a randomized, controlled trial.

    Science.gov (United States)

    Gerke, Alicia K; Pezzulo, Alejandro A; Tang, Fan; Cavanaugh, Joseph E; Bair, Thomas B; Phillips, Emily; Powers, Linda S; Monick, Martha M

    2014-03-26

    Vitamin D deficiency has been implicated as a factor in a number of infectious and inflammatory lung diseases. In the lung, alveolar macrophages play a key role in inflammation and defense of infection, but there are little data exploring the immunomodulatory effects of vitamin D on innate lung immunity in humans. The objective of this study was to determine the effects of vitamin D supplementation on gene expression of alveolar macrophages. We performed a parallel, double-blind, placebo-controlled, randomized trial to determine the effects of vitamin D on alveolar macrophage gene expression. Vitamin D3 (1000 international units/day) or placebo was administered to adults for three months. Bronchoscopy was performed pre- and post-intervention to obtain alveolar macrophages. Messenger RNA was isolated from the macrophages and subjected to whole genome exon array analysis. The primary outcome was differential gene expression of the alveolar macrophage in response to vitamin D supplementation. Specific genes underwent validation by polymerase chain reaction methods. Fifty-eight subjects were randomized to vitamin D (n = 28) or placebo (n = 30). There was a marginal overall difference between treatment group and placebo group in the change of 25-hydroxyvitaminD levels (4.43 ng/ml vs. 0.2 ng/ml, p = 0.10). Whole genome exon array analysis revealed differential gene expression associated with change in serum vitamin D levels in the treated group. CCL8/MCP-2 was the top-regulated cytokine gene and was further validated. Although only a non-significant increased trend was seen in serum vitamin D levels, subjects treated with vitamin D supplementation had immune-related differential gene expression in alveolar macrophages. ClinicalTrials.org: NCT01967628.

  9. Immunohistochemical detection of virus through its nuclear cytopathic effect in idiopathic interstitial pneumonia other than acute exacerbation

    Directory of Open Access Journals (Sweden)

    G.C. dos Santos

    2013-11-01

    Full Text Available Idiopathic interstitial pneumonias include complex diseases that have a strong interaction between genetic makeup and environmental factors. However, in many cases, no infectious agent can be demonstrated, and these clinical diseases rapidly progress to death. Theoretically, idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them. To test the hypothesis that immunohistochemistry provides more accurate results than the mere histological demonstration of viral inclusions, this method was applied to 37 open lung biopsies obtained from patients with idiopathic interstitial pneumonias. As a result, immunohistochemistry detected measles virus and cytomegalovirus in diffuse alveolar damage-related histological patterns of acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia in 38 and 10% of the cases, respectively. Alveolar epithelium infection by cytomegalovirus was observed in 25% of organizing pneumonia patterns. These findings were coincident with nuclear cytopathic effects but without demonstration of cytomegalovirus inclusions. These data indicate that diffuse alveolar damage-related cytomegalovirus or measles virus infections enhance lung injury, and a direct involvement of these viruses in diffuse alveolar damage-related histological patterns is likely. Immunohistochemistry was more sensitive than the histological demonstration of cytomegalovirus or measles virus inclusions. We concluded that all patients with diffuse alveolar damage-related histological patterns should be investigated for cytomegalovirus and measles virus using sensitive immunohistochemistry in conjunction with routine procedures.

  10. A TNF-Regulated Recombinatorial Macrophage Immune Receptor Implicated in Granuloma Formation in Tuberculosis

    Science.gov (United States)

    Streich, Roswita; Breysach, Caroline; Raddatz, Dirk; Oniga, Septimia; Peccerella, Teresa; Findeisen, Peter; Kzhyshkowska, Julia; Gratchev, Alexei; Schweyer, Stefan; Saunders, Bernadette; Wessels, Johannes T.; Möbius, Wiebke; Keane, Joseph; Becker, Heinz; Ganser, Arnold; Neumaier, Michael; Kaminski, Wolfgang E.

    2011-01-01

    Macrophages play a central role in host defense against mycobacterial infection and anti- TNF therapy is associated with granuloma disorganization and reactivation of tuberculosis in humans. Here, we provide evidence for the presence of a T cell receptor (TCR) αβ based recombinatorial immune receptor in subpopulations of human and mouse monocytes and macrophages. In vitro, we find that the macrophage-TCRαβ induces the release of CCL2 and modulates phagocytosis. TNF blockade suppresses macrophage-TCRαβ expression. Infection of macrophages from healthy individuals with mycobacteria triggers formation of clusters that express restricted TCR Vβ repertoires. In vivo, TCRαβ bearing macrophages abundantly accumulate at the inner host-pathogen contact zone of caseous granulomas from patients with lung tuberculosis. In chimeric mouse models, deletion of the variable macrophage-TCRαβ or TNF is associated with structurally compromised granulomas of pulmonary tuberculosis even in the presence of intact T cells. These results uncover a TNF-regulated recombinatorial immune receptor in monocytes/macrophages and demonstrate its implication in granuloma formation in tuberculosis. PMID:22114556

  11. A TNF-regulated recombinatorial macrophage immune receptor implicated in granuloma formation in tuberculosis.

    Directory of Open Access Journals (Sweden)

    Alexander W Beham

    2011-11-01

    Full Text Available Macrophages play a central role in host defense against mycobacterial infection and anti- TNF therapy is associated with granuloma disorganization and reactivation of tuberculosis in humans. Here, we provide evidence for the presence of a T cell receptor (TCR αβ based recombinatorial immune receptor in subpopulations of human and mouse monocytes and macrophages. In vitro, we find that the macrophage-TCRαβ induces the release of CCL2 and modulates phagocytosis. TNF blockade suppresses macrophage-TCRαβ expression. Infection of macrophages from healthy individuals with mycobacteria triggers formation of clusters that express restricted TCR Vβ repertoires. In vivo, TCRαβ bearing macrophages abundantly accumulate at the inner host-pathogen contact zone of caseous granulomas from patients with lung tuberculosis. In chimeric mouse models, deletion of the variable macrophage-TCRαβ or TNF is associated with structurally compromised granulomas of pulmonary tuberculosis even in the presence of intact T cells. These results uncover a TNF-regulated recombinatorial immune receptor in monocytes/macrophages and demonstrate its implication in granuloma formation in tuberculosis.

  12. Interaction with Epithelial Cells Modifies Airway Macrophage Response to Ozone

    Science.gov (United States)

    The initial innate immune response to ozone (03) in the lung is orchestrated by structural cells, such as epithelial cells, and resident immune cells, such as airway macrophages (Macs). We developed an epithelial cell-Mac coculture model to investigate how epithelial cell-derived...

  13. The role of macrophage derived growth factors in pulmonary fibrosis

    International Nuclear Information System (INIS)

    Pickrell, J.A.; Jarpe, M.; Benson, J.M.; Henderson, R.F.

    1988-01-01

    Factors released from rat alveolar macrophages exposed to high (95 μg/mL) concentrations of the fibrogenic agent, nickel subsulfide, were found to inhibit the proliferation of cultured lung epithelial cells and stimulate the growth of fibroblasts. Such factors, if present in the alveoli of rats exposed by inhalation to nickel subsulfide in vivo, may play a role in inhibiting re-epithelization of nickel-damaged lungs and in stimulating fibroblast proliferation, leading to pulmonary fibrosis. (author)

  14. A Case of Yellow Nail Syndrome Accompanying Idiopathic Interstitial Pneumonia; Successful Treatment with Clarithromycin, Methylprednisolone, and Alpha-Tocopherol

    Directory of Open Access Journals (Sweden)

    Bilge Yılmaz Kara

    2017-12-01

    Full Text Available A 51-year-old woman presented with complaints of dyspnea, fatigue, and non-productive cough. Chest X-ray showed bilateral lung infiltrates. Nonspecific air-space consolidation on anterior segment of the right lower lobe, bilateral bronchiectasis and infiltrates, patchy ground-glass opacities, and interstitial thickening were reported on thorax computed tomography which was non-responsive to antibiotics. After tru-cut biopsy which only revealed a single granuloma in a particular area, alveolar septal thickening and fibrosis, slight chronic inflammation with findings of congestion, lung involvement was considered to be associated with nonspecific interstitial pneumonia. The nails on all fingers displayed yellow discoloration with mild edema in the face and the legs. The final diagnosis was yellow nail syndrome. Short-term clarithromycin and long-term oral methylprednisolone with vitamin E treatment were successful. After 4 months, all components of the syndrome almost completely regressed.

  15. Requirement for C-X-C chemokines (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) in IgG immune complex-induced lung injury

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Warner, R L

    1997-01-01

    chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC). Both mRNA and protein for MIP-2 and CINC appeared in a time-dependent manner after initiation of IgG immune complex deposition in lung. There exists a 69% homology between the amino acid sequences...... for these proteins, and we found cross-reactivity between polyclonal Abs raised to these chemokines. By purifying the blocking Abs using double affinity methods (with Ag-immobilized beads), this cross-reactivity was removed. Individually, anti-MIP-2 and anti-CINC Ab significantly reduced lung injury (as measured...... activity in BAL fluids collected 2 h after injury from animals undergoing immune complex deposition could be shown to be chiefly due to the combined contributions of MIP-2 (39%), CINC (28%), and C5a (21%). When either MIP-2 or CINC was blocked in vivo, up-regulation of Mac-1 expression on neutrophils...

  16. Energetics of formation and migration of self-interstitials and self-interstitial clusters in α-iron

    International Nuclear Information System (INIS)

    Wirth, B.D.; Odette, G.R.; California Univ., Santa Barbara, CA; Maroudas, D.; Lucas, G.E.; California Univ., Santa Barbara, CA

    1997-01-01

    Energetic primary recoil atoms from fast neutron irradiation generate both isolated point defects and clusters of vacancies and interstitials. Self-interstitial mobility as well as defect cluster stability and mobility play key roles in the subsequent fate of defects and, hence, in the overall microstructural evolution under irradiation. Self-interstitials and two, three and four-member self-interstitial clusters are highly mobile at low temperatures as observed in molecular-dynamics simulations and high mobility probably also extends to larger clusters. In this study, the morphology, energetics and mobility of self-interstitials and small self-interstitial clusters in α-iron are studied by molecular-statics and molecular-dynamics simulations using a Finnis-Sinclair many-body interatomic potential. Self-interstitial migration is found to be a two-step process consisting of a rotation out of the split-dumbbell configuration into the split-dumbbell configuration and translational jumps through the crowdion configuration before returning to the dumbbell configuration. Self-interstitial clusters of type split-interstitials assembled on adjacent {110} planes migrate along directions in an amoeba-like fashion by sequential local dissociation and re-association processes. (orig.)

  17. Fibrotic idiopathic interstitial pneumonias: HRCT findings that predict mortality

    Energy Technology Data Exchange (ETDEWEB)

    Edey, Anthony J.; Hansell, David M. [The Royal Brompton Hospital, Department of Radiology, London (United Kingdom); Devaraj, Anand A. [St. George' s NHS Foundation Trust, Department of Radiology, Tooting (United Kingdom); Barker, Robert P. [Frimley Park Hosptal, Department of Radiology, Frimley, Surrey (United Kingdom); Nicholson, Andrew G. [The Royal Brompton Hospital, Department of Histopathology, London (United Kingdom); Wells, Athol U. [The Royal Brompton Hospital, Interstitial Lung Disease Unit, London (United Kingdom)

    2011-08-15

    The study aims were to identify CT features that predict outcome of fibrotic idiopathic interstitial pneumonia (IIP) when information from lung biopsy data is unavailable. HRCTs of 146 consecutive patients presenting with fibrotic IIP were studied. Visual estimates were made of the extent of abnormal lung and proportional contribution of fine and coarse reticulation, microcystic (cysts {<=}4 mm) and macrocystic honeycombing. A score for severity of traction bronchiectasis was also assigned. Using death as our primary outcome measure, variables were analysed using the Cox proportional hazards model. CT features predictive of a worse outcome were coarse reticulation, microcystic and macrocystic honeycombing, as well as overall extent of lung abnormality (p < 0.001). Importantly, increased severity of traction bronchiectasis, corrected for extent of parenchymal abnormality, was predictive of poor prognosis regardless of the background pattern of abnormal lung (HR = 1.04, CI = 1.03-1.06, p < 0.001). On bivariate Cox analysis microcystic honeycombing was a more powerful determinant of a poor prognosis than macrocystic honeycombing. In fibrotic IIPs we have shown that increasingly severe traction bronchiectasis is indicative of higher mortality irrespective of the HRCT pattern and extent of disease. Extent of microcystic honeycombing is a more powerful determinant of outcome than macrocystic honeycombing. (orig.)

