Airway inflammation in severe chronic obstructive pulmonary disease

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Turato, Graziella; Zuin, Renzo; Miniati, Massimo

2002-01-01

Very few studies have been made in-patient with severe chronic obstructive pulmonary disease and some of them carried out, have demonstrated an increment in the intensity of the inflammatory answer in the space and these patients' alveolar walls. However, there are not enough studies on the inflammatory answer in the small airway and in the lung glasses, object of the present study, comparing it with patient with light (COPD) or without COPD, in spite of similar history of smoker

Pulmonary Alveolar Proteinosis in Setting of Inhaled Toxin Exposure and Chronic Substance Abuse

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Meirui Li

2018-01-01

Full Text Available Pulmonary alveolar proteinosis (PAP is a rare lung disorder in which defects in alveolar macrophage maturation or function lead to the accumulation of proteinaceous surfactant in alveolar space, resulting in impaired gas exchange and hypoxemia. PAP is categorized into three types: hereditary, autoimmune, and secondary. We report a case of secondary PAP in a 47-year-old man, whose risk factors include occupational exposure to inhaled toxins, especially aluminum dust, the use of anabolic steroids, and alcohol abuse, which in mice leads to alveolar macrophage dysfunction through a zinc-dependent mechanism that inhibits granulocyte macrophage-colony stimulating factor (GM-CSF receptor signalling. Although the rarity and vague clinical presentation of PAP can pose diagnostic challenges, clinician awareness of PAP risk factors may facilitate the diagnostic process and lead to more prompt treatment.

Primary pulmonary alveolar proteinosis: computed tomography features at diagnosis

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Berteloot, Laureline; Emond-Gonsard, Sophie; Mamou-Mani, Tania; Lambot, Karen; Grevent, David; Taam, Rola Abou; Le Bourgeois, Muriel; Elie, Caroline; Delacourt, Christophe; Blic, Jacques de; Brunelle, Francis

2014-01-01

Pulmonary alveolar proteinosis (PAP) is characterized by an abnormal accumulation of periodic acid-schiff-positive lipoproteinaceous material in the alveoli. Early diagnosis allows setting up of therapeutic lung lavages, which reduces the need for oxygen supplementation and weight gain. To provide a description of radiological features by CT at the onset of primary PAP in children. The clinical and radiological data of 24 patients, including 16 boys and 8 girls (median age: 12 months), diagnosed with a primary form of PAP between April 1992 and May 2012 in a tertiary referral hospital, were retrospectively reviewed. CT images were examined for the presence of alveolar and interstitial elementary lesions. Correlation between clinical and radiological findings was assessed. The types of elementary lesions detected were: ground-glass opacities (n = 24), intralobular lines (n = 24), thickened interlobular septa (n = 22), thickened fissures (n = 21), airspace consolidation (n = 16), hyperinflation (n = 16), cystic lesions (n = 2) and micronodules (n = 1). A crazy-paving pattern was found in 92% of cases. Consolidation and hyperinflation were especially detected in younger children (median age, 8 months, P < 0.01). A density dependent gradient was found. The distribution of the lesions was symmetrical. There was no correlation between radiological and clinical data of severity of the disease. CT findings are suggestive of diagnosis of PAP in immunocompetent children with chronic respiratory failure. (orig.)

Primary pulmonary alveolar proteinosis: computed tomography features at diagnosis

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Berteloot, Laureline; Emond-Gonsard, Sophie; Mamou-Mani, Tania; Lambot, Karen; Grevent, David [Hopital Necker Enfants-Malades, Department of Pediatric Radiology, Paris (France); Taam, Rola Abou; Le Bourgeois, Muriel [Hopital Necker Enfants-Malades, Department of Pediatric Pneumology and Allergology, Paris (France); Elie, Caroline [Hopital Necker Enfants-Malades, Department of Biostatistics, Paris (France); Paris Descartes University, Paris (France); Delacourt, Christophe; Blic, Jacques de [Hopital Necker Enfants-Malades, Department of Pediatric Pneumology and Allergology, Paris (France); Paris Descartes University, Paris (France); Brunelle, Francis [Hopital Necker Enfants-Malades, Department of Pediatric Radiology, Paris (France); Paris Descartes University, Paris (France)

2014-07-15

Pulmonary alveolar proteinosis (PAP) is characterized by an abnormal accumulation of periodic acid-schiff-positive lipoproteinaceous material in the alveoli. Early diagnosis allows setting up of therapeutic lung lavages, which reduces the need for oxygen supplementation and weight gain. To provide a description of radiological features by CT at the onset of primary PAP in children. The clinical and radiological data of 24 patients, including 16 boys and 8 girls (median age: 12 months), diagnosed with a primary form of PAP between April 1992 and May 2012 in a tertiary referral hospital, were retrospectively reviewed. CT images were examined for the presence of alveolar and interstitial elementary lesions. Correlation between clinical and radiological findings was assessed. The types of elementary lesions detected were: ground-glass opacities (n = 24), intralobular lines (n = 24), thickened interlobular septa (n = 22), thickened fissures (n = 21), airspace consolidation (n = 16), hyperinflation (n = 16), cystic lesions (n = 2) and micronodules (n = 1). A crazy-paving pattern was found in 92% of cases. Consolidation and hyperinflation were especially detected in younger children (median age, 8 months, P < 0.01). A density dependent gradient was found. The distribution of the lesions was symmetrical. There was no correlation between radiological and clinical data of severity of the disease. CT findings are suggestive of diagnosis of PAP in immunocompetent children with chronic respiratory failure. (orig.)

Sandstorm appearance of pulmonary alveolar microlithiasis incidentally detected in a young, asymptomatic male

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Ching, Li Shyan; Bux, Shaik Ismail; Liam, Chong Kin; Rahman, Nazarina Abdul; Ho, Choon Yan [Faculty of Medicine, University Malaya Medical Center, Kuala Lumpur (Malaysia)

2013-10-15

Pulmonary alveolar microlithiasis (PAM) is a rare chronic disease with paucity of symptoms in contrast to the imaging findings. We present a case of a 24-year-old Malay man having an incidental abnormal pre-employment chest radiograph of dense micronodular opacities giving the classical 'sandstorm' appearance. High-resolution computed tomography of the lungs showed microcalcifications with subpleural cystic changes. Open lung biopsy showed calcospherites within the alveolar spaces. The radiological and histopathological findings were characteristic of PAM.

Pulmonary alveolar proteinosis: Quantitative CT and pulmonary functional correlations

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Guan, Yubao, E-mail: yubaoguan@163.com [Department of Radiology, the First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120 (China); State Key Laboratory of Respiratory Disease, Guangzhou 510120 (China); Zeng, Qingsi [Department of Radiology, the First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120 (China); Yang, Haihong; Zheng, Jinping; Li, Shiyue; Gao, Yi [State Key Laboratory of Respiratory Disease, Guangzhou 510120 (China); Deng, Yu [Department of Radiology, the First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120 (China); Mei, Jiang [State Key Laboratory of Respiratory Disease, Guangzhou 510120 (China); He, Jianxing, E-mail: jianxing63@163.com [State Key Laboratory of Respiratory Disease, Guangzhou 510120 (China); Zhong, Nanshan, E-mail: nanshan@vip.163.com [State Key Laboratory of Respiratory Disease, Guangzhou 510120 (China)

2012-09-15

Objective: We assessed the relationship between quantitative computer tomography (qCT) and the pulmonary function test (PFT) or blood gas analysis in pulmonary alveolar proteinosis (PAP) patients, as well as the utility of these analyses to monitor responses to whole lung lavage (WLL) therapy. Methods: Thirty-eight PAP patients simultaneously received a CT scan and PFT. Fifteen of these patients, undergoing sequential WLL for a total of 20 lavages, also underwent chest CT scans and blood gas analysis before and after WLL, and 14 of 15 patients underwent simultaneous PFT analysis. Differences between the qCT and PFT results were analyzed by canonical correlation. Results: PAP patients with low predicted values for FVC, FEV1, D{sub LCO} and D{sub LCO}/VA indicated small airspace volume and mean lung inflation, low airspace volume/total lung volume ratio and high mean lung density. Correlation and regression analysis revealed a strong correlation between D{sub LCO} and PaO{sub 2} values with CT results. The qCT results indicated that WLL significantly decreased lung weights and mean lung densities, and improved the total airspace volume/total lung volume ratios and mean lung inflations. Conclusion: Quantitative CT may be a sensitive tool for measuring the response of PAP patients to medical interventions such as WLL.

The Role of Mitochondrial DNA in Mediating Alveolar Epithelial Cell Apoptosis and Pulmonary Fibrosis

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Kim, Seok-Jo; Cheresh, Paul; Jablonski, Renea P.; Williams, David B.; Kamp, David W.

2015-01-01

Convincing evidence has emerged demonstrating that impairment of mitochondrial function is critically important in regulating alveolar epithelial cell (AEC) programmed cell death (apoptosis) that may contribute to aging-related lung diseases, such as idiopathic pulmonary fibrosis (IPF) and asbestosis (pulmonary fibrosis following asbestos exposure). The mammalian mitochondrial DNA (mtDNA) encodes for 13 proteins, including several essential for oxidative phosphorylation. We review the evidence implicating that oxidative stress-induced mtDNA damage promotes AEC apoptosis and pulmonary fibrosis. We focus on the emerging role for AEC mtDNA damage repair by 8-oxoguanine DNA glycosylase (OGG1) and mitochondrial aconitase (ACO-2) in maintaining mtDNA integrity which is important in preventing AEC apoptosis and asbestos-induced pulmonary fibrosis in a murine model. We then review recent studies linking the sirtuin (SIRT) family members, especially SIRT3, to mitochondrial integrity and mtDNA damage repair and aging. We present a conceptual model of how SIRTs modulate reactive oxygen species (ROS)-driven mitochondrial metabolism that may be important for their tumor suppressor function. The emerging insights into the pathobiology underlying AEC mtDNA damage and apoptosis is suggesting novel therapeutic targets that may prove useful for the management of age-related diseases, including pulmonary fibrosis and lung cancer. PMID:26370974

Primary Pulmonary Plasmacytoma with Diffuse Alveolar Consolidation: A Case Report

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Zohreh Mohammad Taheri

2010-01-01

Full Text Available Solitary extramedullary plasmacytomas are plasma cell tumors that tend to develop in mucosa-associated lymphoid tissues including the sinonasal or nasopharyngeal regions. Primary plasmacytoma of the lung is exceedingly rare and often presents as a solitary mass or nodule in mid-lung or hilar areas and diagnosed after resection. Herein, we report a case of primary pulmonary plasmacytoma that presented with diffuse alveolar consolidation and diagnosed by transbronchial lung biopsy.

Recurrence of alveolar capillary dysplasia with misalignment of pulmonary veins in two consecutive siblings

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Gabriel Nuncio Benevides

2015-03-01

Full Text Available Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV is a rare, developmental lung disorder, which has been increasingly reported. This entity usually presents as neonatal persistent pulmonary hypertension that is unresponsive to treatment, and is known to be uniformly fatal. Recent discoveries in the genetic field, and intensive treatments, may change the natural course of this disease, permitting easier diagnosis and giving new hope for the dismal prognosis. The authors present two cases of siblings, with two years of difference, from different fathers - one of them was a first-degree and the other a second-degree cousin of the mother. Both patients were full-term babies born apparently without malformations and were sent to the nursery. Both siblings near 35 hours of age presented severe respiratory failure due to pulmonary hypertension. The outcome was fatal in both cases and at autopsy ACD/MPV was diagnosed. The authors call attention to this entity in the differential diagnosis of acute respiratory distress in early life.

Anaesthetic, procedure and complications management of serial whole-lung lavage in an obese patient with pulmonary alveolar proteinosis: case report.

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Rebelo, Helena Marta; Guedes, Luisa; Veiga, Dalila; Fiuza, Antonio C; Abelha, Fernando

2012-01-01

The first case of Pulmonary Alveolar Proteinosis (PAP) was described by Rose in 1958, but it is still a rare disorder. PAP is characterized by deposition of lipoproteinaceous material secondary to abnormal processing of surfactant by macrophages. Patients may suffer from progressive dyspnea and cough that at times is accompanied by worsening hypoxia and its course can vary from progressive deterioration to spontaneous improvement. Many therapies have been used to treat PAP including antibiotics, postural drainage, and intermittent positive pressure breathing with aerosolized Acetylcysteine, heparin and saline. At present, the mainstay of treatment is whole lung lavage (WLL). Although generally well tolerated, WLL can be associated with some complications. We report a case of severe PAP through the anaesthetic, procedure and complications management of pulmonary alveolar proteinosis in one patient who has undergone multiple, alternating, single-lung lavages over the past seven years, the last three in our hospital, with improvements in her symptoms following each therapy. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

Retention of inhaled plutonium oxide. Elimination procedures by pulmonary lavage and effect of the alveolar macrophage

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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

Pulmonary Alveolar Proteinosis in Association with Congenital Dyserythropoietic Anemia: A Case Report

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Marcus A. Carden

2012-01-01

Full Text Available A two-year-old girl with congenital dyserythropoietic anemia (CDA acutely developed fever, tachypnea, and increased oxygen requirement. Chest X-ray revealed bilateral interstitial infiltrates and mild cardiomegaly. Blood cultures grew no infectious agents, while pulmonary specimens grew cytomegalovirus (CMV. Treatment with intravenous ganciclovir was initiated but without response. Final cytologic preparations of bronchoalveolar lavage (BAL fluid revealed eosinophilic amorphous material consistent with pulmonary alveolar proteinosis (PAP. CDA and PAP are extremely rare disorders in pediatrics. PAP should be considered in patients with hematological disorders who present with acute interstitial pneumonia, after infectious causes are ruled out.

Teaching the effects of gravity and intravascular and alveolar pressures on the distribution of pulmonary blood flow using a classic paper by West et al.

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Levitzky, Michael G

2006-03-01

"Distribution of blood flow in isolated lung; relation to vascular and alveolar pressures" by J. B. West, C. T. Dollery, and A. Naimark (J Appl Physiol 19: 713-724, 1964) is a classic paper, although it has not yet been included in the Essays on the American Physiological Society Classic Papers Project (http://www.the-aps.org/publications/classics/). This is the paper that originally described the "zones of the lung." The final figure in the paper, which synthesizes the results and discussion, is now seen in most textbooks of physiology or respiratory physiology. The paper is also a model of clear, concise writing. The paper and its final figure can be used to teach or review a number of physiological concepts. These include the effects of gravity on pulmonary blood flow and pulmonary vascular resistance; recruitment and distention of pulmonary vessels; the importance of the transmural pressure on the diameter of collapsible distensible vessels; the Starling resistor; the interplay of the pulmonary artery, pulmonary vein, and alveolar pressures; and the vascular waterfall. In addition, the figure can be used to generate discovery learning and discussion of several physiological or pathophysiological effects on pulmonary vascular resistance and the distribution of pulmonary blood flow.

Recurrence of alveolar capillary dysplasia with misalignment of pulmonary veins in two consecutive siblings

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Benevides, Gabriel Nuncio; Picciarelli de Lima, Patricia; Felipe-Silva, Aloisio; Lovisolo, Silvana Maria; Pereira de Melo, Ana Maria Andrello Gonçalves

2015-01-01

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, developmental lung disorder, which has been increasingly reported. This entity usually presents as neonatal persistent pulmonary hypertension that is unresponsive to treatment, and is known to be uniformly fatal. Recent discoveries in the genetic field, and intensive treatments, may change the natural course of this disease, permitting easier diagnosis and giving new hope for the dismal prognosis. The autho...

Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.

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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.

Alveolar epithelial fluid transport capacity in reperfusion lung injury after lung transplantation.

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Ware, L B; Golden, J A; Finkbeiner, W E; Matthay, M A

1999-03-01

Reperfusion lung injury is an important cause of morbidity and mortality after orthotopic lung transplantation. The purpose of this study was to investigate the function of the alveolar epithelium in the setting of reperfusion lung injury. Simultaneous samples of pulmonary edema fluid and plasma were collected from eight patients with severe post-transplantation reperfusion edema. The edema fluid to plasma protein ratio was measured, an indicator of alveolar-capillary barrier permeability. The initial edema fluid to plasma protein ratio was > 0.75 in six of eight patients, confirming the presence of increased permeability of the alveolar-capillary barrier. Graft ischemic time was positively correlated with the degree of permeability (r = 0.77, p mean +/- SD). Alveolar fluid clearance was calculated from serial samples in six patients. Intact alveolar fluid clearance correlated with less histologic injury, rapid resolution of hypoxemia, and more rapid resolution of radiographic infiltrates. The two patients with no net alveolar fluid clearance had persistent hypoxemia and more severe histologic injury. This study provides the first direct evidence that increased permeability to protein is the usual cause of reperfusion edema after lung transplantation, with longer ischemic times associated with greater permeability to protein in the transplanted lung. The high rates of alveolar fluid clearance indicate that the fluid transport capacity of the alveolar epithelium may be well preserved in the allograft despite reperfusion lung injury. The ability to reabsorb fluid from the alveolar space was a marker of less severe reperfusion injury, whereas the degree of alveolar-capillary barrier permeability to protein was not. Measurement of alveolar fluid clearance may be useful to assess the severity of reperfusion lung injury and to predict outcome when pulmonary edema develops after lung transplantation.

Pulmonary capillary haemangiomatosis: a rare cause of pulmonary hypertension.

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Babu, K Anand; Supraja, K; Singh, Raj B

2014-01-01

Pulmonary capillary haemangiomatosis (PCH) is a rare disorder of unknown aetiology, characterised by proliferating capillaries that invade the pulmonary interstitium, alveolar septae and the pulmonary vasculature. It is often mis-diagnosed as primary pulmonary hypertension and pulmonary veno-occlusive disease. Pulmonary capillary haemangiomatosis is a locally aggressive benign vascular neoplasm of the lung. We report the case of a 19-year-old female who was referred to us in the early post-partum period with severe pulmonary artery hypertension, which was diagnosed as PCH by open lung biopsy.

Manobra de recrutamento alveolar na contusão pulmonar: relato de caso e revisão da literatura Alveolar recruitment in pulmonary contusion: case report and literature review

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Lívia Maria Vitório Trindade

2009-03-01

Full Text Available O tratamento da contusão pulmonar quando instituído de forma correta é bastante simples na maioria das vezes. As alterações fisiopatológicas acontecem como decorrência dos efeitos produzidos pela perda da integridade da parede torácica, acúmulo de líquidos na cavidade pleural, obstrução da via aérea e disfunção pulmonar. A manobra de recrutamento alveolar consiste na reabertura de áreas pulmonares colapsadas através do aumento da pressão inspiratória na via aérea. O objetivo deste relato foi apresentar um caso de contusão pulmonar, avaliando a efetividade da manobra de recrutamento alveolar e revisão da literatura. Paciente do sexo masculino, 33 anos, com quadro clínico de trauma de tórax bilateral e trauma crânio-encefálico, evoluiu com rebaixamento do nível de consciência, insuficiência respiratória aguda, choque hipovolêmico, hemoptise. Foi submetido a toracocentese, drenagem torácica bilateral e submetido a ventilação mecânica invasiva. Após 48 horas de ventilação mecânica invasiva, segundo os preceitos da estratégia protetora, iniciou-se manobras de recrutamento alveolar modo, Pressão controlada 10 cmH2O, freqüência respiratória 10rpm, tempo inspiratório 3.0, pressão positiva no final da expiração 30 cmH2O, FIO2 100%, durante dois minutos. Após a aplicação da manobra de recrutamento alveolar O paciente apresentou melhora pulmonar significativa da oxigenação, caracterizada por aumento da relação PaO2/FiO2, porém houve variação da mesma entre 185 a 322. Obteve alta da unidade na terapia intensiva após 22 dias e hospitalar após 32 dias da admissão. A manobra de recrutamento alveolar neste paciente apresentou resultados significativos no tratamento da contusão pulmonar, melhorando a oxigenação arterial, prevenindo o colapso alveolar e revertendo quadros de atelectasias.Treatment of pulmonary contusion when adequately established is very simple in most cases. Pathophysiological

Estimation of pulmonary water distribution and pulmonary congestion by computed tomography

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Morooka, Nobuhiro; Watanabe, Shigeru; Masuda, Yoshiaki; Inagaki, Yoshiaki

1982-01-01

Computed tomography (CT) of the lung in normal subjects and patients with congestive heart failure was performed in the supine position with deep inspiration to obtain pulmonary CT values and images. The mean CT value in normal subjects was higher in the posterior than anterior lung field, presumably because blood vessels were more dilated in the former than the latter due to the effects of gravity. The mean pulmonary CT value in patients with congestive heart failure was significantly increased possibly due to an increase in blood flow per unit lung volume arising from either pulmonary congestion or pulmonary interstitial and alveolar edema. The mean pulmonary CT value increased parallel to the severity of pulmonary congestion, interstitial or alveolar edema and was well correlated with the pulmonary arterial wedge pressure, indicating that such a correlation was a valuable tool in assessing therapeutic effects. The results of the present study indicatethat pulmonary CT is useful for the noninvasive estimation of intrapulmonary water content and its distribution, thereby providing an effective diagnostic clue to various conditions in congestive heart failure. (author)

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

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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. �

Celiac disease with pulmonary haemosiderosis and cardiomyopathy

OpenAIRE

Işikay, Sedat; Yilmaz, Kutluhan; Kilinç, Metin

2012-01-01

Celiac disease or pulmonary haemosiderosis can be associated with several distinguished conditions. Pulmonary haemosiderosis is a rare, severe and fatal disease characterised by recurrent episodes of alveolar haemorrhage, haemoptysis and anaemia. Association of pulmonary haemosiderosis and celiac disease is extremely rare. We describe a case of celiac disease presented with dilated cardiomyopathy and pulmonary haemosiderosis without gastrointestinal symptoms of celiac disease. In addition, vi...

Radiosensitivity of pulmonary alveolar macrophages in rats exposed to local X-irradiation

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Gong Yifen; Fei Lihua; Wu Dechang

1987-01-01

The radiosensitivity of pulmonary alveolar macrophages (PAMs) in rats exposed to local thoracic X-irradiatoin was studied. The percentages of mitotic and labeling cells were used as biological endpoints. The parameters of radiosensitivity of PAMs obtained on the second day after local exposure are as follows: D 0 = 0.68 Gy, Dq = 0.06 Gy, n = 1.1 for mitotic cells and D 0 = 1.04 Gy, Dq = 0.12 Gy, n = 1.12 for labeling cells. The parameters of radiosensitivity of PAMs in bronchical lavage obtained immediately after X-irradiation are: D 0 = 3.56 Gy, Dq = 0.77 Gy, n = 1.24 for labeling cells and D 0 = 3.69 Gy, Dq = 0.35 Gy, n = 1.1 for mitotic cells. The comparison of thses results indicates that the radiation effect on PAMs obtained immediately after X-irradiation is less severe than that of PAMs obtained 2 days later. It might be caused by the delay of cell cycle within 2 days after X-irradiation

Alveolar recruitment manoeuvre is safe in children prone to pulmonary hypertensive crises following open heart surgery: a pilot study.

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Amorim, Erica de Freitas; Guimaraes, Viviane Assuncao; Carmona, Fabio; Carlotti, Ana Paula de Carvalho Panzeri; Manso, Paulo Henrique; Ferreira, Cesar Augusto; Klamt, Jyrson Guilherme; Vicente, Walter Villela de Andrade

2014-05-01

To test the tolerance and safety of an alveolar recruitment manoeuvre performed in the immediate postoperative period of corrective open heart surgery in children with congenital heart disease associated with excessive pulmonary blood flow and pulmonary arterial hypertension due to left-to-right shunt. Ten infants aged 1-24 months with congenital heart disease associated with excessive pulmonary blood flow and pulmonary artery hypertension (mean pulmonary artery pressure ≥ 25 mmHg) were evaluated. The alveolar recruitment manoeuvre was performed in the operating theatre right after skin closure, and consisted of three successive stages of 30 s each, intercalated by a 1-min interval of baseline ventilation. Positive end-expiratory pressure was set to 10 cmH2O in the first stage and to 15 cmH2O in the two last ones, while the peak inspiratory pressure was kept at to 30 cmH2O in the first stage and at 35 cmH2O in the latter ones. Haemodynamic and respiratory variables were recorded. There was a slight but significant increase in mean pulmonary artery pressure from baseline to Stage 3 (P = 0.0009), as well as between Stages 1 and 2 (P = 0.0001), and 1 and 3 (P = 0.001), with no significant difference between Stages 2 and 3 (P = 0.06). Upon completion of the third stage, there were significant increases in arterial haemoglobin saturation as measured by pulse oximetry (P = 0.0009), arterial blood partial pressure of oxygen (P = 0.04), venous blood oxygen saturation of haemoglobin (P = 0.03) and arterial oxygen partial pressure over inspired oxygen fraction ratio (P = 0.04). A significant reduction in arterial blood partial pressure of carbon dioxide (P = 0.01) and in end tidal carbon dioxide also occurred (P = 0.009). The manoeuvre was well tolerated and besides a slight and transitory elevation in mean pulmonary artery, no other adverse haemodynamic or ventilatory effect was elicited. The alveolar recruitment manoeuvre seemed to be safe and well tolerated immediately

A novel immunodeficiency syndrome as a rare cause of secondary pulmonary alveolar proteinosis: A diagnosis after 5 decades

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Pedro G. Ferreira

2014-09-01

Full Text Available Case report of a male patient with a five-decade follow-up history in a tertiary care hospital distinguished for malabsorption syndrome, failure-to-thrive, meningitis and recurrent bacterial, fungal and mycobacterial pulmonary infections. Additionally, he developed epidermodysplasia verruciformis, several in situ spinocellular carcinomas and an uncharacteristic parenchymal lung disease. Surgical lung biopsy suggested pulmonary alveolar proteinosis with fibrotic change. Retrospectively, severe monocytopenia had been overlooked in the past, as well as low B and NK cell blood counts. Flow cytometry confirmed the absence of the previous cell subsets along with an undetectable population of dendritic blood cells.Dendritic cell, monocyte, B and NK lymphoid Human Deficiency Syndrome (DCMLS is a novel rare immunodeficiency described in 2010, linked to GATA-2 mutation. This syndrome should be highlighted as a rare cause of acquired PAP, with a radiological pattern encompassing potential fibrotic change. Failure to recognize monocytopenia may impede the chance to diagnose. Resumo: Relato de um caso clínico de um doente do sexo masculino com um historial de acompanhamento de cinco décadas, num hospital de cuidados terciários, caracterizado por um síndrome de malabsorção, insuficiência de crescimento, meningite e infecções pulmonares bacterianas, fúngicas e micobacterianas recorrentes. Além disso, desenvolveu epidermodisplasia verruciforme, diversos carcinomas espinocelulares in situ e uma doença pulmonar parenquimatosa não definida. Uma biópsia pulmonar cirúrgica sugeriu uma Proteinose Alveolar Pulmonar com alterações fibróticas. Em retrospectiva, uma monocitopenia grave negligenciada no passado, bem como uma baixa contagem de células B (linfócitos B e NK (células ‘natural killer’. Uma citometria de fluxo confirmou a ausência dos subconjuntos de células anteriores, juntamente

Rapid Progression of Metastatic Pulmonary Calcification and Alveolar Hemorrhage in a Patient with Chronic Renal Failure and Primary Hyperparathyroidism

International Nuclear Information System (INIS)

Yoon, Eun Joo; Kim, Dong Hun; Yoon, Seong Ho; Suk, Eun Ha

2013-01-01

Metastatic pulmonary calcification (MPC) is common in patients with chronic renal failure. The authors experienced a patient with chronic renal failure and primary hyperparathyroidism by parathyroid adenoma accompanied with rapid progressions of MPC and alveolar hemorrhage. Recent chest radiographs, compared with previous chest radiographs, showed rapid accumulation of calcification in both upper lungs. Following up on the high-resolution CT scan after five years demonstrates more increased nodules in size and ground glass opacity. The patient was diagnosed with MPC and alveolar hemorrhage by transbronchial lung biopsy. We assumed rapid progression of MPC and alveolar hemorrhage in underlying chronic renal failures could be a primary hyperparathyroidism which may be caused by parathyroid adenoma detected incidentally. Therefore parathyroid adenoma was treated with ethanol injections. Herein, we have reported on CT findings of MPC with alveolar hemorrhage and reviewed our case along with other articles.

Pulmonary alveolar microlithiliasis

International Nuclear Information System (INIS)

Fasihuddin, S.; Alawi, Malak H.; Abdulshakoor, Bothania M.

2004-01-01

We report a patient with plmonary alveolar microlithiliasis who was admitted to King Abdul-Aziz Hospital, Makkah, Kingdom of Saudi Arabia with chest pain, shortness of breath dry cough and swelling of lower limbs.The patient underwent chest radiolgraphs and computerized tomography scan showing multiple diffuse, almost symmetrical bilateral micronodulor opacities of calicific density. The diagnosis was confirmed after percuraneous lung biopsy from the patient. Cardiokinetics, diuretics and oxygen were administerd with slight improvement. (author)

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

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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)

Increased iron sequestration in alveolar macrophages in chronic obstructive pulmonary disease.

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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

Amiloride-Sensitive Sodium Channels and Pulmonary Edema

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Mike Althaus

2011-01-01

Full Text Available The development of pulmonary edema can be considered as a combination of alveolar flooding via increased fluid filtration, impaired alveolar-capillary barrier integrity, and disturbed resolution due to decreased alveolar fluid clearance. An important mechanism regulating alveolar fluid clearance is sodium transport across the alveolar epithelium. Transepithelial sodium transport is largely dependent on the activity of sodium channels in alveolar epithelial cells. This paper describes how sodium channels contribute to alveolar fluid clearance under physiological conditions and how deregulation of sodium channel activity might contribute to the pathogenesis of lung diseases associated with pulmonary edema. Furthermore, sodium channels as putative molecular targets for the treatment of pulmonary edema are discussed.

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

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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

Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis.

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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.

Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis

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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

Modeling Alveolar Epithelial Cell Behavior In Spatially Designed Hydrogel Microenvironments

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Lewis, Katherine Jean Reeder

The alveolar epithelium consists of two cell phenotypes, elongated alveolar type I cells (AT1) and rounded alveolar type II cells (ATII), and exists in a complex three-dimensional environment as a polarized cell layer attached to a thin basement membrane and enclosing a roughly spherical lumen. Closely surrounding the alveolar cysts are capillary endothelial cells as well as interstitial pulmonary fibroblasts. Many factors are thought to influence alveolar epithelial cell differentiation during lung development and wound repair, including physical and biochemical signals from the extracellular matrix (ECM), and paracrine signals from the surrounding mesenchyme. In particular, disrupted signaling between the alveolar epithelium and local fibroblasts has been implicated in the progression of several pulmonary diseases. However, given the complexity of alveolar tissue architecture and the multitude of signaling pathways involved, designing appropriate experimental platforms for this biological system has been difficult. In order to isolate key factors regulating cellular behavior, the researcher ideally should have control over biophysical properties of the ECM, as well as the ability to organize multiple cell types within the scaffold. This thesis aimed to develop a 3D synthetic hydrogel platform to control alveolar epithelial cyst formation, which could then be used to explore how extracellular cues influence cell behavior in a tissue-relevant cellular arrangement. To accomplish this, a poly(ethylene glycol) (PEG) hydrogel network containing enzymatically-degradable crosslinks and bioadhesive pendant peptides was employed as a base material for encapsulating primary alveolar epithelial cells. First, an array of microwells of various cross-sectional shapes was photopatterned into a PEG gel containing photo-labile crosslinks, and primary ATII cells were seeded into the wells to examine the role of geometric confinement on differentiation and multicellular arrangement

Ontogeny of pulmonary alveolar epithelial markers of differentiation.

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Joyce-Brady, M F; Brody, J S

1990-02-01

We studied differentiation of the pulmonary epithelium in the periphery of fetal rat lung in vivo and in vitro by comparing the ontogeny of cell-surface glycoconjugates with that of surfactant phospholipids. Apical surface binding of the lectin Maclura pomifera agglutinin (MPA) and expression of a 200-kDa MPA-binding glycoprotein (MPA-gp200) was evident at 20 days gestation in type 2 cells, but did not correlate with ultrastructural features of type 2 cell differentiation. Epithelial cells isolated from peripheral lung of 18-day gestation fetal rats displayed hormone-sensitive surfactant synthesis prior to the hormone-insensitive expression of MPA-gp200. Expression of MPA-gp200 occurred in association with the appearance of many new apical surface proteins suggesting a hormone-independent process of polar membrane differentiation. Thus membrane and secretory differentiation are discordant and can be dissociated. In vivo binding of Ricinus communis 1 agglutinin (RCA1), an apical marker of the differentiated alveolar type 1 cell occurred in undifferentiated peripheral lung epithelial cells as early as 18 days gestation, disappeared from differentiating type 2 cells and appeared in differentiated type 1 cells. Both undifferentiated fetal epithelial cells at 18 days gestation and fully differentiated type 1 cells express multiple glycoproteins with terminal beta-linked galactose residues which bind RCA1. Some of these RCA1-binding glycoproteins appear to be similar. These observations suggest that alveolar epithelial type 1 cells may derive directly from undifferentiated peripheral lung epithelial cells as well as from fully differentiated type 2 cells. In addition, terminal differentiation of fetal lung peripheral epithelium into type 1 and type 2 cells may involve repression as well as induction of differentiation-related genes.

Mechanisms of alveolar fibrosis after acute lung injury.

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Marinelli, W A; Henke, C A; Harmon, K R; Hertz, M I; Bitterman, P B

1990-12-01

In patients who die after severe acute lung injury, a dramatic fibroproliferative response occurs within the alveolar air space, interstitium, and microvessels. Profound shunt physiology, dead space ventilation, and pulmonary hypertension are the physiologic consequences of this fibroproliferative response. The anatomic pattern of the response is unique within each alveolar compartment. For example, the air space is obliterated by granulation tissue, with replicating mesenchymal cells, their connective tissue products, and an expanding network of intra-alveolar capillaries. In contrast, the vascular fibroproliferative response is dominated by mesenchymal cell replication and connective tissue deposition within the walls of microvessels. Despite the unique anatomic features of these fibroproliferative processes, the regulatory signals involved are likely to be similar. Although our current understanding of the signals regulating the fibroproliferative response to acute lung injury is limited, inferences can be made from in vitro studies of mesenchymal cell behavior and several better understood fibroproliferative processes, including wound healing and chronic fibrotic lung diseases. As clinicians, our future ability to enhance effective lung repair will likely utilize therapeutic strategies specifically targeted to the signals that regulate the fibroproliferative process within the alveolar microenvironment.

Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice

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Danyi Peng

2017-12-01

Full Text Available Alveolar epithelial cells (AECs injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis (PF. Nevertheless, the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear. SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is essential for kidney and heart fibrosis. We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II (ATII cells. Moreover, we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/(tetO7-Cre/SMARCA4f/f mice (SOSM4Δ/Δ model, as well as a new SMARCA4-deleted alveolar type II (ATII-like mle-12 cell line. We found that the bleomycin-induced PF was more aggressive in SOSM4Δ/Δ mice. Also, the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro. In addition, we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections. These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells, which might affect the progression of PF.

Intravascular bronchio-alveolar tumor

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Mata, J.M.; Caceres, J.; Prat, J.; Lopez, J.I.; Velilla, O.

1991-01-01

In 1975 Dail and Liebow described the clinical and pathological characteristics of a pulmonary tumor which they dominated intravascular bronchio-alveolar tumor (IVBAT). Our aim is to acquaint radiologists with the existence of this tumor by describing the radiologic findings in 2 patients with IVBAT, 1 with hepatic involvement ant the other with pulmonary osteoarthropathy. (author). 7 refs.; 2 figs

A familial case of alveolar capillary dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human

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Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare developmental lung disorder that is uniformly lethal. Affected infants die within the first few weeks of their life despite aggressive treatment, although a few cases of late manifestation and longer survival have ...

High resolution computed tomographic features of pulmonary alveolar microlithiasis

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Deniz, Omer; Ors, Fatih; Tozkoparan, Ergun; Ozcan, Ayhan; Gumus, Seyfettin; Bozlar, Ugur; Bilgic, Hayati; Ekiz, Kudret; Demirci, Necmettin

2005-01-01

Background: Pulmonary alveolar microlithiasis (PAM) is a rare, chronic lung disease with unknown etiology and with a nonuniform clinical course. Nonuniformity of clinical course might be related to the degree of pulmonary parenchymal alterations, which can be revealed with high resolution computed tomography (HRCT). However, HRCT findings of PAM were not fully described in the current literature. Aim: The aim of this study was to interpret and to contribute to describe HRCT findings of PAM and to investigate a correlation between profusion of micro nodules (MN) and pulmonary parenchymal alterations in patients with PAM. Material and methods: Ten male patients with PAM (mean age: 22 ± 3.2) were included into the study. HRCT images were assessed for patterns, distribution, and profusion of pulmonary abnormalities. Dividing the lungs into three zones, profusion of abnormalities was assessed. A profusion score (1-4) was given and the scores of each zone were then summed to obtain a global profusion score for HRCT ranging from 0 to 12. Also a parenchymal alteration score (PAS) was defined with respect to profusion of abnormalities. Chest X-rays were also scored. Results: All of ten patients with PAM had findings of interstitial lung disease in varying degrees on their HRCTs. HRCT findings of patients with PAM were as following: MN, parenchymal bands (PB), ground glass opacity (GGO) and, sub pleural interstitial thickening (SPIT) in 10 patients; interlobular septal thickening (ILST), in 9 patients; paraseptal emphysema (PSA) in 8 patients; centrilobular emphysema (CLA) in 7 patients; bronchiectasis (BE), confluent micro nodules (CMN) in 6 patients; peri bronchovascular interstitial thickening (PBIT) in 5 patients; panacinar emphysema (PANAA) in 3 patients; pleural calcification (PC) in 2 patients. A significant correlation between MN scores and PAS (r = 0.68, p = 0.031, MN scores and GGO scores (r = 0.69, p = 0.027) and, MN scores and CLA scores (r = 0.67, p = 0

Variations in alveolar partial pressure for carbon dioxide and oxygen have additive not synergistic acute effects on human pulmonary vasoconstriction.

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Croft, Quentin P P; Formenti, Federico; Talbot, Nick P; Lunn, Daniel; Robbins, Peter A; Dorrington, Keith L

2013-01-01

The human pulmonary vasculature constricts in response to hypercapnia and hypoxia, with important consequences for homeostasis and adaptation. One function of these responses is to direct blood flow away from poorly-ventilated regions of the lung. In humans it is not known whether the stimuli of hypercapnia and hypoxia constrict the pulmonary blood vessels independently of each other or whether they act synergistically, such that the combination of hypercapnia and hypoxia is more effective than the sum of the responses to each stimulus on its own. We independently controlled the alveolar partial pressures of carbon dioxide (Paco 2) and oxygen (Pao 2) to examine their possible interaction on human pulmonary vasoconstriction. Nine volunteers each experienced sixteen possible combinations of four levels of Paco 2 (+6, +1, -4 and -9 mmHg, relative to baseline) with four levels of Pao 2 (175, 100, 75 and 50 mmHg). During each of these sixteen protocols Doppler echocardiography was used to evaluate cardiac output and systolic tricuspid pressure gradient, an index of pulmonary vasoconstriction. The degree of constriction varied linearly with both Paco 2 and the calculated haemoglobin oxygen desaturation (1-So2). Mixed effects modelling delivered coefficients defining the interdependence of cardiac output, systolic tricuspid pressure gradient, ventilation, Paco 2 and So2. No interaction was observed in the effects on pulmonary vasoconstriction of carbon dioxide and oxygen (p>0.64). Direct effects of the alveolar gases on systolic tricuspid pressure gradient greatly exceeded indirect effects arising from concurrent changes in cardiac output.

Wnt-inducible protein (WISP-1 is a key regulator of alveolar epithelial cell hyperplasia in pulmonary fibrosis

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Melanie Königshoff

2006-12-01

Full Text Available Fibrotic lung disease is characterized by distorted lung architecture and severe loss of respiratory function secondary to alveolar epithelial cell (AEC hyperplasia, enhanced extracellular matrix (ECM deposition and fibroblast proliferation. Repetitive epithelial injuries with impaired alveolar wound healing and altered AEC gene expression represent a trigger mechanism for development of fibrosis. To reveal gene regulatory networks in lung fibrosis, we compared gene expression profiles of freshly isolated AEC obtained from mice 14 days after saline or bleomycin (BM instillation using whole genome microarray analysis. Several genes of the Wnt signaling pathway, in particular WISP-1, a member of the CCN family, were highly regulated. WISP-1 protein expression was demonstrated in proliferating AEC in BM-treated lungs by immunofluorescence. When analyzing all six CCN family members, WISP-1 was upregulated the most 14 days after BM challenge, as analyzed by qRT-PCR. To elucidate WISP-1 function, cultured primary mouse AEC were stimulated with WISP-1 and demonstrated a 230% increase in proliferation, analyzed by 3H-thymidine incorporation. This was mediated through enhanced phosphorylation, but not expression of protein kinase B (PKB/Akt, as detected by immunoblot. Finally, increased expression of WISP-1 was detected in lung homogenates and isolated AEC from IPF patients, using qRT-PCR. Immunohistochemical analysis of WISP-1 and Ki67 verified the existence of hyperplastic and proliferative AEC expressing WISP-1 in vivo. Our study thus identifies WISP-1 as a novel regulator of AEC injury and repair, and suggests that WISP-1 is a key mediator in pulmonary fibrosis.

Proteinosis alveolar pulmonar en pacientes hematológicos: Reporte de 2 casos Pulmonary alveolar proteinosis in hematologic patients: Report of 2 cases

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Humberto Cabrera Rojas

1999-12-01

Full Text Available La proteinosis alveolar pulmonar (PAP es un raro trastorno caracterizado por la acumulación de material proteináceo en los alvéolos pulmonares de los individuos afectados. En pacientes con enfermedades hematológicas se ha reportado una incidencia de PAP de 5,3 %, de los cuales el 10 % corresponde a trastornos en las líneas granulopoyéticas. Esta entidad se ha comunicado también en el curso de las leucemias mieloides crónicas (LMC. En este trabajo comunicamos 2 casos de pacientes hematológicos, el primero de una paciente femenina de 54 años con una LMC fallecida por un cuadro de insuficiencia respiratoria; el segundo una paciente de 49 años portadora de una aplasia medular posterior a tratamiento con cloranfenicol, que presentó síntomas de infecciones respiratorias a repetición hasta su ingreso final y fallecimiento. Ambas pacientes se diagnosticaron en el estudio necrópsico. Se realizó revisión de la literaturaPulmonary alveolar proteinosis (PAP is a rare disorder characterized by the accumulation of protein in the pulmonary alveoli of the affected individuals. In patients with hematologic diseases it has been reported an incidence of PAP of 5.3 %, of which 10 % corresponds to disorders in the granulopoietic lines. This entity has also been observed in the course of chronic myeloid leukemia (CML. In this paper 2 cases of hematologic patients are presented. The first was a 54-year-old woman with CML who died due to respiratory failure. The second was a 49-year-old female carrier of medullary aplasia after a treatment with chloramphenicol that presented symptoms of respiratory infections repeatedly until her final admission and death. Both patients were diagnosed on necropsy. A review of the literature was made

Nuclear scan of pulmonary hemorrhage in radiopathic pulmonary hemosiderosis

International Nuclear Information System (INIS)

Miller, T.; Tanaka, T.

1979-01-01

Idiopathic pulmonary hemosiderosis, a disease of unknown etiology most often occuring in children, is characterized by recurring episodes of alveolar consolidation. Exacerbations of pulmonary hemorrhage coincide with episodes of alveolar filling; repeated episodes lead to progressive interstitial fibrosis and eventually to corpulmonale. Serial nuclear scans of the lungs after injection of radiolabeled red blood cells should parallel the pathologic and radiographic findings. We observed the accumulation of radiolabeled red blood cells in the lungs on scan images, a finding not previously reported

Microlitíase alveolar pulmonar: achados na tomografia computadorizada de alta resolução do tórax em 10 pacientes Pulmonary alveolar microlithiasis: high-resolution computed tomography findings in 10 patients

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Edson Marchiori

2007-10-01

Full Text Available OBJETIVO: Apresentar os achados na tomografia computadorizada de alta resolução (TCAR do tórax da microlitíase alveolar pulmonar. MÉTODOS: Foram estudadas, retrospectivamente, as tomografias de dez pacientes adultos, sete mulheres e três homens, com idade média de 38,7 anos. Os exames foram analisados por dois radiologistas, de forma independente, e as decisões finais foram obtidas por consenso. RESULTADOS: Os achados mais freqüentes foram as opacidades em vidro fosco e as calcificações subpleurais, ambas presentes em 90% dos pacientes estudados. Os outros achados de maior relevância foram pequenos nódulos parenquimatosos, calcificação ao longo dos septos interlobulares, cissuras nodulares, nódulos subpleurais, cistos subpleurais, consolidações densas e padrão de pavimentação em mosaico. CONCLUSÕES: A microlitíase alveolar pulmonar apresenta aspectos na TCAR que são altamente sugestivos da doença, na maior parte dos casos dispensando a realização de biópsias pulmonares.OBJECTIVE: To present the high-resolution computed tomography (HRCT findings of pulmonary alveolar microlithiasis. METHODS: The HRCT scans of 10 adult patients (seven females and three males; mean age, 38.7 years were retrospectively analyzed. The films were studied independently by two radiologists. RESULTS: The most common tomographic findings were ground-glass attenuation and linear subpleural calcifications, which were seen in 90% of the patients. Other relevant findings were small parenchymal nodules, calcification along the interlobular septa, nodular cissures, subpleural nodules, subpleural cysts, dense consolidations, and a mosaic pattern of attenuation. CONCLUSIONS: The HRCT findings presented by individuals with pulmonary alveolar microlithiasis are distinct. In most cases, such findings can form the basis of the diagnosis, eliminating the need to perform a lung biopsy.

Characteristic aspects of alveolar proteinosis diagnosis Aspectos característicos do diagnóstico da proteinose alveolar

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Thiago Prudente Bártholo

2012-02-01

Full Text Available Alveolar proteinosis is an uncommon pulmonary disease characterized by an accumulation of surfactant in terminal airway and alveoli, thereby impairing gas exchange and engendering respiratory insufficiency in some cases. Three clinically and etiologically distinct forms of pulmonary alveolar proteinosis are recognized: congenital, secondary and idiopathic, the latter corresponding to 90% of the cases. In this case report we present a young male patient that was diagnosed with alveolar proteinosis. Computed tomography of the thorax, bronchoscopy and transbronchial biopsy were performed. The histopathologic aspect was characteristic. The patient was discharged in good health conditions and remains asymptomatic to date.Proteinose alveolar é uma doença pulmonar incomum caracterizada pelo acúmulo de surfactante nas vias aéreas terminais e nos alvéolos, alterando a troca gasosa e, em alguns casos, promovendo insuficiência respiratória. Três formas clínicas e etiologicamente distintas de proteinose alveolar são reconhecidas: congênitas, secundárias e idiopáticas (mais de 90% dos casos são de etiologia idiopática. Neste relato, apresentamos um homem jovem que foi diagnosticado com proteinose pulmonar. Tomografia computadorizada de tórax, broncoscopia e biópsia transbrônquica foram realizadas. O aspecto histopatológico foi característico. O paciente teve alta, com boas condições de saúde, e encontra-se assintomático nos dias de hoje.

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

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Szafranski, Przemyslaw; Gambin, Tomasz; Dharmadhikari, Avinash V; Akdemir, Kadir Caner; Jhangiani, Shalini N; Schuette, Jennifer; Godiwala, Nihal; Yatsenko, Svetlana A; Sebastian, Jessica; Madan-Khetarpal, Suneeta; Surti, Urvashi; Abellar, Rosanna G; Bateman, David A; Wilson, Ashley L; Markham, Melinda H; Slamon, Jill; Santos-Simarro, Fernando; Palomares, María; Nevado, Julián; Lapunzina, Pablo; Chung, Brian Hon-Yin; Wong, Wai-Lap; Chu, Yoyo Wing Yiu; Mok, Gary Tsz Kin; Kerem, Eitan; Reiter, Joel; Ambalavanan, Namasivayam; Anderson, Scott A; Kelly, David R; Shieh, Joseph; Rosenthal, Taryn C; Scheible, Kristin; Steiner, Laurie; Iqbal, M Anwar; McKinnon, Margaret L; Hamilton, Sara Jane; Schlade-Bartusiak, Kamilla; English, Dawn; Hendson, Glenda; Roeder, Elizabeth R; DeNapoli, Thomas S; Littlejohn, Rebecca Okashah; Wolff, Daynna J; Wagner, Carol L; Yeung, Alison; Francis, David; Fiorino, Elizabeth K; Edelman, Morris; Fox, Joyce; Hayes, Denise A; Janssens, Sandra; De Baere, Elfride; Menten, Björn; Loccufier, Anne; Vanwalleghem, Lieve; Moerman, Philippe; Sznajer, Yves; Lay, Amy S; Kussmann, Jennifer L; Chawla, Jasneek; Payton, Diane J; Phillips, Gael E; Brosens, Erwin; Tibboel, Dick; de Klein, Annelies; Maystadt, Isabelle; Fisher, Richard; Sebire, Neil; Male, Alison; Chopra, Maya; Pinner, Jason; Malcolm, Girvan; Peters, Gregory; Arbuckle, Susan; Lees, Melissa; Mead, Zoe; Quarrell, Oliver; Sayers, Richard; Owens, Martina; Shaw-Smith, Charles; Lioy, Janet; McKay, Eileen; de Leeuw, Nicole; Feenstra, Ilse; Spruijt, Liesbeth; Elmslie, Frances; Thiruchelvam, Timothy; Bacino, Carlos A; Langston, Claire; Lupski, James R; Sen, Partha; Popek, Edwina; Stankiewicz, Paweł

2016-05-01

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV.

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

[Fatal alveolar haemorrhage following a "bang" of cannabis].

Science.gov (United States)

Grassin, F; André, M; Rallec, B; Combes, E; Vinsonneau, U; Paleiron, N

2011-09-01

The new methods of cannabis consumption (home made water pipe or "bang") may be responsible for fatal respiratory complications. We present a case, with fatal outcome, of a man of 19 years with no previous history other than an addiction to cannabis using "bang". He was admitted to intensive care with acute dyspnoea. A CT scan showed bilateral, diffuse alveolar shadowing. He was anaemic with an Hb of 9.3g/l. Bronchoalveolar lavage revealed massive alveolar haemorrhage. Investigations for infection and immunological disorder were negative and toxicology was negative except for cannabis. Antibiotic treatment was given and favourable progress allowed early discharge. Death occurred 15 days later due to alveolar haemorrhage following a further "bang" of cannabis. Autopsy showed toxic alveolar haemorrhage. The probable mechanism is pulmonary damage due to acid anhydrides released by the incomplete combustion of cannabis in contact with plastic. These acids have a double effect on the lungs: a direct toxicity with severe inflammation of the mucosa leading to alveolar haemorrhage and subsequently the acid anhydrides may lead to the syndrome of intra-alveolar haemorrhage and anaemia described in occupational lung diseases by Herbert in Oxford in 1979. It manifests itself by haemoptysis and intravascular haemolysis. We draw attention to the extremely serious potential consequences of new methods of using cannabis, particularly the use of "bang" in homemade plastic materials. Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Development of occlusive neointimal lesions in distal pulmonary arteries of endothelin B receptor-deficient rats: a new model of severe pulmonary arterial hypertension.

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Ivy, D Dunbar; McMurtry, Ivan F; Colvin, Kelley; Imamura, Masatoshi; Oka, Masahiko; Lee, Dong-Seok; Gebb, Sarah; Jones, Peter Lloyd

2005-06-07

Human pulmonary arterial hypertension (PAH) is characterized by proliferation of vascular smooth muscle and, in its more severe form, by the development of occlusive neointimal lesions. However, few animal models of pulmonary neointimal proliferation exist, thereby limiting a complete understanding of the pathobiology of PAH. Recent studies of the endothelin (ET) system demonstrate that deficiency of the ET(B) receptor predisposes adult rats to acute and chronic hypoxic PAH, yet these animals fail to develop neointimal lesions. Herein, we determined and thereafter showed that exposure of ET(B) receptor-deficient rats to the endothelial toxin monocrotaline (MCT) leads to the development of neointimal lesions that share hallmarks of human PAH. The pulmonary hemodynamic and morphometric effects of 60 mg/kg MCT in control (MCT(+/+)) and ET(B) receptor-deficient (MCT(sl/sl)) rats at 6 weeks of age were assessed. MCT(sl/sl) rats developed more severe PAH, characterized by elevated pulmonary artery pressure, diminished cardiac output, and right ventricular hypertrophy. In MCT(sl/sl) rats, morphometric evaluation revealed the presence of neointimal lesions within small distal pulmonary arteries, increased medial wall thickness, and decreased arterial-to-alveolar ratio. In keeping with this, barium angiography revealed diminished distal pulmonary vasculature of MCT(sl/sl) rat lungs. Cells within neointimal lesions expressed smooth muscle and endothelial cell markers. Moreover, cells within neointimal lesions exhibited increased levels of proliferation and were located in a tissue microenvironment enriched with vascular endothelial growth factor, tenascin-C, and activated matrix metalloproteinase-9, factors already implicated in human PAH. Finally, assessment of steady state mRNA showed that whereas expression of ET(B) receptors was decreased in MCT(sl/sl) rat lungs, ET(A) receptor expression increased. Deficiency of the ET(B) receptor markedly accelerates the progression of

Development of Occlusive Neointimal Lesions in Distal Pulmonary Arteries of Endothelin B Receptor–Deficient Rats: A New Model of Severe Pulmonary Arterial Hypertension

Science.gov (United States)

Ivy, D. Dunbar; McMurtry, Ivan F.; Colvin, Kelley; Imamura, Masatoshi; Oka, Masahiko; Lee, Dong-Seok; Gebb, Sarah; Jones, Peter Lloyd

2007-01-01

Background Human pulmonary arterial hypertension (PAH) is characterized by proliferation of vascular smooth muscle and, in its more severe form, by the development of occlusive neointimal lesions. However, few animal models of pulmonary neointimal proliferation exist, thereby limiting a complete understanding of the pathobiology of PAH. Recent studies of the endothelin (ET) system demonstrate that deficiency of the ETB receptor predisposes adult rats to acute and chronic hypoxic PAH, yet these animals fail to develop neointimal lesions. Herein, we determined and thereafter showed that exposure of ETB receptor–deficient rats to the endothelial toxin monocrotaline (MCT) leads to the development of neointimal lesions that share hallmarks of human PAH. Methods and Results The pulmonary hemodynamic and morphometric effects of 60 mg/kg MCT in control (MCT+/+) and ETB receptor–deficient (MCTsl/sl) rats at 6 weeks of age were assessed. MCTsl/sl rats developed more severe PAH, characterized by elevated pulmonary artery pressure, diminished cardiac output, and right ventricular hypertrophy. In MCTsl/sl rats, morphometric evaluation revealed the presence of neointimal lesions within small distal pulmonary arteries, increased medial wall thickness, and decreased arterial-to-alveolar ratio. In keeping with this, barium angiography revealed diminished distal pulmonary vasculature of MCTsl/sl rat lungs. Cells within neointimal lesions expressed smooth muscle and endothelial cell markers. Moreover, cells within neointimal lesions exhibited increased levels of proliferation and were located in a tissue microenvironment enriched with vascular endothelial growth factor, tenascin-C, and activated matrix metalloproteinase-9, factors already implicated in human PAH. Finally, assessment of steady state mRNA showed that whereas expression of ETB receptors was decreased in MCTsl/sl rat lungs, ETA receptor expression increased. Conclusions Deficiency of the ETB receptor markedly

Diffuse Pulmonary Hemorrhage: Classification, physiopathology and Radiologic Manifestations

International Nuclear Information System (INIS)

Carrillo Bayona, Jorge Alberto; Quintana, Jose; Ortiz Ruiz, Guillermo

2008-01-01

Diffuse pulmonary hemorrhage is a syndrome characterized by hemoptysis, anemia and alveolar opacities in the chest radiograph (Fig. 1). Differential diagnoses include all entities with focal or diffuse alveolar opacities. In this article we review the most important causes of diffuse pulmonary hemorrhage.

Diffuse Alveolar Hemorrhage due to Acute Mitral Valve Regurgitation

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Creticus P. Marak

2013-01-01

Full Text Available Diffuse alveolar hemorrhage (DAH can be caused by several etiologies including vasculitis, drug exposure, anticoagulants, infections, mitral valve stenosis, and regurgitation. Chronic mitral valve regurgitation (MR has been well documented as an etiological factor for DAH, but there have been only a few cases which have reported acute mitral valve regurgitation as an etiology of DAH. Acute mitral valve regurgitation can be a life-threatening condition and often requires urgent intervention. In rare cases, acute mitral regurgitation may result in a regurgitant jet which is directed towards the right upper pulmonary vein and may specifically cause right-sided pulmonary edema and right-sided DAH. Surgical repair of the mitral valve results in rapid resolution of DAH. Acute MR should be considered as a possible etiology in patients presenting with unilateral pulmonary edema, hemoptysis, and DAH.

Alveolar type II epithelial cell dysfunction in rat experimental hepatopulmonary syndrome (HPS.

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Wenli Yang

Full Text Available The hepatopulmonary syndrome (HPS develops when pulmonary vasodilatation leads to abnormal gas exchange. However, in human HPS, restrictive ventilatory defects are also observed supporting that the alveolar epithelial compartment may also be affected. Alveolar type II epithelial cells (AT2 play a critical role in maintaining the alveolar compartment by producing four surfactant proteins (SPs, SP-A, SP-B, SP-C and SP-D which also facilitate alveolar repair following injury. However, no studies have evaluated the alveolar epithelial compartment in experimental HPS. In this study, we evaluated the alveolar epithelial compartment and particularly AT2 cells in experimental HPS induced by common bile duct ligation (CBDL. We found a significant reduction in pulmonary SP production associated with increased apoptosis in AT2 cells after CBDL relative to controls. Lung morphology showed decreased mean alveolar chord length and lung volumes in CBDL animals that were not seen in control models supporting a selective reduction of alveolar airspace. Furthermore, we found that administration of TNF-α, the bile acid, chenodeoxycholic acid, and FXR nuclear receptor activation (GW4064 induced apoptosis and impaired SP-B and SP-C production in alveolar epithelial cells in vitro. These results imply that AT2 cell dysfunction occurs in experimental HPS and is associated with alterations in the alveolar epithelial compartment. Our findings support a novel contributing mechanism in experimental HPS that may be relevant to humans and a potential therapeutic target.

[Obstetric management in patients with severe pulmonary hypertension].

Science.gov (United States)

Castillo-Luna, Rogelio; Miranda-Araujo, Osvaldo

2015-12-01

Pulmonary hypertension is a disease of poor prognosis when is associated with pregnancy. A maternal mortality of 30-56% and a neonatal survival of approximately 85% is reported. Surveillance of patients with severe pulmonary hypertension during pregnancy must be multidisciplinary, to provide information and optimal treatment during and after gestation. Targeted therapy for pulmonary arterial hypertension during pregnancy significantly reduces mortality. The critical period with respect to mortality, is the first month after birth. Propose an algorithm for management during pregnancy for patients with severe pulmonary hypertension who want to continue with it. The recommendations established with clinical evidence for patients with severe pulmonary hypertension and pregnancy are presented: diagnosis, treatment, obstetrics and cardiology management, preoperative recommendations for termination of pregnancy, post-partum care and contraception. The maternal mortality remains significantly higher in patients with severe pulmonary hypertension and pregnancy, in these cases should be performed multidisciplinary management in hospitals that have experience in the management of this disease and its complications.

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

Human decidua-derived mesenchymal stem cells differentiate into functional alveolar type II-like cells that synthesize and secrete pulmonary surfactant complexes.

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Alejandro Cerrada

Full Text Available Lung alveolar type II (ATII cells are specialized in the synthesis and secretion of pulmonary surfactant, a lipid-protein complex that reduces surface tension to minimize the work of breathing. Surfactant synthesis, assembly and secretion are closely regulated and its impairment is associated with severe respiratory disorders. At present, well-established ATII cell culture models are not available. In this work, Decidua-derived Mesenchymal Stem Cells (DMSCs have been differentiated into Alveolar Type II- Like Cells (ATII-LCs, which display membranous cytoplasmic organelles resembling lamellar bodies, the organelles involved in surfactant storage and secretion by native ATII cells, and accumulate disaturated phospholipid species, a surfactant hallmark. Expression of characteristic ATII cells markers was demonstrated in ATII-LCs at gene and protein level. Mimicking the response of ATII cells to secretagogues, ATII-LCs were able to exocytose lipid-rich assemblies, which displayed highly surface active capabilities, including faster interfacial adsorption kinetics than standard native surfactant, even in the presence of inhibitory agents. ATII-LCs could constitute a highly useful ex vivo model for the study of surfactant biogenesis and the mechanisms involved in protein processing and lipid trafficking, as well as the packing and storage of surfactant complexes.

Roles of preoperative arterial blood gas tests in the surgical treatment of scoliosis with moderate or severe pulmonary dysfunction.

Science.gov (United States)

Liu, Jia-Ming; Shen, Jian-Xiong; Zhang, Jian-Guo; Zhao, Hong; Li, Shu-Gang; Zhao, Yu; Qiu, Giu-Xing

2012-01-01

It has been stated that preoperative pulmonary function tests are essential to assess the surgical risk in patients with scoliosis. Arterial blood gas tests have also been used to evaluate pulmonary function before scoliotic surgery. However, few studies have been reported. The aim of this study was to investigate the roles of preoperative arterial blood gas tests in the surgical treatment of scoliosis with moderate or severe pulmonary dysfunction. This study involved scoliotic patients with moderate or severe pulmonary dysfunction (forced vital capacity treatment between January 2002 and April 2010. A total of 73 scoliotic patients (23 males and 50 females) with moderate or severe pulmonary dysfunction were included. The average age of the patients was 16.53 years (ranged 10 - 44). The demographic distribution, medical records, and radiographs of all patients were collected. All patients received arterial blood gas tests and pulmonary function tests before surgery. The arterial blood gas tests included five parameters: partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, alveolar-arterial oxygen tension gradient, pH, and standard bases excess. The pulmonary function tests included three parameters: forced expiratory volume in 1 second ratio, forced vital capacity ratio, and peak expiratory flow ratio. All five parameters of the arterial blood gas tests were compared between the two groups with or without postoperative pulmonary complications by variance analysis. Similarly, all three parameters of the pulmonary function tests were compared. The average coronal Cobb angle before surgery was 97.42° (range, 50° - 180°). A total of 15 (20.5%) patients had postoperative pulmonary complications, including hypoxemia in 5 cases (33.3%), increased requirement for postoperative ventilatory support in 4 (26.7%), pneumonia in 2 (13.3%), atelectasis in 2 (13.3%), pneumothorax in 1 (6.7%), and hydrothorax in 1 (6.7%). No significant differences

Cytogenetic effects of cigarette smoke on pulmonary alveolar macrophages of the rat

International Nuclear Information System (INIS)

Ritchideh, K.; Chen, B.T.; Mauderly, J.L.; Brooks, A.L.

1988-01-01

This study was part of a larger investigation of the health effects resulting from different methods of exposing rats to cigarette smoke. Cytogenetic effects of cigarette smoke on rat pulmonary alveolar macrophages (PAMs) were evaluated. Fischer 344/N, male rats (4/group) were randomly assigned to 5 different exposure groups: (1) nose-only sham-exposed control, (2) whole-body sham-exposed control, (3) nose-only intermittent, (4) nose-only continuous, and (5) whole-body continuous. Sham controls were exposed to clean air. PAMs were obtained by lung lavage and chromosomal damage was measured. Multiple comparison demonstrated no significant differences between smoke-exposed groups and their respective sham-exposed controls, between the sham-exposed groups, or among the three smoke exposed groups. Highly significant smoke-induced differences in both structural and numerical aberrations were observed when data for the respective control groups and exposed groups were pooled and compared. Results from this study demonstrate the clastogenicity of cigarette smoke on rat PAM. (author)

The alveolar to arterial oxygen partial pressure difference is associated with pulmonary diffusing capacity in heart failure patients.

Science.gov (United States)

Morosin, Marco; Vignati, Carlo; Novi, Angela; Salvioni, Elisabetta; Veglia, Fabrizio; Alimento, Marina; Merli, Guido; Sciomer, Susanna; Sinagra, Gianfranco; Agostoni, Piergiuseppe

2016-11-01

In chronic heart failure (HF), the alveolar-capillary membrane undergoes a remodeling process that negatively affects gas exchange. In case of alveolar-capillary gas diffusion impairment, arterial desaturation (SaO 2 ) is rarely observed in HF patients. At play are 3 factors: overall pulmonary diffusing capacity (assessed as lung diffusion for CO, DLCO), global O 2 consumption (VO 2 ) and alveolar (A) to arterial (a) pO 2 gradient (AaDO 2 ). In 100 consecutive stable HF patients, DLCO, resting respiratory gases and arterial blood gases were measured to determine VO 2, paO 2 , pAO 2 and AaDO 2 . DLCO was poorly but significantly related to AaDO 2 . The correlation improved after correcting AaDO 2 for VO 2 (p<0.001, r=0.49). Both VO 2 and AaDO 2 were independently associated with DLCO (p<0.001). Patients with reduced DLCO showed no differences as regards paO 2 and pAO 2 . AaDO 2 /VO 2 showed a higher gradient in patients with lower DLCO. AaDO 2 increase and VO 2 reduction allow preventing low SaO 2 in HF patients with reduced DLCO. Accordingly, we suggest considering AaDO 2 and VO 2 combined and reporting AaDO 2 /VO 2 . Copyright © 2016 Elsevier B.V. All rights reserved.