  18. Doenças pulmonares intersticiais: Acuidade diagnóstica e riscos da biópsia pulmonar cirúrgica Interstitial lung disease: Diagnostic accuracy and safety of surgical lung biopsy

    Directory of Open Access Journals (Sweden)

    Miguel Guerra

    2009-05-01

    Full Text Available Os autores descrevem a sua casuística de biópsias pulmonares cirúrgicas em doentes com doença pulmonar intersticial, de forma a determinar a acuidade diagnóstica, os riscos e a morbimortalidade associados ao procedimento. Entre Janeiro de 1998 e Dezembro de 2007, 53 doentes (idade média de 47,2±13 anos foram referenciados para a realização de biópsia pulmonar cirúrgica, dos quais 22 eram mulheres (41,5%. As biópsias pulmonares foram realizadas quer por videotoracoscopia (37 doentes, 69,8%, quer por minitoracotomia (16 doentes, 30,2%. Foi escolhido o pulmão direito para biopsar em 88,7% dos casos. Registaram-se complicações pós-operatórias em 5 doentes (9,4%: fuga aérea prolongada em 3 doentes (5,7%, persistência de loca de pneumotórax num doente (1,9% e hemorragia com necessidade de revisão de hemostase noutro doente (1,9%. Ocorreu um óbito de causa desconhecida num doente sem risco acrescido. A duração média da drenagem foi de 4,4±3 dias e o tempo de internamento médio de 5,5±4 dias. O diagnóstico histológico definitivo foi conseguido em 50 doentes, registando-se uma acuidade diagnóstica de 94,3%. Em conclusão, o potencial benefício de um diagnóstico histopatológico conclusivo através de uma biópsia pulmonar cirúrgica deve ser balanceado com os riscos associados ao procedimento cirúrgico, especialmente para aqueles doentes com disfunção cardiopulmonar severa.This study reports our experience, diagnostic accuracy and safety of surgical lung biopsy in patients with interstitial lung diseases. From January 1998 – December 2007 surgical lung biopsy was performed in 53 patients (22 female [41.5%]; age 47.2±13 years. A total of 37 patients (69.8% underwent videothoracoscopic lung biopsy and minithoracotomy was performed in 16 patients (30.2%. Right lung was the choice in 47 patients (88.7%. Postoperative complications were rare (9.4% and included three prolonged air leaks (5.7%, one pneumothorax requiring a

  19. Granulomatous interstitial pneumonia in a miniature swine associated with repeated intravenous injections of Tc-99m human serum albumin: concise communication

    International Nuclear Information System (INIS)

    Whinnery, J.E.; Young, J.T.

    1980-01-01

    Albumin lung-scanning agents have a proven high degree of safety, with the only contraindication to their use being allergic hypersensitivity. We have used these agents to investigate the physiologic effects of high G/sub z/ acceleratory forces on pulmonary perfusion using the miniature swine. Multiple doses of human macroaggregated albumin and human-albumin microspheres were given to a miniature swine at various levels of centrifugal acceleration over a 6-wk period. The dosages given were the same per kilogram as those used for routine clinical human studies. The animal subsequently died from a severe granulomatous interstitial pneumonia. The granulomatous lesions suggest that the pathogenesis may have involved a cell-mediated delayed hypersensitivity. This interstitial pneumonia may represent the end point in a chronic hypersensitivity response to the human-albumin lung-scanning agents

  20. INTERSTITIAL LUNG-DISEASE AND MYOSITIS IN A PATIENT WITH SIMULTANEOUSLY OCCURRING SARCOIDOSIS AND SCLERODERMA

    NARCIS (Netherlands)

    GROEN, H; POSTMA, DS; KALLENBERG, CGM

    1993-01-01

    A patient initially presented with sarcoidosis in combination with myositis of sarcoid origin and Raynaud's phenomenon. During the course of his disease, he additionally developed scleroderma. Bronchoalveolar lavage, performed because of increase of interstitial markings in the presence of enlarged

  1. Observer agreement in the diagnosis of interstitial lung diseases based on HRCT scans

    International Nuclear Information System (INIS)

    Antunes, Viviane Baptista; Meirelles, Gustavo de Souza Portes; Jasinowodolinski, Dany; Verrastro, Carlos Gustavo Yuji; Torlai, Fabiola Goda

    2010-01-01

    Objective: to determine the interobserver and intraobserver agreement in the diagnosis of interstitial lung diseases (ILDs) based on HRCT scans and the impact of observer expertise, clinical data and confidence level on such agreement. Methods: two thoracic radiologists and two general radiologists independently reviewed the HRCT images of 58 patients with ILDs on two distinct occasions: prior to and after the clinical anamnesis. The radiologists selected up to three diagnostic hypotheses for each patient and defined the confidence level for these hypotheses. One of the thoracic and one of the general radiologists re-evaluated the same images up to three months after the first readings. In the coefficient analyses, the kappa statistic was used. Results: the thoracic and general radiologists, respectively, agreed on at least one diagnosis for each patient in 91.4% and 82.8% of the patients. The thoracic radiologists agreed on the most likely diagnosis in 48.3% (κ = 0.42) and 62.1% (κ = 0.58) of the cases, respectively, prior to and after the clinical anamnesis; likewise, the general radiologists agreed on the most likely diagnosis in 37.9% (κ 0.32) and 36.2% (κ = 0.30) of the cases. For the thoracic radiologist, the intraobserver agreement on the most likely diagnosis was 0.73 and 0.63 prior to and after the clinical anamnesis, respectively. That for the general radiologist was 0.38 and 0.42.The thoracic radiologists presented almost perfect agreement for the diagnostic hypotheses defined with the high confidence level. Conclusions: Interobserver and intraobserver agreement in the diagnosis of ILDs based on HRCT scans ranged from fair to almost perfect and was influenced by radiologist expertise, clinical history and confidence level. (author)

  2. Prognostic factors in a cohort of antisynthetase syndrome (ASS): serologic profile is associated with mortality in patients with interstitial lung disease (ILD).

    Science.gov (United States)

    Rojas-Serrano, Jorge; Herrera-Bringas, Denisse; Mejía, Mayra; Rivero, Hermes; Mateos-Toledo, Heidegger; Figueroa, José E

    2015-09-01

    The objectives of the present study were to compare the survival function of antisynthetase syndrome (ASS) Jo1-positive patients with ASS non-Jo1 patients, all with interstitial lung disease (ILD), and to evaluate other factors such as the extension of pulmonary disease and the time between the onset of symptoms and diagnosis and its association to survival in a cohort of ASS patients. Patients with ASS, all with ILD, were included. At the baseline, pulmonary function tests were realized and a high-resolution chest tomography was obtained; lung inflammation and fibrosis were measured with the Goh score and the Kazerooni index. The following autoantibodies were measured: Jo1, Ej, Oj, PL7, and PL12. Patients had to be positive for one of them in order to be included in the study. The survival function was estimated and compared with the log rank test, and the hazard ratio (HR) was estimated using Cox regression procedure. Forty-three patients were included, of which six patients died (14 %). Patients who died were different in comparison with survivors as regards the frequency of anti-Jo1 positivity: Survivors had anti-Jo1 autoantibodies more frequently (86 %) than patients who died (50 %). The univariate Cox regression analysis identified four variables associated with survival: Jo1 status, arthritis, extent of ground glass, and consolidation (inflammation) in high-resolution computed tomography (HRCT) and baseline forced vital capacity. The serological status of patients (Jo1-positive vs non-Jo1), the extent of lung inflammation in the HRCT scan, a low forced vital capacity, and arthritis are associated with survival in ASS patients.

  3. Extracorporeal Membrane Oxygenation for End-Stage Interstitial Lung Disease With Secondary Pulmonary Hypertension at Rest and Exercise: Insights From Simulation Modeling.

    Science.gov (United States)

    Chicotka, Scott; Burkhoff, Daniel; Dickstein, Marc L; Bacchetta, Matthew

    Interstitial lung disease (ILD) represents a collection of lung disorders with a lethal trajectory with few therapeutic options with the exception of lung transplantation. Various extracorporeal membrane oxygenation (ECMO) configurations have been used for bridge to transplant (BTT), yet no optimal configuration has been clearly demonstrated. Using a cardiopulmonary simulation, we assessed different ECMO configurations for patients with end-stage ILD to assess the physiologic deficits and help guide the development of new long-term pulmonary support devices. A cardiopulmonary ECMO simulation was created, and changes in hemodynamics and blood gases were compared for different inflow and outflow anatomic locations and for different sweep gas and blood pump flow rates. The system simulated the physiologic response of patients with severe ILD at rest and during exercise with central ECMO, peripheral ECMO, and with no ECMO. The output parameters were total cardiac output (CO), mixed venous oxygen (O2) saturation, arterial pH, and O2 delivery (DO2)/O2 utilization (VO2) at different levels of exercise. The model described the physiologic state of progressive ILD and showed the relative effects of using various ECMO configurations to support them. It elucidated the optimal device configurations and required physiologic pump performance and provided insight into the physiologic demands of exercise in ILD patients. The simulation program was able to model the pathophysiologic state of progressive ILD with PH and demonstrate how mechanical support devices can be implemented to improve cardiopulmonary function at rest and during exercise. The information generated from simulation can be used to optimize ECMO configuration selection for BTT patients and provide design guidance for new devices to better meet the physiologic demands of exercise associated with normal activities of daily living.

  4. Histopathology of lung disease in the connective tissue diseases.

    Science.gov (United States)

    Vivero, Marina; Padera, Robert F

    2015-05-01

    The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Elemental analysis of occupational and environmental lung diseases by electron probe microanalyzer with wavelength dispersive spectrometer.

    Science.gov (United States)

    Takada, Toshinori; Moriyama, Hiroshi; Suzuki, Eiichi

    2014-01-01

    Occupational and environmental lung diseases are a group of pulmonary disorders caused by inhalation of harmful particles, mists, vapors or gases. Mineralogical analysis is not generally required in the diagnosis of most cases of these diseases. Apart from minerals that are encountered rarely or only in specific occupations, small quantities of mineral dusts are present in the healthy lung. As such when mineralogical analysis is required, quantitative or semi-quantitative methods must be employed. An electron probe microanalyzer with wavelength dispersive spectrometer (EPMA-WDS) enables analysis of human lung tissue for deposits of elements by both qualitative and semi-quantitative methods. Since 1993, we have analyzed 162 cases of suspected occupational and environmental lung diseases using an EPMA-WDS. Our institute has been accepting online requests for elemental analysis of lung tissue samples by EPMA-WDS since January 2011. Hard metal lung disease is an occupational interstitial lung disease that primarily affects workers exposed to the dust of tungsten carbide. The characteristic pathological findings of the disease are giant cell interstitial pneumonia (GIP) with centrilobular fibrosis, surrounded by mild alveolitis with giant cells within the alveolar space. EPMA-WDS analysis of biopsied lung tissue from patients with GIP has demonstrated that tungsten and/or cobalt is distributed in the giant cells and centrilobular fibrosing lesion in GIP. Pneumoconiosis, caused by amorphous silica, and acute interstitial pneumonia, associated with the giant tsunami, were also elementally analyzed by EPMA-WDS. The results suggest that commonly found elements, such as silicon, aluminum, and iron, may cause occupational and environmental lung diseases. Copyright © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  6. The Alveolar Microenvironment of Patients Infected with Human Immunodeficiency Virus Does Not Modify Alveolar Macrophage Interactions with Streptococcus pneumoniae

    Science.gov (United States)

    Jagoe, R. Thomas; Jarman, Elizabeth R.; North, James C.; Pridmore, Alison; Musaya, Janelisa; French, Neil; Zijlstra, Eduard E.; Molyneux, Malcolm E.; Read, Robert C.

    2013-01-01

    We tested the hypothesis that HIV infection results in activation of alveolar macrophages and that this might be associated with impaired defense against pneumococcus. We compared alveolar macrophages and lymphocytes in 131 bronchoalveolar lavage samples from HIV-infected and healthy controls using inflammatory gene microarrays, flow cytometry, real-time PCR, and enzyme-linked immunosorbent assay (ELISA) to determine the pattern of macrophage activation associated with HIV infection and the effect of this activation on defense against pneumococcus. We used gamma interferon (IFN-γ) priming to mimic the cellular milieu in HIV-infected lungs. InnateDB and BioLayout 3D were used to analyze the interactions of the upregulated genes. Alveolar macrophages from HIV-infected adults showed increased gene expression and cytokine production in a classical pattern. Bronchoalveolar lavage from HIV-infected subjects showed excess CD8+ lymphocytes with activated phenotype. Toll-like receptor 4 (TLR4) expression was increased in macrophages from HIV-infected subjects, but function was similar between the groups; lung lavage fluid did not inhibit TLR function in transfected HeLa cells. Alveolar macrophages from HIV-infected subjects showed normal binding and internalization of opsonized pneumococci, with or without IFN-γ priming. Alveolar macrophages from HIV-infected subjects showed classical activation compared to that of healthy controls, but this does not alter macrophage interactions with pneumococci. PMID:23576675

  7. Interstitial inflammatory lesions of the pulmonary allograft: a retrospective analysis of 2697 transbronchial biopsies

    DEFF Research Database (Denmark)

    Burton, C.M.; Iversen, M.; Carlsen, J.