Negative-Pressure Pulmonary Edema.

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Bhattacharya, Mallar; Kallet, Richard H; Ware, Lorraine B; Matthay, Michael A

2016-10-01

Negative-pressure pulmonary edema (NPPE) or postobstructive pulmonary edema is a well-described cause of acute respiratory failure that occurs after intense inspiratory effort against an obstructed airway, usually from upper airway infection, tumor, or laryngospasm. Patients with NPPE generate very negative airway pressures, which augment transvascular fluid filtration and precipitate interstitial and alveolar edema. Pulmonary edema fluid collected from most patients with NPPE has a low protein concentration, suggesting hydrostatic forces as the primary mechanism for the pathogenesis of NPPE. Supportive care should be directed at relieving the upper airway obstruction by endotracheal intubation or cricothyroidotomy, institution of lung-protective positive-pressure ventilation, and diuresis unless the patient is in shock. Resolution of the pulmonary edema is usually rapid, in part because alveolar fluid clearance mechanisms are intact. In this review, we discuss the clinical presentation, pathophysiology, and management of negative-pressure or postobstructive pulmonary edema. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Increased alveolar soluble Annexin V promotes lung inflammation and fibrosis

OpenAIRE

Buckley, S.; Shi, W.; Xu, W.; Frey, M.R.; Moats, R.; Pardo, A.; Selman, M.; Warburton, D.

2015-01-01

The causes underlying the self-perpetuating nature of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal disease, remain unknown. We hypothesized that alveolar soluble Annexin V contributes to lung fibrosis, based on the observation that human IPF BALF containing high Annexin V levels promoted fibroblast involvement in alveolar epithelial wound healing that was reduced when Annexin V was depleted from the BALF.

Early alveolar and systemic mediator release in patients at different risks for ARDS after multiple trauma.

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Raymondos, Konstantinos; Martin, Michael U; Schmudlach, Tanja; Baus, Stefan; Weilbach, Christian; Welte, Tobias; Krettek, Christian; Frink, Michael; Hildebrand, Frank

2012-02-01

Alveolar IL-8 has been reported to early identify patients at-risk to develop ARDS. However, it remains unknown how alveolar IL-8 is related to pulmonary and systemic inflammation in patients predisposed for ARDS. We studied 24 patients 2-6h after multiple trauma. Patients with IL-8 >200 pg/ml in bronchoalveolar lavage (BAL) were assigned to the group at high risk for ARDS (H, n = 8) and patients with BAL IL-8 mediators. The enhanced alveolar and systemic inflammation associated with alveolar IL-8 release should be considered to identify high-risk patients for pulmonary complications after multiple trauma to adjust surgical and other treatment strategies to the individual risk profile. Copyright © 2011 Elsevier Ltd. All rights reserved.

Neonatal Pulmonary Hemosiderosis

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Boris Limme

2014-01-01

Full Text Available Idiopathic pulmonary hemosiderosis (IPH is a rare complex entity characterized clinically by acute or recurrent episodes of hemoptysis secondary to diffuse alveolar hemorrhage. The radiographic features are variable, including diffuse alveolar-type infiltrates, and interstitial reticular and micronodular patterns. We describe a 3-week-old infant presenting with hemoptysis and moderate respiratory distress. Idiopathic pulmonary hemosiderosis was the first working diagnosis at the Emergency Department and was confirmed, 2 weeks later, by histological studies (bronchoalveolar lavage. The immunosuppressive therapy by 1 mg/kg/d prednisone was immediately started, the baby returned home on steroid therapy at a dose of 0,5 mg/kg/d. The diagnosis of idiopathic pulmonary hemosiderosis should be evocated at any age, even in the neonate, when the clinical presentation (hemoptysis and abnormal radiological chest images is strongly suggestive.

Mutations in MARS identified in a specific type of pulmonary alveolar proteinosis alter methionyl-tRNA synthetase activity.

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Comisso, Martine; Hadchouel, Alice; de Blic, Jacques; Mirande, Marc

2018-05-18

Biallelic missense mutations in MARS are responsible for rare but severe cases of pulmonary alveolar proteinosis (PAP) prevalent on the island of La Réunion. MARS encodes cytosolic methionyl-tRNA synthetase (MetRS), an essential translation factor. The multisystemic effects observed in patients with this form of PAP are consistent with a loss-of-function defect in an ubiquitously expressed enzyme. The pathophysiological mechanisms involved in MARS-related PAP are currently unknown. In this work, we analyzed the effect of the PAP-related mutations in MARS on the thermal stability and on the catalytic parameters of the MetRS mutants, relative to wild-type. The effect of these mutations on the structural integrity of the enzyme as a member of the cytosolic multisynthetase complex was also investigated. Our results establish that the PAP-related substitutions in MetRS impact the tRNA Met -aminoacylation reaction especially at the level of methionine recognition, and suggest a direct link between the loss of activity of the enzyme and the pathological disorders in PAP. © 2018 Federation of European Biochemical Societies.

Exogenous hydrogen sulfide (H2S protects alveolar growth in experimental O2-induced neonatal lung injury.

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Arul Vadivel

Full Text Available Bronchopulmonary dysplasia (BPD, the chronic lung disease of prematurity, remains a major health problem. BPD is characterized by impaired alveolar development and complicated by pulmonary hypertension (PHT. Currently there is no specific treatment for BPD. Hydrogen sulfide (H2S, carbon monoxide and nitric oxide (NO, belong to a class of endogenously synthesized gaseous molecules referred to as gasotransmitters. While inhaled NO is already used for the treatment of neonatal PHT and currently tested for the prevention of BPD, H2S has until recently been regarded exclusively as a toxic gas. Recent evidence suggests that endogenous H2S exerts beneficial biological effects, including cytoprotection and vasodilatation. We hypothesized that H2S preserves normal alveolar development and prevents PHT in experimental BPD.We took advantage of a recently described slow-releasing H2S donor, GYY4137 (morpholin-4-ium-4-methoxyphenyl(morpholino phosphinodithioate to study its lung protective potential in vitro and in vivo.In vitro, GYY4137 promoted capillary-like network formation, viability and reduced reactive oxygen species in hyperoxia-exposed human pulmonary artery endothelial cells. GYY4137 also protected mitochondrial function in alveolar epithelial cells. In vivo, GYY4137 preserved and restored normal alveolar growth in rat pups exposed from birth for 2 weeks to hyperoxia. GYY4137 also attenuated PHT as determined by improved pulmonary arterial acceleration time on echo-Doppler, pulmonary artery remodeling and right ventricular hypertrophy. GYY4137 also prevented pulmonary artery smooth muscle cell proliferation.H2S protects from impaired alveolar growth and PHT in experimental O2-induced lung injury. H2S warrants further investigation as a new therapeutic target for alveolar damage and PHT.

Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury

NARCIS (Netherlands)

D. Hasan (Djo); P. Blankman (Paul); G.F. Nieman (Gary F.)

2017-01-01

textabstractSevere pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high

Pulmonary arterial lesions in explanted lungs after transplantation correlate with severity of pulmonary hypertension in chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Carlsen, Jørn; Andersen, Kasper Hasseriis; Boesgaard, Søren

2013-01-01

BACKGROUND: Pulmonary vascular findings are largely unreported in end-stage chronic obstructive pulmonary disease (COPD). METHODS: Pulmonary vascular lesions in explanted lungs from 70 patients with COPD/emphysema or α-1-antitrypsin deficiency were analyzed retrospectively. Patients were stratified...... of pulmonary vascular lesions in COPD correlate with the severity of PH. Morphologic lesions similar to those characteristic of IPAH can be observed as PH in COPD progresses to levels characteristic of IPAH....... by the presence and severity of pulmonary hypertension (PH) assessed by right-heart catheterization in 3 hemodynamically distinct groups: (1) non-PH (mean pulmonary arterial pressure [mPAP]50 mm Hg; median HE Grade 4 (range 3-6), with generalized arterial dilatation and plexiform lesions. CONCLUSIONS: The extent...

Pulmonary Contusion in Mechanically Ventilated Subjects After Severe Trauma.

Science.gov (United States)

Dhar, Sakshi Mathur; Breite, Matthew D; Barnes, Stephen L; Quick, Jacob A

2018-03-13

Pulmonary contusions are thought to worsen outcomes. We aimed to evaluate the effects of pulmonary contusion on mechanically ventilated trauma subjects with severe thoracic injuries and hypothesized that contusion would not increase morbidity. We conducted a single-center, retrospective review of 163 severely injured trauma subjects (injury severity score ≥ 15) with severe thoracic injury (chest abbreviated injury score ≥ 3), who required mechanical ventilation for >24 h at a verified Level 1 trauma center. Subject data were analyzed for those with radiographic documentation of pulmonary contusion and those without. Statistical analysis was performed to determine the effects of coexisting pulmonary contusion in severe thoracic trauma. Pulmonary contusion was present in 91 subjects (55.8%), whereas 72 (44.2%) did not have pulmonary contusions. Mean chest abbreviated injury score (3.54 vs 3.47, P = .53) and mean injury severity score (32.6 vs 30.2, P = .12) were similar. There was no difference in mortality (11 [12.1%] vs 9 [12.5%], P > .99) or length of stay (16.29 d vs 17.29 d, P = .60). Frequency of ventilator-associated pneumonia was comparable (43 [47.3%] vs 32 [44.4%], P = .75). Subjects with contusions were more likely to grow methicillin-sensitive Staphylococcus aureus in culture (33 vs 10, P = .004) as opposed to Pseudomonas aeruginosa in culture (6 vs 13, P = .003). Overall, no significant differences were noted in mortality, length of stay, or pneumonia rates between severely injured trauma subjects with and without pulmonary contusions. Copyright © 2018 by Daedalus Enterprises.

[Treatment of a patient with considerably thin alveolar bone and severe open bite].

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Haiya, Zhuo; Zhou, Hu; Qing, Zhao

2018-02-01

This case report describes the treatment of a 25-year-old woman with a severe open bite. This patient presented a grade Ⅲ open bite, considerably thin alveolar bone, and evident labial buccal and lingual root form. The open bite was corrected by fixed orthodontic treatment and masticatory exercises. However, the increased pressure in the labial muscle caused by lip muscle exercise suppressed the canines, which resulted in the protrusion of the apices of canine roots out of the alveolar bone. Afterward, HX brackets, instead of self-locking, were used and bonded reversely in the occlusal-gingival direction on the upper canines. The lip muscle exercises were decreased. After adjustment, the roots penetrated back into the cancellous bone, the severe open bite was corrected, and a normal overbite and overjet were achieved. ClassⅠcanine and molar relationships were established. The masticatory function and profile were both considerably improved. This case report showed that a severe nonskeletal open bite can be corrected using orthodontic treatments combined with masticatory exercises.

Interleukin-22 Inhibits Bleomycin-Induced Pulmonary Fibrosis

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Minrui Liang

2013-01-01

Full Text Available Pulmonary fibrosis is a progressive and fatal fibrotic disease of the lungs with unclear etiology. Recent insight has suggested that early injury/inflammation of alveolar epithelial cells could lead to dysregulation of tissue repair driven by multiple cytokines. Although dysregulation of interleukin- (IL- 22 is involved in various pulmonary pathophysiological processes, the role of IL-22 in fibrotic lung diseases is still unclear and needs to be further addressed. Here we investigated the effect of IL-22 on alveolar epithelial cells in the bleomycin- (BLM- induced pulmonary fibrosis. BLM-treated mice showed significantly decreased level of IL-22 in the lung. IL-22 produced γδT cells were also decreased significantly both in the tissues of lungs and spleens. Administration of recombinant human IL-22 to alveolar epithelial cell line A549 cells ameliorated epithelial to mesenchymal transition (EMT and partially reversed the impaired cell viability induced by BLM. Furthermore, blockage of IL-22 deteriorated pulmonary fibrosis, with elevated EMT marker (α-smooth muscle actin (α-SMA and overactivated Smad2. Our results indicate that IL-22 may play a protective role in the development of BLM-induced pulmonary fibrosis and may suggest IL-22 as a novel immunotherapy tool in treating pulmonary fibrosis.

Comparison of high resolution computed tomography and pulmonary function tests in diagnosis of mild emphysema

International Nuclear Information System (INIS)

Kuwano, Kazuyoshi; Matsuba, Kenichi; Ikeda, Togo

1989-01-01

To assess the ability of high resolution CT scan and pulmonary function tests in detecting and grading mild emphysema, we correlated the high resolution CT scan and pulmonary function tests with the pathologic grade of emphysema and the destructive index of lung specimens from 42 patients undergoing thoracotomy for solitary pulmonary nodules. Using the high resolution CT scan, we could identify the pathologic grade of mild and moderate emphysema. By measuring diffusing capacity per unit alveolar gas volume (DLco/VA), it seemed to be possible to detect the mildest degree of alveolar destruction assessed by the destructive index, which was not detected by high resolution CT scan. The reason for these results seemed to be that we assessed the severity of emphysema by detecting the air space enlargement on high resolution CT scan images caused by the destruction of alveolar walls, which were detectable by measuring DLco/VA. We conclude that it is possible to detect mild emphysema using the combination of high resolution CT scan and pulmomary function tests. (author)

Lung inhalation scintigraphy with radioactive aerosols in several pulmonary diseases

International Nuclear Information System (INIS)

Martins, L.R.; Marioni Filho, H.; Romaldini, H.; Uehara, C.; Alonso, G.

1983-01-01

The pulmonary ventilation scintigraphy with 99m Tc diethylene-triamine-pentaacetate (99mTc-DTPA) delivered through a new nebulizer system when analyzed together with the classic lung perfusion scintigraphy with 99mTc-labeled albumin macroaggregates (99mTcMAA) is a very important diagnostic tool in several pulmonary diseases. Several aspects of the lung ventilation-perfusion scintigraphy are studied in 15 people with no lung disease, smokers and nonsmokers. The findings with the lung ventilation-perfusion scintigraphy are also discussed in 34 patients with several pulmonary diseases: lung cancer, chronic obstructive lung disease, policystic pulmonary disease, and pulmonary embolims. The authors concluded that the procedure is a valuable diagnostic tool in several pulmonary diseases, especially because good lung images are obtained, no side effects were detected, the technique is ease and low cost, and it brings new informations, not available with other diagnostic methods. (author)

Balloon catheter dilatation for mitral stenosis and severe pulmonary hypertension

International Nuclear Information System (INIS)

Wang Manhong

2002-01-01

Objective: To determine the safety and efficacy of percutaneous balloon mitral valvuloplasty (PBMV) for patients with mitral stenosis and severe pulmonary hypertension, and to assess the changes in pulmonary systolic pressure during follow-up. Methods: Forty-two patients with rheumatic mitral stenosis and severe pulmonary hypertension (pulmonary systolic pressure > 75 mmHg) underwent PBMV using standard Inoue technique, and the changes in clinical functional status and echo Doppler pulmonary systolic pressure during follow-up were assessed. Results: PBMV was successful in 39 patients. Immediately after the procedure, mitral valve area increased from (0.83 +- 0.12) cm 2 to (1.75 +- 0.11) cm 2 , pulmonary systolic pressure decreased from (85 +- 7) mmHg to (61 +- 13) mmHg (all P < 0.001). Severe mitral regurgitation occurred in 3 patients, one of whom underwent mitral valve replacement. During follow-up (average 6 months), in 39 patients with successful PBMV, the clinical functional status was improved and pulmonary systolic pressure was further decreased despite unchanged mitral valve area. Conclusions: PBMV was safe and effective for patients with mitral stenosis and severe pulmonary hypertension. Clinical functional status was improved and pulmonary systolic pressure was continuously decreased during the short-term follow-up

Determinants of pulmonary blood flow distribution.

Science.gov (United States)

Glenny, Robb W; Robertson, H Thomas

2011-01-01

The primary function of the pulmonary circulation is to deliver blood to the alveolar capillaries to exchange gases. Distributing blood over a vast surface area facilitates gas exchange, yet the pulmonary vascular tree must be constrained to fit within the thoracic cavity. In addition, pressures must remain low within the circulatory system to protect the thin alveolar capillary membranes that allow efficient gas exchange. The pulmonary circulation is engineered for these unique requirements and in turn these special attributes affect the spatial distribution of blood flow. As the largest organ in the body, the physical characteristics of the lung vary regionally, influencing the spatial distribution on large-, moderate-, and small-scale levels. © 2011 American Physiological Society.

Legionella pneumonia associated with severe acute respiratory distress syndrome and diffuse alveolar hemorrhage - A rare association

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Muhammad Kashif

2017-01-01

Full Text Available Legionella pneumophila is a common, usually underreported and undiagnosed cause of community acquired pneumonia which can lead to significant morbidity and mortality. Diffuse alveolar hemorrhage rarely have been associated with legionella infection. We present a 61-year-old man with hypertension, diabetes mellitus and obesity admitted with severe acute respiratory distress syndrome. He was found to have Legionella pneumonia with associated diffuse alveolar hemorrhage diagnosed with bronchoscopic sequential bronchoalveolar lavage. He was successfully managed with antibiotics, lung protective strategies and intravenous pulse dose steroids. This patient highlights the unusual association of Legionella infection and diffuse alveolar hemorrhage. Additionally, the case re-enforces the need for early and aggressive evaluation and management of patients presenting with pneumonia and progressive hypoxia despite adequate treatment.

Clinical application of radioaerosol studies - pulmonary embolism, inhalation burns and glue-sniffers and COPD

International Nuclear Information System (INIS)

Sundram, Felix

1994-01-01

The alveolar epithelium and the capillary endothelium together form the alveolar capillary membrane. Fluid exchange occurs across this membrane, and is dependent on intravascular and interstitial hydrostatic and oncotic pressures, and on permeability of this membrane. Damage to either the alveolar or capillary component can result in a high permeability pulmonary oedema, even though the alveolar epithelium forms an extremely tight membrane which is ten times less permeable than the capillary endothelium. Nuclear medicine methods can be used to observe changes in integrity of pulmonary capillary endothelium (with first pass dual-indicator dilution technique using successive injections of radiotracer), and of alveolar epithelium, and it is important that the damage should be detected before patients develop clinical pulmonary oedema so that intensive therapy can be instituted early. We have used 99m Tc DTPA radioaerosol to measure alteration in pulmonary epithelial permeability and to image the distribution of ventilation in normal and some pathological states. In some clinical studies Tc-99m (tin) colloid radioaerosol has been used to obtain the ventilation images

Model of pulmonary fluid traffic homeostasis based on respiratory cycle pressure, bidirectional bronchiolo-pulmonar shunting and water evaporation.

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Kurbel, Sven; Kurbel, Beatrica; Gulam, Danijela; Spajić, Borislav

2010-06-01

The main puzzle of the pulmonary circulation is how the alveolar spaces remain dry over a wide range of pulmonary vascular pressures and blood flows. Although normal hydrostatic pressure in pulmonary capillaries is probably always below 10 mmHg, well bellow plasma colloid pressure of 25 mmHg, most textbooks state that some fluid filtration through capillary walls does occur, while the increased lymph drainage prevents alveolar fluid accumulation. The lack of a measurable pressure drop along pulmonary capillaries makes the classic description of Starling forces unsuitable to the low pressure, low resistance pulmonary circulation. Here presented model of pulmonary fluid traffic describes lungs as a matrix of small vascular units, each consisting of alveoli whose capillaries are anastomotically linked to the bronchiolar capillaries perfused by a single bronchiolar arteriole. It proposes that filtration and absorption in pulmonary and in bronchiolar capillaries happen as alternating periods of low and of increased perfusion pressures. The model is based on three levels of filtration control: short filtration phases due to respiratory cycle of the whole lung are modulated by bidirectional bronchiolo-pulmonar shunting independently in each small vascular unit, while fluid evaporation from alveolar groups further tunes local filtration. These mechanisms are used to describe a self-sustaining regulator that allows optimal fluid traffic in different settings. The proposed concept is used to describe development of pulmonary edema in several clinical entities (exercise in wet or dry climate, left heart failure, people who rapidly move to high altitudes, acute cyanide and carbon monoxide poisoning, large pulmonary embolisms). .

Pulmonary alveolar hemorrhage mimicking a pneumopathy: a rare ...

African Journals Online (AJOL)

Diffuse alveolar hemorrhage after percutaneous coronary intervention (PCI) is a rare complication. The diagnosis is difficult and can mimic by clinical and radiological features other diagnosis as pneumopathy. We herein report the case of a 63-year-old female admitted to the hospital for ST elevation myocardial infarction.

Alveolar pulmonary proteinosis: case report and literature review

International Nuclear Information System (INIS)

Vergara, Erika; Saenz, Alberto; Ojeda, Paulina

2009-01-01

We describe the case of a young women with primary alveolar proteinosis, with a short period of symptoms that are uncommon for this disease, without risk factors for this entity, the clinical evolution of the patient and some complications with the treatment. We review the literature for this entity.

Training modifies innate immune responses in blood monocytes and in pulmonary alveolar macrophages.

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Frellstedt, Linda; Waldschmidt, Ingrid; Gosset, Philippe; Desmet, Christophe; Pirottin, Dimitri; Bureau, Fabrice; Farnir, Frédéric; Franck, Thierry; Dupuis-Tricaud, Marie-Capucine; Lekeux, Pierre; Art, Tatiana

2014-07-01

In humans, strenuous exercise causes increased susceptibility to respiratory infections associated with down-regulated expression of Toll-like receptors (TLRs) and costimulatory and antigen-presenting molecules. Lower airway diseases are also a common problem in sport and racing horses. Because innate immunity plays an essential role in lung defense mechanisms, we assessed the effect of acute exercise and training on innate immune responses in two different compartments. Blood monocytes and pulmonary alveolar macrophages (PAMs) were collected from horses in untrained, moderately trained, intensively trained, and deconditioned states before and after a strenuous exercise test. The cells were analyzed for TLR messenger ribonucleic acid (mRNA) expression by real-time PCR in vitro, and cytokine production after in vitro stimulation with TLR ligands was measured by ELISA. Our results showed that training, but not acute exercise, modified the innate immune responses in both compartments. The mRNA expression of TLR3 was down-regulated by training in both cell types, whereas the expression of TLR4 was up-regulated in monocytes. Monocytes treated with LPS and a synthetic diacylated lipoprotein showed increased cytokine secretion in trained and deconditioned subjects, indicating the activation of cells at the systemic level. The production of TNF-α and IFN-β in nonstimulated and stimulated PAMs was decreased in trained and deconditioned horses and might therefore explain the increased susceptibility to respiratory infections. Our study reports a dissociation between the systemic and the lung response to training that is probably implicated in the systemic inflammation and in the pulmonary susceptibility to infection.

Pulmonary Vascular Congestion: A Mechanism for Distal Lung Unit Dysfunction in Obesity.

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Oppenheimer, Beno W; Berger, Kenneth I; Ali, Saleem; Segal, Leopoldo N; Donnino, Robert; Katz, Stuart; Parikh, Manish; Goldring, Roberta M

2016-01-01

Obesity is characterized by increased systemic and pulmonary blood volumes (pulmonary vascular congestion). Concomitant abnormal alveolar membrane diffusion suggests subclinical interstitial edema. In this setting, functional abnormalities should encompass the entire distal lung including the airways. We hypothesize that in obesity: 1) pulmonary vascular congestion will affect the distal lung unit with concordant alveolar membrane and distal airway abnormalities; and 2) the degree of pulmonary congestion and membrane dysfunction will relate to the cardiac response. 54 non-smoking obese subjects underwent spirometry, impulse oscillometry (IOS), diffusion capacity (DLCO) with partition into membrane diffusion (DM) and capillary blood volume (VC), and cardiac MRI (n = 24). Alveolar-capillary membrane efficiency was assessed by calculation of DM/VC. Mean age was 45±12 years; mean BMI was 44.8±7 kg/m2. Vital capacity was 88±13% predicted with reduction in functional residual capacity (58±12% predicted). Despite normal DLCO (98±18% predicted), VC was elevated (135±31% predicted) while DM averaged 94±22% predicted. DM/VC varied from 0.4 to 1.4 with high values reflecting recruitment of alveolar membrane and low values indicating alveolar membrane dysfunction. The most abnormal IOS (R5 and X5) occurred in subjects with lowest DM/VC (r2 = 0.31, ppulmonary vascular congestion and failure to achieve the high output state of obesity. Pulmonary vascular congestion and consequent fluid transudation and/or alterations in the structure of the alveolar capillary membrane may be considered often unrecognized causes of airway dysfunction in obesity.

A manobra de recrutamento alveolar em crianças submetidas à ventilação mecânica em unidade de terapia intensiva pediátrica Alveolar recruitment maneuver in mechanic ventilation pediatric intensive care unit children

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Valéria Cabral Neves

2009-12-01

-chave: estratégia ventilatória protetora, manobra de recrutamento alveolar, pediatria e ventilação mecânica.Recent changes were introduced in acute hypoxemic respiratory failure children ventilation methods. There are evidences that less aggressive ventilation strategies can improve severe pulmonary injury survival. Experimental trials evidenced a relationship between inappropriate ventilatory measures and delayed acute pulmonary injury improvement, or even worsening. From this, a protective ventilatory measure arises in combination with alveolar recruitment maneuver. This association is believed in clinical practice to determine importantly reduced morbidity and mortality as well as reduced mechanic ventilation-induced injuries. It is indicated for acute lung injury patients, generally from pneumonia or sepsis, with severe hypoxemia. Its main contraindications are homodynamic instability, pneumothorax and intracranial hypertension. Experimental trials showed beneficial maneuver effects on both oxygenation and alveolar collapse. Adult studies showed improved pulmonary function with hypoxemia reversion. In children, the maneuver lead to significant inspired oxygen fraction and alveolar collapse reductions, less oxygen dependency, improved pulmonary complacency, and reduced bronchopulmonary dysplasia. However, studies in children are limited. Additional investigation is warranted on this matter, and its clinical application evidence. A literature review was conducted based on textbooks and MEDLINE, Pubmed, Cochrane library, SciELO, and Ovid databases, from 1998 to 2009, both in Portuguese and English. Publications on alveolar recruitment maneuver both in adults and children, review articles, experimental and clinical trials were included using the key words: protective ventilatory strategy, alveolar recruitment maneuver, pediatrics and mechanic ventilation.

[Application of continuous intra-arterial blood gas monitoring system "Paratrend 7" for pulmonary lavage of a patient with alveolar proteinosis].

Science.gov (United States)

Harigae, M; Hirose, Y; Gamo, M; Hirose, M; Fujiwara, C; Matsuo, K

1999-03-01

We applied a continuous intra-arterial blood gas monitoring system (Paratrend 7) to a patient with pulmonary alveolar proteinosis during pulmonary lavage. Lavage was performed under general anesthesia with one lung ventilation. We inserted the sensor of Patatrend 7 through a 20 G catheter into the radial artery, and monitored pH, PaCO2 and PaO2 continuously throughout the procedure. SpO2 and EtCO2 were also monitored. Saline 1000-1500 ml was instilled and drained repeatedly by volume limited methods. PaO2 values by Paratrend 7 increased during instillation and decreased during drainage of the irrigating fluid. In contrast, PaCO2 value by Paratrend 7 decreased slightly during instillation and increased during drainage. The change of SpO2 was almost the same as that by Paratrend 7, but the response time of pulse oxymetry was a little quicker than Paratrend 7. During the lavage procedure, respiratory and circulatory condition changed very rapidly, and it is necessary to monitor blood gas change intensively. Paratrend 7 is useful as a perioperative monitoring system, but pulse oxymetry might be sufficient during pulmonary lavage considering its cost.

Tricuspid valve dysplasia with severe tricuspid regurgitation: fetal pulmonary artery size predicts lung viability in the presence of small lung volumes.

Science.gov (United States)

Nathan, A T; Marino, B S; Dominguez, T; Tabbutt, S; Nicolson, S; Donaghue, D D; Spray, T L; Rychik, J

2010-01-01

Congenital tricuspid valve disease (Ebstein's anomaly, tricuspid valve dysplasia) with severe tricuspid regurgitation and cardiomegaly is associated with poor prognosis. Fetal echocardiography can accurately measure right atrial enlargement, which is associated with a poor prognosis in the fetus with tricuspid valve disease. Fetal lung volumetric assessments have been used in an attempt to predict viability of fetuses using ultrasonogram and prenatal MRI. We describe a fetus with tricuspid dysplasia, severe tricuspid regurgitation, right atrial enlargement and markedly reduced lung volumes. The early gestational onset of cardiomegaly with bilateral lung compression raised the possibility of severe lung hypoplasia with decreased broncho-alveolar development. Use of fetal echocardiography with measurement of pulmonary artery size combined with prenatal MRI scanning of lung volumes resulted in an improved understanding of this anomaly and directed the management strategy towards a successful Fontan circulation. 2010 S. Karger AG, Basel.

Alveolar cell carcinoma: diagnostic pitfalls in evaluating the chest roentgenogram

International Nuclear Information System (INIS)

Shin, M.S.; Bailey, W.C.

1985-01-01

A report is given of two patients with initial symptoms of congestive heart failure who had an extensive work-up that failed to reveal any signs of pulmonary malignancy. Subsequent biopsy by fiberoptic bronchoscopy confirmed alveolar cell carcinoma in both cases, suggesting that bronchoscopy with biopsy should be considered in patients with congestive heart failure if pulmonary edema does not resolve with appropriate therapy. 11 references, 2 figures

Radioisotopic studies on pulmonary function in experimental burn shock

International Nuclear Information System (INIS)

Lambrecht, W.; Barcikowski, S.; Maziarz, Z.; Zajgner, J.; Markiewicz, A.

1980-01-01

Disturbances in pulmonary ventilation and perfusion, which can initiate severe complications, often lead to many therapeutic failures in burn shock. Early recognition of respiratory disturbances is often required to improve results of treatment of burn shock. The authors investigated changes in pulmonary ventilation and perfusion in napalm-burnt rabbits using 133 Xe. Simultaneously, they determined effect of treatment with cytochrome C on pulmonary ventilation and perfusion in animals burnt with napalm. It was found that in napalm-burnt rabbits burn shock was accompanied by a significant deterioration in pulmonary ventilation and perfusion. The most marked changes were observed one and two days after burn. It was also found a beneficial effect of treatment with cytochrome C on alveolar ventilation. The authors pointed out the usefulness of radioisotopic investigations of pulmonary ventilation and perfusion in burn shock. (author)

Long-term follow-up and treatment of congenital alveolar proteinosis

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Muensterer Oliver J

2011-08-01

Full Text Available Abstract Background Clinical presentation, diagnosis, management and outcome of molecularly defined congenital pulmonary alveolar proteinosis (PAP due to mutations in the GM-CSF receptor are not well known. Case presentation A 2 1/2 years old girl was diagnosed as having alveolar proteinosis. Whole lung lavages were performed with a new catheter balloon technique, feasible in small sized airways. Because of some interstitial inflammation in the lung biopsy and to further improve the condition, empirical therapy with systemic steroids and azathioprin, and inhaled and subcutaneous GMCSF, were used. Based on clinical measures, total protein and lipid recovered by whole lung lavages, all these treatments were without benefit. Conversely, severe respiratory viral infections and an invasive aspergillosis with aspergilloma formation occurred. Recently the novel homozygous stop mutation p.Ser25X of the GMCSF receptor alpha chain was identified in the patient. This mutation leads to a lack of functional GMCSF receptor and a reduced response to GMCSF stimulation of CD11b expression of mononuclear cells of the patient. Subsequently a very intense treatment with monthly lavages was initiated, resulting for the first time in complete resolution of partial respiratory insufficiency and a significant improvement of the overall somato-psychosocial condition of the child. Conclusions The long term management from early childhood into young adolescence of severe alveolar proteinosis due to GMCSF receptor deficiency requires a dedicated specialized team to perform technically demanding whole lung lavages and cope with complications.

Chronic obstructive pulmonary disease severity is associated with severe pneumonia

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Jung Seop Eom

2015-01-01

Full Text Available CONTEXT: Chronic obstructive pulmonary disease (COPD is a heterogeneous disorder, and various aspects of COPD may be associated with the severity of pneumonia in such patients. AIMS: We examined the risk factors associated with severe pneumonia in a COPD population. MATERIALS AND METHODS: We performed a retrospective observational study using a prospectively collected database of pneumonia patients who were admitted to our hospital through emergency department between 2008 and 2012. Patients with hospital-acquired pneumonia and those with an immunocompromised status were excluded. RESULTS: Of 148 pneumonia patients with COPD for whom chest computed tomography (CT scans were available, 106 (71.6% and 42 (28.4% were classified as non-severe and severe pneumonia, respectively. Multivariate logistic regression analysis revealed that the severity of airflow limitation [odds ratio (OR, 2.751; 95% confidence interval (CI, 1.074-7.050; P = 0.035] and the presence of emphysema on a chest CT scan (OR, 3.366; 95% CI, 1.104-10.265; P = 0.033 were independently associated with severe pneumonia in patients with COPD. CONCLUSIONS: The severity of COPD including the airflow limitation grade and the presence of pulmonary emphysema were independently associated with the development of severe pneumonia.

Cigarette Smoke Enhances the Expression of Profibrotic Molecules in Alveolar Epithelial Cells.

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Marco Checa

Full Text Available Idiopathic pulmonary fibrosis (IPF is a progressive and lethal disease of unknown etiology. A growing body of evidence indicates that it may result from an aberrant activation of alveolar epithelium, which induces the expansion of the fibroblast population, their differentiation to myofibroblasts and the excessive accumulation of extracellular matrix. The mechanisms that activate the alveolar epithelium are unknown, but several studies indicate that smoking is the main environmental risk factor for the development of IPF. In this study we explored the effect of cigarette smoke on the gene expression profile and signaling pathways in alveolar epithelial cells. Lung epithelial cell line from human (A549, was exposed to cigarette smoke extract (CSE for 1, 3, and 5 weeks at 1, 5 and 10% and gene expression was evaluated by complete transcriptome microarrays. Signaling networks were analyzed with the Ingenuity Pathway Analysis software. At 5 weeks of exposure, alveolar epithelial cells acquired a fibroblast-like phenotype. At this time, gene expression profile revealed a significant increase of more than 1000 genes and deregulation of canonical signaling pathways such as TGF-β and Wnt. Several profibrotic genes involved in EMT were over-expressed, and incomplete EMT was observed in these cells, and corroborated in mouse (MLE-12 and rat (RLE-6TN epithelial cells. The secretion of activated TGF-β1 increased in cells exposed to cigarette smoke, which decreased when the integrin alpha v gene was silenced. These findings suggest that the exposure of alveolar epithelial cells to CSE induces the expression and release of a variety of profibrotic genes, and the activation of TGF-β1, which may explain at least partially, the increased risk of developing IPF in smokers.

Successful treatment of idiopathic pulmonary capillaritis with intravenous cyclophosphamide.

LENUS (Irish Health Repository)

Flanagan, Frances

2013-03-01

Idiopathic pulmonary hemosiderosis (IPH), a subtype of diffuse alveolar hemorrhage is a rare condition, first described by Virchow in 1864. Historically, it manifests in children in the first decade of life with the combination of hemoptysis, iron deficiency anemia, and alveolar infiltrates on chest radiograph. More recently, diffuse alveolar hemorrhage has been classified by the absence or presence of pulmonary capillaritis (PC), the latter carrying a potential for a poorer outcome. While systemic corticosteroids remain the first line treatment option, other immune modulators have been trailed including hydroxychloroquine, azathioprine, 6-mercaptopurine, and cyclophosphamide with varying results. Our case demonstrates for the first time, the successful use of intravenous cyclophosphamide in the management of chronic idiopathic PC.

Pulmonary lesions induced by inhaled plutonium in beagles

International Nuclear Information System (INIS)

Dagle, G.E.; Lund, J.E.; Park, J.F.

1975-01-01

The histopathologic features of pulmonary fibrosis and bronchiolo-alveolar carcinoma in beagles exposed to aerosols of plutonium oxide were reviewed. A hypothesis of the pathogenesis of radiation pneumonitis induced by inhalation of plutonium oxide was presented; this hypothesis included phagocytosis of plutonium particles, fibrosis responding to the necrosis, and alveolar cell hyperplasia compensating for alveolar cells killed by alpha radiation. Histopathologic features of the epithelial changes suggest a progression from hyperplasia to metaplasia and, finally, to bronchiolo-alveolar carcinoma. The possibility of concurrent radiation-induced lymphopenia contributing to the development of bronchiolo-alveolar carcinoma through a loss of immunologic surveillance was discussed

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

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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.

Role of alveolar topology on acinar flows and convective mixing.

Science.gov (United States)

Hofemeier, Philipp; Sznitman, Josué

2014-06-01

Due to experimental challenges, computational simulations are often sought to quantify inhaled aerosol transport in the pulmonary acinus. Commonly, these are performed using generic alveolar topologies, including spheres, toroids, and polyhedra, to mimic the complex acinar morphology. Yet, local acinar flows and ensuing particle transport are anticipated to be influenced by the specific morphological structures. We have assessed a range of acinar models under self-similar breathing conditions with respect to alveolar flow patterns, convective flow mixing, and deposition of fine particles (1.3 μm diameter). By tracking passive tracers over cumulative breathing cycles, we find that irreversible flow mixing correlates with the location and strength of the recirculating vortex inside the cavity. Such effects are strongest in proximal acinar generations where the ratio of alveolar to ductal flow rates is low and interalveolar disparities are most apparent. Our results for multi-alveolated acinar ducts highlight that fine 1 μm inhaled particles subject to alveolar flows are sensitive to the alveolar topology, underlining interalveolar disparities in particle deposition patterns. Despite the simplicity of the acinar models investigated, our findings suggest that alveolar topologies influence more significantly local flow patterns and deposition sites of fine particles for upper generations emphasizing the importance of the selected acinar model. In distal acinar generations, however, the alveolar geometry primarily needs to mimic the space-filling alveolar arrangement dictated by lung morphology.

Pulmonary function in space

Science.gov (United States)

West, J. B.; Elliott, A. R.; Guy, H. J.; Prisk, G. K.

1997-01-01

The lung is exquisitely sensitive to gravity, and so it is of interest to know how its function is altered in the weightlessness of space. Studies on National Aeronautics and Space Administration (NASA) Spacelabs during the last 4 years have provided the first comprehensive data on the extensive changes in pulmonary function that occur in sustained microgravity. Measurements of pulmonary function were made on astronauts during space shuttle flights lasting 9 and 14 days and were compared with extensive ground-based measurements before and after the flights. Compared with preflight measurements, cardiac output increased by 18% during space flight, and stroke volume increased by 46%. Paradoxically, the increase in stroke volume occurred in the face of reductions in central venous pressure and circulating blood volume. Diffusing capacity increased by 28%, and the increase in the diffusing capacity of the alveolar membrane was unexpectedly large based on findings in normal gravity. The change in the alveolar membrane may reflect the effects of uniform filling of the pulmonary capillary bed. Distributions of blood flow and ventilation throughout the lung were more uniform in space, but some unevenness remained, indicating the importance of nongravitational factors. A surprising finding was that airway closing volume was approximately the same in microgravity and in normal gravity, emphasizing the importance of mechanical properties of the airways in determining whether they close. Residual volume was unexpectedly reduced by 18% in microgravity, possibly because of uniform alveolar expansion. The findings indicate that pulmonary function is greatly altered in microgravity, but none of the changes observed so far will apparently limit long-term space flight. In addition, the data help to clarify how gravity affects pulmonary function in the normal gravity environment on Earth.

Edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia injury: heme oxygenase-1 and PI3K/Akt pathway may be involved.

Science.gov (United States)

Cao, Huifang; Feng, Ying; Ning, Yunye; Zhang, Zinan; Li, Weihao; Li, Qiang

2015-01-01

Hyperoxic acute lung injury (HALI) is a clinical syndrome as a result of prolonged supplement of high concentrations of oxygen. As yet, no specific treatment is available for HALI. The present study aims to investigate the effects of edaravone on hyperoxia-induced oxidative injury and the underlying mechanism. We treated rats and human pulmonary alveolar epithelial cells with hyperoxia and different concentration of edaravone, then examined the effects of edaravone on cell viability, cell injury and two oxidative products. The roles of heme oxygenase-1 (HO-1) and PI3K/Akt pathway were explored using Western blot and corresponding inhibitors. The results showed that edaravone reduced lung biochemical alterations induced by hyperoxia and mortality of rats, dose-dependently alleviated cell mortality, cell injury, and peroxidation of cellular lipid and DNA oxidative damage. It upregulated cellular HO-1 expression and activity, which was reversed by PI3K/Akt pathway inhibition. The administration of zinc protoporphyrin-IX, a HO-1 inhibitor, and LY249002, a PI3K/Akt pathway inhibitor, abolished the protective effects of edaravone in cells. This study indicates that edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia-induced injury and the antioxidant effect may be related to upregulation of HO-1, which is regulated by PI3K/Akt pathway.

Mechanisms underlying gas exchange alterations in an experimental model of pulmonary embolism

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J.H.T. Ferreira

2006-09-01

Full Text Available The aim of the present study was to determine the ventilation/perfusion ratio that contributes to hypoxemia in pulmonary embolism by analyzing blood gases and volumetric capnography in a model of experimental acute pulmonary embolism. Pulmonary embolization with autologous blood clots was induced in seven pigs weighing 24.00 ± 0.6 kg, anesthetized and mechanically ventilated. Significant changes occurred from baseline to 20 min after embolization, such as reduction in oxygen partial pressures in arterial blood (from 87.71 ± 8.64 to 39.14 ± 6.77 mmHg and alveolar air (from 92.97 ± 2.14 to 63.91 ± 8.27 mmHg. The effective alveolar ventilation exhibited a significant reduction (from 199.62 ± 42.01 to 84.34 ± 44.13 consistent with the fall in alveolar gas volume that effectively participated in gas exchange. The relation between the alveolar ventilation that effectively participated in gas exchange and cardiac output (V Aeff/Q ratio also presented a significant reduction after embolization (from 0.96 ± 0.34 to 0.33 ± 0.17 fraction. The carbon dioxide partial pressure increased significantly in arterial blood (from 37.51 ± 1.71 to 60.76 ± 6.62 mmHg, but decreased significantly in exhaled air at the end of the respiratory cycle (from 35.57 ± 1.22 to 23.15 ± 8.24 mmHg. Exhaled air at the end of the respiratory cycle returned to baseline values 40 min after embolism. The arterial to alveolar carbon dioxide gradient increased significantly (from 1.94 ± 1.36 to 37.61 ± 12.79 mmHg, as also did the calculated alveolar (from 56.38 ± 22.47 to 178.09 ± 37.46 mL and physiological (from 0.37 ± 0.05 to 0.75 ± 0.10 fraction dead spaces. Based on our data, we conclude that the severe arterial hypoxemia observed in this experimental model may be attributed to the reduction of the V Aeff/Q ratio. We were also able to demonstrate that V Aeff/Q progressively improves after embolization, a fact attributed to the alveolar ventilation redistribution

Local anesthetic-induced myotoxicity as a cause of severe trismus after inferior alveolar nerve block.

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Smolka, Wenko; Knoesel, Thomas; Mueller-Lisse, Ullrich

2018-01-01

A case of a 60-year-old man with severe trismus after inferior alveolar nerve block is presented. MRI scans as well as histologic examination revealed muscle fibrosis and degeneration of the medial part of the left temporal muscle due to myotoxicity of a local anesthetic agent.

Physiologic effects of alveolar recruitment and inspiratory pauses during moderately-high-frequency ventilation delivered by a conventional ventilator in a severe lung injury model.

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Ricardo Luiz Cordioli

Full Text Available To investigate whether performing alveolar recruitment or adding inspiratory pauses could promote physiologic benefits (VT during moderately-high-frequency positive pressure ventilation (MHFPPV delivered by a conventional ventilator in a porcine model of severe acute respiratory distress syndrome (ARDS.Prospective experimental laboratory study with eight pigs. Induction of acute lung injury with sequential pulmonary lavages and injurious ventilation was initially performed. Then, animals were ventilated on a conventional mechanical ventilator with a respiratory rate (RR = 60 breaths/minute and PEEP titrated according to ARDS Network table. The first two steps consisted of a randomized order of inspiratory pauses of 10 and 30% of inspiratory time. In final step, we removed the inspiratory pause and titrated PEEP, after lung recruitment, with the aid of electrical impedance tomography. At each step, PaCO2 was allowed to stabilize between 57-63 mmHg for 30 minutes.The step with RR of 60 after lung recruitment had the highest PEEP when compared with all other steps (17 [16,19] vs 14 [10, 17]cmH2O, but had lower driving pressures (13 [13,11] vs 16 [14, 17]cmH2O, higher P/F ratios (212 [191,243] vs 141 [105, 184] mmHg, lower shunt (23 [20, 23] vs 32 [27, 49]%, lower dead space ventilation (10 [0, 15] vs 30 [20, 37]%, and a more homogeneous alveolar ventilation distribution. There were no detrimental effects in terms of lung mechanics, hemodynamics, or gas exchange. Neither the addition of inspiratory pauses or the alveolar recruitment maneuver followed by decremental PEEP titration resulted in further reductions in VT.During MHFPPV set with RR of 60 bpm delivered by a conventional ventilator in severe ARDS swine model, neither the inspiratory pauses or PEEP titration after recruitment maneuver allowed reduction of VT significantly, however the last strategy decreased driving pressures and improved both shunt and dead space.

Familial idiopathic pulmonary fibrosis. Evidence of lung inflammation in unaffected family members

International Nuclear Information System (INIS)

Bitterman, P.B.; Rennard, S.I.; Keogh, B.A.; Wewers, M.D.; Adelberg, S.; Crystal, R.G.

1986-01-01

We evaluated 17 clinically unaffected members of three families with an autosomal dominant form of idiopathic pulmonary fibrosis for evidence of alveolar inflammation. Each person in the study was examined by gallium-67 scanning for a general estimate of pulmonary inflammation, and by bronchoalveolar lavage for characterization of the types of recovered cells and their state of activation. Eight of the 17 subjects had evidence of alveolar inflammation on the lavage studies. Supporting data included increased numbers of neutrophils and activated macrophages that released one or more neutrophil chemoattractants, and growth factors for lung fibroblasts--findings similar to those observed in patients with overt idiopathic pulmonary fibrosis. Four of these eight also had a positive gallium scan; in all the other clinically unaffected subjects the scan was normal. During a follow-up of two to four years in seven of the eight subjects who had evidence of inflammation, no clinical evidence of pulmonary fibrosis has appeared. These results indicate that alveolar inflammation occurs in approximately half the clinically unaffected family members at risk of inheriting autosomal dominant idiopathic pulmonary fibrosis. Whether these persons with evidence of pulmonary inflammation but no fibrosis will proceed to have clinically evident pulmonary fibrosis is not yet known

Off-pump coronary bypass surgery adversely affects alveolar gas exchange.

Science.gov (United States)

Gasparović, Hrvoje; Unić, Daniel; Sutlić, Zeljko; Husedzinović, Ino; Biocina, Bojan; Rudez, Igor; Nikić, Nada; Jelić, Ivan

2008-03-01

While the introduction of off-pump myocardial revascularization (OPCAB) has initially shown promise in reducing respiratory complications inherent to conventional coronary surgery, it has failed to eradicate them. Our study focused on quantifying the lactate release from the lungs and the dysfunction at the level of the alveolar-capillary membrane precipitated by OPCAB at different time points after the insult. Furthermore, we aimed to determine the impact of pulmonary lactate production on systemic lactic acid concentrations. The study was conducted in a prospective observational fashion. Forty consecutive patients undergoing OPCAB were analyzed. The mean patient age was 60 +/- 10 years. The mean EUROScore was 3.8 +/- 2.9. The alveolar-arterial O2 gradient increased from 19 [range 9 to 30] to 26 [range 20 to 34] kPa (P pump myocardial revascularization was evidenced by a prompt increase in the alveolar-arterial oxygen gradient. The alveolar-arterial O2 gradient correlated with the duration of mechanical ventilation.

Pulmonary lesions induced by inhaled plutonium in beagles

International Nuclear Information System (INIS)

Dagle, G.E.; Lund, J.E.; Park, J.F.

1976-01-01

The histopathologic features of pulmonary fibrosis and bronchiolo-alveolar carcinoma in beagles exposed to aerosols of 238 Pu or 239 Pu oxide are reviewed. A hypothesis of the pathogenesis of radiation pneumonitis induced by inhalation of plutonium oxide is presented; this hypothesis included phagocytosis of Pu particles, fibrosis responding to the necrosis, and alveolar cell hyperplasia compensating for alveolar cells killed by alpha radiation. Histopathologic features of the epithelial changes suggest a progression from hyperplasia to metaplasia and, finally, to bronchiolo-alveolar carcinoma. The possibility of concurrent radiation-induced lymphopenia contributing to the development of bronchiolo-alveolar carcinoma through a loss of immunologic surveillance is discussed

Leptospirose pulmonar Pulmonary leptospirosis

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João Cláudio Barroso Pereira

2007-12-01

Full Text Available No presente artigo, os autores discutem brevemente sobre a leptospirose, realçando a forma pulmonar da doença. Revê-se a patologia, achados clínicos, diagnóstico por métodos de imagem e broncoscopia e tratamento da leptospirose pulmonar. É também lembrado o diagnóstico clínico e radiológico precoces, para que se possa iniciar terapêutica adequada. Os autores concluem que a forma pulmonar da leptospirose deve ser sempre considerada como causa e diagnóstico diferencial da hemorragia alveolar difusa e síndroma de dificuldade respiratória do adulto.In this article, the authors discuss briefly the leptospirosis, emphasizing mainly the pulmonary form of disease. The authors review pathology, clinical findings, imaging and broncoscopy diagnosis, treatment of pulmonary leptospirosis. It is also remembered about early clinics and radiology diagnosis to start therapeutics. The authors conclude that pulmonary form of disease must always be remembered and considered as cause and differential diagnosis of Diffuse Alveolar Hemorrhage and Adult Respiratory Distress Syndrome.

Pulmonary function tests and impulse oscillometry in severe chronic obstructive pulmonary disease patients′ offspring

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Babak Amra

2015-01-01

Full Text Available Background: Several studies have showed an increased prevalence of airflow obstruction in first degree relatives of individuals with chronic obstructive pulmonary disease (COPD. Considering no specific research had evaluated airway resistance in offspring of patients with severe COPD, we utilized a spirometry and a impulse oscillometry (IO to evaluate this population. Materials and Methods: In this case control study, from November 2011 to July 2012, we consecutively evaluated 54 offsprings of severe COPD patients (case group admitted in the pulmonary ward, affiliated to the Isfahan University of Medical Sciences and control group. Pulmonary function tests and the IO were obtained for both groups. Student′s t-test was used for inter-group comparisons, and P values below 0.05 were taken as significant. Results: Abnormal increased airway resistance was seen in cases in comparison with controls (R5 Hz [46.29%, P = 0.01], R25 Hz [42.59%, P < 0.001]. Also, considering the spirometry, case group had pulmonary function parameters less than control group (forced vital capacity [FVC]; P = 0.02, forced expiratory volume in 1 st s; P < 0.001, forced expiratory flow (FEF 25-75; P < 0.001, FEF 25-75/FVC; P < 0.001 but they were in normal range. Conclusion: This study demonstrated increased airway resistance among the severe COPD offsprings. The IO may be a sensitive tool for detection of high risk subjects in families with COPD.

An Uncommon Procedure for a Rare Ailment: Massive Bronchoalveolar Lavage in a Patient with Pulmonary Alveolar Proteinosis

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Belgin Samurkaşoğlu

2012-09-01

Full Text Available As a rare procedure, massive bronchoalveolar lavage (MBAL is a large-volume lavage which necessitates general anesthesia and one-lung ventilation (OLV. During MBAL isotonic saline is instilled into one lung and drained through one lumen of a double-lumen tube. MBAL is the most effective treatment for symptomatic pulmonary alveolar proteinosis (PAP. A 27-year-old male with PAP was scheduled for therapeutic MBALs. After standard preoxygenation, monitoring and anesthesia induction, a double-lumen tube was placed. Tube position was verified by a fiberoptic bronchoscope. The internal jugular vein, radial and pulmonary arteries were cannulated. A temperature probe and foley catheter were inserted. The nonventilated lung was filled with 1000 mL saline and then drained in each session. The left and right lung were lavaged with an interval of 2 weeks. A total of 20 L saline was used in each MBAL without retention. MBALs were terminated after the effluent became clear. Duration of the left and right MBALs were 325 and 275 minutes, respectively. Despite increased shunt fraction, oxygenation was within acceptable limits during OLV. The trachea was extubated in the operating room uneventfully after each MBAL. The patient’s clinical and laboratory findings were evidently improved. Consequently, if proper conditions are provided, MBAL is safe and beneficial despite its risks and the long duration.

Orthopantomographic study of the alveolar bone level on periodontal disease

International Nuclear Information System (INIS)

Lee, Ki Sik; You, Dong Soo

1972-01-01

The author had measured the alveolar bone level of periodontal disease on 50 cases of orthopantomogram to detect the degree of alveolar bone resorption of both sexes of Korean. The results were obtained as follows; 1. Alveolar bone resorption of mesial and distal portion was similar in same patient. 2. The order of alveolar bone resorption was mandibular anterior region, posterior region, canine and premolar region of both jaws. 3. The degree of alveolar bone destruction was severe in shorter root length than longer one. 4. The degree of alveolar bone resorption was severe in fourth decades.

Orthopantomographic study of the alveolar bone level on periodontal disease

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Lee, Ki Sik; You, Dong Soo [College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

1972-11-15

The author had measured the alveolar bone level of periodontal disease on 50 cases of orthopantomogram to detect the degree of alveolar bone resorption of both sexes of Korean. The results were obtained as follows; 1. Alveolar bone resorption of mesial and distal portion was similar in same patient. 2. The order of alveolar bone resorption was mandibular anterior region, posterior region, canine and premolar region of both jaws. 3. The degree of alveolar bone destruction was severe in shorter root length than longer one. 4. The degree of alveolar bone resorption was severe in fourth decades.

Egg and banana sign of severe pulmonary arterial hypertension.

Science.gov (United States)

Veean, Satyam; Nixon, William; Keshavamurthy, Jayanth

2018-01-01

The egg and banana sign can be seen on chest computed tomography (CT) in patients with severe pulmonary arterial hypertension (PAH). It is identified by the presence of the pulmonary artery (PA) lateral to the aortic arch with the aortic arch being described as the banana and the PA as the egg.

Technical modification enabling pulmonary valve-sparing repair of a severely hypoplastic pulmonary annulus in patients with tetralogy of Fallot.

Science.gov (United States)

Ito, Hiroki; Ota, Noritaka; Murata, Masaya; Tosaka, Yuko; Ide, Yujiro; Tachi, Maiko; Sugimoto, Ai; Sakamoto, Kisaburo

2013-06-01

Although pulmonary valve-sparing repair is preferable for patients with tetralogy of Fallot, the repair of very small pulmonary valves is challenging. The present study evaluates our modification for preserving severely hypoplastic pulmonary valves in patients with tetralogy of Fallot. Sixty-eight consecutive patients who underwent complete repair of a tetralogy of Fallot between 2005 and 2011 were retrospectively reviewed. Patients with pulmonary atresia, absence of a pulmonary valve, atrioventricular septal defect and/or subarterial ventricular septal defect were excluded. There were 19 (28%) patients with a severely hypoplastic pulmonary annulus determined by preoperative echocardiography (z-score -4 group. In the z tetralogy of Fallot could not be applied in all patients, this strategy enabled acceptable growth of the valve annulus, with only mild stenosis during the early to mid-term follow-up. This modification seems to be an option, even for a very small pulmonary valve.

CT pulmonary angiography: increasingly diagnosing less severe pulmonary emboli.

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Andrew J Schissler

Full Text Available It is unknown whether the observed increase in computed tomography pulmonary angiography (CTPA utilization has resulted in increased detection of pulmonary emboli (PEs with a less severe disease spectrum.Trends in utilization, diagnostic yield, and disease severity were evaluated for 4,048 consecutive initial CTPAs performed in adult patients in the emergency department of a large urban academic medical center between 1/1/2004 and 10/31/2009. Transthoracic echocardiography (TTE findings and peak serum troponin levels were evaluated to assess for the presence of PE-associated right ventricular (RV abnormalities (dysfunction or dilatation and myocardial injury, respectively. Statistical analyses were performed using multivariate logistic regression.268 CTPAs (6.6% were positive for acute PE, and 3,780 (93.4% demonstrated either no PE or chronic PE. There was a significant increase in the likelihood of undergoing CTPA per year during the study period (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.04-1.07, P<0.01. There was no significant change in the likelihood of having a CTPA diagnostic of an acute PE per year (OR 1.03, 95% CI 0.95-1.11, P = 0.49. The likelihood of diagnosing a less severe PE on CTPA with no associated RV abnormalities or myocardial injury increased per year during the study period (OR 1.39, 95% CI 1.10-1.75, P = 0.01.CTPA utilization has risen with no corresponding change in diagnostic yield, resulting in an increase in PE detection. There is a concurrent rise in the likelihood of diagnosing a less clinically severe spectrum of PEs.

CT Pulmonary Angiography: Increasingly Diagnosing Less Severe Pulmonary Emboli

Science.gov (United States)

Schissler, Andrew J.; Rozenshtein, Anna; Kulon, Michal E.; Pearson, Gregory D. N.; Green, Robert A.; Stetson, Peter D.; Brenner, David J.; D'Souza, Belinda; Tsai, Wei-Yann; Schluger, Neil W.; Einstein, Andrew J.

2013-01-01

Background It is unknown whether the observed increase in computed tomography pulmonary angiography (CTPA) utilization has resulted in increased detection of pulmonary emboli (PEs) with a less severe disease spectrum. Methods Trends in utilization, diagnostic yield, and disease severity were evaluated for 4,048 consecutive initial CTPAs performed in adult patients in the emergency department of a large urban academic medical center between 1/1/2004 and 10/31/2009. Transthoracic echocardiography (TTE) findings and peak serum troponin levels were evaluated to assess for the presence of PE-associated right ventricular (RV) abnormalities (dysfunction or dilatation) and myocardial injury, respectively. Statistical analyses were performed using multivariate logistic regression. Results 268 CTPAs (6.6%) were positive for acute PE, and 3,780 (93.4%) demonstrated either no PE or chronic PE. There was a significant increase in the likelihood of undergoing CTPA per year during the study period (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.04–1.07, P<0.01). There was no significant change in the likelihood of having a CTPA diagnostic of an acute PE per year (OR 1.03, 95% CI 0.95–1.11, P = 0.49). The likelihood of diagnosing a less severe PE on CTPA with no associated RV abnormalities or myocardial injury increased per year during the study period (OR 1.39, 95% CI 1.10–1.75, P = 0.01). Conclusions CTPA utilization has risen with no corresponding change in diagnostic yield, resulting in an increase in PE detection. There is a concurrent rise in the likelihood of diagnosing a less clinically severe spectrum of PEs. PMID:23776522

Morphometric changes of pulmonary tissues after 20 Gy external irradiation of rat chest

International Nuclear Information System (INIS)

Cao Zhenshan; Ye Changqing; Yuan Lizhen

1996-01-01

The changes in the main parameters of the lungs at different periods of early stage after local 20 Gy external irradiation of the lungs were measured with morphometric method. The results indicated that the walls of pulmonary arterioles and venules thickened and the vascular permeability index (area of vascular lumen/total area of blood vessel) decreased 7 days after irradiation (P 2 , r = -0.919), indicating that narrowing of the vascular lumen was the result of thickening of the vascular wall. Fifteen days after irradiation, the pulmonary alveolar wall thickened, the area of alveolar cavity decreased and the area of pulmonary interstitial space increased (P<0.01). Electron microscopic examination demonstrated profuse exudation surrounding the microvessels, obvious evacuation of pulmonary type-II cells and increase in cellular types and quantity of pulmonary tissues

Emodin suppresses TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells through Notch signaling pathway

International Nuclear Information System (INIS)

Gao, Rundi; Chen, Ruilin; Cao, Yu; Wang, Yuan; Song, Kang; Zhang, Ya; Yang, Junchao

2017-01-01

Pulmonary fibrosis is characterized by the destruction of lung tissue architecture and the formation of fibrous foci, currently has no satisfactory treatment. Emodin is a component of Chinese herb that has been reported to be medicament on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been established yet. In the present study, we investigated the hypothesis that Emodin plays an inhibitory role in TGF-β1 induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cell, and Emodin exerts its effect through the Notch signaling pathway. Emodin inhibits the proliferation of Rat alveolar type II epithelial cells RLE-6TN in a concentration-dependent manner; reduces the expression of Collagen I, α-SMA and Vimentin, promotes the expression of E-cadherin. Moreover, Emodin could regulate the expression patterns of the Notch signaling pathway-related factors and reduce the Notch-1 nucleus translocation. Knockdown of Notch-1 enhances the inhibitory effect of Emodin on TGF-β1-induced EMT in RLE-6TN cells. In conclusion, the data of the present study suggests that Emodin suppresses TGF-β1-induced EMT in alveolar epithelial cells through Notch signaling pathway and shows the potential to be effective in the treatment of pulmonary fibrosis. - Highlights: • Emodin inhibits TGF-β1-induced EMT in alveolar epithelial cells. • Emodin regulates the expression patterns of the Notch signaling pathway-related factors. • Emodin inhibits TGF-β1-induced Notch-1 nucleus translocation and activation.

Emodin suppresses TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells through Notch signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Gao, Rundi; Chen, Ruilin; Cao, Yu [Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China); Wang, Yuan [Department of Pulmonary Function, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China); Song, Kang [Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China); Zhang, Ya [Zhejiang Chinese Medicine University, No. 548, Binwen Road, Binjiang District, Hangzhou, Zhejiang Province 310006 (China); Yang, Junchao, E-mail: yangjunchaozj@zcmu.edu.cn [Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China)

2017-03-01

Pulmonary fibrosis is characterized by the destruction of lung tissue architecture and the formation of fibrous foci, currently has no satisfactory treatment. Emodin is a component of Chinese herb that has been reported to be medicament on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been established yet. In the present study, we investigated the hypothesis that Emodin plays an inhibitory role in TGF-β1 induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cell, and Emodin exerts its effect through the Notch signaling pathway. Emodin inhibits the proliferation of Rat alveolar type II epithelial cells RLE-6TN in a concentration-dependent manner; reduces the expression of Collagen I, α-SMA and Vimentin, promotes the expression of E-cadherin. Moreover, Emodin could regulate the expression patterns of the Notch signaling pathway-related factors and reduce the Notch-1 nucleus translocation. Knockdown of Notch-1 enhances the inhibitory effect of Emodin on TGF-β1-induced EMT in RLE-6TN cells. In conclusion, the data of the present study suggests that Emodin suppresses TGF-β1-induced EMT in alveolar epithelial cells through Notch signaling pathway and shows the potential to be effective in the treatment of pulmonary fibrosis. - Highlights: • Emodin inhibits TGF-β1-induced EMT in alveolar epithelial cells. • Emodin regulates the expression patterns of the Notch signaling pathway-related factors. • Emodin inhibits TGF-β1-induced Notch-1 nucleus translocation and activation.

Clinical Features of Patients with Diffuse Alveolar Hemorrhage due to Negative-Pressure Pulmonary Edema.

Science.gov (United States)

Contou, Damien; Voiriot, Guillaume; Djibré, Michel; Labbé, Vincent; Fartoukh, Muriel; Parrot, Antoine

2017-08-01

Diffuse alveolar hemorrhage (DAH) with negative-pressure pulmonary edema (NPPE) is an uncommon yet life-threatening condition. We aimed at describing the circumstances, clinical, radiological, and bronchoscopic features, as well as the outcome of patients with NPPE-related DAH. We performed a retrospective, observational cohort study, using data prospectively collected over 35 years in an intensive care unit (ICU). Of the 149 patients admitted for DAH, we identified 18 NPPE episodes in 15 patients, one admitted four times for recurrent NPPE-related DAH. The patients were primarily young, male, and athletic. The NPPE setting was postoperative (n = 12/18, 67%) or following generalized tonic-clonic seizures (n = 6/18, 33%). Hemoptysis was almost constant (n = 17/18, 94%), yet rarely massive (>200 cc, n = 1/18, 6%), with anemia observed in 10 (56%) episodes. The DAH triad (hemoptysis, anemia, and pulmonary infiltrates) was observed in 50% of episodes (n = 9/18), and acute respiratory failure in 94% (n = 17/18). Chest computed tomography revealed diffuse bilateral ground glass opacities (n = 10/10, 100%), while bronchoscopy detected bilateral hemorrhage (n = 12/12, 100%) and macroscopically bloody bronchoalveolar lavage, with siderophage absence in most (n = 7/8, 88%), indicating acute DAH. While one episode proved fatal, the other 17 recovered rapidly, with a mean ICU stay lasting 4.6 (2-15) days. Typically, the evolution was rapidly favorable under supportive care. NPPE-related DAH is a rare life-threatening condition occurring primarily after tonic-clonic generalized seizure or generalized anesthesia. Clinical circumstances are a key to its diagnosis. Early diagnosis and recognition likely allow for successful management of this potentially serious complication, whereas ictal-DAH appears ominous in epileptic patients.