    2008-01-01

    . The strongest histological correlations were between ACR and lymphocytic bronchiolitis (OR 5.1, Pfibrosis (OR 3.2, Ppulmonary hemosiderosis were also more likely to demonstrate the finding of interstitial fibrosis (OR 3.0 and 3.7, P..., incidence and possible associations between commonly identified inflammatory and fibrotic lesions in the pulmonary allograft. METHODS: Retrospective chart review of all transbronchial biopsies performed within the first 2 years of 299 lung-transplanted patients in the period 1996 to 2006. RESULTS: A total...... (BOOP) and interstitial pneumonitis occurred at 4 to 6 weeks, and 6 to 12 weeks, respectively. There was a steady increase in the cumulative proportion of patients with fibrosis and bronchiolitis obliterans, at each successive scheduled surveillance time point beyond 3 months posttransplantation...

  8. [Use of lung ultrasound as a prognostic tool in outpatients with heart failure].

    Science.gov (United States)

    Tojo Villanueva, María Del Carmen; Fernández López, María; Canora Lebrato, Jesús; Satué Bartolomé, José Ángel; San Martín Prado, Alberto; Zapatero Gaviria, Antonio

    2016-07-01

    To assess the prognostic value of lung ultrasound for patients with chronic heart failure. Prospective observational cohort study, in which a lung ultrasound was performed on 54 patients at a heart failure outpatient consultation. Ultrasonography was classified as positive or negative for ultrasound interstitial syndrome depending on the number of B lines observed. Patients were followed up for six months; considering emergency visits, readmissions and deaths due to heart failure as markers of poor prognosis. 53.7% (29) of the patients had ultrasound interstitial syndrome. Among them, 48.3% (14) were readmitted, compared to 16% (4) of those without the syndrome (P=.012). Considering any of the events previously described as end points (readmissions, emergencies and deaths), we found that in the group of patients with ultrasound interstitial syndrome, 55.2% (16) had at least one of these complications, compared to 20% (5) of participants without the syndrome (P=.008). Lung ultrasound in the outpatient setting is useful in predicting which patients are at increased risk of heart failure decompensation in the mid-term. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  9. Resident alveolar macrophages are susceptible to and permissive of Coxiella burnetii infection.

    Directory of Open Access Journals (Sweden)

    Matthew Calverley

    Full Text Available Coxiella burnetii, the causative agent of Q fever, is a zoonotic disease with potentially life-threatening complications in humans. Inhalation of low doses of Coxiella bacteria can result in infection of the host alveolar macrophage (AM. However, it is not known whether a subset of AMs within the heterogeneous population of macrophages in the infected lung is particularly susceptible to infection. We have found that lower doses of both phase I and phase II Nine Mile C. burnetii multiply and are less readily cleared from the lungs of mice compared to higher infectious doses. We have additionally identified AM resident within the lung prior to and shortly following infection, opposed to newly recruited monocytes entering the lung during infection, as being most susceptible to infection. These resident cells remain infected up to twelve days after the onset of infection, serving as a permissive niche for the maintenance of bacterial infection. A subset of infected resident AMs undergo a distinguishing phenotypic change during the progression of infection exhibiting an increase in surface integrin CD11b expression and continued expression of the surface integrin CD11c. The low rate of phase I and II Nine Mile C. burnetii growth in murine lungs may be a direct result of the limited size of the susceptible resident AM cell population.

  10. Lung congestion in chronic heart failure: haemodynamic, clinical, and prognostic implications

    DEFF Research Database (Denmark)

    Melenovsky, Vojtech; Andersen, Mads Jønsson; Andress, Krystof

    2015-01-01

    AIMS:The goal of the study was to examine the prognostic impact, haemodynamic and clinical features associated with lung congestion in patients with chronic heart failure (HF). METHODS AND RESULTS:HF patients (n = 186) and HF-free controls (n = 21) underwent right heart catheterization...... days (interquartile range 80-875), 59 patients (32%) died. Lung congestion was associated with reduced survival (P renal dysfunction. CONCLUSION:Interstitial lung oedema is associated with pulmonary vascular disease, RV overload...

  11. A mast cell secretagogue, compound 48/80, prevents the accumulation of hyaluronan in lung tissue injured by ionizing irradiation

    International Nuclear Information System (INIS)

    Nilsson, K.; Bjermer, L.; Hellstroem, S.H.; Henriksson, R.; Haellgren, R.

    1990-01-01

    Irradiation with a single dose of 30 Grey on the basal regions of the lungs of Sprague-Dawley rats induced a peribronchial and alveolar inflammation. Infiltration of mast cells in the edematous alveolar interstitial tissue and also in the peribronchial tissue were characteristic features of the lesion. The appearance of mast cells was already seen 4 wk after irradiation and by weeks 6 to 8 there was a heavy infiltration. The staining properties suggested that they were connective tissue-type mast cells. The infiltration of mast cells was paralleled by an accumulation of hyaluronan (hyaluronic acid) in the alveolar interstitial tissue 6 and 8 wk after irradiation. The recovery of hyaluronan (HA) during bronchoalveolar lavage (BAL) of the lungs also increased at this time. Treatment with a mast cell secretagogue, compound 48/80, induced a distinct reduction of granulated mast cells in the alveolar tissue. Regular treatment with compound 48/80 from the time of irradiation considerably reduced the HA recovery during BAL and the HA accumulation in the interstitial tissue but did not affect the interstitial infiltration of mononuclear cells and polymorphonuclear leukocytes. By contrast, an accumulation of HA in the alveolar interstitial space was induced when compound 48/80 was given not until mast cell infiltration of the lung had started. The effects of compound 48/80 indicate that the connective tissue response after lung irradiation is dependent on whether or not mast cell degranulation is induced before or after the mast cell infiltration of the alveolar tissue

  12. Drug-induced lung disease: High-resolution CT and histological findings

    International Nuclear Information System (INIS)

    Cleverley, Joanne R.; Screaton, Nicholas J.; Hiorns, Melanie P.; Flint, Julia D.A.; Mueller, Nestor L.

    2002-01-01

    AIM: To compare the parenchymal high-resolution computed tomography (HRCT) appearances with histological findings in patients with drug-induced lung disease and to determine the prognostic value of HRCT. MATERIALS AND METHODS: Drug history, HRCT features, histological findings and outcome at 3 months in 20 patients with drug induced-lung disease were reviewed retrospectively. The HRCT images were assessed for the pattern and distribution of abnormalities and classified as most suggestive of interstitial pneumonitis/fibrosis, diffuse alveolar damage (DAD), organizing pneumonia (OP) reaction, or a hypersensitivity reaction. RESULTS: On histopathological examination there were eight cases of interstitial pneumonitis/fibrosis, five of DAD, five of OP reactions, one of hypersensitivity reaction and one of pulmonary eosinophilia. The most common abnormalities on HRCT were ground-glass opacities (n = 17), consolidation (n = 14), interlobular septal thickening (n = 15) and centrilobular nodules (n 8). HRCT interpretation and histological diagnosis were concordant in only nine (45%) of 20 patients. The pattern, distribution, and extent of HRCT abnormalities were of limited prognostic value: all eight patients with histological findings of OP, hypersensitivity reaction, or eosinophilic infiltrate improved on follow-up compared to only five of 13 patients with interstitial pneumonitis/fibrosis or DAD. CONCLUSION: In many cases of drug-induced lung injury HRCT is of limited value in determining the histological pattern and prognosis. Cleverly, J.R. et al

  13. Depletion of alveolar macrophages in CD11c diphtheria toxin receptor mice produces an inflammatory response

    Science.gov (United States)

    Roberts, Lydia M; Ledvina, Hannah E; Tuladhar, Shraddha; Rana, Deepa; Steele, Shaun P; Sempowski, Gregory D; Frelinger, Jeffrey A

    2015-01-01

    Alveolar macrophages play a critical role in initiating the immune response to inhaled pathogens and have been shown to be the first cell type infected following intranasal inoculation with several pathogens, including Francisella tularensis. In an attempt to further dissect the role of alveolar macrophages in the immune response to Francisella, we selectively depleted alveolar macrophages using CD11c.DOG mice. CD11c.DOG mice express the diphtheria toxin receptor (DTR) under control of the full CD11c promoter. Because mice do not express DTR, tissue restricted expression of the primate DTR followed by treatment with diphtheria toxin (DT) has been widely used as a tool in immunology to examine the effect of acute depletion of a specific immune subset following normal development. We successfully depleted alveolar macrophages via intranasal administration of DT. However, alveolar macrophage depletion was accompanied by many other changes to the cellular composition and cytokine/chemokine milieu in the lung that potentially impact innate and adaptive immune responses. Importantly, we observed a transient influx of neutrophils in the lung and spleen. Our experience serves as a cautionary note to other researchers using DTR mice given the complex changes that occur following DT treatment that must be taken into account when analyzing data. PMID:26029367

  14. Cicatricial organising pneumonia mimicking a fibrosing interstitial pneumonia.

    Science.gov (United States)

    Churg, Andrew; Wright, Joanne L; Bilawich, AnaMaria

    2018-04-01

    Organising pneumonia (OP) is composed of loose granulation tissue plugs in distal airspaces; these disappear with steroid treatment. Recently a variant labelled 'cicatricial' OP has been described in which the granulation tissue organised to much denser fibrous tissue but still retained the usual pattern of OP. Here we report 10 patients thought to have an interstitial lung disease, and who on biopsy had a variant of cicatricial OP characterised by linear bands or small nodular masses of dense fibrous tissue that does not resemble ordinary OP. The bands/nodules were usually distributed randomly but occasionally resembled fibrotic non-specific interstitial pneumonia in local areas. Small foci of loose granulation tissue at the edge of the fibrotic bands sometimes mimicked fibroblast foci. Recognisable conventional OP was always present, but often in very small amounts. Four cases, including one patient with Ehlers-Danlos syndrome, showed formation of bone in the fibrotic bands and nodules. On computerised tomography (CT) scan of the chest some cases looked like typical OP, but some demonstrated only irregularly distributed linear opacities, sometimes with associated calcification. Follow-up imaging on six cases showed that the process either markedly improved or remained stable over time; no case had progressive disease. Cicatricial OP with this pathological pattern represents an uncommon form of OP that appears to be a generally benign process which may have persisting linear opacities on CT scan but that does not progress; however, it can be confused on biopsy and CT with a fibrosing interstitial pneumonia. © 2017 John Wiley & Sons Ltd.

  15. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis.

    Science.gov (United States)

    Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y; Fong, Guo-Hua; Sakmar, Thomas P; Rafii, Shahin; Ding, Bi-Sen

    2016-02-01

    Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin-dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladapted hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis.

  16. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis

    Science.gov (United States)

    Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y.; Fong, Guo-Hua; Sakmar, Thomas P.; Rafii, Shahin; Ding, Bi-Sen

    2016-01-01

    Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin–dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladaptbed hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis. PMID:26779814

  17. Estimation of 123I-metaiodobenzylguanidine lung uptake in heart and lung diseases. With reference to lung uptake ratio and decrease of lung uptake

    International Nuclear Information System (INIS)

    Fujii, Tadashige; Tanaka, Masao; Yazaki, Yoshikazu; Kitabayashi, Hiroshi; Koizumi, Tomonori; Sekiguchi, Morie; Gomi, Tsutomu; Yano, Kesato; Itoh, Atsuko.

    1997-01-01

    123 I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was performed in 64 patients with heart and lung diseases. Distribution of MIBG in the chest was evaluated by planar images, using counts ratios of the heart to the mediastinum (H/M) and the unilateral lung to the mediastinum (Lu/M). Most of patients with heart diseases showed obvious lung uptake of MIBG. The ratios of H/M were 1.75±0.20 in the group without heart failure and 1.55±0.19 in the group with heart failure. The ratios of Lu/M in the right and left lung were 1.56±0.16 and 1.28±0.16 in the group without heart failure. And those were 1.45±0.16 and 1.19±0.15 in the group with heart failure. But 3 patients complicated with chronic pulmonary emphysema and one patient with interstitial pneumonia due to dermatomyositis showed markedly decreased lung uptake. The ratios of Lu/M in the right and left lung of these patients were 1.20, 1.17; 1.17, 1.13; 1.01, 0.97 and 1.27, 0.94, respectively. These results suggest that the lung uptake of MIBG may reflect the state of pulmonary endothelial cell function in clinical situations, considering that it has been demonstrated that MIBG may be useful as a marker of pulmonary endothelial cell function in the isolated rat lung. (author)

  18. Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II

    DEFF Research Database (Denmark)

    Dahl, Morten; Bauer, Alison K; Arredouani, Mohamed

    2007-01-01

    Alveolar macrophages (AMs) express the class A scavenger receptors (SRAs) macrophage receptor with collagenous structure (MARCO) and scavenger receptor AI/II (SRA-I/II), which recognize oxidized lipids and provide innate defense against inhaled pathogens and particles. Increased MARCO expression...... in lungs of ozone-resistant mice suggested an additional role protecting against inhaled oxidants. After ozone exposure, MARCO-/- mice showed greater lung injury than did MARCO+/+ mice. Ozone is known to generate oxidized, proinflammatory lipids in lung lining fluid, such as 5beta,6beta......-epoxycholesterol (beta-epoxide) and 1-palmitoyl-2-(9'-oxo-nonanoyl)-glycerophosphocholine (PON-GPC). Intratracheal instillation of either lipid caused substantial neutrophil influx in MARCO-/- mice, but had no effect in MARCO+/+ mice. Normal AMs showed greater uptake in vitro of beta-epoxide compared with MARCO-/- AMs...

  19. Peribronchiolar fibrosis in lungs of cats chronically exposed to diesel exhaust

    International Nuclear Information System (INIS)

    Hyde, D.M.; Plopper, C.G.; Weir, A.J.; Murnane, R.D.; Warren, D.L.; Last, J.A.; Pepelko, W.E.

    1985-01-01

    This study reports the quantitative changes in the pulmonary proximal acinar region following chronic exposure to diesel exhaust and following an additional 6 months in clean air. Cats (13 months of age) from a minimum disease colony were exposed to clean air (eight cats for 27 months and nine cats for 33 months), diesel exhaust for 8 hours/day, 7 days/week (nine cats for 27 months), or diesel exhaust for 27 months followed by 6 months in clean air (10 cats). Morphologic and morphometric evaluation using light microscopy and scanning and transmission electron microscopy revealed two major exposure-related lesions in proximal acinar regions of lungs of cats: peribronchiolar fibrosis associated with significant increases in lymphocytes, fibroblasts, and interstitial macrophages containing diesel particulate-like inclusions and bronchiolar epithelial metaplasia associated with the presence of ciliated and basal cells and alveolar macrophages containing diesel particulate-like inclusions. Peribronchiolar fibrosis was greater at the end of the 6 months in clean air following exposure, whereas the bronchiolar epithelial metaplasia was most severe at the end of exposure. Following an additional 6 months in clean air the epithelium more closely resembled the control epithelial cell population. The labeling index of terminal bronchiolar epithelium was significantly increased at the end of exposure but was not significantly different from controls or exposed cats following an additional 6 months in clean air. The ultrastructural appearance of epithelial cells remained relatively unchanged following diesel exhaust exposure with the exception of diesel particulate-like inclusions

  20. Gastroesophageal reflux and lung disease.

    Science.gov (United States)

    Meyer, Keith C

    2015-08-01

    Gastroesophageal reflux (GER) can cause respiratory symptoms and may trigger, drive and/or worsen airway disorders, interstitial lung diseases and lung allograft dysfunction. Whether lifestyle changes and acid suppression alone can counter and prevent the adverse effects of GER on the respiratory tract remains unclear. Recent data suggest that antireflux surgery may be more effective in preventing lung disease progression in patients with idiopathic pulmonary fibrosis or lung transplant recipients who have evidence of allograft dysfunction associated with the presence of excessive GER. Additional research and clinical trials are needed to determine the role of GER in various lung disorders and identify which interventions are most efficacious in preventing the respiratory consequences of gastroesophageal reflux disease. In addition, measuring biomarkers that indicate that gastric refluxate has been aspirated into the lower respiratory tract (e.g., pepsin and bile acid concentrations in bronchoalveolar lavage fluid) may prove helpful in both diagnosis and therapeutic decision making.

  1. Follistatin, an Activin Antagonist, Ameliorates Renal Interstitial Fibrosis in a Rat Model of Unilateral Ureteral Obstruction

    Directory of Open Access Journals (Sweden)

    Akito Maeshima

    2014-01-01

    Full Text Available Activin, a member of the TGF-β superfamily, regulates cell growth and differentiation in various cell types. Activin A acts as a negative regulator of renal development as well as tubular regeneration after renal injury. However, it remains unknown whether activin A is involved in renal fibrosis. To clarify this issue, we utilized a rat model of unilateral ureteral obstruction (UUO. The expression of activin A was significantly increased in the UUO kidneys compared to that in contralateral kidneys. Activin A was detected in glomerular mesangial cells and interstitial fibroblasts in normal kidneys. In UUO kidneys, activin A was abundantly expressed by interstitial α-SMA-positive myofibroblasts. Administration of recombinant follistatin, an activin antagonist, reduced the fibrotic area in the UUO kidneys. The number of proliferating cells in the interstitium, but not in the tubules, was significantly lower in the follistatin-treated kidneys. Expression of α-SMA, deposition of type I collagen and fibronectin, and CD68-positive macrophage infiltration were significantly suppressed in the follistatin-treated kidneys. These data suggest that activin A produced by interstitial fibroblasts acts as a potent profibrotic factor during renal fibrosis. Blockade of activin A action may be a novel approach for the prevention of renal fibrosis progression.

  2. Pulmonary fibrosis in rheumatoid arthritis: a review of clinical features and therapy.

    Science.gov (United States)

    Roschmann, R A; Rothenberg, R J

    1987-02-01

    During the past four decades there has been a growing appreciation of the frequency of pulmonary abnormalities associated with RA. Approximately 30% to 40% of patients with RA demonstrate either radiographic or pulmonary function abnormalities indicative of interstitial fibrosis or restrictive lung disease. The severity of pulmonary fibrosis is not associated with rheumatologic symptoms or the duration of the associated RA, nor is there any clear relation to the extraarticular features of RA or serologic findings. Survival rates in patients with coexisting RA and pulmonary fibrosis are similar to those of patients with idiopathic pulmonary fibrosis. However, the spectrum of disease activity is quite variable. The majority of patients with progressive pulmonary symptomatology, when treated with corticosteroids, will have equivocal results. Some patients appear to respond to immunosuppressive or cytotoxic medications. The role of macrophages may be central to the injury to lung. Recent studies suggest a potential treatment role for cyclosporine, which may be able to interrupt lymphocyte-stimulated macrophage activation, and thus, fibroblast-mediated fibrosis in patients with pulmonary interstitial fibrosis. Bronchoalveolar lavage studies may delineate subgroups of patients who are more likely to respond to immunosuppressive agents, especially when treatment is started early.

  3. Pattern of interstitial lung disease detected by high resolution ...

    African Journals Online (AJOL)

    Background: Diffuse lung diseases constitute a major cause of morbidity and mortality worldwide. High Resolution Computed Tomography (HRCT) is the recommended imaging technique in the diagnosis, assessment and followup of these diseases. Objectives: To describe the pattern of HRCT findings in patients with ...

  4. Interstitial lung disease associated with collagen vascular disorders: disease quantification using a computer-aided diagnosis tool

    Energy Technology Data Exchange (ETDEWEB)

    Marten, K.; Engelke, C. [University Hospital of Goettingen, Department of Radiology, Goettingen (Germany); Dicken, V. [MeVis Research GmbH, Bremen (Germany); Kneitz, C. [University Hospital of Wuerzburg, Dept. of Rheumatology and Clinical Immunology, Medizinische Klinik and Poliklinik, Wuerzburg (Germany); Hoehmann, M.; Kenn, W.; Hahn, D. [University Hospital of Wuerzburg, Department of Radiology, Wuerzburg (Germany)

    2009-02-15

    The purpose of this study was to evaluate a computer-aided diagnosis (CAD) tool compared to human observers in quantification of interstitial lung disease (ILD) in patients with collagen-vascular disorders. A total of 52 patients with rheumatoid arthritis (n=24), scleroderma (n=14) and systemic lupus erythematosus (n=14) underwent thin-section CT. Two independent observers assessed the extent of ILD (EoILD), reticulation (EoRet) and ground-glass opacity (EoGGO). CAD assessed EoILD twice. Pulmonary function tests were obtained. Statistical evaluation used 95% limits of agreement and linear regression analysis. CAD correlated well with diffusing capacity (DL{sub CO}) (R=-0.531, P<0.0001) and moderately with forced vital capacity (FVC) (R=-0.483, P=0.0008). There was close correlation between CAD and the readers (EoILD vs. CAD: R=0.716, P<0.0001; EoRet vs. CAD: R=0.69, P<0.0001). Subgroup analysis including patients with minimal EoGGO (<15%) strengthened the correlations between CAD and the readers, readers and PFT, and CAD and PFT. EoILD by readers correlated strongly with DL{sub CO} (R=-0.705, P<0.0001) and moderately with FVC (R=-0.559, P=0.0002). EoRet correlated closely with DL{sub CO} and moderately with FVC (DL{sub CO}: R=-0.663; FVC: R=-0.436; P{<=}0.005). The CAD system is a promising tool for ILD quantification, showing close correlation with human observers and physiologic impairment. (orig.)

  5. Mortality in patients with interstitial lung disease treated with rituximab or TNFi as a first biologic.

    Science.gov (United States)

    Druce, Katie L; Iqbal, Kundan; Watson, Kath D; Symmons, Deborah P M; Hyrich, Kimme L; Kelly, Clive

    2017-01-01

    Guidelines cautioned prescribing of tumour necrosis factor inhibitors (TNFi) to patients with rheumatoid arthritis and interstitial lung disease (RA-ILD) after reports of new or worsening of ILD. Less is known about outcomes among patients with RA-ILD who receive rituximab (RTX). This study compares mortality in patients with RA-ILD who received RTX or TNFi as their first biologic. Participants with RA-ILD recruited to the British Society for Rheumatology Biologics Register for RA were included. Death rates were calculated and risk comparisons were made using Cox regression. Causes of death, including the frequency in which ILD was recorded on death certificates were examined. 43 patients on RTX and 309 on TNFi were included. RTX recipients had shorter disease duration and less disability. Death rates were 94.8 (95%CI: 74.4 to 118.7) and 53.0 (22.9 to 104.6) per 1000 person years, respectively. The adjusted mortality risk was halved in the RTX cohort, but the difference was not statistically significant (HR 0.53, 95% CI: 0.26 to 1.10). ILD was the underlying cause of death in 1 of 7 RTX deaths (14%) and 12 of 76 TNFi deaths (16%). Patients with RA-ILD who received RTX had lower mortality rates compared to TNFi. The absence of information on ILD severity or subtype prevents conclusions of which drug represents the best choice in patients with RA-ILD and active arthritis.

  6. Pathogenic mechanism in lung fibrosis

    International Nuclear Information System (INIS)

    Witschi, H.; Haschek, W.M.; Meyer, K.R.; Ullrich, R.L.; Dalbey, W.E.