A Novel Procedure for the Immediate Reconstruction of Severely Resorbed Alveolar Sockets for Advanced Periodontal Disease.

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Aimetti, Mario; Manavella, Valeria; Cricenti, Luca; Romano, Federica

2017-01-01

Background. Several clinical techniques and a variety of biomaterials have been introduced over the years in an effort to overcome bone remodeling and resorption after tooth extraction. However, the predictability of these procedures in sockets with severely resorbed buccal/lingual plate due to periodontal disease is still unknown. Case Description. A patient with advanced periodontitis underwent extraction of upper right lateral and central incisors. The central incisor exhibited complete buccal bone plate loss and a 9 mm vertical bone deficiency on its palatal side. The alveolar sockets were filled with collagen sponge and covered with a nonresorbable high-density PTFE membrane. Primary closure was not attained and any rigid scaffold material was not used. Histologic analysis provided evidence of new bone formation. At 12 months a cone-beam computed tomographic scan revealed enough bone volume to insert two conventional dental implants in conjunction with minor horizontal bone augmentation procedures. Clinical Implications. This case report would seem to support the potential of the proposed reconstructive approach in changing the morphology of severely resorbed alveolar sockets, minimizing the need for advanced bone regeneration procedures during implant placement.

A Novel Procedure for the Immediate Reconstruction of Severely Resorbed Alveolar Sockets for Advanced Periodontal Disease

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Mario Aimetti

2017-01-01

Full Text Available Background. Several clinical techniques and a variety of biomaterials have been introduced over the years in an effort to overcome bone remodeling and resorption after tooth extraction. However, the predictability of these procedures in sockets with severely resorbed buccal/lingual plate due to periodontal disease is still unknown. Case Description. A patient with advanced periodontitis underwent extraction of upper right lateral and central incisors. The central incisor exhibited complete buccal bone plate loss and a 9 mm vertical bone deficiency on its palatal side. The alveolar sockets were filled with collagen sponge and covered with a nonresorbable high-density PTFE membrane. Primary closure was not attained and any rigid scaffold material was not used. Histologic analysis provided evidence of new bone formation. At 12 months a cone-beam computed tomographic scan revealed enough bone volume to insert two conventional dental implants in conjunction with minor horizontal bone augmentation procedures. Clinical Implications. This case report would seem to support the potential of the proposed reconstructive approach in changing the morphology of severely resorbed alveolar sockets, minimizing the need for advanced bone regeneration procedures during implant placement.

Optical techniques in pulmonary medicine. SPIE photonics West.

Science.gov (United States)

Suter, Melissa J; Lam, Stephen; Brenner, Matthew

2012-04-01

There is ongoing interest in the emerging field of pulmonary photonic-based diagnostics. Potential clinical need areas that are being actively investigated at this time include airway and peripheral lung cancer diagnostics, pulmonary parenchymal and interstitial disorders, alveolar structure function, inhalation injury, ciliary function analysis, asthma and obstructive lung diseases.

Anthrax Lethal Toxin Impairs Innate Immune Functions of Alveolar Macrophages and Facilitates Bacillus anthracis Survival

National Research Council Canada - National Science Library

Ribot, Wilson J; Panchal, Rekha G; Brittingham, Katherine C; Ruthel, Gordon; Kenny, Tara A; Lane, Douglas; Curry, Bob; Hoover, Timothy A; Friedlander, Arthur M; Bavari, Sina

2006-01-01

Alveolar macrophages (AM) are very important for pulmonary innate immune responses against invading inhaled pathogens because they directly kill the organisms and initiate a cascade of innate and adaptive immune responses...

Effects of in vitro cultivated Calculus Bovis compound on pulmonary lesions in rabbits with schistosomiasis.

Science.gov (United States)

Li, Tao; Yang, Zhen; Cai, Hong-Jiao; Song, Li-Wei; Lu, Ke-Yu; Zhou, Zheng; Wu, Zai-De

2010-02-14

To explore the interventional effects and mechanism of in vitro cultivated Calculus Bovis compound preparation (ICCBco) on pulmonary lesions in portal hypertensive rabbits with schistosomiasis. The experimental group included 20 portal hypertensive rabbits with schistosomiasis treated by ICCBco. The control group included 20 portal hypertensive rabbits with schistosomiasis treated by praziquantel. The morphological changes of the pulmonary tissues were observed under light and electron microscopy. The expression of fibronectin (FN) and laminin (LN) in the lung tissues was analyzed by immunohistochemistry. Under light microscope, the alveolar exudation in the lung tissue was more frequently observed in the control group, while the alveolar space was fairly dry in the lung tissue of ICCBco group. Under electron microscope, more alveolar exudation in the lung tissue, and more macrophages, alveolar angiotelectasis and the blurred three-tier structure of alveolar-capillary barrier could be seen in the control group. In ICCBco group, fibers within the alveolar interspace slightly increased in some lung regions, and the structure of type I epithelium, basement membrane and endodermis was complete, and no obvious exudation from the alveolar space, and novascular congestion could be observed. There was a positive or strong positive expression of FN and LN in the lung tissue of the control group, while there was a negative or weak positive expression of FN and LN in ICCBco group. ICCBco can effectively prevent pulmonary complications in portal hypertensive rabbits with schistosomiasis by means of improving lung microcirculation and lowering the content of extracellular matrix.

A new model of progressive pulmonary fibrosis in rats

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Last, J.A.; Gelzleichter, T.R.; Pinkerton, K.E.; Walker, R.M.; Witschi, H. (Univ. of California, Davis (United States))

1993-08-01

Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.

Pulmonary hypertension and right heart failure due to severe hypernatremic dehydration.

Science.gov (United States)

Chiwane, Saurabh; Ahmed, Tageldin M; Bauerfeld, Christian P; Chauhan, Monika

2017-07-01

Neonates are at risk of developing hypernatremic dehydration and its associated complications, such as stroke, dural sinus thrombosis and renal vein thrombosis. Pulmonary hypertension has not been described as a complication of hypernatremia. We report a case of a seven-day-old neonate with severe hypernatremic dehydration who went on to develop pulmonary hypertension and right heart failure needing extracorporeal membrane oxygenation (ECMO). Normal or high anion gap metabolic acidosis commonly accompanies hypernatremic dehydration. The presence of acidosis and/or hypoxia can delay the normal drop in pulmonary vascular resistance (PVR) after birth, causing pulmonary hypertension and right ventricular failure. A high index of suspicion is paramount to diagnose pulmonary hypertension and aggressive correction of the acidosis and hypoxia is needed. In the presence of severe right ventricular failure, ECMO can be used as a bridge to recovery while underlying metabolic derangements are being corrected.

Simultaneous Sinus Lifting and Alveolar Distraction of a Severely Atrophic Posterior Maxilla for Oral Rehabilitation with Dental Implants

Science.gov (United States)

Kanno, Takahiro; Mitsugi, Masaharu; Paeng, Jun-Young; Sukegawa, Shintaro; Furuki, Yoshihiko; Ohwada, Hiroyuki; Nariai, Yoshiki; Ishibashi, Hiroaki; Katsuyama, Hideaki; Sekine, Joji

2012-01-01

We retrospectively reviewed a new preimplantation regenerative augmentation technique for a severely atrophic posterior maxilla using sinus lifting with simultaneous alveolar distraction, together with long-term oral rehabilitation with implants. We also analyzed the regenerated bone histomorphologically. This study included 25 maxillary sinus sites in 17 patients. The technique consisted of alveolar osteotomy combined with simultaneous sinus lifting. After sufficient sinus lifting, a track-type vertical alveolar distractor was placed. Following a latent period, patient self-distraction was started. After the required augmentation was achieved, the distractor was left in place to allow consolidation. The distractor was then removed, and osseointegrated implants (average of 3.2 implants per sinus site, 80 implants) were placed. Bone for histomorphometric analysis was sampled from six patients and compared with samples collected after sinus lifting alone as controls (n = 4). A sufficient alveolus was regenerated, and all patients achieved stable oral rehabilitation. The implant survival rate was 96.3% (77/80) after an average postloading followup of 47.5 months. Good bone regeneration was observed in a morphological study, with no significant difference in the rate of bone formation compared with control samples. This new regenerative technique could be a useful option for a severely atrophic maxilla requiring implant rehabilitation. PMID:22792105

Simultaneous Sinus Lifting and Alveolar Distraction of a Severely Atrophic Posterior Maxilla for Oral Rehabilitation with Dental Implants

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Takahiro Kanno

2012-01-01

Full Text Available We retrospectively reviewed a new preimplantation regenerative augmentation technique for a severely atrophic posterior maxilla using sinus lifting with simultaneous alveolar distraction, together with long-term oral rehabilitation with implants. We also analyzed the regenerated bone histomorphologically. This study included 25 maxillary sinus sites in 17 patients. The technique consisted of alveolar osteotomy combined with simultaneous sinus lifting. After sufficient sinus lifting, a track-type vertical alveolar distractor was placed. Following a latent period, patient self-distraction was started. After the required augmentation was achieved, the distractor was left in place to allow consolidation. The distractor was then removed, and osseointegrated implants (average of 3.2 implants per sinus site, 80 implants were placed. Bone for histomorphometric analysis was sampled from six patients and compared with samples collected after sinus lifting alone as controls (n=4. A sufficient alveolus was regenerated, and all patients achieved stable oral rehabilitation. The implant survival rate was 96.3% (77/80 after an average postloading followup of 47.5 months. Good bone regeneration was observed in a morphological study, with no significant difference in the rate of bone formation compared with control samples. This new regenerative technique could be a useful option for a severely atrophic maxilla requiring implant rehabilitation.

Sildenafil attenuates pulmonary inflammation and fibrin deposition, mortality and right ventricular hypertrophy in neonatal hyperoxic lung injury

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Boersma Hester

2009-04-01

Full Text Available Abstract Background Phosphodiesterase-5 inhibition with sildenafil has been used to treat severe pulmonary hypertension and bronchopulmonary dysplasia (BPD, a chronic lung disease in very preterm infants who were mechanically ventilated for respiratory distress syndrome. Methods Sildenafil treatment was investigated in 2 models of experimental BPD: a lethal neonatal model, in which rat pups were continuously exposed to hyperoxia and treated daily with sildenafil (50–150 mg/kg body weight/day; injected subcutaneously and a neonatal lung injury-recovery model in which rat pups were exposed to hyperoxia for 9 days, followed by 9 days of recovery in room air and started sildenafil treatment on day 6 of hyperoxia exposure. Parameters investigated include survival, histopathology, fibrin deposition, alveolar vascular leakage, right ventricular hypertrophy, and differential mRNA expression in lung and heart tissue. Results Prophylactic treatment with an optimal dose of sildenafil (2 × 50 mg/kg/day significantly increased lung cGMP levels, prolonged median survival, reduced fibrin deposition, total protein content in bronchoalveolar lavage fluid, inflammation and septum thickness. Treatment with sildenafil partially corrected the differential mRNA expression of amphiregulin, plasminogen activator inhibitor-1, fibroblast growth factor receptor-4 and vascular endothelial growth factor receptor-2 in the lung and of brain and c-type natriuretic peptides and the natriuretic peptide receptors NPR-A, -B, and -C in the right ventricle. In the lethal and injury-recovery model we demonstrated improved alveolarization and angiogenesis by attenuating mean linear intercept and arteriolar wall thickness and increasing pulmonary blood vessel density, and right ventricular hypertrophy (RVH. Conclusion Sildenafil treatment, started simultaneously with exposure to hyperoxia after birth, prolongs survival, increases pulmonary cGMP levels, reduces the pulmonary

Alveolar Macrophages Play a Key Role in Cockroach-Induced Allergic Inflammation via TNF-α Pathway

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Kim, Joo Young; Sohn, Jung Ho; Choi, Je-Min; Lee, Jae-Hyun; Hong, Chein-Soo; Lee, Joo-Shil; Park, Jung-Won

2012-01-01

The activity of the serine protease in the German cockroach allergen is important to the development of allergic disease. The protease-activated receptor (PAR)-2, which is expressed in numerous cell types in lung tissue, is known to mediate the cellular events caused by inhaled serine protease. Alveolar macrophages express PAR-2 and produce considerable amounts of tumor necrosis factor (TNF)-α. We determined whether the serine protease in German cockroach extract (GCE) enhances TNF-α production by alveolar macrophages through the PAR-2 pathway and whether the TNF-α production affects GCE-induced pulmonary inflammation. Effects of GCE on alveolar macrophages and TNF-α production were evaluated using in vitro MH-S and RAW264.6 cells and in vivo GCE-induced asthma models of BALB/c mice. GCE contained a large amount of serine protease. In the MH-S and RAW264.7 cells, GCE activated PAR-2 and thereby produced TNF-α. In the GCE-induced asthma model, intranasal administration of GCE increased airway hyperresponsiveness (AHR), inflammatory cell infiltration, productions of serum immunoglobulin E, interleukin (IL)-5, IL-13 and TNF-α production in alveolar macrophages. Blockade of serine proteases prevented the development of GCE induced allergic pathologies. TNF-α blockade also prevented the development of such asthma-like lesions. Depletion of alveolar macrophages reduced AHR and intracellular TNF-α level in pulmonary cell populations in the GCE-induced asthma model. These results suggest that serine protease from GCE affects asthma through an alveolar macrophage and TNF-α dependent manner, reflecting the close relation of innate and adaptive immune response in allergic asthma model. PMID:23094102

Role of Alveolar Macrophages in Chronic Obstructive Pulmonary Disease

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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...

Molecular and cellular mechanisms of pulmonary fibrosis

Science.gov (United States)

2012-01-01

Pulmonary fibrosis is a chronic lung disease characterized by excessive accumulation of extracellular matrix (ECM) and remodeling of the lung architecture. Idiopathic pulmonary fibrosis is considered the most common and severe form of the disease, with a median survival of approximately three years and no proven effective therapy. Despite the fact that effective treatments are absent and the precise mechanisms that drive fibrosis in most patients remain incompletely understood, an extensive body of scientific literature regarding pulmonary fibrosis has accumulated over the past 35 years. In this review, we discuss three broad areas which have been explored that may be responsible for the combination of altered lung fibroblasts, loss of alveolar epithelial cells, and excessive accumulation of ECM: inflammation and immune mechanisms, oxidative stress and oxidative signaling, and procoagulant mechanisms. We discuss each of these processes separately to facilitate clarity, but certainly significant interplay will occur amongst these pathways in patients with this disease. PMID:22824096

Cardiovascular parameters to assess the severity of acute pulmonary embolism with computed tomography

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Dian-Jiang Zhao; Da-Qing Ma; Wen He; Jian-Jun Wang; Yan Xu; Chun-Shuang Guan (Dept. of Radiology, Beijing Friendship Hospital, Capital Medical Univ., Beijing (China)), e-mail: madaqing@263.net

2010-05-15

Background: Computed tomographic pulmonary angiography (CTPA) has been established as a first-line test in the acute pulmonary embolism (APE) diagnostic algorithm, but the assessment of the severity of APE by this method remains to be explored. Purpose: To retrospectively evaluate right ventricular (RV) dysfunction and severity in patients with APE without underlying cardiopulmonary disease using helical computed tomography (CT). Material and Methods: Seventy-three patients (35 men and 38 women) were divided into two groups according to the clinical findings: severe APE (n=22) and non-severe APE (n=51). Pulmonary artery CT obstruction index was calculated according to the location and degree of clots in the pulmonary arteries. Cardiovascular parameters including RV short axis and left ventricular (LV) short axis, RV short axis to LV short axis (RV/LV) ratio, main pulmonary artery, azygous vein, and superior vena cava diameters were measured. Leftward bowing of the interventricular septum, reflux of contrast medium into the inferior vena cava and azygous vein, and bronchial artery dilatation were also recorded. The results were analyzed by Mann-Whitney U test, x2 test, Spearman's rank correlation coefficient, and the area under the receiver operating characteristic curve (Az). Results: CT obstruction index in patients with severe APE (median 43%) was higher than that of patients with non-severe APE (median 20%). Comparison of cardiovascular parameters between patients with severe and non-severe pulmonary embolism showed significant differences in RV short axis, LV short axis, RV/LV ratio, RV wall thickness, main pulmonary artery diameter, azygous vein diameter, leftward bowing of the interventricular septum, and bronchial artery dilatation. The correlation between CT obstruction indexes and cardiovascular parameters was significant. Spearman's rank correlation coefficient was highest between RV/LV ratio and CT obstruction index. Az values were

Circulating microparticles in severe pulmonary arterial hypertension increase intercellular adhesion molecule-1 expression selectively in pulmonary artery endothelium

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Leslie A. Blair

2016-10-01

Full Text Available Abstract Background Microparticles (MPs stimulate inflammatory adhesion molecule expression in systemic vascular diseases, however it is unknown whether circulating MPs stimulate localized ICAM-1 expression in the heterogeneically distinct pulmonary endothelium during pulmonary arterial hypertension (PAH. Pulmonary vascular lesions with infiltrating inflammatory cells in PAH form in the pulmonary arteries and arterioles, but not the microcirculation. Therefore, we sought to determine whether circulating MPs from PAH stimulate pulmonary artery endothelial cell-selective ICAM-1 expression. Results Pulmonary artery endothelial cells (PAECs were exposed to MPs isolated from the circulation of a rat model of severe PAH. During late-stage (8-weeks PAH, but not early-stage (3-weeks, an increase in ICAM-1 was observed. To determine whether PAH MP-induced ICAM-1 was selective for a specific segment of the pulmonary circulation, pulmonary microvascular endothelial cells (PMVECs were exposed to late-stage PAH MPs and no increase in ICAM-1 was detected. A select population of circulating MPs, the late-stage endoglin + MPs, were used to assess their ability to stimulate ICAM-1 and it was determined that the endoglin + MPs were sufficient to promote ICAM-1 increases in the whole cell, but not surface only expression. Conclusions Late-stage, but not early-stage, MPs in a model of severe PAH selectively induce ICAM-1 in pulmonary artery endothelium, but not pulmonary microcirculation. Further, the selected endoglin + PAH MPs, but not endoglin + MPs from control, are sufficient to promote whole cell ICAM-1 in PAECs. The implications of this work are that MPs in late-stage PAH are capable of inducing ICAM-1 expression selectively in the pulmonary artery. ICAM-1 likely plays a significant role in the observed inflammatory cell recruitment, specifically to vascular lesions in the pulmonary artery and not the pulmonary microcirculation.

Biodegradable polymeric nanocarriers for pulmonary drug delivery.

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Rytting, Erik; Nguyen, Juliane; Wang, Xiaoying; Kissel, Thomas

2008-06-01

Pulmonary drug delivery is attractive for both local and systemic drug delivery as a non-invasive route that provides a large surface area, thin epithelial barrier, high blood flow and the avoidance of first-pass metabolism. Nanoparticles can be designed to have several advantages for controlled and targeted drug delivery, including controlled deposition, sustained release, reduced dosing frequency, as well as an appropriate size for avoiding alveolar macrophage clearance or promoting transepithelial transport. This review focuses on the development and application of biodegradable polymers to nanocarrier-based strategies for the delivery of drugs, peptides, proteins, genes, siRNA and vaccines by the pulmonary route. The selection of natural or synthetic materials is important in designing particles or nanoparticle clusters with the desired characteristics, such as biocompatibility, size, charge, drug release and polymer degradation rate.

The Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis

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Huang, Long Shuang; Mathew, Biji; Zhao, Yutong; Noth, Imre; Reddy, Sekhar P.; Harijith, Anantha; Usatyuk, Peter V.; Berdyshev, Evgeny V.; Kaminski, Naftali; Zhou, Tong; Zhang, Wei; Zhang, Yanmin; Rehman, Jalees; Kotha, Sainath R.; Gurney, Travis O.; Parinandi, Narasimham L.; Lussier, Yves A.; Garcia, Joe G. N.

2014-01-01

Rationale: Lysocardiolipin acyltransferase (LYCAT), a cardiolipin-remodeling enzyme regulating the 18:2 linoleic acid pattern of mammalian mitochondrial cardiolipin, is necessary for maintaining normal mitochondrial function and vascular development. We hypothesized that modulation of LYCAT expression in lung epithelium regulates development of pulmonary fibrosis. Objectives: To define a role for LYCAT in human and murine models of pulmonary fibrosis. Methods: We analyzed the correlation of LYCAT expression in peripheral blood mononuclear cells (PBMCs) with the outcomes of pulmonary functions and overall survival, and used the murine models to establish the role of LYCAT in fibrogenesis. We studied the LYCAT action on cardiolipin remodeling, mitochondrial reactive oxygen species generation, and apoptosis of alveolar epithelial cells under bleomycin challenge. Measurements and Main Results: LYCAT expression was significantly altered in PBMCs and lung tissues from patients with idiopathic pulmonary fibrosis (IPF), which was confirmed in two preclinical murine models of IPF, bleomycin- and radiation-induced pulmonary fibrosis. LYCAT mRNA expression in PBMCs directly and significantly correlated with carbon monoxide diffusion capacity, pulmonary function outcomes, and overall survival. In both bleomycin- and radiation-induced pulmonary fibrosis murine models, hLYCAT overexpression reduced several indices of lung fibrosis, whereas down-regulation of native LYCAT expression by siRNA accentuated fibrogenesis. In vitro studies demonstrated that LYCAT modulated bleomycin-induced cardiolipin remodeling, mitochondrial membrane potential, reactive oxygen species generation, and apoptosis of alveolar epithelial cells, potential mechanisms of LYCAT-mediated lung protection. Conclusions: This study is the first to identify modulation of LYCAT expression in fibrotic lungs and offers a novel therapeutic approach for ameliorating lung inflammation and pulmonary fibrosis. PMID

Gas Exchange Disturbances Regulate Alveolar Fluid Clearance during Acute Lung Injury

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István Vadász

2017-07-01

Full Text Available Disruption of the alveolar–capillary barrier and accumulation of pulmonary edema, if not resolved, result in poor alveolar gas exchange leading to hypoxia and hypercapnia, which are hallmarks of acute lung injury and the acute respiratory distress syndrome (ARDS. Alveolar fluid clearance (AFC is a major function of the alveolar epithelium and is mediated by the concerted action of apically-located Na+ channels [epithelial Na+ channel (ENaC] and the basolateral Na,K-ATPase driving vectorial Na+ transport. Importantly, those patients with ARDS who cannot clear alveolar edema efficiently have worse outcomes. While hypoxia can be improved in most cases by O2 supplementation and mechanical ventilation, the use of lung protective ventilation settings can lead to further CO2 retention. Whether the increase in CO2 concentrations has deleterious or beneficial effects have been a topic of significant controversy. Of note, both low O2 and elevated CO2 levels are sensed by the alveolar epithelium and by distinct and specific molecular mechanisms impair the function of the Na,K-ATPase and ENaC thereby inhibiting AFC and leading to persistence of alveolar edema. This review discusses recent discoveries on the sensing and signaling events initiated by hypoxia and hypercapnia and the relevance of these results in identification of potential novel therapeutic targets in the treatment of ARDS.

Alveolar Thin Layer Flows and Surfactant Dynamics

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Roumie, Ahmad; Jbaily, Abdulrahman; Szeri, Andrew J.

2017-11-01

Pulmonary surfactants play a vital role in everyday respiration. They regulate surface tension in the lungs by diffusing through the hypophase, a liquid layer that lines the interior surface of the alveoli, and adsorbing to the existing air-fluid interface. This decreases the equilibrium surface tension value by as much as a factor of 3, minimizing breathing effort and preventing lung collapse at the end of exhalation. Given that the hypophase thickness h lies within the range 0.1 μm < h <0.5 μm , and that the average alveolar radius R is 100 μm , for some purposes the hypophase may usefully be modeled as a fluid layer on a flat sheet representing the alveolar wall. Moreover, because of the large aspect ratio, the lubrication approximation can be applied. The aim of the present work is to study the interaction between the straining of the alveolar wall and the fluid flow in the hypophase. The analysis is governed by the relative magnitudes of the time scales of surfactant diffusion, adsorption, desorption, viscous dissipation and sheet straining. Cases of particular interest include non-uniform surfactant concentration at the interface, leading to Marangoni flows and a non-uniform hypophase thickness profile. The analytical formulation and numerical simulations are presented. This work is motivated by a need to understand alveolar deformation during breathing, and to do so in a way that derives from improved understanding of the fluid mechanics of the problem.

Pulmonary alveolar proteinosis versus exogenous lipoid pneumonia showing crazy-paving pattern: Comparison of their clinical features and high-resolution CT findings

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Choi, Hei Kyung; Park, Chang Min; Goo, Jin Mo; Lee, Hyun Ju (Dept. of Radiology, Seoul National Univ. College of Medicine, and Inst. of Radiation Medicine, Seoul National Univ. Medical Research Center, Seoul (Korea)), e-mail: cmpark@radiol.snu.ac.kr

2010-05-15

Background: Although pulmonary alveolar proteinosis (PAP) and exogenous lipoid pneumonia (ELP) require different treatment strategies, both manifest as a crazy-paving pattern on CT and often have similar clinical manifestations and radiologic features. Purpose: To investigate the clinical features and high-resolution computed tomography (HRCT) findings of PAP and ELP showing the crazy-paving pattern. Material and Methods: The clinical features and HRCT findings of eight patients with pathologically proven PAP and six patients with pathologically proven ELP showing the crazy-paving pattern were retrospectively evaluated. Two radiologists analyzed the HRCT findings of PAP and ELP in consensus in terms of the presence, severity, and extent of illdefined centrilobular nodules, consolidations, ground-glass opacities (GGOs), reticulations, and the crazy-paving pattern. Results: With respect to the clinical features of these two diseases, all patients with ELP were retrospectively found to have a history of oil ingestion. In terms of the HRCT findings, ill-defined centrilobular nodules were seen in five of six patients (83%) with ELP, whereas they were not present in any patient with PAP (P=0.003). Consolidation was also more frequently present in patients with ELP (83%) than in those with PAP (11%), which was statistically different (P=0.0265). In terms of the severity and extent, the crazy-paving pattern and reticulations on HRCT were significantly more extensive and severe in patients with PAP than in those with ELP. Conclusion: PAP and ELP with the crazy-paving pattern have several distinctive characteristics with respect to their HRCT findings as well as history of oil ingestion, and can therefore be distinguished from one another

Pulmonary hemorrhage following anabolic agent abuse: Two cases

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Hvid-Jensen, Helene S.; Rasmussen, Finn; Bendstrup, Elisabeth

2016-01-01

Numerous adverse effects follow anabolic agent abuse. Pulmonary hemorrhage is not considered one of them. We present two cases of young male bodybuilders who developed diffuse alveolar bleeding as a result of anabolic steroid abuse. Diffuse alveolar hemorrhage associated with anabolic agent abuse has not been described previously in the literature. Both patients developed acute dyspnea and hemoptysis with consistent radiological findings. In both cases symptoms promptly resolved with cessatio...

Alveolar occupation infiltrations, eosinophilia in peripheral blood and bronchoalveolar lavage

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Hincapie Diaz, Gustavo Adolfo; Yama Mosquera, Erica; Guevara, Jairo

2006-01-01

A case of a patient of 25 years old is shown with the antecedent of no potable water consumption who entered for having pulmonary symptoms, fever, presence of alveolar occupation infiltrations and eosinophilia in peripheral blood treatment with antiparasitary started with a significant improvement of the symptoms, infiltrations and eosinophilia. It is considered eosinophilic pneumonia diagnostic by parasitary infection (Loefffers Syndrome)

Alveolar occupation infiltrations, eosinophilia in peripheral blood and bronchoalveolar lavage

International Nuclear Information System (INIS)

Hincapie Diaz, Gustavo Adolfo; Yama Mosquera, Erica; Guevara, Jairo

2006-01-01

A case of a patient of 25 years old is shown with the antecedent of no potable water consumption who entered for having pulmonary symptoms. Fever, presence of alveolar occupation infiltrations and eosinophilia in peripheral blood a treatment with antiparasitary started with a significant improvement of the symptoms, infiltrations and eosinophilia. it is considered eosinophilic pneumonia diagnostic by parasitary infection (Loeffler's syndrome)

MCPIP1 Regulates Alveolar Macrophage Apoptosis and Pulmonary Fibroblast Activation After in vitro Exposure to Silica.

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Wang, Xingang; Zhang, Yuxia; Zhang, Wei; Liu, Haijun; Zhou, Zewei; Dai, Xiaoniu; Cheng, Yusi; Fang, Shencun; Zhang, Yingming; Yao, Honghong; Chao, Jie

2016-05-01

Silicosis is a fatal and fibrotic pulmonary disease caused by the inhalation of silica. After arriving at the alveoli, silica is ingested by alveolar macrophages (AMOs), in which monocyte chemotactic protein-induced protein 1 (MCPIP1) plays an essential role in controlling macrophage-mediated inflammatory responses. However, the mechanism of action of MCPIP1 in silicosis is poorly understood. Primary rat AMOs were isolated and treated with SiO2 (50 µg/cm(2)). MCPIP1 and AMO activation/apoptosis markers were detected by immunoblotting. MCPIP1 was down-regulated using siRNA in AMOs. The effects of AMOs on fibroblast activation and migration were evaluated using a gel contraction assay, a scratch assay, and a nested collagen matrix migration model. After exposure to SiO2, MCPIP1 was significantly increased in rat AMOs. Activation and apoptosis markers in AMOs were up-regulated after exposure to SiO2 Following siRNA-mediated silencing of MCPIP1 mRNA, the markers of AMO activation and apoptosis were significantly decreased. Rat pulmonary fibroblasts (PFBs) cultured in conditional medium from AMOs treated with MCPIP1 siRNA and SiO2 showed significantly less activation and migration compared with those cultured in conditional medium from AMOs treated with control siRNA and SiO2 CONCLUSION: Our data suggest a vital role for MCPIP1 in AMO apoptosis and PFB activation/migration induced by SiO2. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Cyclophosphamide-induced pulmonary toxicity

International Nuclear Information System (INIS)

Siemann, D.W.; Macler, L.; Penney, D.P.

1986-01-01

Unlike radiation effects, pulmonary toxicity following drug treatments may develop soon after exposure. The dose-response relationship between Cyclophosphamide and lung toxicity was investigated using increased breathing frequency assays used successfully for radiation induced injury. The data indicate that release of protein into the alveolus may play a significant role in Cy induced pulmonary toxicity. Although the mechanism responsible for the increased alveolar protein is as yet not identified, the present findings suggest that therapeutic intervention to inhibit protein release may be an approach to protect the lungs from toxic effects. (UK)

Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

International Nuclear Information System (INIS)

Kelsey, Chris R.; Horwitz, Mitchell E.; Chino, Junzo P.; Craciunescu, Oana; Steffey, Beverly; Folz, Rodney J.; Chao, Nelson J.; Rizzieri, David A.; Marks, Lawrence B.

2011-01-01

Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meier method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.

Pulmonary Artery Size in Interstitial Lung Disease and Pulmonary Hypertension: Association with Interstitial Lung Disease Severity and Diagnostic Utility

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Matthew Chin

2018-06-01

Full Text Available PurposeIt is postulated that ILD causes PA dilatation independent of the presence of pulmonary hypertension (PH, so the use of PA size to screen for PH is not recommended. The aims of this study were to investigate the association of PA size with the presence and severity of ILD and to assess the diagnostic accuracy of PA size for detecting PH.MethodsIncident patients referred to a tertiary PH centre underwent baseline thoracic CT, MRI and right heart catheterisation (RHC. Pulmonary artery diameter was measured on CT pulmonary angiography and pulmonary arterial areas on MRI. A thoracic radiologist scored the severity of ILD on CT from 0 to 4, 0 = absent, 1 = 1–25%, 2 = 26–50%, 3 = 51–75%, and 4 = 76–100% extent of involvement. Receiver operating characteristic analysis and linear regression were employed to assess diagnostic accuracy and independent associations of PA size.Results110 had suspected PH due to ILD (age 65 years (SD 13, M:F 37:73 and 379 had suspected PH without ILD (age 64 years (SD 13, M:F 161:218. CT derived main PA diameter was accurate for detection of PH in patients both with and without ILD - AUC 0.873, p =< 0.001, and AUC 0.835, p =< 0.001, respectively, as was MRI diastolic PA area, AUC 0.897, p =< 0.001, and AUC 0.857, p =< 0.001, respectively Significant correlations were identified between mean pulmonary arterial pressure (mPAP and PA diameter in ILD (r = 0.608, p < 0.001, and non-ILD cohort (r = 0.426, p < 0.001. PA size was independently associated with mPAP (p < 0.001 and BSA (p = 0.001, but not with forced vital capacity % predicted (p = 0.597, Transfer factor of the lungs for carbon monoxide (TLCO % predicted (p = 0.321 or the presence of ILD on CT (p = 0.905. The severity of ILD was not associated with pulmonary artery dilatation (r = 0.071, p = 0.459.ConclusionsPulmonary arterial pressure elevation leads to pulmonary arterial dilation, which is not independently influenced by the presence or severity of

Pulmonary nodules secondary to total parenteral alimentation

International Nuclear Information System (INIS)

Landry, B.A.; Melhem, R.E.

1989-01-01

A seven-year-old male, who had a retroperitoneal alveolar rhabdomyosarcoma and was on total parenteral alimentation (TPN) developed muliple pulmonary nodules, indistinguishable from metastases. These proved to be multiple lipid emboli on open biopsy. (orig.)

Pulmonary hypertension in chronic obstructive pulmonary disease

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Aguirre F, Carlos E; Torres D, Carlos A.

2010-01-01

Pulmonary hypertension (PH) is a relatively common complication of chronic obstructive pulmonary disease (COPD). Its appearance during the course of COPD is associated with a worsened prognosis, due to reduced life expectancy and greater use of health care resources. Although a well-defined lineal relationship has not been shown, the prevalence of PH in patients with COPD is higher in cases characterized by greater obstruction and severity. PH is infrequent in cases of mild and moderate COPD. In cases of COPD, PH is generally mild or moderate, and seldom impairs right ventricular function. In many cases it is not apparent during rest, and manifests itself during exercise. PH can be severe or out of proportion with the severity of COPD. In this situation, the possibility of associated conditions should be explored, although COPD might be the only final explanation. There is scarce knowledge about the prevalence and behavior of PH in patients with COPD residing at intermediate and high altitudes (>2.500 meters above sea level), which is a common situation in Latin America and Asia. PH in COPD is not exclusively related with hypoxia/hypoxaemia and hypercapnia. The mechanical disturbances related with COPD (hyper inflation and high alveolar pressure) and inflammation may prevail as causes of endothelial injury and remodeling of pulmonary circulation, which contribute to increased pulmonary vascular pressure and resistance. The appearance of signs of cor p ulmonale indicates advanced PH. This condition should therefore be suspected early when dyspnoea, hypoxaemia, and impairment of diffusion are not in keeping with the degree of obstruction. PH is confirmed by Doppler echocardiography. Right heart catheterization may be justified in selected cases. Long-term oxygen therapy is the only intervention proven to be temporarily useful. Conventional vasodilators do not produce medium- or long-term improvement and can be detrimental to the ventilation-perfusion relation

Hemorragia Alveolar Difusa - a propósito de um caso clínico de Hemossiderose Pulmonar Idiopática.

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Paula Esteves

1999-09-01

Full Text Available RESUMO: Devido à sua raridade, a Hemorragia Alveolar Difusa (HAD é muitas vezes urn diagnóstico esquecido. Os autores apresentam uma revisião desta entidade a propósito do caso clínico de um homem de 71 anos, internado por febre, tosse seu, falência respiratória progressiva e com o diagnóstico de admissão de pneumonia da comunidade. Os exames efectuados foram compatíveis com HAD e após realização de biópsia pulmonar cirúrgica foi admitido Hemossiderose Pulmonar Idiopática como diagnóstico de exclusão.REV PORT PNEUMOL 1999; V (5: 499-505 ABSTRACT: Due to its rarity, the diffuse alveolar hemorrhage (DAH is very often a forgotten diagnosis. The authors present a revision of this entity, in relation to a clinical case of a 71 years old men, who was admitted b fever, dry cough, progressive respiratory failure and community-acquired pneumonia as admission’s diagnostic. The exams performed suggested DAH and after chirurgical pulmonary biopsy, idiopathic pulmonary hemosiderosis was established by exclusion.REV PORT PNEUMOL 1999; V (5: 499-505 Palavras chave: Hemorragia alveolar, Hemossiderose Pulmonar, Key-words: Alveolar Hemorrhage, Idiopathic Pulmonary Hemosiderosis

Pulmonary tumors induced in the rat by the internal α irradiation; target cells and sensitive cells

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Fritsch, P.; Masse, R.; Nolibe, D.; Metivier, H.; Morin, M.; Lafuma, J.

1977-01-01

Over, 500 rat pulmonary tumors induced by inhalation of various radionuclides have been examined by means of the usual histological methods and ultrastructurally for part of them. Tumor grafts were obtained and several lines have been preserved for several years. The malignity of some varieties: circumscribed epidermoid carcinoma, fibrosarcoma derived from stromareaction, bronchiolo alveolar carcinoma was thus established. It was not possible to establish any relation between the turnover per day and the incidence of pulmonary tumors whatever the correction factor applied taking account of the distribution of the delivered dose. The possibility of showing unapparent lesions of the target cells by grafts of immunodepressed animals suggested that local regulating mechanisms are of particular significance [fr

The experiment of interventional pulmonary lobectomy

International Nuclear Information System (INIS)

You Yufeng; Gan Wanchong; Ke Wei; Ying Wenhua

2006-01-01

Objective: To study the feasibility of interventional pulmonary lobectomy by animal experiment. Methods: Twelve healthy dogs were divided into three groups randomly, with 4 in each. Group A: the target bronchus and alveoli were filled with emulsion of lipiodol and alveolar cells damage liquors and then the target bronchus was occluded with Polymethylmethacrylate (PMMA) . Group B: The target bronchus was only occluded with PMMA. Group C: Pulmonary lobe was resected surgically. Arterial blood gases were measured at the time of pre-procedure and post-procedure and then 1st, 2nd, 3rd and 4th week after the procedure respectively. Chest radiography histology and bacterial culture of tissue of target lung lobe were made after 4 weeks. Results: There was a significant difference in arterial blood-gas among 3 groups pre-procedure in comparison with those of post-procedure immediately (P 0.05) in comparing with 1st, 2nd, 3rd and 4th week after the procedure. Atelectasis was shown radiologically with histological formation of fibrosis of target lung lobe but no bacteria grew in target tissue 4th week after the procedure. There were two cases of lung atelectasis but no pulmonary fibrosis occluded in group B. Conclusions: Interventional pulmonary lobectomy might be obtained after the target bronchus and pulmonary alveoli were filled with emulsion of lipiodol and alveolar cells damage liquors and then the target bronchus was occluded with PMMA. (authors)

In-effort perfusion pulmonary tomo-scintigraphies for pre-surgery evaluation of severe emphysema

International Nuclear Information System (INIS)

Poiseau, E.; Roue, C.; Bonnin, F.; Stievenart, J.L.; Fournier, M.; Bok, B.

1997-01-01

The pulmonary reduction surgery improves the in-effort tolerance of certain severe emphysema, possibly by the compression of zones of adjacent healthy pulmonary parenchyma. Six patients afflicted with severe emphysema (5 M and 1 F, 20 to 63 years old) benefited at each 3 days by an at-rest and in-effort perfusion pulmonary tomo-scintigraphy (PPTS), after a trial interval of 6 minutes. After injection IV of 6 mCi of MAA- 99m Tc, in sitting position, 120 projection images were acquired with a single-head camera on a 128 x 128 matrix, with a high resolution collimator. After reconstruction with a Metz filter, without corrections of attenuations, the coronal and cross sections were recorded on films in a standard procedure. These were visually interpreted by two independent senior physicians. The procedure has been tolerated by all the patients. Differences of pulmonary perfusion occurred at rest in comparison with the in-effort condition in 4 patients. In all the cases concerned were the zones of pulmonary parenchyma appearing as strongly injured in tomodensitometry. The in-effort pulmonary perfusion improves in 3 patients and impairs in one patient. The role of bubble and implied pulmonary diseases in the deterioration of pulmonary function, respectively, is difficult to estimate. The improvement of in-effort pulmonary perfusion could suggest the persistence of functional pulmonary tissue. On the other side, its deterioration could express the compressive character of bubbles and thus could be an indicator of severity. The observation during this pilot study of the differences between at-rest and in-effort pulmonary perfusion urges utilisation of a tool of analysis of image superposition (PPTS and scans) to study in a group of patients the correlations between the perfusion variations and the post-surgery development, in order to know better the pathophysiology of diseases and select better the patients

Cytokine–Ion Channel Interactions in Pulmonary Inflammation

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Hamacher, Jürg; Hadizamani, Yalda; Borgmann, Michèle; Mohaupt, Markus; Männel, Daniela Narcissa; Moehrlen, Ueli; Lucas, Rudolf; Stammberger, Uz

2018-01-01

The lungs conceptually represent a sponge that is interposed in series in the bodies’ systemic circulation to take up oxygen and eliminate carbon dioxide. As such, it matches the huge surface areas of the alveolar epithelium to the pulmonary blood capillaries. The lung’s constant exposure to the exterior necessitates a competent immune system, as evidenced by the association of clinical immunodeficiencies with pulmonary infections. From the in utero to the postnatal and adult situation, there is an inherent vital need to manage alveolar fluid reabsorption, be it postnatally, or in case of hydrostatic or permeability edema. Whereas a wealth of literature exists on the physiological basis of fluid and solute reabsorption by ion channels and water pores, only sparse knowledge is available so far on pathological situations, such as in microbial infection, acute lung injury or acute respiratory distress syndrome, and in the pulmonary reimplantation response in transplanted lungs. The aim of this review is to discuss alveolar liquid clearance in a selection of lung injury models, thereby especially focusing on cytokines and mediators that modulate ion channels. Inflammation is characterized by complex and probably time-dependent co-signaling, interactions between the involved cell types, as well as by cell demise and barrier dysfunction, which may not uniquely determine a clinical picture. This review, therefore, aims to give integrative thoughts and wants to foster the unraveling of unmet needs in future research. PMID:29354115

Studying the Effects of Fasting during Ramadan on Pulmonary Functioning Test and Asthma Severity

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Seyyed Hassan Adeli

2015-03-01

Full Text Available Background and Objectives: Studies have shown that fasting can have an impact on the course and severity of chronic diseases. There are a few studies on the association of fasting and asthma. Therefore, this study has been conducted with the purpose of examining the effects of fasting on asthma severity and pulmonary functioning tests. Methods: 30 patients with asthma who attended a pulmonology clinic in Qom were enrolled in this study. The severity of patients’ asthma has been studied by questionnaire and spirometry of pulmonary functioning in the month of Shaban, Ramadan and Shawwal. The results of Asthma Control Questionnaire and the pulmonary functioning tests in three months have been compared. Results: The average age of patients was 43.42 years and 43.3% of patients were males. The Average score for asthma severity questionnaire in three months were 20.4, 21 and 20.17 respectively. Statistically, there haven’t been any significant differences between the results of pulmonary functioning test and asthma severity before Ramadan (Shaban, during Ramadan and after that (Shawwal. Conclusion: The findings of this study showed that fasting in patients with asthma has no effect on pulmonary function and asthma severity.

Cigarette smoking decreases global microRNA expression in human alveolar macrophages.

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Joel W Graff

Full Text Available Human alveolar macrophages are critical components of the innate immune system. Cigarette smoking-induced changes in alveolar macrophage gene expression are linked to reduced resistance to pulmonary infections and to the development of emphysema/COPD. We hypothesized that microRNAs (miRNAs could control, in part, the unique messenger RNA (mRNA expression profiles found in alveolar macrophages of cigarette smokers. Activation of macrophages with different stimuli in vitro leads to a diverse range of M1 (inflammatory and M2 (anti-inflammatory polarized phenotypes that are thought to mimic activated macrophages in distinct tissue environments. Microarray mRNA data indicated that smoking promoted an "inverse" M1 mRNA expression program, defined by decreased expression of M1-induced transcripts and increased expression of M1-repressed transcripts with few changes in M2-regulated transcripts. RT-PCR arrays identified altered expression of many miRNAs in alveolar macrophages of smokers and a decrease in global miRNA abundance. Stratification of human subjects suggested that the magnitude of the global decrease in miRNA abundance was associated with smoking history. We found that many of the miRNAs with reduced expression in alveolar macrophages of smokers were predicted to target mRNAs upregulated in alveolar macrophages of smokers. For example, miR-452 is predicted to target the transcript encoding MMP12, an important effector of smoking-related diseases. Experimental antagonism of miR-452 in differentiated monocytic cells resulted in increased expression of MMP12. The comprehensive mRNA and miRNA expression profiles described here provide insight into gene expression regulation that may underlie the adverse effects cigarette smoking has on alveolar macrophages.

Intermittent Hypoxia Increases the Severity of Bleomycin-Induced Lung Injury in Mice

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Thomas Gille

2018-01-01

Full Text Available Background. Severe obstructive sleep apnea (OSA with chronic intermittent hypoxia (IH is common in idiopathic pulmonary fibrosis (IPF. Here, we evaluated the impact of IH on bleomycin- (BLM- induced pulmonary fibrosis in mice. Methods. C57BL/6J mice received intratracheal BLM or saline and were exposed to IH (40 cycles/hour; FiO2 nadir: 6%; 8 hours/day or intermittent air (IA. In the four experimental groups, we evaluated (i survival; (ii alveolar inflammation, pulmonary edema, lung oxidative stress, and antioxidant enzymes; (iii lung cell apoptosis; and (iv pulmonary fibrosis. Results. Survival at day 21 was lower in the BLM-IH group (p<0.05. Pulmonary fibrosis was more severe at day 21 in BLM-IH mice, as assessed by lung collagen content (p=0.02 and histology. At day 4, BLM-IH mice developed a more severe neutrophilic alveolitis, (p<0.001. Lung oxidative stress was observed, and superoxide dismutase and glutathione peroxidase expression was decreased in BLM-IH mice (p<0.05 versus BLM-IA group. At day 8, pulmonary edema was observed and lung cell apoptosis was increased in the BLM-IH group. Conclusion. These results show that exposure to chronic IH increases mortality, lung inflammation, and lung fibrosis in BLM-treated mice. This study raises the question of the worsening impact of severe OSA in IPF patients.

[Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease].

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Barberán, José; Mensa, José

2014-01-01

Invasive pulmonary aspergillosis (IPA) is a common infection in immunocompromised patients with hematological malignancies or allogenic stem cell transplantation, and is less frequent in the context of chronic obstructive pulmonary disease (COPD). Mucociliary activity impairment, immunosuppression due to the inhibition of alveolar macrophages and neutrophils by steroids, and receiving broad-spectrum antibiotics, play a role in the development of IPA in COPD patients. Colonized patients or those with IPA are older, with severe CODP stage (GOLD≥III), and have a higher number of comorbidities. The mortality rate is high due to the fact that having a definitive diagnosis of IPA in COPD patients is often difficult. The main clinical and radiological signs of IPA in these types of patients are non-specific, and tissue samples for definitive diagnosis are often difficult to obtain. The poor prognosis of IPA in COPD patients could perhaps be improved by faster diagnosis and prompt initiation of antifungal treatment. Some tools, such as scales and algorithms based on risk factors of IPA, may be useful for its early diagnosis in these patients. Copyright © 2014 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Small-for-Size Liver Transplantation Increases Pulmonary Injury in Rats: Prevention by NIM811

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Qinlong Liu

2012-01-01

Full Text Available Pulmonary complications after liver transplantation (LT often cause mortality. This study investigated whether small-for-size LT increases acute pulmonary injury and whether NIM811 which improves small-for-size liver graft survival attenuates LT-associated lung injury. Rat livers were reduced to 50% of original size, stored in UW-solution with and without NIM811 (5 μM for 6 h, and implanted into recipients of the same or about twice the donor weight, resulting in half-size (HSG and quarter-size grafts (QSG, respectively. Liver injury increased and regeneration was suppressed after QSG transplantation as expected. NIM811 blunted these alterations >75%. Pulmonary histological alterations were minimal at 5–18 h after LT. At 38 h, neutrophils and monocytes/macrophage infiltration, alveolar space exudation, alveolar septal thickening, oxidative/nitrosative protein adduct formation, and alveolar epithelial cell/capillary endothelial apoptosis became overt in the lungs of QSG recipients, but these alterations were mild in full-size and HSG recipients. Liver pretreatment with NIM811 markedly decreased pulmonary injury in QSG recipients. Hepatic TNFα and IL-1β mRNAs and pulmonary ICAM-1 expression were markedly higher after QSG transplantation, which were all decreased by NIM811. Together, dysfunctional small-for-size grafts produce toxic cytokines, leading to lung inflammation and injury. NIM811 decreased toxic cytokine formation, thus attenuating pulmonary injury after small-for-size LT.

Treatment for unstable pulmonary sequestration injury in patient with severe blunt trauma: A case report.

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Hiraki, Sakiko; Okada, Yohei; Arai, Yusuke; Ishii, Wataru; Iiduka, Ryoji

2017-08-01

Pulmonary sequestration is a congenital malformation characterized by nonfunctioning tissue not communicating with the tracheobronchial tree. As the blood pressure in the artery feeding the sequestrated lung tissue is higher than that in the normal pulmonary artery, the risk of massive hemorrhage in pulmonary sequestration is high. We herein present the first case of a severe blunt trauma patient with unstable pulmonary sequestration injury. The mechanism of pulmonary sequestration injury is vastly different than that of injury to normal lung. We suggest that proximal feeding artery embolization should be performed before surgical intervention in patients with massive hemorrhage of pulmonary sequestration due to severe chest trauma.

Inferior alveolar nerve block: Alternative technique.

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Thangavelu, K; Kannan, R; Kumar, N Senthil

2012-01-01

Inferior alveolar nerve block (IANB) is a technique of dental anesthesia, used to produce anesthesia of the mandibular teeth, gingivae of the mandible and lower lip. The conventional IANB is the most commonly used the nerve block technique for achieving local anesthesia for mandibular surgical procedures. In certain cases, however, this nerve block fails, even when performed by the most experienced clinician. Therefore, it would be advantageous to find an alternative simple technique. The objective of this study is to find an alternative inferior alveolar nerve block that has a higher success rate than other routine techniques. To this purpose, a simple painless inferior alveolar nerve block was designed to anesthetize the inferior alveolar nerve. This study was conducted in Oral surgery department of Vinayaka Mission's dental college Salem from May 2009 to May 2011. Five hundred patients between the age of 20 years and 65 years who required extraction of teeth in mandible were included in the study. Out of 500 patients 270 were males and 230 were females. The effectiveness of the IANB was evaluated by using a sharp dental explorer in the regions innervated by the inferior alveolar, lingual, and buccal nerves after 3, 5, and 7 min, respectively. This study concludes that inferior alveolar nerve block is an appropriate alternative nerve block to anesthetize inferior alveolar nerve due to its several advantages.

Treatment for unstable pulmonary sequestration injury in patient with severe blunt trauma: A case report

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Sakiko Hiraki

2017-08-01

Full Text Available Case: Pulmonary sequestration is a congenital malformation characterized by nonfunctioning tissue not communicating with the tracheobronchial tree. As the blood pressure in the artery feeding the sequestrated lung tissue is higher than that in the normal pulmonary artery, the risk of massive hemorrhage in pulmonary sequestration is high. We herein present the first case of a severe blunt trauma patient with unstable pulmonary sequestration injury. Outcome and conclusion: The mechanism of pulmonary sequestration injury is vastly different than that of injury to normal lung. We suggest that proximal feeding artery embolization should be performed before surgical intervention in patients with massive hemorrhage of pulmonary sequestration due to severe chest trauma. Keywords: Blunt trauma, Coil embolization, Massive hemorrhage, Pulmonary sequestration

Proinflammatory and anti-inflammatory cytokine balance in gasoline exhaust induced pulmonary injury in mice.

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Sureshkumar, Veerapandian; Paul, Bholanath; Uthirappan, Mani; Pandey, Renu; Sahu, Anand Prakash; Lal, Kewal; Prasad, Arun Kumar; Srivastava, Suresh; Saxena, Ashok; Mathur, Neeraj; Gupta, Yogendra Kumar

2005-03-01

Proinflammatory and anti-inflammatory cytokine balance and associated changes in pulmonary bronchoalveolar lavage fluid (BALF) of unleaded gasoline exhaust (GE) exposed mice were investigated. Animals were exposed to GE (1 L/min of GE mixed with 14 L/min of compressed air) using a flow-past, nose-only, dynamic inhalation exposure chamber for different durations (7, 14, and 21 days). The particulate content of the GE was found to be 0.635, +/-0.10 mg PM/m3. Elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were observed in BALF of GE-exposed mice, but interleukin 1beta(IL-1beta) and the anti-inflammatory cytokine interleukin-10 (IL-10) remained unaffected. GE induced higher activities of alkaline phosphatase (ALP), gamma-glutamyl transferase (gammaGT), and lactate dehydrogenase (LDH) in the BALF, indicating Type II alveolar epithelial cell injury, Clara-cell injury, and general toxicity, respectively. Total protein in the BALF increased after 14 and 21 days of exposure, indicating enhanced alveolar-capillary permeability. However, the difference in the mean was found statistically insignificant in comparison to the compressed air control. Total cell count in the BALF of GE-exposed mice ranged between 0.898 and 0.813x10(6) cells/ml, whereas the compressed air control showed 0.65x10(6) cells/mL. The histopathological changes in GE-exposed lung includes perivascular, and peribronchiolar cuffing of mononuclear cells, migration of polymorphonuclear cells in the alveolar septa, alveolar thickening, and mild alveolar edematous changes indicating inflammation. The shift in pro- and anti-inflammatory cytokine balance and elevation of the pulmonary marker enzymes indicate toxic insult of GE. This study will help in our understanding of the mechanism of pulmonary injury by GE in the light of cytokine profiles, pulmonary marker enzymes, and lung architecture.

Pulmonary emphysema induced by methylphenidate: experimental study.

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Rapello, Gabriel Victor Guimarães; Antoniolli, Andréia; Pereira, Daniel Martins; Facco, Gilberto; Pêgo-Fernandes, Paulo Manuel; Pazetti, Rogério

2015-01-01

Methylphenidate is the most widely used drug for treating attention deficit hyperactivity disorder. However, it has important side effects, such as abdominal pain, insomnia, anorexia and loss of appetite, and also some cases of early severe emphysema after drug abuse have been reported. Our aim was to investigate the development of pulmonary emphysema in rats that were subjected to different doses of methylphenidate. Experimental study carried out at the laboratory of a public university. Eighteen male Wistar rats were divided into three groups: control (0.9% saline solution); MP 0.8 (methylphenidate, 0.8 mg/kg); MP 1.2 (methylphenidate, 1.2 mg/kg). After 90 days of daily gavage, the animals were sacrificed and lung tissue samples were prepared for analysis on the mean alveolar diameter (Lm). The Lm was greater in MP 0.8 (47.91 ± 3.13; P pulmonary emphysema.

Clinical studies of alveolar-capillary permeability using technetium-99m DTPA aerosol

International Nuclear Information System (INIS)

Sundram, F.X.

1995-01-01

Soluble radioaerosols such as technetium-99m diethylene triamine pentacetate (DTPA) permit simple quantitative studies of alveolar-capillary permeability to be performed, since the submicronic aerosols are deposited mainly at the lung periphery and are cleared across the alveolar-capillary membrane. Regional alterations in permeability can also be noted using this radionuclide technique. We have measured the pulmonary epithelial permeability in normal subjects and the alteration in smokers, glue-sniffers, patients with inhalation burns, chronic obstructive pulmonary disease (COPD) and patients with lung metastases from thyroid cancer treated with radioiodine 131 I. In the normal volunteers, the time taken for 50% of inhaled 99m Tc DTPA to be cleared from the lungs (T1/2) was 66 minutes±1 sd of 12 mins. The smokers had a mean T1/2 of 20 mins±1 sd 4 min. In the hard-core glue-sniffing group, the majority were smokers who had stopped smoking and glue-sniffing for periods varying from 1 day to 42 days, and it was possible to note the changes in clearance times against period of abstinence. In the patients with inhalation burns, there was change in lung clearance arising from pulmonary epithelial damage; these patients showed increased rate of clearance (short T1/2) with mean T1/2 of 36 min±1 sd of 11 mins, while the retention images revealed regional lung damage in moderately severe inhalation burns. Twenty-four patients with COPD had inhalation scans done with Tc-99m tin colloid radioaerosol, and these images were compared with the perfusion lung scans done with 99m Tc macroaggregated albumin (MAA); in general the perfusion images matched the defects noted in the inhalation scans. The 99m Tc DTPA clearance rate in these patients was normal i.e. T1/2=78±14 mins. In the thyroid cancer patients with lung metastases, who had high doses of radioiodine treatment, the T1/2 values were normal or prolonged slightly, mean T1/2=76 min±23. (author)

Primary pulmonary sarcoma in a rhesus monkey after inhalation of plutonium dioxide

International Nuclear Information System (INIS)

Hahn, F.F.; Brooks, A.L.; Mewhinney, J.A.

1987-01-01

A pulmonary fibrosarcoma of bronchial origin was discovered in a Rhesus monkey that died of pulmonary fibrosis 9 years after inhalation of plutonium-239 dioxide and with a radiation dose to lung of 1400 rad (14 Gy). It grew around the major bronchus of the right cardiac lung lobe and extended into the bronchial lumen and into surrounding pulmonary parenchyma. It also readily invaded muscular pulmonary arteries, resulting in infarction and scarring in the right cardiac lobe. Despite this aggressive growth, the tumor did not metastasize. The primary cause of death was severe pulmonary fibrosis involving the alveolar septa and and perivascular and peribronchial interstitium. Bullous or pericitrical emphysema was prominent. The initial lung burden of plutonium in this monkey was 270 nCi (10 kBq) which is equivalent to approximately 500 times the maximum permissible lung burden for man on a radioactivity per unit body weight basis. The time-dose relationship for survival is consistent with that of dogs and baboons that inhaled plutonium dioxide and died with lung tumors

Computed tomographic pulmonary angiography in the assessment of severity of chronic thromboembolic pulmonary hypertension and right ventricular dysfunction

International Nuclear Information System (INIS)

Liu Min; Ma Zhanhong; Guo Xiaojuan; Zhang Hongxia; Yang Yuanhua; WangChen

2011-01-01

Purpose: The aim was to investigate the role of computed tomographic pulmonary angiography (CTPA) in the assessment of severity and right ventricular function in chronic thromboembolic pulmonary hypertension (CTEPH). Materials and methods: Clinical and radiological data of 56 patients with CTEPH January 2006–October 2009 were retrospectively reviewed in the present study. All patients received CTPA with a 64-row CT using the retrospective ECG-Gated mode before digital subtraction pulmonary angiography and right-heart catheterization. CTPA findings including Right Ventricular diameter (RVd) and left ventricular diameter (LVd) were measured at the end diastole. CT Pulmonary Artery Obstruction Indexes including Qanadli Index and Mastora Index were used in the assessment of severity of pulmonary arterial obstruction. Hemodynamic parameters and pulmonary hypertension classification were evaluated by right-heart catheterization in all patients. Right ventricular function was measured with echocardiography in 49 patients. Results: Qanadli Index and Mastora Index respectively were (37.93 ± 14.74)% and (30.92 ± 16.91)%, which showed a significant difference (Z = −5.983, P = 0.000) and a good correlation (r = 0.881, P = 0.000). Neither Qanadli nor Mastora Index correlated with pulmonary hypertension classification (r = −0.009, P = 0.920) or New York Heart Association heart function classification (r = −0.031, P = 0.756). Neither Qanadli nor Mastora Index correlated with any echocardiographic right ventricular parameters (P > 0.05), while RVd/LVd by CTPA correlated with echocardiographic right ventricular functional parameters (P 2 . CTPA findings correlated with hemodynamic variables. Backward linear regression analysis revealed that the RVd/LVd, Right Ventricular Anterior Wall Thickness (RVAWT), Main Pulmonary Artery trunk diameter (MPAd) were shown to be independently associated with mean Pulmonary Artery Pressure (mPAP) levels (model: r 2 = 0.351, P = 0.025; RVd

Multibreath alveolar oxygen tension imaging.

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Clapp, Justin; Hamedani, Hooman; Kadlecek, Stephen; Xin, Yi; Shaghaghi, Hoora; Siddiqui, Sarmad; Rossman, Milton D; Rizi, Rahim R

2016-10-01

This study tested the ability of a multibreath hyperpolarized HP (3) He MRI protocol to increase the accuracy of regional alveolar oxygen tension (PA O2 ) measurements by lessening the influence of gas-flow artifacts. Conventional single-breath PA O2 measurement has been susceptible to error induced by intervoxel gas flow, particularly when used to study subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD). Both single-breath and multibreath PA O2 imaging schemes were implemented in seven human subjects (one healthy, three asymptomatic smokers, and three COPD). The number and location of voxels with nonphysiologic PA O2 values generated by intervoxel gas flow were compared between the two protocols. The multibreath scheme resulted in a significantly lower total percentage of nonphysiologic PA O2 values (6.0%) than the single-breath scheme (13.7%) (P = 0.006). PA O2 maps showed several patterns of gas-flow artifacts that were present in the single-breath protocol but mitigated by the multibreath approach. Multibreath imaging also allowed for the analysis of slow-filling areas that presented no signal after a single breath. A multibreath approach enhances the accuracy and completeness of noninvasive PA O2 measurement by significantly lessening the proportion of nonphysiologic values generated by intervoxel gas flow. Magn Reson Med 76:1092-1101, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages.

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Ueno, Manabu; Maeno, Toshitaka; Nishimura, Satoshi; Ogata, Fusa; Masubuchi, Hiroaki; Hara, Kenichiro; Yamaguchi, Kouichi; Aoki, Fumiaki; Suga, Tatsuo; Nagai, Ryozo; Kurabayashi, Masahiko

2015-03-10

Alveolar macrophages play a crucial role in the pathogenesis of emphysema, for which there is currently no effective treatment. Bisphosphonates are widely used to treat osteoclast-mediated bone diseases. Here we show that delivery of the nitrogen-containing bisphosphonate alendronate via aerosol inhalation ameliorates elastase-induced emphysema in mice. Inhaled, but not orally ingested, alendronate inhibits airspace enlargement after elastase instillation, and induces apoptosis of macrophages in bronchoalveolar fluid via caspase-3- and mevalonate-dependent pathways. Cytometric analysis indicates that the F4/80(+)CD11b(high)CD11c(mild) population characterizing inflammatory macrophages, and the F4/80(+)CD11b(mild)CD11c(high) population defining resident alveolar macrophages take up substantial amounts of the bisphosphonate imaging agent OsteoSense680 after aerosol inhalation. We further show that alendronate inhibits macrophage migratory and phagocytotic activities and blunts the inflammatory response of alveolar macrophages by inhibiting nuclear factor-κB signalling. Given that the alendronate inhalation effectively induces apoptosis in both recruited and resident alveolar macrophages, we suggest this strategy may have therapeutic potential for the treatment of emphysema.

A novel image processing technique for 3D volumetric analysis of severely resorbed alveolar sockets with CBCT.

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Manavella, Valeria; Romano, Federica; Garrone, Federica; Terzini, Mara; Bignardi, Cristina; Aimetti, Mario

2017-06-01

The aim of this study was to present and validate a novel procedure for the quantitative volumetric assessment of extraction sockets that combines cone-beam computed tomography (CBCT) and image processing techniques. The CBCT dataset of 9 severely resorbed extraction sockets was analyzed by means of two image processing software, Image J and Mimics, using manual and automated segmentation techniques. They were also applied on 5-mm spherical aluminum markers of known volume and on a polyvinyl chloride model of one alveolar socket scanned with Micro-CT to test the accuracy. Statistical differences in alveolar socket volume were found between the different methods of volumetric analysis (Psockets showed more accurate results, excellent inter-observer similarity and increased user friendliness. The clinical application of this method enables a three-dimensional evaluation of extraction socket healing after the reconstructive procedures and during the follow-up visits.

Pulmonary microRNA profiling: implications in upper lobe predominant lung disease.

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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

Biological, pathobiological and bioclinical bases of pulmonary surfactant metabolism in the human species

International Nuclear Information System (INIS)

Garcia, Alfonso; Ojeda, Paulina

2008-01-01

The surfactant metabolism dysfunction pulmonary (SMDP), classically termed as Pulmonary Alveolar Proteinosis (PAP) are a unusual respiratory disorder characterized by abundant and excessive accumulation of surfactant-derived phospholipids and protein components in the pulmonary alveoli and distal airways, with disturbances associated secondary of pulmonary gas exchange and engendering respiratory insufficiency. At least three general pathophysiologic mechanisms may lead to the characteristic feature of PAP: Primary (idiopathic, essential, acquired or adult), secondary and congenital.