    1979-01-01

    The purpose of the study was to examine whether an interaction between two agents causing alveolar epithelial damage would produce lung fibrosis. In mouse lung, intraperitoneal injection of the antioxidant butylated hydroxytoluene causes diffuse alveolar type I cell necrosis, followed by proliferation of type II alveolar cells. In animals exposed to 70% O 2 or 100-200 rad x rays during the phase of type II cell proliferation following BHT, diffuse interstitial lung fibrosis developed within 2 weeks. Quantitative analysis of the lungs for hydroxyproline showed that the interaction between BHT and O 2 or x rays was synergistic. If exposure to O 2 or x rays was delayed until epithelial recovery was complete, no fibrosis was seen. Abnormally high levels of lung collagen persisted up to 6 months after one single treatment with BHT and 100 rad x rays. A commonly seen form of chronic lung damage may thus be caused by an acute interaction between a bloodborne agent which damages the alveolar cell and a toxic inhalant or x rays, provided a critically ordered sequence of exposure is observed

  7. Comparison of clinicoradiologic manifestation of nonspecific interstitial pneumonia and usual interstitial pneumonia/idiopathic pulmonary fibrosis: A report from NRITLD

    Directory of Open Access Journals (Sweden)

    Tafti Saeid

    2008-01-01

    Full Text Available Background: Ever since Katzenstein and Fiorelli introduced the term nonspecific interstitial pneumonia (NSIP to denote those cases of interstitial pneumonia that cannot be categorized as any of the other types of idiopathic interstitial pneumonias (IIP, there has been continuing debate on whether it is a real clinical entity or not. The American Thoracic Society/European Respiratory Symposium task group tried to identify idiopathic NSIP as a separate disease and exclude it from the category of IIP. However, it appears that the clinical presentation of NSIP and usual interstitial pneumonia (UIP are the same. Objective : To show that the radiologic features of NSIP and UIP should be relied upon, instead of clinical presentation and pathologic findings, to differentiate between the two. Materials and Methods: Consecutive patients who had received a diagnosis of either NSIP or UIP on the basis of open lung biopsy between January 2001 and December 2007 were identified for inclusion in this retrospective review. The study included 61 subjects: 32 men and 29 women with a mean age of 59.39 ± 14.5 years. Chest computed tomography images of all the cases were collected for a review. High resolution computed tomography (HRCT and all pathologic specimens were also evaluated. A weighted kappa coefficient was used to evaluate whether radiology can be used instead of biopsy for the diagnosis of NSIP and UIP. Comparison of the mean ages and the time intervals (i.e., interval between symptom onset and the time of diagnosis in the UIP and NSIP groups was done using the Mann-Whitney U test. Association between gender and biopsy result was evaluated by the Fisher exact test. Data were evaluated using SPSS, v.13. Results : Sixty-one patients were included in this study, 32 were male and 29 were female. On the basis of biopsy findings, 50 (82% patients had UIP and 11 (18% had NSIP. Thirty (60% of the 50 patients who had UIP were male and 20 (40% were female; 2 (18

  8. Quantitative computed tomography applied to interstitial lung diseases.

    Science.gov (United States)

    Obert, Martin; Kampschulte, Marian; Limburg, Rebekka; Barańczuk, Stefan; Krombach, Gabriele A

    2018-03-01

    To evaluate a new image marker that retrieves information from computed tomography (CT) density histograms, with respect to classification properties between different lung parenchyma groups. Furthermore, to conduct a comparison of the new image marker with conventional markers. Density histograms from 220 different subjects (normal = 71; emphysema = 73; fibrotic = 76) were used to compare the conventionally applied emphysema index (EI), 15 th percentile value (PV), mean value (MV), variance (V), skewness (S), kurtosis (K), with a new histogram's functional shape (HFS) method. Multinomial logistic regression (MLR) analyses was performed to calculate predictions of different lung parenchyma group membership using the individual methods, as well as combinations thereof, as covariates. Overall correct assigned subjects (OCA), sensitivity (sens), specificity (spec), and Nagelkerke's pseudo R 2 (NR 2 ) effect size were estimated. NR 2 was used to set up a ranking list of the different methods. MLR indicates the highest classification power (OCA of 92%; sens 0.95; spec 0.89; NR 2 0.95) when all histogram analyses methods were applied together in the MLR. Highest classification power among individually applied methods was found using the HFS concept (OCA 86%; sens 0.93; spec 0.79; NR 2 0.80). Conventional methods achieved lower classification potential on their own: EI (OCA 69%; sens 0.95; spec 0.26; NR 2 0.52); PV (OCA 69%; sens 0.90; spec 0.37; NR 2 0.57); MV (OCA 65%; sens 0.71; spec 0.58; NR 2 0.61); V (OCA 66%; sens 0.72; spec 0.53; NR 2 0.66); S (OCA 65%; sens 0.88; spec 0.26; NR 2 0.55); and K (OCA 63%; sens 0.90; spec 0.16; NR 2 0.48). The HFS method, which was so far applied to a CT bone density curve analysis, is also a remarkable information extraction tool for lung density histograms. Presumably, being a principle mathematical approach, the HFS method can extract valuable health related information also from histograms from complete different areas

  9. Changes in lung morphology and cell number in radiation pneumonitis and fibrosis: a quantitative ultrastructural study

    International Nuclear Information System (INIS)

    Vergara, J.A.; Raymond, U.; Thet, L.A.

    1987-01-01

    We used stereologic-morphometric techniques to obtain a detailed quantitative picture of the changes in lung ultrastructure of rats at 12 and 26 weeks after unilateral thoracic irradiation with 3000 cGy. At 12 weeks post-radiation, the total number type 1 epithelial cells, type 2 epithelial cells and capillary endothelial cells were decreased 50-70%, total type 1 epithelial and capillary surface areas were decreased 55-60%, and the total volume of intracapillary blood was decreased 75%. The interstitial cells and matrix together accounted for more than 9% of the peripheral lung tissue volume including air, compared to 3% in controls. The numerical density of interstitial cells was increased to 3-fold the control value. The numerical density of interstitial cells was increased to 3-fold the control value. Although fibroblasts still comprised the largest interstitial cell subgroup, the numerical density of mast cells was increased over 150-fold and other inflammatory and immune cells were increased to a lesser extent. At 26 weeks post-radiation, the number, volume, and surface area of the type 1 epithelium and capillary endothelium had further decreased to only 5-10% of control values. The total number of type 2 epithelial cells was reduced by 75% but the volume density was actually increased because of a 4-fold increase in the mean cell volume. The interstitial cells and matrix now comprised over 77% of total peripheral lung tissue volume including air as compared to 6% in controls. Mast cells and plasma cells comprised 11% and 19% of all interstitial cells respectively and the densities of these cells were 540 and 180-fold the control value respectively. The relation of these morphometric findings to the results of previous morphologic studies is discussed

  10. Loperamide Restricts Intracellular Growth of Mycobacterium tuberculosis in Lung Macrophages.

    Science.gov (United States)

    Juárez, Esmeralda; Carranza, Claudia; Sánchez, Guadalupe; González, Mitzi; Chávez, Jaime; Sarabia, Carmen; Torres, Martha; Sada, Eduardo

    2016-12-01

    New approaches for improving tuberculosis (TB) control using adjunct host-directed cellular and repurposed drug therapies are needed. Autophagy plays a crucial role in the response to TB, and a variety of autophagy-inducing drugs that are currently available for various medical conditions may serve as an adjunct treatment in pulmonary TB. Here, we evaluated the potential of loperamide, carbamazepine, valproic acid, verapamil, and rapamycin to enhance the antimicrobial immune response to Mycobacterium tuberculosis (Mtb). Human monocyte-derived macrophages (MDMs) and murine alveolar cells (MACs) were infected with Mtb and treated with loperamide, carbamazepine, valproic acid, verapamil, and rapamycin in vitro. Balb/c mice were intraperitoneally administered loperamide, valproic acid, and verapamil, and MACs were infected in vitro with Mtb. The induction of autophagy, the containment of Mtb within autophagosomes and the intracellular Mtb burden were determined. Autophagy was induced by all of the drugs in human and mouse macrophages, and loperamide significantly increased the colocalization of microtubule-associated protein 1 light chain 3 with Mtb in MDMs. Carbamazepine, loperamide, and valproic acid induced microtubule-associated protein 1 light chain 3 and autophagy related 16- like protein 1 gene expression in MDMs and in MACs. Loperamide also induced a reduction in TNF-α production. Loperamide and verapamil induced autophagy, which was associated with a significant reduction in the intracellular growth of Mtb in MACs and alveolar macrophages. The intraperitoneal administration of loperamide and valproic acid induced autophagy in freshly isolated MACs. The antimycobacterial activity in MACs was higher after loperamide treatment and was associated with the degradation of p62. In conclusion, loperamide shows potential as an adjunctive therapy for the treatment of TB.

  11. Interstitial pregnancy: role of MRI

    International Nuclear Information System (INIS)

    Filhastre, M.; Lesnik, A.; Dechaud, H.; Taourel, P.

    2005-01-01

    We report the MRI features of two cases of interstitial pregnancy. In both cases, MRI was able to localize the ectopic pregnancy by showing a gestational structure surrounded by a thick wall in the upper part of the uterine wall separated from the endometrium by an uninterrupted junctional zone. Because US may confuse angular and interstitial pregnancies and because interstitial pregnancy has a particular evolutive course, MR imaging may play a key role in the diagnosis and management of women with interstitial pregnancy. (orig.)

  12. Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages

    DEFF Research Database (Denmark)

    Jantzen, Kim; Roursgaard, Martin; Madsen, Claus Desler

    2012-01-01

    Studies in mono-culture of cells have shown that diesel exhaust particles (DEPs) increase the production of reactive oxygen species (ROS) and oxidative stress-related damage to DNA. However, the level of particle-generated genotoxicity may depend on interplay between different cell types, e.g. lung...... treatment with standard reference DEPs, SRM2975 and SRM1650b. The exposure to DEPs did not affect the colony-forming ability of A549 cells in co-culture with THP-1a cells. The DEPs generated DNA strand breaks and oxidatively damaged DNA, measured using the alkaline comet assay as formamidopyrimidine...... relationship between levels of respiration and ROS production. In conclusion, exposure of mono-cultured cells to DEPs generated oxidative stress to DNA, whereas co-cultures with macrophages had lower levels of oxidatively damaged DNA than A549 epithelial cells....

  13. Low Levels of IGF-1 Contribute to Alveolar Macrophage Dysfunction in Cystic Fibrosis1

    Science.gov (United States)

    Bessich, Jamie L.; Nymon, Amanda B.; Moulton, Lisa A; Dorman, Dana; Ashare, Alix

    2013-01-01

    Alveolar macrophages are major contributors to lung innate immunity. Although alveolar macrophages from CFTR−/− mice have impaired function, no study has investigated primary alveolar macrophages in adults with cystic fibrosis (CF). CF patients have low levels of insulin-like growth factor 1 (IGF-1), and our prior studies demonstrate a relationship between IGF-1 and macrophage function. We hypothesize that reduced IGF-1 in CF leads to impaired alveolar macrophage function and chronic infections. Serum and bronchoalveolar lavage (BAL) samples were obtained from 8 CF subjects and 8 healthy subjects. Macrophages were isolated from BAL fluid. We measured the ability of alveolar macrophages to kill Pseudomonas aeruginosa. Subsequently, macrophages were incubated with IGF-1 prior to inoculation with bacteria to determine the effect of IGF-1 on bacterial killing. We found a significant decrease in bacterial killing by CF alveolar macrophages compared to controls. CF subjects had lower serum and BAL IGF-1 levels compared to healthy controls. Exposure to IGF-1 enhanced alveolar macrophage macrophages in both groups. Finally, exposing healthy alveolar macrophages to CF BAL fluid decreased bacterial killing, and this was reversed by the addition of IGF-1, while IGF-1 blockade worsened bacterial killing. Our studies demonstrate that alveolar macrophage function is impaired in patients with CF. Reductions in IGF-1 levels in CF contribute to the impaired alveolar macrophage function. Exposure to IGF-1 ex vivo, results in improved function of CF alveolar macrophages. Further studies are needed to determine whether alveolar macrophage function can be enhanced in vivo with IGF-1 treatment. PMID:23698746

  14. Myositis-associated usual interstitial pneumonia has a better survival than idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Aggarwal, Rohit; McBurney, Christine; Schneider, Frank; Yousem, Samuel A; Gibson, Kevin F; Lindell, Kathleen; Fuhrman, Carl R; Oddis, Chester V

    2017-03-01

    To compare the survival outcomes between myositis-associated usual interstitial pneumonia (MA-UIP) and idiopathic pulmonary fibrosis (IPF-UIP). Adult MA-UIP and IPF-UIP patients were identified using CTD and IPF registries. The MA-UIP cohort included myositis or anti-synthetase syndrome patients with interstitial lung disease while manifesting UIP on high-resolution CT chest and/or a lung biopsy revealing UIP histology. IPF subjects met American Thoracic Society criteria and similarly had UIP histopathology. Kaplan-Meier survival curves compared cumulative and pulmonary event-free survival (event = transplant or death) between (i) all MA-UIP and IPF-UIP subjects, (ii) MA-UIP with biopsy proven UIP (n = 25) vs IPF-UIP subjects matched for age, gender and baseline forced vital capacity (±10%). Cox proportional hazards ratios compared the survival controlling for co-variates. Eighty-one IPF-UIP and 43 MA-UIP subjects were identified. The median cumulative and event-free survival time in IPF vs MA-UIP was 5.25/1.8 years vs 16.2/10.8 years, respectively. Cumulative and event-free survival was significantly worse in IPF-UIP vs MA-UIP [hazards ratio of IPF-UIP was 2.9 (95% CI: 1.5, 5.6) and 5.0 (95% CI: 2.8, 8.7) (P < 0.001), respectively]. IPF-UIP event-free survival (but not cumulative) remained significantly worse than MA-UIP with a hazards ratio of 6.4 (95% CI: 3.0, 13.8) after controlling for age at interstitial lung disease diagnosis, gender, ethnicity and baseline forced vital capacity%. Respiratory failure was the most common cause of death in both groups. A sub-analysis of 25 biopsy-proven MA-UIP subjects showed similar results. MA-UIP patients demonstrated a significant survival advantage over a matched IPF cohort, suggesting that despite similar histological and radiographic findings at presentation, the prognosis of MA-UIP is superior to that of IPF-UIP. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology

  15. Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

    International Nuclear Information System (INIS)

    Malur, Anagha; Huizar, Isham; Wells, Greg; Barna, Barbara P.; Malur, Achut G.; Thomassen, Mary Jane

    2011-01-01

    Highlights: ► Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. ► Up-regulation of ABCG1 improves lung function. ► Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPARγ) and the PPARγ-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte–macrophage colony stimulating factor (GM-CSF), an upregulator of PPARγ. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO) mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPARγ plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPARγ or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as shown by analysis of bronchoalveolar lavage fluid. Lung compliance was diminished in untreated GMCSF KO mice

  16. Prognostic Role of Exhaled Breath Condensate pH and Fraction Exhaled Nitric Oxide in Systemic Sclerosis Related Interstitial Lung Disease.

    Science.gov (United States)

    Guillen-Del Castillo, Alfredo; Sánchez-Vidaurre, Sara; Simeón-Aznar, Carmen P; Cruz, María J; Fonollosa-Pla, Vicente; Muñoz, Xavier

    2017-03-01

    Interstitial lung disease (ILD) is one of the major causes of death in systemic sclerosis (SSc). This study investigated exhaled breath (EB) and exhaled breath condensate (EBC) biomarkers in patients with SSc and analyzed their role as a prognostic tool in SSc-related ILD. Fraction exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) measured in EB, together with pH, nitrite, nitrate and interleukin-6 levels measured in EBC were prospectively analyzed in 35 patients with SSc. Twelve patients had established ILD by chest high-resolution computed tomography (HRCT), and 23 patients showed no evidence of ILD. EB and EBC biomarkers were determined at inclusion, and pulmonary function tests were annually performed during 4 years of follow-up. No differences at baseline biomarkers levels were found between groups. In all patients studied, low EBC pH levels were associated with a decreased diffusing capacity for carbon monoxide (DLCO) during follow-up. Low FeNO levels were correlated with lower forced vital capacity (FVC) at baseline, 4years of follow-up and with a decrease in FVC and DLCO during monitoring. Among ILD patients, high eCO levels were correlated with lower baseline FVC. In the global cohort, a worse progression-free survival was identified in patients with EBC pH values lower than 7.88 and FeNO levels lower than 10.75ppb (Log Rank P=.03 and P<.01, respectively). EB and EBC could help to detect patients likely to present a deterioration on lung function during follow up. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Association of serum KL-6 levels with interstitial lung disease in patients with connective tissue disease: a cross-sectional study.

    Science.gov (United States)

    Oguz, Ekin Oktay; Kucuksahin, Orhan; Turgay, Murat; Yildizgoren, Mustafa Turgut; Ates, Askin; Demir, Nalan; Kumbasar, Ozlem Ozdemir; Kinikli, Gulay; Duzgun, Nursen

    2016-03-01

    It was aimed to evaluate KL-6 glycoprotein levels to determine if it may be a diagnostic marker for the connective tissue diseases (CTDs) predicting CTD-related interstitial lung diseases (ILDs) (CTD-ILD) development and to examine if there was a difference between patients and healthy controls. The study included 113 patients with CTD (45 CTD without lung involvement, 68 CTD-ILD) and 45 healthy control subjects. KL-6 glycoprotein levels were analyzed with ELISA in patients and the control group. The relationship between KL-6 glycoprotein levels and CTD-ILD was assessed. In the comparison of all the groups in the study, significantly higher levels of KL-6 were determined in the CTD-ILD group than in either the CTD without pulmonary involvement group or the healthy control group (p connective tissue diseases in the diagnostic groups (systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, scleroderma, polymyositis/ dermatomyositis). In the healthy control group, there was a statistically significant difference between KL-6 levels in smokers and non-smokers. Smokers had significantly higher serum KL-6 levels compared with non-smokers (p < 0.05). There was no statistically significant difference between smoking status (pack-year) and serum KL-6 levels. There was no statistically significant correlation between serum KL-6 levels and time since diagnosis of CTD and CTD-ILD. The level of KL-6 as a predictive factor could be used to identify the clinical development of ILD before it is detected on imaging modality. Further prospective clinical studies are needed to define whether levels of KL-6 might have prognostic value or might predict progressive ILD.

  18. Formation and annealing of metastable (interstitial oxygen)-(interstitial carbon) complexes in n- and p-type silicon

    CERN Document Server

    Makarenko, L F; Lastovskii, S B; Murin, L I; Moll, M; Pintilie, I

    2014-01-01

    It is shown experimentally that, in contrast to the stable configuration of (interstitial carbon)-(interstitial oxygen) complexes (CiOi), the corresponding metastable configuration (CiOi{*}) cannot be found in n-Si based structures by the method of capacitance spectroscopy. The rates of transformation CiOi{*} -> CiOi are practically the same for both n- and p-Si with a concentration of charge carriers of no higher than 10(13) cm(-3). It is established that the probabilities of the simultaneous formation of stable and metastable configurations of the complex under study in the case of the addition of an atom of interstitial carbon to an atom of interstitial oxygen is close to 50\\%. This is caused by the orientation dependence of the interaction potential of an atom of interstitial oxygen with an interstitial carbon atom, which diffuses to this oxygen atom.

  19. Enhanced tumor growth in the remaining lung after major lung resection.

    Science.gov (United States)

    Sano, Fumiho; Ueda, Kazuhiro; Murakami, Junichi; Hayashi, Masataro; Nishimoto, Arata; Hamano, Kimikazu

    2016-05-01

    Pneumonectomy induces active growth of the remaining lung in order to compensate for lost lung tissue. We hypothesized that tumor progression is enhanced in the activated local environment. We examined the effects of mechanical strain on the activation of lung growth and tumor progression in mice. The mechanical strain imposed on the right lung after left pneumonectomy was neutralized by filling the empty space that remained after pneumonectomy with a polypropylene prosthesis. The neutralization of the strain prevented active lung growth. According to an angiogenesis array, stronger monocyte chemoattractant protein-1 (MCP-1) expression was found in the strain-induced growing lung. The neutralization of the strain attenuated the release of MCP-1 from the lung cells. The intravenous injection of Lewis lung cancer cells resulted in the enhanced development of metastatic foci in the strain-induced growing lung, but the enhanced development was canceled by the neutralization of the strain. An immunohistochemical analysis revealed the prominent accumulation of tumor-associated macrophages in tumors arising in the strain-induced growing lung, and that there was a relationship between the accumulation and the MCP-1 expression status. Our results suggested that mechanical lung strain, induced by pulmonary resection, triggers active lung growth, thereby creating a tumor-friendly environment. The modification of that environment, as well as the minimizing of surgical stress, may be a meaningful strategy to improve the therapeutic outcome after lung cancer surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. A possible mechanism in the recruitment of eosinophils and Th2 cells through CD163(+) M2 macrophages in the lesional skin of eosinophilic cellulitis.

    Science.gov (United States)

    Fujimura, Taku; Kambayashi, Yumi; Furudate, Sadanori; Kakizaki, Aya; Aiba, Setsuya

    2014-01-01

    M2 macrophages play a critical role in the recruitment of T helper 2 (Th2) regulatory T cells (Treg). To study the role of M2 macrophages and Treg cells in eosinophilic celulitis. We employed immunohistochemical staining for CD163( )and CD206 (macrophages) as well as FoxP3 (Treg), in lesional skin of four cases of eosinophilic cellulitis. CD163(+) CD206(+) M2 macrophages, which were previously reported to produce CCL17 to induce Th2 cells and Treg cells, were predominantly infiltrating the subcutaneous tissues and interstitial area of the dermis. M2 macrophages derived from PBMC showed significantly increased expression of CCL11, CCL17, CCL24 and CCL26 mRNA and production of CCL17 and CCL24, when stimulated by IL-4 or IL- 13. In addition, CCL17-producing cells and CCL24-producing cells were prominent in the lesional skin of EC. Our study sheds light on one of the possible immunological mechanisms of eosinophilic cellulitis.

  1. Examination of the fine interstitial changes of pneumoconiosis with high resolution computed tomography (HR-CT)

    International Nuclear Information System (INIS)

    Kido, Masamitsu; Miyazaki, Nobuyoshi; Harada, Susumu; Nakata, Hajime

    1986-01-01

    High resolution CT was performed in 14 patients with fine interstitial changes of pneumoconiosis and Review image was evaluated for the diagnostic accuracy as compared with conventional chest roentgenogram. Of the 14 Patients in the study, 7 were divided category 1 by the ILO U/C classification, 4 were category 2, 3 were category 3. Studies of lung function showed obstructive ventilatory disturbance characterized by moderate reduction in FEV 1.0% (58.6 ± 16.5 %) and V25/H (0.34 ± 0.24 l/sec/m). HR-CT defined more sensitive in the presence of fine lung nodules than conventional X-p, and showed high contrast interfaces provided by the aerated lung. HR-CT was also of value in detecting bulla, bleb, peripleural changes and hilar lymphadenopathy. Radiologic-pathologic correlation was examined on tne specimens of transbronchial lung biopsy in 4 patients, and revealed the diagnostic usefullness of HR-CT. (author)

  2. Characteristic patterns in the fibrotic lung. Comparing idiopathic pulmonary fibrosis with chronic lung allograft dysfunction.

    Science.gov (United States)

    Fernandez, Isis E; Heinzelmann, Katharina; Verleden, Stijn; Eickelberg, Oliver

    2015-03-01

    Tissue fibrosis, a major cause of death worldwide, leads to significant organ dysfunction in any organ of the human body. In the lung, fibrosis critically impairs gas exchange, tissue oxygenation, and immune function. Idiopathic pulmonary fibrosis (IPF) is the most detrimental and lethal fibrotic disease of the lung, with an estimated median survival of 50% after 3-5 years. Lung transplantation currently remains the only therapeutic alternative for IPF and other end-stage pulmonary disorders. Posttransplant lung function, however, is compromised by short- and long-term complications, most importantly chronic lung allograft dysfunction (CLAD). CLAD affects up to 50% of all transplanted lungs after 5 years, and is characterized by small airway obstruction with pronounced epithelial injury, aberrant wound healing, and subepithelial and interstitial fibrosis. Intriguingly, the mechanisms leading to the fibrotic processes in the engrafted lung exhibit striking similarities to those in IPF; therefore, antifibrotic therapies may contribute to increased graft function and survival in CLAD. In this review, we focus on these common fibrosis-related mechanisms in IPF and CLAD, comparing and contrasting clinical phenotypes, the mechanisms of fibrogenesis, and biomarkers to monitor, predict, or prognosticate disease status.

  3. Influence of industrial dust of uranium ore on rats' lung tissue

    International Nuclear Information System (INIS)

    Jumasheva, R.T.