Acute exacerbation of idiopathic pulmonary fibrosis triggered by Aspergillus empyema

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Atsushi Suzuki

Full Text Available Acute exacerbation (AE is a severe and life-threatening complication of idiopathic pulmonary fibrosis (IPF. In 2016, the definition and diagnostic criteria for AE-IPF were updated by an international working group. The new definition includes any acute, clinically significant respiratory deterioration (both idiopathic and triggered events characterized by evidence of new widespread alveolar abnormality in patients with IPF. There are no currently proven beneficial management strategies for idiopathic and triggered AE-IPF. This is the first report describing AE-IPF triggered by Aspergillus empyema, which was improved by a combination of corticosteroid, systemic antifungal therapy, local antifungal therapy, and additional pharmacological therapies. Future research may reveal optimal strategies for both idiopathic and triggered AE-IPF. Keywords: Idiopathic pulmonary fibrosis, Acute exacerbation, AE-IPF, Triggered AE, Aspergillus infection

Fatal acute pulmonary injury associated with everolimus.

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Depuydt, Pieter; Nollet, Joke; Benoit, Dominique; Praet, Marleen; Caes, Frank

2012-03-01

To report a case of fatal alveolar hemorrhage associated with the use of everolimus in a patient who underwent a solid organ transplant. In a 71-year-old cardiac transplant patient, cyclosporine was replaced with everolimus because of worsening renal function. Over the following weeks, the patient developed nonproductive cough and increasing dyspnea. His condition deteriorated to acute respiratory failure with hemoptysis, requiring hospital admission. Bilateral patchy alveolar infiltrates were apparent on chest X-ray and computed tomography. Cardiac failure was ruled out and empiric antimicrobial therapy was initiated. Additional extensive workup could not document opportunistic infection. Everolimus was discontinued and high-dose corticosteroid therapy was initiated. Despite this, the patient required invasive mechanical ventilation and died because of refractory massive hemoptysis. Autopsy revealed diffuse alveolar hemorrhage. Everolimus is a mammalian target of rapamycin inhibitor approved for use as an immunosuppressant and antineoplastic agent. Its main advantage over calcineurin inhibitors (tacrolimus and cyclosporine) is a distinct safety profile. Although it has become clear that everolimus induces pulmonary toxicity more frequently than initially thought, most published cases thus far represented mild and reversible disease, and none was fatal. Here, we report a case of pulmonary toxicity developing over weeks following the introduction of everolimus, in which a fatal outcome could not be prevented by drug withdrawal and corticosteroid treatment. The association of everolimus and this syndrome was probable according to the Naranjo probability scale. This case indicates that with the increasing use of everolimus, clinicians should be aware of the rare, but life-threatening manifestation of pulmonary toxicity.

Low pulmonary artery flush perfusion pressure combined with high positive end-expiratory pressure reduces oedema formation in isolated porcine lungs

International Nuclear Information System (INIS)

Schumann, Stefan; Schließmann, Stephan J; Wagner, Giskard; Goebel, Ulrich; Priebe, Hans-Joachim; Guttmann, Josef; Kirschbaum, Andreas

2010-01-01

Flush perfusion of the pulmonary artery with organ protection solution is a standard procedure before lung explantation. However, rapid flush perfusion may cause pulmonary oedema which is deleterious in the lung transplantation setting. In this study we tested the hypotheses that high pulmonary perfusion pressure contributes to the development of pulmonary oedema and positive end-expiratory pressure (PEEP) counteracts oedema formation. We expected oedema formation to increase weight and decrease compliance of the lungs on the basis of a decrease in alveolar volume as fluid replaces alveolar air spaces. The pulmonary artery of 28 isolated porcine lungs was perfused with a low-potassium dextrane solution at low (mean 27 mmHg) or high (mean 40 mmHg) pulmonary artery pressure (PAP) during mechanical ventilation at low (4 cmH 2 O) or high (8 cmH 2 O) PEEP, respectively. Following perfusion and storage, relative increases in lung weight were smaller (p < 0.05) during perfusion at low PAP (62 ± 32% and 42 ± 26%, respectively) compared to perfusion at high PAP (133 ± 54% and 87 ± 30%, respectively). Compared to all other PAP–PEEP combinations, increases in lung weight were smallest (44 ± 9% and 27 ± 12%, respectively), nonlinear intratidal lung compliance was largest (46% and 17% respectively, both p < 0.05) and lung histology showed least infiltration of mononuclear cells in the alveolar septa, and least alveolar destruction during the combination of low perfusion pressure and high PEEP. The findings suggest that oedema formation during pulmonary artery flush perfusion in isolated and ventilated lungs can be reduced by choosing low perfusion pressure and high PEEP. PAP–PEEP titration to minimize pulmonary oedema should be based on lung mechanics and PAP monitoring

Pulmonary rehabilitation and severe exacerbations of COPD: solution or white elephant?

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William D-C. Man

2015-10-01

Full Text Available Hospitalisations for severe exacerbations of chronic obstructive pulmonary disease are associated with significant physical and psychological consequences including an increase in symptom severity, severe reductions in physical activity, a deleterious effect on skeletal muscle, impaired exercise tolerance/ability to self-care, decline in quality of life, and increased anxiety and depression. As these consequences are potentially amenable to exercise training, there is a clear rationale for pulmonary rehabilitation in the peri/post-exacerbation setting. Although a 2011 Cochrane review was overwhelmingly positive, subsequent trials have shown less benefit and real-life observational studies have revealed poor acceptability. Qualitative studies have demonstrated that the patient experience is a determining factor while the presence of comorbidities may influence referral, adherence and response to pulmonary rehabilitation. Systematic reviews of less supervised interventions, such as self-management, have shown limited benefits in the post-exacerbation setting. The recent update of the Cochrane review of peri-exacerbation pulmonary rehabilitation showed that benefits were associated with the “comprehensive” nature of the intervention (the number of sessions received, the intensity of exercise training and education delivered, and the degree of supervision but implementation is demanding. The challenge is to develop interventions that are deliverable and acceptable around the time of an acute exacerbation but also deliver the desired clinical impact.

Reconstruction of a Severely Atrophied Alveolar Ridge by Computer-Aided Gingival Simulation and 3D-Printed Surgical Guide: A Case Report.

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Song, In-Seok; Lee, Mi-Ran; Ryu, Jae-Jun; Lee, Ui-Lyong

Dental implants positioned in severely atrophied anterior maxillae require esthetic or functional compromises. This case report describes the rehabilitation of a severely atrophied alveolar ridge with a three-dimensional (3D) computer-aided design/computer-aided manufacture (CAD/CAM) surgical guide. A 50-year-old woman had a severely atrophied anterior maxilla with unfavorably positioned dental implants. Functional and esthetic prosthodontic restoration was difficult to achieve. An anterior segmental osteotomy was planned to reposition the dental implants. A 3D surgical guide was designed for precise relocation of the segment. The surgical guide firmly grasped the impression copings of the dental implants, minimizing surgical errors. Three-dimensional gingival simulation was used preoperatively to estimate the appropriate position of the gingiva. Rigid fixation to the surrounding bone allowed immobilization of the implant-bone segment. Satisfactory esthetic and functional outcomes were attained 6 months after surgery. Finally, a severely atrophied alveolar ridge with unfavorably positioned dental implants was recovered with minimal esthetic and functional deterioration using gingival simulation and a 3D CAD/CAM surgical guide.

Plasma Vascular Endothelial Growth Factor Concentration and Alveolar Nitric Oxide as Potential Predictors of Disease Progression and Mortality in Idiopathic Pulmonary Fibrosis

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Jalpa Kotecha

2016-09-01

Full Text Available Background: Declining lung function signifies disease progression in idiopathic pulmonary fibrosis (IPF. Vascular endothelial growth factor (VEGF concentration is associated with declining lung function in 6 and 12-month studies. Alveolar nitric oxide concentration (CANO is increased in patients with IPF, however its significance is unclear. This study investigated whether baseline plasma VEGF concentration and CANO are associated with disease progression or mortality in IPF. Methods: 27 IPF patients were studied (maximum follow-up 65 months. Baseline plasma VEGF concentration, CANO and pulmonary function tests (PFTs were measured. PFTs were performed the preceding year and subsequent PFTs and data regarding mortality were collected. Disease progression was defined as one of: death, relative decrease of ≥10% in baseline forced vital capacity (FVC % predicted, or relative decrease of ≥15% in baseline single breath diffusion capacity of carbon monoxide (TLCO-SB % predicted. Results: Plasma VEGF concentration was not associated with progression-free survival or mortality. There was a trend towards shorter time to disease progression and death with higher CANO. CANO was significantly higher in patients with previous declining versus stable lung function. Conclusion: The role of VEGF in IPF remains uncertain. It may be of value to further investigate CANO in IPF.

Clinical significance of gallium-67 scintigraphy in assessing pulmonary lesions of sarcoidosis and idiopathic pulmonary fibrosis

International Nuclear Information System (INIS)

Fujishima, Seitaro; Kanazawa, Minoru; Yamasawa, Fumihiro; Kubo, Atsushi; Hashimoto, Shozo; Yokoyama, Tetsuro

1992-01-01

To evaluate whether one can predict the course and prognosis of interstitial lung diseases from lung gallium-67 ( 67 Ga) uptake, we studied 31 subjects with sarcoidosis and 28 with idiopathic pulmonary fibrosis (IPF) retrospectively. We quantified the lung 67 Ga uptake using posterior scans by Line's method, and calculated a visual index (VI). The normal range of 67 Ga uptake was defined as less than 65 VI values, obtained from the 95 percent confidence interval of the control subjects. All subjects with stage I sarcoidosis, having only bilateral hilar lymphadenopathy (BHL) on chest X-ray, revealed normal lung 67 Ga uptake. Fifty percent of patients with stage II sarcoidosis, with both BHL and pulmonary involvement on chest X-ray, showed increased lung 67 Ga uptake. The patients with increased lung 67 Ga uptake showed decreased percent vital capacity and increased alveolar-arterial oxygen tension difference, but none of them showed clinical deterioration during the follow-up period of more than 6 months. Fifty-four percent of subjects with IPF sowed increased lung 67 Ga uptake. But there was no difference between the subgroups with normal and increased lung 67 Ga uptake with respect to the severity of dyspnea, percent vital capacity, arterial oxygen tension, or alveolar-arterial oxygen tension difference. There was also no difference between the two subgroups of IPF in the cumulative percent survival after either the onset of symptoms or the 67 Ga scintigram. We conclude that lung 67 Ga uptake was not able to predict the clinical course or the prognosis of patients with sarcoidosis and IPF. (author)

Pulmonary toxicity of cytostatic drugs: cell kinetics

International Nuclear Information System (INIS)

Witschi, H.; Godfrey, G.; Frome, E.; Lindenschmidt, R.C.

1987-01-01

Mice were treated with three cytostatic drugs: cyclophosphamide, busulfan, or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The alveolar labeling index was measured following drug administration with a pulse of 3 H-labeled thymidine and autoradiography. In cyclophosphamide-treated animals, peak alveolar cell proliferation was seen 5 days after injection of the drug. In animals treated with busulfan or BCNU, proliferation was even more delayed (occurring 2-3 weeks after administration). In contrast, with oleic acid, the highest alveolar cell labeling was found 2 days after intravenous administration. In animals exposed to a cytostatic drug, proliferation of type II alveolar cells was never a prominent feature whereas in animals treated with oleic acid there was an initial burst of type II cell proliferation. It is concluded that the patterns of pulmonary repair vary between chemicals designed to interfere with DNA replication as compared to agents which produce acute lung damage such as oleic acid

Pulmonary perfusion scintigraphy in the evaluation of the severity of bronchopulmonary dysplasia

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Soler, C. [Neonatal Unit, Dept. of Pediatrics, Casa Maternitat Hospital, Clinical Hospital and Sant Joan de Deu Hospital, Univ. of Barcelona (Spain); Figueras, J. [Neonatal Unit, Dept. of Pediatrics, Casa Maternitat Hospital, Clinical Hospital and Sant Joan de Deu Hospital, Univ. of Barcelona (Spain)]|[Servicio de Neonatologia, Hospital Clinico, Barcelona (Spain); Roca, I. [Nuclear Medicine Unit, Autonomous Univ. of Barcelona (Spain); Perez, J.M. [Neonatal Unit, Dept. of Pediatrics, Casa Maternitat Hospital, Clinical Hospital and Sant Joan de Deu Hospital, Univ. of Barcelona (Spain); Jimenez, R. [Neonatal Unit, Dept. of Pediatrics, Casa Maternitat Hospital, Clinical Hospital and Sant Joan de Deu Hospital, Univ. of Barcelona (Spain)

1997-01-01

Objective. The objectives of this study were to analyze the changes in pulmonary perfusion in bronchopulmonary dysplasia (BPD) and to assess the advantages of this method in evaluating the severity of BPD. Patients and methods. The study group was made up of 10 children with BPD, matched with a control group of 12 children. The criteria for matching were birth weight, gestational age and need for ventilation for more than 3 days. Clinical and roentgenographic scoring systems were applied on the 21st day of life. At 6 months of corrected age, clinical evolutive severity was evaluated and a pulmonary perfusion scintigraphy using technetium-99 was performed in each child. The scintigraphic findings were classified in five categories ranging from normal to severely affected, depending on the degree and localization of perfusion abnormalities. Another score was obtained by assigning a value from 1 to 5 to each pulmonary lobe, depending on the concentration of the tracer. Results. The study of clinical, roentgenographic and evolutive scores always showed higher values in children with BPD, with good correlation between methods (P < 0.001). In the BPD group, abnormal lung perfusion patterns were more frequent and more severe (P < 0.05), the lobe scoring was higher (P < 0.05), and a lower count rate was found (P < 0.01). Conclusion. Pulmonary scintigraphy is a useful technique in evaluating the severity of BPD. (orig.). With 1 fig., 3 tabs.

Pulmonary perfusion scintigraphy in the evaluation of the severity of bronchopulmonary dysplasia

International Nuclear Information System (INIS)

Soler, C.; Figueras, J.; Roca, I.; Perez, J.M.; Jimenez, R.

1997-01-01

Objective. The objectives of this study were to analyze the changes in pulmonary perfusion in bronchopulmonary dysplasia (BPD) and to assess the advantages of this method in evaluating the severity of BPD. Patients and methods. The study group was made up of 10 children with BPD, matched with a control group of 12 children. The criteria for matching were birth weight, gestational age and need for ventilation for more than 3 days. Clinical and roentgenographic scoring systems were applied on the 21st day of life. At 6 months of corrected age, clinical evolutive severity was evaluated and a pulmonary perfusion scintigraphy using technetium-99 was performed in each child. The scintigraphic findings were classified in five categories ranging from normal to severely affected, depending on the degree and localization of perfusion abnormalities. Another score was obtained by assigning a value from 1 to 5 to each pulmonary lobe, depending on the concentration of the tracer. Results. The study of clinical, roentgenographic and evolutive scores always showed higher values in children with BPD, with good correlation between methods (P < 0.001). In the BPD group, abnormal lung perfusion patterns were more frequent and more severe (P < 0.05), the lobe scoring was higher (P < 0.05), and a lower count rate was found (P < 0.01). Conclusion. Pulmonary scintigraphy is a useful technique in evaluating the severity of BPD. (orig.). With 1 fig., 3 tabs

Prognostic role of alveolar-arterial oxygen pressure difference in acute pulmonary embolism

International Nuclear Information System (INIS)

Hsu Jente; Chang Shihtai; Cheng Huiwen; Chung Changmin; Chu, Chiming; Cheng Nyejan; Ho Wanching

2006-01-01

This study investigated the utility of the alveolar-arterial oxygen pressure difference (AaDO 2 ) in predicting the short-term prognosis of acute pulmonary embolism (PE). This study retrospectively enrolled 114 consecutive patients with acute PE, diagnosed by either spiral computed tomography or high probability ventilation-perfusion lung scans. During the first 24 h of admission, all patients had initial artery blood gas collected under room air. Patient exclusion criteria were chronic lung disease, septic emboli, and moderate and low probability lung scans. Patients were assigned to 2 groups based on either 30-day death or a 30-day composite event. Receiver operating characteristic analyses was used to determine the AaDO 2 cut-off value for predicting primary and composite endpoints. Statistical analysis demonstrated significant differences in AaDO 2 between the 30-day composite endpoint group and the 30-day composite event-free survival group (p=0.012). The AaDO 2 had a strong trend between the 30-day death group and the survival group (p=0.062). The best cut-off value for AaDO 2 was 53 mmHg and using this, the positive predictive value for 30-day death was 25% and the negative predictive value was 92%. For the 30-day composite endpoint, the positive predictive value for AaDO 2 was 35%, and the negative predictive value was 84%. In this study, thrombocytopenia was also an indicator of poor prognosis for patients with acute PE. The AaDO 2 measurement is a highly useful and simple measurement for predicting short-term prognosis in patients with acute PE. It has high negative predictive value and moderate positive predictive value for 30-day death and 30-day composite event. Aggressive thrombolytic treatment strategies should be considered for patients with an initial poor prognostic parameter (ie, AaDO 2 ≥53 mmHg). (author)

Acrolein - a pulmonary hazard.

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Bein, Kiflai; Leikauf, George D

2011-09-01

Acrolein is a respiratory irritant that can be generated during cooking and is in environmental tobacco smoke. More plentiful in cigarette smoke than polycyclic aromatic hydrocarbons (PAH), acrolein can adduct tumor suppressor p53 (TP53) DNA and may contribute to TP53-mutations in lung cancer. Acrolein is also generated endogenously at sites of injury, and excessive breath levels (sufficient to activate metalloproteinases and increase mucin transcripts) have been detected in asthma and chronic obstructive pulmonary disease (COPD). Because of its reactivity with respiratory-lining fluid or cellular macromolecules, acrolein alters gene regulation, inflammation, mucociliary transport, and alveolar-capillary barrier integrity. In laboratory animals, acute exposures have lead to acute lung injury and pulmonary edema similar to that produced by smoke inhalation whereas lower concentrations have produced bronchial hyperreactivity, excessive mucus production, and alveolar enlargement. Susceptibility to acrolein exposure is associated with differential regulation of cell surface receptor, transcription factor, and ubiquitin-proteasome genes. Consequent to its pathophysiological impact, acrolein contributes to the morbidly and mortality associated with acute lung injury and COPD, and possibly asthma and lung cancer. Copyright © 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Survival in a case of diffuse alveolar hemorrhage due to Strongyloides stercoralis hyperinfection.

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Steinhaus, Daniel A; Gainor, Justin F; Vernovsky, Inna; Winsett, Julie; Beer, Dennis J

2012-01-01

Strongyloides stercoralis is an intestinal nematode endemic to tropical and sub-tropical regions. Although infection is typically asymptomatic or self-limited, immunocompromised individuals can develop a severe form of disease marked by hyperinfection. Pulmonary involvement accompanies hyperinfection in a majority of cases, though manifestations range from asymptomatic infiltrates to diffuse alveolar hemorrhage (DAH) and respiratory failure. When complicated by DAH, the hyperinfection syndrome is usually fatal. We report a case of a 65-year-old Guatemalan woman with chronic inflammatory demyelinating polyneuropathy (CIDP) treated with chronic steroids who presented with Escherichia coli urosepsis. She was initially treated with antibiotics and corticosteroids. She subsequently developed DAH due to disseminated strongyloidiasis. She was treated with oral and subcutaneous ivermectin and had complete recovery.

Receptor for advanced glycation endproducts (RAGE maintains pulmonary structure and regulates the response to cigarette smoke.

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Lisa Wolf

Full Text Available The receptor for advanced glycation endproducts (RAGE is highly expressed in the lung but its physiological functions in this organ is still not completely understood. To determine the contribution of RAGE to physiological functions of the lung, we analyzed pulmonary mechanics and structure of wildtype and RAGE deficient (RAGE-/- mice. RAGE deficiency spontaneously resulted in a loss of lung structure shown by an increased mean chord length, increased respiratory system compliance, decreased respiratory system elastance and increased concentrations of serum protein albumin in bronchoalveolar lavage fluids. Pulmonary expression of RAGE was mainly localized on alveolar epithelial cells and alveolar macrophages. Primary murine alveolar epithelial cells isolated from RAGE-/- mice revealed an altered differentiation and defective barrier formation under in vitro conditions. Stimulation of interferone-y (IFNy-activated alveolar macrophages deficient for RAGE with Toll-like receptor (TLR ligands resulted in significantly decreased release of proinflammatory cytokines and chemokines. Exposure to chronic cigarette smoke did not affect emphysema-like changes in lung parenchyma in RAGE-/- mice. Acute cigarette smoke exposure revealed a modified inflammatory response in RAGE-/- mice that was characterized by an influx of macrophages and a decreased keratinocyte-derived chemokine (KC release. Our data suggest that RAGE regulates the differentiation of alveolar epithelial cells and impacts on the development and maintenance of pulmonary structure. In cigarette smoke-induced lung pathology, RAGE mediates inflammation that contributes to lung damage.

Inhalation of activated protein C inhibits endotoxin-induced pulmonary inflammation in mice independent of neutrophil recruitment

NARCIS (Netherlands)

Slofstra, S. H.; Groot, A. P.; Maris, N. A.; Reitsma, P. H.; Cate, H. Ten; Spek, C. A.

2006-01-01

BACKGROUND AND PURPOSE: Intravenous administration of recombinant human activated protein C (rhAPC) is known to reduce lipopolysaccharide (LPS)-induced pulmonary inflammation by attenuating neutrophil chemotaxis towards the alveolar compartment. Ideally, one would administer rhAPC in pulmonary

Chronic Alcohol Ingestion Changes the Landscape of the Alveolar Epithelium

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Charles A. Downs

2013-01-01

Full Text Available Similar to effects of alcohol on the heart, liver, and brain, the effects of ethanol (EtOH on lung injury are preventable. Unlike other vital organ systems, however, the lethal effects of alcohol on the lung are underappreciated, perhaps because there are no signs of overt pulmonary disorder until a secondary insult, such as a bacterial infection or injury, occurs in the lung. This paper provides overview of the complex changes in the alveolar environment known to occur following both chronic and acute alcohol exposures. Contemporary animal and cell culture models for alcohol-induced lung dysfunction are discussed, with emphasis on the effect of alcohol on transepithelial transport processes, namely, epithelial sodium channel activity (ENaC. The cascading effect of tissue and phagocytic Nadph oxidase (Nox may be triggered by ethanol exposure, and as such, alcohol ingestion and exposure lead to a prooxidative environment; thus impacting alveolar macrophage (AM function and oxidative stress. A better understanding of how alcohol changes the landscape of the alveolar epithelium can lead to improvements in treating acute respiratory distress syndrome (ARDS for which hospitalized alcoholics are at an increased risk.

Idiopathic pulmonary hemosiderosis: Alveoli are an answer to anemia

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S Bhatia

2011-01-01

Full Text Available Idiopathic pulmonary hemosiderosis (IPH is a rare disorder (triad of iron-deficiency anemia, hemoptysis, and alveolar infiltrates. A 3-year-old male presented with mild fever, breathlessness, dry cough, and bluish nail discoloration for 8 days. He had required five blood transfusions in the past 1 year (last transfusion was given 4 months ago. He had a respiratory rate of 58/min with respiratory distress, cyanosis, and grade III clubbing. Respiratory system examination was normal. Several previous reports of hemoglobin were as low as 3.6 g/dl with hypochromic and microcytic anemia. There were transient increases in the hemoglobin and normalization of red cell morphology with blood transfusions. Serum iron, G6PD enzyme assay, hemoglobin electrophoresis, the sickling test, Coomb′s test, stool and urine analysis, and a Meckel′s scan were normal. HIV antibody and dsDNA were negative. The chest radiograph revealed symmetrical patchy infiltrates sparing lung apices (confirmed on high-resolution computed tomography. Lung biopsy diagnosed pulmonary hemosiderosis (interstitial lung disease with hemosiderin-laden macrophages scattered in the alveoli and areas of fibrosis in the alveolar septa. The patient showed marked clinical improvement in 10 days of therapy with prednisolone. IPH should be listed in the differential diagnosis of a child presenting with unexplained hypochromic, microcytic anemia and respiratory symptoms.

Alternatives to Autologous Bone Graft in Alveolar Cleft Reconstruction: The State of Alveolar Tissue Engineering.

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Liang, Fan; Leland, Hyuma; Jedrzejewski, Breanna; Auslander, Allyn; Maniskas, Seija; Swanson, Jordan; Urata, Mark; Hammoudeh, Jeffrey; Magee, William

2018-05-01

Alveolar cleft reconstruction has historically relied on autologous iliac crest bone grafting (ICBG), but donor site morbidity, pain, and prolonged hospitalization have prompted the search for bone graft substitutes. The authors evaluated bone graft substitutes with the highest levels of evidence, and highlight the products that show promise in alveolar cleft repair and in maxillary augmentation. This comprehensive review guides the craniofacial surgeon toward safe and informed utilization of biomaterials in the alveolar cleft.A literature search was performed to identify in vitro human studies that fulfilled the following criteria: Level I or Level II of evidence, ≥30 subjects, and a direct comparison between a autologous bone graft and a bone graft substitute. A second literature search was performed that captured all studies, regardless of level of evidence, which evaluated bone graft substitutes for alveolar cleft repair or alveolar augmentation for dental implants. Adverse events for each of these products were tabulated as well.Sixteen studies featuring 6 bone graft substitutes: hydroxyapatite, demineralized bone matrix (DBM), β-tricalcium phosphate (TCP), calcium phosphate, recombinant human bone morphogenic protein-2 (rhBMP-2), and rhBMP7 fit the inclusion criteria for the first search. Through our second search, the authors found that DBM, TCP, rhBMP-2, and rhBMP7 have been studied most extensively in the alveolar cleft literature, though frequently in studies using less rigorous methodology (Level III evidence or below). rhBMP-2 was the best studied and showed comparable efficacy to ICBG in terms of volume of bone regeneration, bone density, and capacity to accommodate tooth eruption within the graft site. Pricing for products ranged from $290 to $3110 per 5 mL.The balance between innovation and safety is a complex process requiring constant vigilance and evaluation. Here, the authors profile several bone graft substitutes that demonstrate the most

NOD2 enhances the innate response of alveolar macrophages to Mycobacterium tuberculosis in humans.

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Juárez, Esmeralda; Carranza, Claudia; Hernández-Sánchez, Fernando; León-Contreras, Juan C; Hernández-Pando, Rogelio; Escobedo, Dante; Torres, Martha; Sada, Eduardo

2012-04-01

A role for the nucleotide-binding oligomerization domain 2 (NOD2) receptor in pulmonary innate immune responses has recently been explored. In the present study, we investigated the role that NOD2 plays in human alveolar macrophage innate responses and determined its involvement in the response to infection with virulent Mycobacterium tuberculosis. Our results showed that NOD2 was expressed in human alveolar macrophages, and significant amounts of IL-1β, IL-6, and TNF-α were produced upon ligand recognition with muramyldipeptide (MDP). NOD2 ligation induced the transcription and protein expression of the antimicrobial peptide LL37 and the autophagy enzyme IRGM in alveolar macrophages, demonstrating a novel function for this receptor in these cells. MDP treatment of alveolar macrophages improved the intracellular growth control of virulent M. tuberculosis; this was associated with a significant release of TNF-α and IL-6 and overexpression of bactericidal LL37. In addition, the autophagy proteins IRGM, LC3 and ATG16L1 were recruited to the bacteria-containing autophagosome after treatment with MDP. In conclusion, our results suggest that NOD2 can modulate the innate immune response of alveolar macrophages and play a role in the initial control of respiratory M. tuberculosis infections. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Composition, structure and mechanical properties define performance of pulmonary surfactant membranes and films

DEFF Research Database (Denmark)

Ortiz, Elisa Parra; Perez-Gil, Jesús

2015-01-01

of breathing and avoiding alveolar collapse, especially at the end of expiration. The goal of the present review is to summarize current knowledge regarding the structure, lipid-protein interactions and mechanical features of surfactant membranes and films and how these properties correlate with surfactant...... biological function inside the lungs. Surfactant mechanical properties can be severely compromised by different agents, which lead to surfactant inhibition and ultimately contributes to the development of pulmonary disorders and pathologies in newborns, children and adults. A detailed comprehension...

Non-severe pulmonary embolism: Prognostic CT findings

International Nuclear Information System (INIS)

Moroni, Anne-Line; Bosson, Jean-Luc; Hohn, Noelie; Carpentier, Francoise; Pernod, Gilles; Ferretti, Gilbert R.

2011-01-01

The goal of this study was to retrospectively evaluate CT cardiovascular parameters and pulmonary artery clot load score as predictors of 3-month mortality in patients with clinically non-severe pulmonary embolism (PE). We included 226 CT positive for PE in hemodynamically stable patients (112 women; mean age 67.1 years ±16.9). CT were independently reviewed by two observers. Results were compared with occurrence of death within 3 months using Cox regression. Twenty-four (10.6%) patients died, for whom 9 were considered to be due to PE. Interobserver agreement was moderate for the shape of interventricular septum (κ = 0.41), and for the ratio between the diameters of right and left ventricle (RV/LV) (κ = 0.76). Observers found no association between interventricular septum shape and death. A RV/LV diameter ratio >1 was predictive of death (OR, 3.83; p 1 is predictive of death when the embolic burden is low (<40%).

Multidimensional fatigue in pulmonary hypertension: prevalence, severity and predictors

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Tartavoulle, Todd M.; Karpinski, Aryn C.; Aubin, Andrew; Kluger, Benzi M.; Distler, Oliver; Saketkoo, Lesley Ann

2018-01-01

Pulmonary hypertension is a potentially fatal disease. Despite pharmacological advances in pulmonary hypertension, fatigue remains common in patients with pulmonary hypertension. A convenience sample of 120 participants at an international patient conference completed the Multidimensional Fatigue Inventory (MFI)-20 scale. Data on New York Heart Association Functional Class, body mass index, oxygen use and medication type/use were also collected. There was a high prevalence of “severe” to “very severe” fatigue for each dimension: General Fatigue (60%), Physical Fatigue (55.8%), Reduced Activity (41.7%), Reduced Motivation (32.5%) and Mental Fatigue (27.5%). The mean±sd overall MFI-20 score was 58±5.1. Dimensions with the highest averaged levels were General Fatigue (13.40±3.61), Physical Fatigue (13.23±3.67) and Reduced Activity (11.33±4.16). Body mass index correlated with higher fatigue scores. Phosphodiesterase inhibitor plus endothelin receptor antagonist combination negatively predicted General Fatigue, Physical Fatigue, Reduced Motivation and Reduced Activity. Triple therapy was a significant predictor of General Fatigue, Physical Fatigue and Reduced Activity. There were no significant predictors of Mental Fatigue. Multidimensional fatigue is common and severe in patients with pulmonary hypertension. Phosphodiesterase inhibitor plus endothelin receptor antagonist combination resulted in lower scores in most fatigue dimensions. Comprehensive assessment of fatigue should be considered in the clinical care of patients with pulmonary hypertension and clinical research to develop formal interventions that target this disabling symptom. PMID:29577043

Edema pulmonar de altura: Modelo de estudio de la fisiopatología del edema pulmonar y de la hipertensión pulmonar hipóxica en humanos High altitude pulmonary edema: An experiment of Nature to study the underlying mechanisms of hypoxic pulmonary hypertension and pulmonary edema in humans

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Marcos Schwab

2007-02-01

altitude, but also for the treatment of hypoxemia-related disease states in patients living at low altitude. High-altitude pulmonary edema (HAPE is a life-threatening condition occurring in predisposed, but otherwise healthy subjects, and, therefore, allows to study underlying mechanisms of pulmonary edema in humans, in the absence of confounding factors. Over the past decade, evidence has accumulated that HAPE results from the conjunction of two major defects, augmented alveolar fluid flooding resulting from exaggerated hypoxic pulmonary hypertension, and impaired alveolar fluid clearance related to defective respiratory transepithelial sodium transport. Here, after a brief presentation of the clinical features of HAPE, we review this novel concept. We provide experimental evidence for the novel concept that impaired pulmonary endothelial and epithelial nitric oxide synthesis and/or bioavailability may represent the central underlying defect predisposing to exaggerated hypoxic pulmonary vasoconstriction and alveolar fluid flooding. We demonstrate that exaggerated pulmonary hypertension, while possibly a condition sine qua non, may not be sufficient to cause HAPE, and how defective alveolar fluid clearance may represent a second important pathogenic mechanism. Finally, we outline how this insight gained from studies in HAPE may be translated into the management of hypoxemia related disease states in general.

Imaging alveolar-capillary permeability in experimental respiratory distress syndrome

International Nuclear Information System (INIS)

Suzuki, T.; Watanabe, S.; Wagner, H.N.; Swift, D.L.; Proctor, D.F.