    2010-01-01

    Under the conditions of radiotoxic influence of uranium ore dust (UOD), the respiratory organs are the main system specifically responsible for adaptation to this factor. At the same time, there are not sufficient studies regarding the morphological aspects of structural lung distortions due to inhalational influence by UOD. To identify the nature of morphological changes in the animals' lung tissue at the cellular and subcellular levels under the influence of industrial dust of uranium ore in a dose of 50 MPC. Experimental studies were conducted on 80 white rats (tom) with a body mass of 120-180 g. The experimental animals were subjected to chronic inhalation of UOD in a dose of 50 MPC (107.75 mg/m 3 ). The animals that were kept in similar chambers but that were not exposed to UOD served as control animals. Material from the animals for research was withdrawn in 3, 7, 30 and 60 days after the beginning of the experiment. The animals were withdrawn from the experiment by decapitation after a brief ether anesthesia. The lung tissue was subjected to conventional histological processing. Sections were stained with haematoxylin and eosin according to van Gieson's method. For electronic microscopic examination the lung tissue slices were fixed and embedded by conventional methods. Obtained blocks were used to prepare ultrathin sections. An impact of UOD in a dose of 50 MPC was accompanied by the development of acute focal serous inflammation in the wall of the small bronchi and lung parenchyma in the early stages of the experiment (3-7 days), pneumonic foci of fibrosis, and the development of marked sclerotic changes in the peribronchial lymphoid tissue by the 30-th day. By the 60-th day, an increase of sclerotic changes in the bronchial wall accompanied by inhibition of the reaction on the part of interstitial macrophages and bronchus associated lymphoid tissue were reported. These indicate the intense course of the compensatory processes. Conducted electron

  4. Overexpression of matrix metalloproteinase-12 (MMP-12) correlates with radiation-induced lung fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Myung Gu; Jeong, Ye Ji; Lee, Haejune [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Sujae [Hanyang Univ., Seoul (Korea, Republic of)

    2014-05-15

    MMPs are classified into five subgroups: collagenases (MMP-1, MMP-8, MMP-13), gelatinases (MMP-2, MMP-9), stromelysins (MMP-3, MMP-10, MMP-11), as well as metalloelastase (MMP-12), the membrane-type MMPs (MMP14, MMP15), and other MMPS (e. g., MMP-19, and MMP20). MMP-12 (matrix metalloproteinase12), also known as macrophage metalloelastase, was first identified as an elastolytic metalloproteinase secreted by inflammatory macrophages 30 years ago. MMP-12 degrades extracellular matrix (ECM) components to facilitate tissue remodeling. It can degrade elastin and other substrates, such as type IV collagen, fibronectin, laminin, gelatin, vitronectin, entactin, heparin, and chondroitin sulfates. In the lung, MMP-12 is identified in alveolar macrophages of cigarette smokers as an elastolytic MMP. Inactivation of the MMP-12 gene in knockout mice demonstrates a critical role of MMP-12 in smoking-induced chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the effects of MMP-12 by radiation in lung, so we evaluate that MMP-12 expression pattern in normal lung tissue and cancer cell following radiation. Radiation induced lung injury most commonly occurs as a result of radiation therapy administered to treat cancer. The present study demonstrates that MMP-12 was highly increased in the lung damaged by radiation Thus, MMP-12 might be of potential relevance as a clinically diagnostic tool and sensitive biomarker for radiation induced lung injury and fibrosis.

  5. Overexpression of matrix metalloproteinase-12 (MMP-12) correlates with radiation-induced lung fibrosis

    International Nuclear Information System (INIS)

    Jung, Myung Gu; Jeong, Ye Ji; Lee, Haejune; Lee, Sujae

    2014-01-01

    MMPs are classified into five subgroups: collagenases (MMP-1, MMP-8, MMP-13), gelatinases (MMP-2, MMP-9), stromelysins (MMP-3, MMP-10, MMP-11), as well as metalloelastase (MMP-12), the membrane-type MMPs (MMP14, MMP15), and other MMPS (e. g., MMP-19, and MMP20). MMP-12 (matrix metalloproteinase12), also known as macrophage metalloelastase, was first identified as an elastolytic metalloproteinase secreted by inflammatory macrophages 30 years ago. MMP-12 degrades extracellular matrix (ECM) components to facilitate tissue remodeling. It can degrade elastin and other substrates, such as type IV collagen, fibronectin, laminin, gelatin, vitronectin, entactin, heparin, and chondroitin sulfates. In the lung, MMP-12 is identified in alveolar macrophages of cigarette smokers as an elastolytic MMP. Inactivation of the MMP-12 gene in knockout mice demonstrates a critical role of MMP-12 in smoking-induced chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the effects of MMP-12 by radiation in lung, so we evaluate that MMP-12 expression pattern in normal lung tissue and cancer cell following radiation. Radiation induced lung injury most commonly occurs as a result of radiation therapy administered to treat cancer. The present study demonstrates that MMP-12 was highly increased in the lung damaged by radiation Thus, MMP-12 might be of potential relevance as a clinically diagnostic tool and sensitive biomarker for radiation induced lung injury and fibrosis

  6. First experience with energy dispersive X-ray analysis (EDXA) in lung fibrosis

    International Nuclear Information System (INIS)

    Liebetrau, G.; Wiesner, B.; Strausz, J.; Zglinicki, T. von

    1987-01-01

    Biopsies from 68 patients suffering from interstitial lung disease were examined with regard to minerals using energy dispersive X-ray analysis. In 31 patients a higher portion of minerals or elements were found as pigments. The interpretation of these findings is difficult. If there is a occupational exposure and a reaction of the lung parenchyma the findings could be of clinical value. (author)

  7. Prostaglandin D2 Attenuates Bleomycin-Induced Lung Inflammation and Pulmonary Fibrosis.

    Science.gov (United States)

    Kida, Taiki; Ayabe, Shinya; Omori, Keisuke; Nakamura, Tatsuro; Maehara, Toko; Aritake, Kosuke; Urade, Yoshihiro; Murata, Takahisa

    2016-01-01

    Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Although it is well known that lipid mediator prostaglandins are involved in the development of pulmonary fibrosis, the role of prostaglandin D2 (PGD2) remains unknown. Here, we investigated whether genetic disruption of hematopoietic PGD synthase (H-PGDS) affects the bleomycin-induced lung inflammation and pulmonary fibrosis in mouse. Compared with H-PGDS naïve (WT) mice, H-PGDS-deficient mice (H-PGDS-/-) represented increased collagen deposition in lungs 14 days after the bleomycin injection. The enhanced fibrotic response was accompanied by an increased mRNA expression of inflammatory mediators, including tumor necrosis factor-α, monocyte chemoattractant protein-1, and cyclooxygenase-2 on day 3. H-PGDS deficiency also increased vascular permeability on day 3 and infiltration of neutrophils and macrophages in lungs on day 3 and 7. Immunostaining showed that the neutrophils and macrophages expressed H-PGDS, and its mRNA expression was increased on day 3and 7 in WT lungs. These observations suggest that H-PGDS-derived PGD2 plays a protective role in bleomycin-induced lung inflammation and pulmonary fibrosis.

  8. Biomimetic carbon monoxide delivery based on hemoglobin vesicles ameliorates acute pancreatitis in mice via the regulation of macrophage and neutrophil activity.

    Science.gov (United States)

    Taguchi, Kazuaki; Nagao, Saori; Maeda, Hitoshi; Yanagisawa, Hiroki; Sakai, Hiromi; Yamasaki, Keishi; Wakayama, Tomohiko; Watanabe, Hiroshi; Otagiri, Masaki; Maruyama, Toru

    2018-11-01

    Macrophages play a central role in various inflammatory disorders and are broadly divided into two subpopulations, M1 and M2 macrophage. In the healing process in acute inflammatory disorders, shifting the production of M1 macrophages to M2 macrophages is desirable, because M1 macrophages secrete pro-inflammatory cytokines, whilst the M2 variety secrete anti-inflammatory cytokines. Previous findings indicate that when macrophages are treated with carbon monoxide (CO), the secretion of anti-inflammatory cytokine is increased and the expression of pro-inflammatory cytokines is inhibited, indicating that CO may have a potential to modulate the production of macrophages toward the M2-like phenotype. In this study, we examined the issue of whether CO targeting macrophages using a nanotechnology-based CO donor, namely CO-bound hemoglobin vesicles (CO-HbV), modulates their polarization and show therapeutic effects against inflammatory disorders. The results showed that the CO-HbV treatment polarized a macrophage cell line toward an M2-like phenotype. Furthermore, in an in vivo study using acute pancreatitis model mice as a model of an inflammatory disease, a CO-HbV treatment also tended to polarize macrophages toward an M2-like phenotype and inhibited neutrophil infiltration in the pancreas, resulting in a significant inflammation. In addition to the suppression of acute pancreatitis, CO-HbV diminished a subsequent pancreatitis-associated acute lung injury. This could be due to the inhibition of the systemic inflammation, neutrophil infiltration in the lungs and the production of HMGB-1. These findings suggest that CO-HbV exerts superior anti-inflammatory effects against inflammatory disorders via the regulation of macrophage and neutrophil activity.

  9. DIP (pneumonia intersticial descamativa: como quadro do pulmão do tabaco – apresentação de um caso

    Directory of Open Access Journals (Sweden)

    Vítor Sousa

    2004-09-01

    Full Text Available RESUMO: A DIP (pneumonia intersticial descamativa é uma doença pulmonar intersticial caracterizada pela acumulação difusa e uniforme de macrófagos alveolares. Há forte associação com o tabaco sendo que 90% dos doentes são fumadores. As doenças relacionadas com o tabaco no pulmão são diversas e incluem os tumores, enfisema, bronquite crónica, RBILD (bronquiolite respiratória associada a doença pulmonar intersticial, DIP e histiocitose de células de Langerhans. Os autores apresentam um caso de DIP. É realizada breve revisão teórica e discussão do caso à luz da sua associação com o tabaco.REV PORT PNEUMOL 2004; X (5: 431-435 ABSTRACT: DIP (Desquamative Interstitial Pneumonia is an interstitial lung disease with diffuse and uniform accumulation of alveolar macrophages. There is a strong association with tobacco since 90% of the patients are smokers. The interstitial lung diseases related to tobacco are diverse and include tumours, emphysema, chronic bronchitis, RBILD (Respiratory Bronchilites associated Interstitial Lung Disease, DIP and Langerhans Cell Histiocitosis. The authors present a case of DIP. A brief theorycal revision and discussion of a case is made facing the association with tobacco.REV PORT PNEUMOL 2004; X (5:431-435 Palavras-chave: Pulmão, pneumonia intersticial descamativa, DIP, interstício, Key-words: Lung, desquamative interstitial pneumonia, DIP, interstitium

  10. Lung transplantation: overall approach regarding its major aspects

    Science.gov (United States)

    de Camargo, Priscila Cilene León Bueno; Teixeira, Ricardo Henrique de Oliveira Braga; Carraro, Rafael Medeiros; Campos, Silvia Vidal; Afonso, José Eduardo; Costa, André Nathan; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2015-01-01

    ABSTRACT Lung transplantation is a well-established treatment for patients with advanced lung disease. The evaluation of a candidate for transplantation is a complex task and involves a multidisciplinary team that follows the patient beyond the postoperative period. Currently, the mean time on the waiting list for lung transplantation in the state of São Paulo, Brazil, is approximately 18 months. For Brazil as a whole, data from the Brazilian Organ Transplant Association show that, in 2014, there were 67 lung transplants and 204 patients on the waiting list for lung transplantation. Lung transplantation is most often indicated in cases of COPD, cystic fibrosis, interstitial lung disease, non-cystic fibrosis bronchiectasis, and pulmonary hypertension. This comprehensive review aimed to address the major aspects of lung transplantation: indications, contraindications, evaluation of transplant candidates, evaluation of donor candidates, management of transplant recipients, and major complications. To that end, we based our research on the International Society for Heart and Lung Transplantation guidelines and on the protocols used by our Lung Transplant Group in the city of São Paulo, Brazil. PMID:26785965

  11. Pulmonary adenocarcinoma mutation profile in smokers with smoking-related interstitial fibrosis

    Directory of Open Access Journals (Sweden)

    Primiani A

    2014-05-01

    Full Text Available Andrea Primiani,1 Dora Dias-Santagata,1 A John Iafrate,1 Richard L Kradin1,2 1Pathology Service, 2Pulmonary Medicine/Critical Care Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Abstract: Cigarette smoking is an established cause of lung cancer. However, pulmonary fibrosis is also an independent risk factor for the development of lung cancer. Smoking-related interstitial fibrosis (SRIF has recently been reported. We hypothesized that adenocarcinomas in lungs with SRIF might show distinct molecular changes and examined the molecular phenotype of 168 resected lung adenocarcinomas in lungs with and without SRIF. The diagnosis of SRIF was determined by histological examination, based on the presence of alveolar septal thickening, due to pauci-inflamed, hyalinized, “ropy” collagen, in areas of lung greater than 1 cm away from the tumor. Tumors were concomitantly examined genotypically for mutations in genes frequently altered in cancer, including EGFR and KRAS, by SNaPshot and by fluorescence in situ hybridization for possible ALK rearrangements. Fluorescence in situ hybridization for ROS1 rearrangement (n=36 and/or MET amplification (n=31 were performed when no mutation was identified by either SNaPshot or ALK analysis. Sixty-five cases (38.7% showed SRIF, which was distributed in all lobes of the lungs examined. No differences were observed in sex, average age, or smoking history in patients with and without SRIF. There was no difference in either the percent or types of adenocarcinoma genetic mutations in patients with SRIF versus those without. This data suggests that SRIF does not represent an independent risk factor for the development of the major known and targeted mutations seen in pulmonary adenocarcinoma. However, additional research is required to investigate the potential significance of SRIF in the pathogenesis of lung cancer. Keywords: lung, cancer, smoking, SRIF

  12. Frequency and number of ultrasound lung rockets (B-lines) using a regionally based lung ultrasound examination named vet BLUE (veterinary bedside lung ultrasound exam) in dogs with radiographically normal lung findings.

    Science.gov (United States)

    Lisciandro, Gregory R; Fosgate, Geoffrey T; Fulton, Robert M

    2014-01-01

    Lung ultrasound is superior to lung auscultation and supine chest radiography for many respiratory conditions in human patients. Ultrasound diagnoses are based on easily learned patterns of sonographic findings and artifacts in standardized images. By applying the wet lung (ultrasound lung rockets or B-lines, representing interstitial edema) versus dry lung (A-lines with a glide sign) concept many respiratory conditions can be diagnosed or excluded. The ultrasound probe can be used as a visual stethoscope for the evaluation of human lungs because dry artifacts (A-lines with a glide sign) predominate over wet artifacts (ultrasound lung rockets or B-lines). However, the frequency and number of wet lung ultrasound artifacts in dogs with radiographically normal lungs is unknown. Thus, the primary objective was to determine the baseline frequency and number of ultrasound lung rockets in dogs without clinical signs of respiratory disease and with radiographically normal lung findings using an 8-view novel regionally based lung ultrasound examination called Vet BLUE. Frequency of ultrasound lung rockets were statistically compared based on signalment, body condition score, investigator, and reasons for radiography. Ten left-sided heart failure dogs were similarly enrolled. Overall frequency of ultrasound lung rockets was 11% (95% confidence interval, 6-19%) in dogs without respiratory disease versus 100% (95% confidence interval, 74-100%) in those with left-sided heart failure. The low frequency and number of ultrasound lung rockets observed in dogs without respiratory disease and with radiographically normal lungs suggests that Vet BLUE will be clinically useful for the identification of canine respiratory conditions. © 2014 American College of Veterinary Radiology.

  13. Chlorambucil-Induced Acute Interstitial Pneumonitis

    Directory of Open Access Journals (Sweden)

    Hammad Shafqat

    2014-01-01

    Full Text Available Chlorambucil is an alkylating agent commonly used in treatment of chronic lymphocytic leukemia (CLL. We report a case of interstitial pneumonitis developing in an 83-year-old man 1.5 months after completing a six-month course of chlorambucil for CLL. The interstitial pneumonitis responded to therapy with prednisone. We performed a systematic review of literature and identified 13 other case reports of chlorambucil-induced pulmonary toxicity, particularly interstitial pneumonitis. No unifying risk factor could be discerned and the mechanism of injury remains unknown. In contrast, major randomized trials of chlorambucil therapy in CLL have not reported interstitial pneumonitis as an adverse effect, which may be due to the rarity of the phenomenon or due to underreporting of events occurring after completion of treatment. Clinicians should consider drug-induced interstitial pneumonitis in the differential diagnosis of a suggestive syndrome developing even after discontinuation of chlorambucil.

  14. Usefulness of the second heart sound for predicting pulmonary hypertension in patients with interstitial lung disease

    Directory of Open Access Journals (Sweden)

    Sandra de Barros Cobra

    Full Text Available CONTEXT AND OBJECTIVE: P2 hyperphonesis is considered to be a valuable finding in semiological diagnoses of pulmonary hypertension (PH. The aim here was to evaluate the accuracy of the pulmonary component of second heart sounds for predicting PH in patients with interstitial lung disease. DESIGN AND SETTING: Cross-sectional study at the University of Brasilia and Hospital de Base do Distrito Federal. METHODS: Heart sounds were acquired using an electronic stethoscope and were analyzed using phonocardiography. Clinical signs suggestive of PH, such as second heart sound (S2 in pulmonary area louder than in aortic area; P2 > A2 in pulmonary area and P2 present in mitral area, were compared with Doppler echocardiographic parameters suggestive of PH. Sensitivity (S, specificity (Sp and positive (LR+ and negative (LR- likelihood ratios were evaluated. RESULTS: There was no significant correlation between S2 or P2 amplitude and PASP (pulmonary artery systolic pressure (P = 0.185 and 0.115; P= 0.13 and 0.34, respectively. Higher S2 in pulmonary area than in aortic area, compared with all the criteria suggestive of PH, showed S = 60%, Sp= 22%; LR+ = 0.7; LR- = 1.7; while P2> A2 showed S= 57%, Sp = 39%; LR+ = 0.9; LR- = 1.1; and P2 in mitral area showed: S= 68%, Sp = 41%; LR+ = 1.1; LR- = 0.7. All these signals together showed: S= 50%, Sp = 56%. CONCLUSIONS: The semiological signs indicative of PH presented low sensitivity and specificity levels for clinically diagnosing this comorbidity.

  15. GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization.

    Science.gov (United States)

    Halstead, E Scott; Umstead, Todd M; Davies, Michael L; Kawasawa, Yuka Imamura; Silveyra, Patricia; Howyrlak, Judie; Yang, Linlin; Guo, Weichao; Hu, Sanmei; Hewage, Eranda Kurundu; Chroneos, Zissis C

    2018-01-05

    Influenza A viruses cause life-threatening pneumonia and lung injury in the lower respiratory tract. Application of high GM-CSF levels prior to infection has been shown to reduce morbidity and mortality from pathogenic influenza infection in mice, but the mechanisms of protection and treatment efficacy have not been established. Mice were infected intranasally with influenza A virus (PR8 strain). Supra-physiologic levels of GM-CSF were induced in the airways using the double transgenic GM-CSF (DTGM) or littermate control mice starting on 3 days post-infection (dpi). Assessment of respiratory mechanical parameters was performed using the flexiVent rodent ventilator. RNA sequence analysis was performed on FACS-sorted airway macrophage subsets at 8 dpi. Supra-physiologic levels of GM-CSF conferred a survival benefit, arrested the deterioration of lung mechanics, and reduced the abundance of protein exudates in bronchoalveolar (BAL) fluid to near baseline levels. Transcriptome analysis, and subsequent validation ELISA assays, revealed that excess GM-CSF re-directs macrophages from an "M1-like" to a more "M2-like" activation state as revealed by alterations in the ratios of CXCL9 and CCL17 in BAL fluid, respectively. Ingenuity pathway analysis predicted that GM-CSF surplus during IAV infection elicits expression of anti-inflammatory mediators and moderates M1 macrophage pro-inflammatory signaling by Type II interferon (IFN-γ). Our data indicate that application of high levels of GM-CSF in the lung after influenza A virus infection alters pathogenic "M1-like" macrophage inflammation. These results indicate a possible therapeutic strategy for respiratory virus-associated pneumonia and acute lung injury.

  16. Roles for C-X-C chemokines and C5a in lung injury after hindlimb ischemia-reperfusion

    DEFF Research Database (Denmark)

    Bless, N M; Warner, R L; Padgaonkar, V A

    1999-01-01

    We evaluated the roles of the C-X-C chemokines cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2) as well as the complement activation product C5a in development of lung injury after hindlimb ischemia-reperfusion in rats. During reperfusion, CD11b...... and CD18, but not CD11a, were upregulated on neutrophils [bronchoalveolar lavage (BAL) and blood] and lung macrophages. BAL levels of CINC and MIP-2 were increased during the ischemic and reperfusion periods. Treatment with either anti-CINC or anti-MIP-2 IgG significantly reduced lung vascular......, 58, and 23%, respectively (P MIP-2 as well as the complement activation product C5a are required for lung neutrophil recruitment and full induction of lung injury after hindlimb ischemia-reperfusion in rats....

  17. Trichinella spiralis infection enhances protein kinase C phosphorylation in guinea pig alveolar macrophages.

    Science.gov (United States)

    Dzik, J M; Zieliński, Z; Cieśla, J; Wałajtys-Rode, E

    2010-03-01

    To learn more about the signalling pathways involved in superoxide anion production in guinea pig alveolar macrophages, triggered by Trichinella spiralis infection, protein level and phosphorylation of mitogen activated protein (MAP) kinases and protein kinase C (PKC) were investigated. Infection with T. spiralis, the nematode having 'lung phase' during colonization of the host, enhances PKC phosphorylation in guinea pig alveolar macrophages. Isoenzymes beta and delta of PKC have been found significantly phosphorylated, although their location was not changed as a consequence of T. spiralis infection. Neither in macrophages from T. spiralis-infected guinea pig nor in platelet-activating factor (PAF)-stimulated macrophages from uninfected animals, participation of MAP kinases in respiratory burst activation was statistically significant. The parasite antigens seem to act through macrophage PAF receptors, transducing a signal for enhanced NADPH oxidase activity, as stimulating effect of newborn larvae homogenate on respiratory burst was abolished by specific PAF receptor antagonist CV 6209. A suppressive action of T. spiralis larvae on host alveolar macrophage innate immunological response was reflected by diminished protein level of ERK2 kinase and suppressed superoxide anion production, in spite of high level of PKC phosphorylation.

  18. Bronchoalveolar lavage cellular analyses in conjunction with high-resolution computed tomography imaging as a diagnostic intervention for patients with suspected interstitial lung disease

    Directory of Open Access Journals (Sweden)

    Ammaiyappan Chockalingam

    2016-01-01

    Full Text Available Background: Bronchoalveolar lavage (BAL has gained acceptance for diagnosis of Interstitial lung disease (ILD. The advent of high-resolution computed tomography (HRCT has reduced the clinical utility of BAL. This work has utilized the recommendations of the American Thoracic Society (ATS to optimize BAL and the findings have been associated with clinical examination and HRCT to precisely narrow down the cause of ILD. Materials and Methods: BAL was performed on ILD suspects at the target site chosen based on HRCT. The procedure, transport, processing, and analysis of BAL fluid were performed as per the ATS guidelines. The clinical data, HRCT findings and BAL report were used to narrow down the diagnosis of ILD. The statistical analysis was performed to assess the significance. Results: The BAL procedure was optimized as per the recommendations of the ATS. In a cohort of 50 patients, Idiopathic pulmonary fibrosis, (8 hypersensitivity pneumonitis, (17 connective tissue disorder, (9 sarcoidosis, (3 pneumoconiosis, (5 acute respiratory distress syndrome, (2 eosinophilic lung disease (2 and lymphangitic carcinomatosa, (2 aspiration bronchiolitis (1 and pulmonary histiocytosis (1 were diagnosed. Statistically significant variation in differential counts was found in different ILDs. The different ILDs were classified based on the criteria described by the ATS. Clinical Significance: BAL along with clinical and HRCT findings improved the diagnostic accuracy by incorporating, the acute or chronic nature of the disease and the cause for acute exacerbation, which helped in the better management of ILDs.

  19. Connective tissue diseases, multimorbidity and the ageing lung.

    Science.gov (United States)

    Spagnolo, Paolo; Cordier, Jean-François; Cottin, Vincent

    2016-05-01

    Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients. Copyright ©ERS 2016.

  20. Vascular and epithelial damage in the lung of the mouse after X rays or neutrons

    International Nuclear Information System (INIS)

    Law, M.P.; Ahier, R.G.

    1989-01-01

    The response of the lung was studied in CFLP mice after exposure of the whole thorax to X rays (250 kVp) or cyclotron neutrons (16 MeV deuterons on Be, mean energy 7.5 MeV). To measure blood volume and leakage of plasma proteins, 51Cr-labeled red blood cells and 125I-albumin were injected intravenously and 24 h later lungs were lavaged via the trachea. Radioactivities in lung tissue and lavage fluid were determined to estimate the accumulation of albumin in the interstitial and alveolar spaces indicating damage to blood vessels and alveolar epithelium respectively. Function of type II pneumonocytes was assessed by the amounts of surfactant (assayed as lipid phosphorous) released into the lavage fluid. During the first 6 weeks, lavage protein and surfactant were increased, the neutron relative biological effectiveness (RBE) being unity. During pneumonitis at 12-24 weeks, surfactant levels were normal, blood volume was decreased, and both interstitial and alveolar albumin were increased. Albumin levels then decreased. At late times after exposure (42-64 weeks) alveolar albumin returned to normal but interstitial albumin was still slightly elevated. Values of RBE for changes in blood volume and interstitial and alveolar albumin at 15 weeks and for changes in blood volume and interstitial albumin at 46 weeks were 1.4, comparable with that for animal survival at 180 days. The results indicate that surfactant production is not critical for animal survival. They suggest that changes in blood vessels and alveolar epithelium occur during acute pneumonitis; epithelial repair follows but some vascular damage may persist. The time course of the changes in albumin levels did not correlate with increases in collagen biosynthesis which have been observed as early as 1 month after exposure and persist for up to 1 year