1982-01-01

Pulmonary edema can be induced in dogs by low doses of oleic acid (20 μl/kg) given intravenously, simulating the adult respiratory distress syndrome (ARDS). Alveolar-capillary permeability was measured in dogs, using sup(99m)Tc-DTPA and sup(99m)Tc-albumin fine aerosols produced by a newly designed separator. This separator eliminates the effect of mucociliary movement on aerosol clearance. The small molecular-laden aerosol particles were cleared in the order: sup(99m)-TcO 4 - , sup(99m)Tc-DTPA, and sup(99m)Tc-disofenin; the Tsub(1/2) of lung clearance correlated with molecular sizes. Experimental ARDS increased the lung clearance of sup(99m)Tc-DTPA. Lung clearance of large molecule (sup(99m)Tc-albumin) laden aerosol particles was not accelerated in the ARDS model. Inhalation with fine aerosols revealed increased alveolar permeability in the ARDS model without any change of cardiac output

Pulmonary complications of induction therapy for acute myeloid leukemia in adults. Findings of chest X-rays and computed tomography

International Nuclear Information System (INIS)

Kirchner, J.; Huettmann, C.; Jacobi, V.; Boehme, A.

1998-01-01

To exclude pulmonary complications, 359 chest radiographs and 50 computed tomographs of the lung were performed in 95 patients suffering from acute myeloid leukemia. The radiological findings were registered, described and correlated with clinical findings in the present study on 2395 days of observation. Results: In summary, 52 patients showed alterations of the lung. Pulmonary hyperhydration was seen in 21 cases, bacterial pneumonia was found in 18 cases, invasive pulmonary aspergillosis was documented in 14 cases, and 5 cases of severe haemorrhage were seen. An unexplained pulmonary edema in 13 patients with interstitial and alveolar infiltrates is considered to be a complication of treatment with cytosine-arabinoside. Conclusion: The results demonstrate that chest X-ray and computed tomography have a high impact in detection and treatment of pulmonary complications following intensive chemotherapy. We may expect the development of diffuse opacity following administration of cytosine-arabinoside in medium-sized doses. (orig.) [de

The microbiome at the pulmonary alveolar niche and its role in Mycobacterium tuberculosis infection.

Science.gov (United States)

Adami, Alexander J; Cervantes, Jorge L

2015-12-01

Advances in next generation sequencing (NGS) technology have provided the tools to comprehensively and accurately characterize the microbial community in the respiratory tract in health and disease. The presence of commensal and pathogenic bacteria has been found to have important effects on the lung immune system. Until relatively recently, the lung has received less attention compared to other body sites in terms of microbiome characterization, and its study carries special technological difficulties related to obtaining reliable samples as compared to other body niches. Additionally, the complexity of the alveolar immune system, and its interactions with the lung microbiome, are only just beginning to be understood. Amidst this complexity sits Mycobacterium tuberculosis (Mtb), one of humanity's oldest nemeses and a significant public health concern, with millions of individuals infected with Mtb worldwide. The intricate interactions between Mtb, the lung microbiome, and the alveolar immune system are beginning to be understood, and it is increasingly apparent that improved treatment of Mtb will only come through deep understanding of the interplay between these three forces. In this review, we summarize our current understanding of the lung microbiome, alveolar immunity, and the interaction of each with Mtb. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acute pulmonary emphysema in death by hanging: a morphometric digital study.

Science.gov (United States)

Castiglioni, Claudia; Baumann, Pia; Fracasso, Tony

2016-09-01

Acute pulmonary emphysema (APE) has been described in cases of mechanical asphyxia such as ligature or manual strangulation but not in cases of hanging. In this study, we wanted to verify by morphometric digital analysis of lung tissue whether APE occurs in death by hanging.We investigated 16 cases of hanging (eight complete, eight incomplete), 10 cases of freshwater drowning (positive control group), and 10 cases of acute external bleeding (negative control group). Tissue sections were obtained from each pulmonary lobe. For each slide, five fields were randomly selected. The area of every alveolar space was measured by image analysis software. The mean alveolar area (MAA) was calculated for each group.In incomplete hanging, MAA was significantly higher than that observed in complete hanging and similar to the one observed in freshwater drowning.APE in cases of incomplete hanging can be considered as a sign of vitality. The high number of conditions that can cause alveolar distension (that were excluded in this study) limits the applicability of this vital sign in the routine forensic practice.

Orthodontic treatment of severe anterior open bite and alveolar bone defect complicated by an ankylosed maxillary central incisor: a case report.

Science.gov (United States)

Lin, Feiou; Sun, Hao; Yao, Linjie; Chen, Qiushuo; Ni, Zhenyu

2014-11-21

Incisor trauma is common in children, and can cause severe complications during adolescent growth and development. This report describes the treatment of a 16-year-old patient with severe anterior open bite due to ankylosis of the maxillary left incisor after dental trauma as an 8-year-old. No examination or active treatment was undertaken until he was 16 years old. Clinical examination revealed that the maxillary left incisor was severely intruded accompanied by a vertical alveolar bone defect. Orthodontic treatment combined with surgical luxation took 3 years and 7 months. During treatment, the intruded incisor was moved to the occlusal level and the alveolar bone defect was restored, achieving normal occlusion. After two years of retention, the maxillary left incisor was retained in a stable normal position with a slightly reduced overbite. This case demonstrates that surgical luxation with orthodontic traction can be an effective approach, especially when the ankylosed tooth has a single root. Long-term monitoring of orthodontic stability and the maintenance of periodontal health are crucial in the post-treatment period.

Palliative Senning in the Treatment of Congenital Heart Disease with Severe Pulmonary Hypertension

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Juliano Gomes da Penha

2015-01-01

Full Text Available Background:Transposition of the great arteries (TGA is the most common cyanotic cardiopathy, with an incidence ranging between 0.2 and 0.4 per 1000 live births. Many patients not treated in the first few months of life may progress with severe pulmonary vascular disease. Treatment of these patients may include palliative surgery to redirect the flow at the atrial level.Objective:Report our institutional experience with the palliative Senning procedure in children diagnosed with TGA and double outlet right ventricle with severe pulmonary vascular disease, and to evaluate the early and late clinical progression of the palliative Senning procedure.Methods:Retrospective study based on the evaluation of medical records in the period of 1991 to 2014. Only patients without an indication for definitive surgical treatment of the cardiopathy due to elevated pulmonary pressure were included.Results:After one year of follow-up there was a mean increase in arterial oxygen saturation from 62.1% to 92.5% and a mean decrease in hematocrit from 49.4% to 36.3%. Lung histological analysis was feasible in 16 patients. In 8 patients, pulmonary biopsy grades 3 and 4 were evidenced.Conclusion:The palliative Senning procedure improved arterial oxygen saturation, reduced polycythemia, and provided a better quality of life for patients with TGA with ventricular septal defect, severe pulmonary hypertension, and poor prognosis.

Effects of water immersion to the neck on pulmonary circulation and tissue volume in man

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Begin, R.; Epstein, M.; Sackner, M. A.; Levinson, R.; Dougherty, R.; Duncan, D.

1976-01-01

A rapid noninvasive breathing method is used to obtain serial measurements of the pulmonary capillary blood flow, diffusing capacity per unit of alveolar volume, combined pulmonary tissue plus capillary volume, functional residual capacity, and oxygen consumption in five normal subjects undergoing 6 h of sitting, 4 h of sitting while immersed to the neck in thermoneutral water, and 4 h of lying in thermoneutral water to the neck. The rebreathing method employed a test gas mixture containing 0.5% C2H2, 0.3% C(18)O, 10% He, 21% O2, and balance N2. It is shown that immersion to the neck in the seated posture results in significant increases in sodium excretion cardiac output, and diffusing capacity per unit of alveolar volume. The pulmonary tissue plus capillary volume did not change, demonstrating that the central vascular engorgement induced by water immersion is not accompanied by significant extravasation of fluid into the pulmonary interstitial space.

Severe Cushing's syndrome and bilateral pulmonary nodules: beyond ectopic ACTH.

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Tavares Bello, Carlos; van der Poest Clement, Emma; Feelders, Richard

2017-01-01

Cushing's syndrome is a rare disease that results from prolonged exposure to supraphysiological levels of glucocorticoids. Severe and rapidly progressive cases are often, but not exclusively, attributable to ectopic ACTH secretion. Extreme hypercortisolism usually has florid metabolic consequences and is associated with an increased infectious and thrombotic risk. The authors report on a case of a 51-year-old male that presented with severe Cushing's syndrome secondary to an ACTH-secreting pituitary macroadenoma, whose diagnostic workup was affected by concurrent subclinical multifocal pulmonary infectious nodules. The case is noteworthy for the atypically severe presentation of Cushing's disease, and it should remind the clinician of the possible infectious and thrombotic complications associated with Cushing's syndrome. Severe Cushing's syndrome is not always caused by ectopic ACTH secretion.Hypercortisolism is a state of immunosuppression, being associated with an increased risk for opportunistic infections.Infectious pulmonary infiltrates may lead to imaging diagnostic dilemmas when investigating a suspected ectopic ACTH secretion.Cushing's syndrome carries an increased thromboembolic risk that may even persist after successful surgical management.Antibiotic and venous thromboembolism prophylaxis should be considered in every patient with severe Cushing's syndrome.

Mice with Pulmonary Fibrosis Driven by Telomere Dysfunction

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Juan M. Povedano

2015-07-01

Full Text Available Idiopathic pulmonary fibrosis (IPF is a degenerative disease of the lungs with an average survival post-diagnosis of 2–3 years. New therapeutic targets and treatments are necessary. Mutations in components of the telomere-maintenance enzyme telomerase or in proteins important for telomere protection are found in both familial and sporadic IPF cases. However, the lack of mouse models that faithfully recapitulate the human disease has hampered new advances. Here, we generate two independent mouse models that develop IPF owing to either critically short telomeres (telomerase-deficient mice or severe telomere dysfunction in the absence of telomere shortening (mice with Trf1 deletion in type II alveolar cells. We show that both mouse models develop pulmonary fibrosis through induction of telomere damage, thus providing proof of principle of the causal role of DNA damage stemming from dysfunctional telomeres in IPF development and identifying telomeres as promising targets for new treatments.

Effects of a preemptive alveolar recruitment strategy on arterial oxygenation during one-lung ventilation with different tidal volumes in patients with normal pulmonary function test.

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Jung, Jong Dal; Kim, Sang Hun; Yu, Byung Sik; Kim, Hye Ji

2014-08-01

Hypoxemia during one-lung ventilation (OLV) remains a major concern. The present study compared the effect of alveolar recruitment strategy (ARS) on arterial oxygenation during OLV at varying tidal volumes (Vt) with or without positive end-expiratory pressure (PEEP). In total, 120 patients undergoing wedge resection by video assisted thoracostomy were randomized into four groups comprising 30 patients each: those administered a 10 ml/kg tidal volume with or without preemptive ARS (Group H and Group H-ARS, respectively) and those administered a 6 ml/kg tidal volume and a 8 cmH2O PEEP with or without preemptive ARS (Group L and Group L-ARS, respectively). ARS was performed using pressure-controlled ventilation with a 40 cmH2O plateau airway pressure and a 15 cmH2O PEEP for at least 10 breaths until OLV began. Preemptive ARS significantly improved the PaO2/FiO2 ratio compared to the groups that did not receive ARS (P volume combined with 8 cmH2O PEEP after preemptive ARS may reduce the risk of pulmonary injury caused by high tidal volume during one-lung ventilation in patients with normal pulmonary function.

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

HUMAL ALVEOLAR MACROPHAGE RESPONSES TO AIR POLLUTION PARTICULATES ARE ASSOCIATED WITH INSOLUBLE OCMPONENTS OF COARSE MATERIAL, INCLUDING PARTICULATE ENDOTOXIN

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Inhalation of particulate matter in the ambient air has been shown to cause pulmonary morbidity and exacerbate asthma. Alveolar macrophage (AM) are essential for effective removal of inhaled particles and microbes in the lower airways. While some particles minimally effect AM...

Pulmonary MR imaging with ultra-short TEs: Utility for disease severity assessment of connective tissue disease patients

International Nuclear Information System (INIS)

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Takenaka, Daisuke; Takahashi, Masaya; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Obara, Makoto; Cauteren, Marc van; Sugimura, Kazuro

2013-01-01

Purpose: To evaluate the utility of pulmonary magnetic resonance (MR) imaging with ultra-short echo times (UTEs) at a 3.0 T MR system for pulmonary functional loss and disease severity assessments of connective tissue disease (CTD) patients with interstitial lung disease (ILD). Materials and methods: This prospective study was approved by the institutional review board, and written informed consent was obtained from 18 CTD patients (eight men and ten women) and eight normal subjects with suspected chest disease (three men and five women). All subjects underwent thin-section MDCT, pulmonary MR imaging with UTEs, pulmonary function test and serum KL-6. Regional T2* maps were generated from each MR data set, and mean T2* values were determined from ROI measurements. From each thin-section MDCT data set, CT-based disease severity was evaluated with a visual scoring system. Mean T2* values for normal and CTD subjects were statistically compared by using Student's t-test. To assess capability for pulmonary functional loss and disease severity assessments, mean T2* values were statistically correlated with pulmonary functional parameters, serum KL-6 and CT-based disease severity. Results: Mean T2* values for normal and CTD subjects were significantly different (p = 0.0019) and showed significant correlations with %VC, %DL CO , serum KL-6 and CT-based disease severity of CTD patients (p < 0.05). Conclusion: Pulmonary MR imaging with UTEs is useful for pulmonary functional loss and disease severity assessments of CTD patients with ILD

Pulmonary MR imaging with ultra-short TEs: Utility for disease severity assessment of connective tissue disease patients

Energy Technology Data Exchange (ETDEWEB)

Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.jp [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Nishio, Mizuho [Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Koyama, Hisanobu [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Takenaka, Daisuke [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Department of Radiology, Hyogo Cancer Center, Akashi, Hyogo (Japan); Takahashi, Masaya [Advanced Imaging Research Center, Department of Radiology, University of Texas Southwestern Medical Center, Houston, TX (United States); Yoshikawa, Takeshi; Matsumoto, Sumiaki [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Obara, Makoto; Cauteren, Marc van [Philips Electronics Japan, Tokyo (Japan); Sugimura, Kazuro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan)

2013-08-15

Purpose: To evaluate the utility of pulmonary magnetic resonance (MR) imaging with ultra-short echo times (UTEs) at a 3.0 T MR system for pulmonary functional loss and disease severity assessments of connective tissue disease (CTD) patients with interstitial lung disease (ILD). Materials and methods: This prospective study was approved by the institutional review board, and written informed consent was obtained from 18 CTD patients (eight men and ten women) and eight normal subjects with suspected chest disease (three men and five women). All subjects underwent thin-section MDCT, pulmonary MR imaging with UTEs, pulmonary function test and serum KL-6. Regional T2* maps were generated from each MR data set, and mean T2* values were determined from ROI measurements. From each thin-section MDCT data set, CT-based disease severity was evaluated with a visual scoring system. Mean T2* values for normal and CTD subjects were statistically compared by using Student's t-test. To assess capability for pulmonary functional loss and disease severity assessments, mean T2* values were statistically correlated with pulmonary functional parameters, serum KL-6 and CT-based disease severity. Results: Mean T2* values for normal and CTD subjects were significantly different (p = 0.0019) and showed significant correlations with %VC, %DL{sub CO}, serum KL-6 and CT-based disease severity of CTD patients (p < 0.05). Conclusion: Pulmonary MR imaging with UTEs is useful for pulmonary functional loss and disease severity assessments of CTD patients with ILD.

Beyond the inhaled nitric oxide in persistent pulmonary hypertension of the newborn

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Mei-Yin Lai

2018-02-01

Full Text Available Persistent pulmonary hypertension (PPHN is a consequence of failed pulmonary vascular transition at birth and leads to pulmonary hypertension with shunting of deoxygenated blood across the ductus arteriosus (DA and foramen ovale (FO resulting in severe hypoxemia, and it may eventually lead to life-threatening circulatory failure. PPHN is a serious event affecting both term and preterm infants in the neonatal intensive care unit. It is often associated with diseases such as congenital diaphragmatic hernia, meconium aspiration, sepsis, congenital pneumonia, birth asphyxia and respiratory distress syndrome. The diagnosis of PPHN should include echocardiographic evidence of increased pulmonary pressure, with demonstrable right-to-left shunt across the DA or FO, and the absence of cyanotic heart diseases. The mainstay therapy of PPHN includes treatment of underlying causes, maintenance of adequate systemic blood pressure, optimized ventilator support for lung recruitment and alveolar ventilation, and pharmacologic measures to increase pulmonary vasodilation and decrease pulmonary vascular resistance. Inhaled nitric oxide has been proved to treat PPHN successfully with improved oxygenation in 60–70% of patients and to significantly reduce the need for extracorporeal membrane oxygenation (ECMO. About 14%–46% of the survivors develop long-term impairments such as hearing deficits, chronic lung disease, cerebral palsy and other neurodevelopmental disabilities.

SEVERE PULMONARY HYPERTENSION DUE TO SLEEP-DISORDERED BREATHING IN AN ACHONDROPLASIC CHILD

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Vehbi Dogan

2014-03-01

Full Text Available Achondroplasia is the most common skeletal dysplasia in children. Achondroplasic patients often have respiratory problems associated with upper respiratory tract obstruction and craniaofacial dysmorphology. Chronic hypoxemia in these patients can result in pulmonary hypertension. In this report an achondroplasic child with severe day-time pulmonary hypertension is presented. [J Contemp Med 2014; 4(1.000: 41-43

Clinical significance of gallium-67 scintigraphy in assessing pulmonary lesions of sarcoidosis and idiopathic pulmonary fibrosis

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Fujishima, Seitaro; Kanazawa, Minoru; Yamasawa, Fumihiro; Kubo, Atsushi; Hashimoto, Shozo; Yokoyama, Tetsuro (Keio Univ., Tokyo (Japan). School of Medicine)

1992-03-01

To evaluate whether one can predict the course and prognosis of interstitial lung diseases from lung gallium-67 ({sup 67}Ga) uptake, we studied 31 subjects with sarcoidosis and 28 with idiopathic pulmonary fibrosis (IPF) retrospectively. We quantified the lung {sup 67}Ga uptake using posterior scans by Line's method, and calculated a visual index (VI). The normal range of {sup 67}Ga uptake was defined as less than 65 VI values, obtained from the 95 percent confidence interval of the control subjects. All subjects with stage I sarcoidosis, having only bilateral hilar lymphadenopathy (BHL) on chest X-ray, revealed normal lung {sup 67}Ga uptake. Fifty percent of patients with stage II sarcoidosis, with both BHL and pulmonary involvement on chest X-ray, showed increased lung {sup 67}Ga uptake. The patients with increased lung {sup 67}Ga uptake showed decreased percent vital capacity and increased alveolar-arterial oxygen tension difference, but none of them showed clinical deterioration during the follow-up period of more than 6 months. Fifty-four percent of subjects with IPF sowed increased lung {sup 67}Ga uptake. But there was no difference between the subgroups with normal and increased lung {sup 67}Ga uptake with respect to the severity of dyspnea, percent vital capacity, arterial oxygen tension, or alveolar-arterial oxygen tension difference. There was also no difference between the two subgroups of IPF in the cumulative percent survival after either the onset of symptoms or the {sup 67}Ga scintigram. We conclude that lung {sup 67}Ga uptake was not able to predict the clinical course or the prognosis of patients with sarcoidosis and IPF. (author).

Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary absorption of encapsulated insulin compared with co-administered insulin.

Science.gov (United States)

Chono, Sumio; Togami, Kohei; Itagaki, Shirou

2017-11-01

We have previously shown that aerosolized liposomes with dipalmitoyl phosphatidylcholine (DPPC) enhance the pulmonary absorption of encapsulated insulin. In this study, we aimed to compare insulin encapsulated into the liposomes versus co-administration of empty liposomes and unencapsulated free insulin, where the DPCC liposomes would serve as absorption enhancer. The present study provides the useful information for development of noninvasive treatment of diabetes. Co-administration of empty DPPC liposomes and unencapsulated free insulin was investigated in vivo to assess the potential enhancement in protein pulmonary absorption. Co-administration was compared to DPPC liposomes encapsulating insulin, and free insulin. DPPC liposomes enhanced the pulmonary absorption of unencapsulated free insulin; however, the enhancing effect was lower than that of the DPPC liposomes encapsulating insulin. The mechanism of the pulmonary absorption of unencapsulated free insulin by DPPC liposomes involved the opening of epithelial cell space in alveolar mucosa, and not mucosal cell damage, similar to that of the DPPC liposomes encapsulating insulin. In an in vitro stability test, insulin in the alveolar mucus layer that covers epithelial cells was stable. These findings suggest that, although unencapsulated free insulin spreads throughout the alveolar mucus layer, the concentration of insulin released near the absorption surface is increased by the encapsulation of insulin into DPPC liposomes and the absorption efficiency is also increased. We revealed that the encapsulation of insulin into DPPC liposomes is more effective for pulmonary insulin absorption than co-administration of DPPC liposomes and unencapsulated free insulin.

Pulmonary surfactant and its components inhibit secretion of phosphatidylcholine from cultured rat alveolar type II cells

International Nuclear Information System (INIS)

Dobbs, L.G.; Wright, J.R.; Hawgood, S.; Gonzalez, R.; Venstrom, K.; Nellenbogen, J.

1987-01-01

Pulmonary surfactant is synthesized and secreted by alveolar type II cells. Radioactive phosphatidylcholine has been used as a marker for surfactant secretion. The authors report findings that suggest that surfactant inhibits secretion of 3 H-labeled phosphatidylcholine by cultured rat type II cells. The lipid components and the surfactant protein group of M/sub r/ 26,000-36,000 (SP 26-36) inhibit secretion to different extents. Surfactant lipids do not completely inhibit release; in concentrations of 100 μg/ml, lipids inhibit stimulated secretion by 40%. SP 26-36 inhibits release with an EC 50 of 0.1 μg/ml. At concentrations of 1.0 μg/ml, SP 26-36 inhibits basal secretion and reduces to basal levels secretion stimulated by terbutaline, phorbol 12-myristate 13-acetate, and the ionophore A23187. The inhibitory effect of SP 26-36 can be blocked by washing type II cells after adding SP 26-36, by heating the proteins to 100 0 C for 10 min, by adding antiserum specific to SP 26-36, or by incubating cells in the presence of 0.2 mM EGTA. SP 26-36 isolated from canine and human sources also inhibits phosphatidylcholine release from rat type II cells. Neither type I collagen nor serum apolipoprotein A-1 inhibits secretion. These findings are compatible with the hypothesis that surfactant secretion is under feedback regulatory control

Scintiscanning and Roentgenographic Procedures in Managing Major Pulmonary Disorders

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Taplin, G. V.; Poe, N. D. [UCLA School of Medicine, Los Angeles (United States); Dore, E. K. [Memorial Hospital, Long Beach (United States); Swanson, L. A.; Isawa, T. [Los Angeles County Harbor General Hospital, Torrance (United States); Greenberg, A. [Olive View Hospital, Olive View, CA (United States)

1969-05-15

The need for practical methods which measure regional as well as integrated pulmonary functions is largely fulfilled by two types of scintiscanning procedure. Chest scanning after the intravenous injection of radioalbumin macroaggregates is a safe and widely applicable procedure for measuring relative arterial perfusion to all parts of the lung. The lung scan image is a photograhic pattern of pulmonary arterial blood flow. Its unique capacity to reveal localized ischemia makes scanning a valuable test of regional lung function, because oligemic lung can not conduct gas exchange normally. The scan has no diagnostic significance by itself but when interpreted in conjunction with chest films and pertinent clinical and laboratory data, scanning becomes a useful diagnostic adjunct and supplements the results of pulmonary function tests and roentgenographic procedures. Chest scanning after radioaerosol inhalation delineates the volume of aerated lung and gives a measure of regional alveolar ventilation in normal subjects and patients without obstructive airways disease. In patients with bronchogenic carcinoma, chronic bronchitis, bronchiectasis and emphysema, the inhalation scan reveals the site(s) of partial or total obstruction but does not give a true measure of alveolar ventilation. In such patients, repeated scans performed 6-18 hours later, when excessive aerosol deposits in the airways are removed by the ciliary escalator mechanism, provide more reliable information on regional disturbances of alveolar ventilation. Both types of lung scintiscanning may be performed during the same visit by using radioactive test agents of widely different energy spectra, such as {sup 99m}Tc albumin aerosol followed by {sup 131}I albumin macroaggregates. This report reviews our five years clinical experience with chest scintiscanning and roentgenography in studying nearly 5000 patients with pulmonary disease. The major categories included: suspected pulmonary embolism, proven

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

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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.

Associations between thoracic radiographic changes and severity of pulmonary arterial hypertension diagnosed in 60 dogs via Doppler echocardiography: A retrospective study.

Science.gov (United States)

Adams, Dustin S; Marolf, Angela J; Valdés-Martínez, Alejandro; Randall, Elissa K; Bachand, Annette M

2017-07-01

Doppler echocardiography is a noninvasive method for estimating and grading pulmonary arterial hypertension. No current literature associates significance of radiographic findings with severity of pulmonary arterial hypertension. We hypothesized that the number and conspicuity of radiographic findings suggestive of pulmonary arterial hypertension would be greater based on the severity of pulmonary arterial hypertension. Dogs with pulmonary arterial hypertension and normal control dogs were included in this retrospective, case control study. Three radiologists blinded to echocardiographic results scored thoracic radiographs for right ventricular and main pulmonary artery enlargement and pulmonary lobar artery enlargement, tortuosity, and blunting by multiple methods. Presence or absence of each finding was scored in an additive fashion and averaged for each grade of pulmonary arterial hypertension severity. Seventy-one dogs (60 dogs with pulmonary arterial hypertension and 11 control dogs) of which some had multiple studies were included: 20 mild, 21 moderate, 25 severe, and 11 absent pulmonary arterial hypertension. The following radiographic findings were significantly associated with increasing pulmonary arterial hypertension severity: right ventricular enlargement by "reverse D" and "3/5-2/5 cardiac ratio" methods, main pulmonary artery enlargement, and caudal lobar artery enlargement by the "3rd rib" method. Mean scores for severe pulmonary arterial hypertension and normal dogs were significantly different (P-value < 0.0001). Mean scores between different pulmonary arterial hypertension grades increased with severity but were not statistically significant. Individually and in combination, radiographic findings performed poorly in differentiating severity of pulmonary arterial hypertension. Findings indicated that thoracic radiographs should be utilized in conjunction with Doppler echocardiography in a complete diagnostic work-up for dogs with suspected

Management of Severe Hemoptysis from Pulmonary Aspergilloma Using Endovascular Embolization

International Nuclear Information System (INIS)

Corr, Peter

2006-01-01

Purpose. To determine the effectiveness of endovascular embolization as a temporizing measure in the management of severe hemoptysis caused by intracavitary pulmonary aspergilloma. Methods. Patients presenting with hemoptysis, estimated to be more than 300 ml in the preceding 24 hr, in whom a radiological diagnosis of pulmonary aspergilloma was made on chest radiographs and/or computed tomography of the chest were subjected to bronchial and systemic arteriography and embolization using triacryl microspheres. Results. Twelve patients with upper lobe intracavitary aspergillomas were managed with embolization. In 11 patients hemoptysis stopped within 24 hr and with no recurrence over the next 4 weeks. In 1 patient hemoptysis persisted and an upper lobe lobectomy was performed. Conclusion. Embolization of bronchial and systemic arteries is an effective method for treating acute severe hemoptysis from intracavitary aspergillomas, allowing the patient time to recover for definitive surgical management

[Severe pulmonary embolism revealed by status epilepticus].

Science.gov (United States)

Allou, N; Coolen-Allou, N; Delmas, B; Cordier, C; Allyn, J

2016-12-01

High-risk pulmonary embolism (PE) is associated with high mortality rate (>50%). In some cases, diagnosis of PE remains a challenge with atypical presentations like in this case report with a PE revealed by status epilepticus. We report the case of a 40-year-old man without prior disease, hospitalized in ICU for status epilepticus. All paraclinical examinations at admission did not show any significant abnormalities (laboratory tests, cardiologic and neurological investigations). On day 1, he presented a sudden circulatory collapse and echocardiography showed right intra-auricular thrombus. He was treated by thrombolysis and arteriovenous extracorporeal membrane oxygenation. After stabilization, computed tomography showed severe bilateral PE. He developed multi-organ failure and died 4days after admission. Pulmonary embolism revealed by status epilepticus has rarely been reported and is associated with poor prognosis. Physicians should be aware and think of the possibility of PE in patients with status epilepticus without any history or risk factors of seizure and normal neurological investigations. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Opsonic Phagocytosis in Chronic Obstructive Pulmonary Disease is Enhanced by Nrf2 Agonists.

NARCIS (Netherlands)

Bewley, Martin A; Budd, Richard C; Ryan, Eilise; Cole, Joby; Collini, Paul; Marshall, Jennifer; Kolsum, Umme; Beech, Gussie; Emes, Richard D; Tcherniaeva, Irina; Berbers, Guy A M; Walmsley, Sarah R; Donaldson, Gavin; Wedzicha, Jadwiga A; Kilty, Iain; Rumsey, William; Sanchez, Yolanda; Brightling, Christopher E; Donnelly, Louise E; Barnes, Peter J; Singh, Dave; Whyte, Moira K B; Dockrell, David H

2018-01-01

Previous studies have identified defects in bacterial phagocytosis by alveolar macrophages (AM) in patients with chronic obstructive pulmonary disease (COPD) but the mechanisms and clinical consequences remain incompletely defined.

Inflammasome Inhibition Suppresses Alveolar Cell Permeability Through Retention of Neuregulin-1 (NRG-1

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Rajanbabu Venugopal

2015-07-01

Full Text Available Background: Neuregulin (NRG-1-human epidermal receptor (HER-2 signaling pathway is a key regulator of IL-1β-mediated pulmonary inflammation and epithelial permeability. The inflammasome is a newly discovered molecular platform required for caspase-1 activation and maturation of IL-1β. However, the role of the inflammasome in NRG-1-HER2 signaling-mediated alveolar cell permeability is unknown. Methods: The inflammasome was activated or inhibited in THP-1 cells; supernatants from these cells were added to A549 cells and human small airway epithelial cells (HSAEC. The protein expression of NRG-1 and phospho-HER2 (pHER2 were measured by Western blot analysis and epithelial permeability was measured using Lucifer yellow dye. Results: Results reveal that alveolar permeability in A549 cells and HSAEC is increased when treated with supernatants of inflammasome-activated THP-1 cells. Alveolar permeability is significantly suppressed when treated with supernatant of inflammasome-inhibited THP-1 cells. Inflammasome-mediated permeability is decreased when A549 cells and HSAEC are pretreated with IL-1β receptor antagonist (IL-1βRA. In addition, HER2 kinase inhibitor AG825 or NRG-1 inhibitor TAPI inhibits inflammasome-mediated permeability in A549 cells and HSAEC demonstrating critical roles of IL-1β, NRG-1, and HER2 in inflammasome-mediated alveolar permeability. Conclusion: These findings suggest that inflammasome-induced alveolar cell permeability is mediated by NRG-1/HER2 signaling through IL-1β regulation.

Biophysical Influence of Airborne Carbon Nanomaterials on Natural Pulmonary Surfactant

OpenAIRE

Valle, Russell P.; Wu, Tony; Zuo, Yi Y.

2015-01-01

Inhalation of nanoparticles (NP), including lightweight airborne carbonaceous nanomaterials (CNM), poses a direct and systemic health threat to those who handle them. Inhaled NP penetrate deep pulmonary structures in which they first interact with the pulmonary surfactant (PS) lining at the alveolar air–water interface. In spite of many research efforts, there is a gap of knowledge between in vitro biophysical study and in vivo inhalation toxicology since all existing biophysical models handl...

Pulmonary function vascular index predicts prognosis in idiopathic interstitial pneumonia

NARCIS (Netherlands)

Corte, Tamera J.; Wort, Stephen J.; MacDonald, Peter S.; Edey, Anthony; Hansell, David M.; Renzoni, Elisabetta; Maher, Toby M.; Nicholson, Andrew G.; Bandula, Steven; Bresser, Paul; Wells, Athol U.

2012-01-01

Background and objective: Pulmonary hypertension (PH) is associated with increased mortality in fibrotic idiopathic interstitial pneumonia (IIP). We hypothesize that baseline KCO (diffusing capacity of carbon monoxide/alveolar volume) and 6-month decline in KCO reflect PH, thus predicting mortality

Computed chest tomography in rats with pulmonary damage due to microembolism

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Wegener, T.; Wegenius, G.; Hemmingsson, A.; Jung, B.; Saldeen, T.

Computed chest tomography was performed in 13 rats with pulmonary damage due to microembolism, caused by injection of thrombin (500 NIH/kg body weight) and tranexamic acid, a fibrinolytic inhibitor (200 mg/kg body weight), and in 9 control rats. The purpose of the investigation was to perform attenuation measurements at two levels of the right lung, each with three regions of interest (anterior, mid and posterior). Alterations in attenuation, compared with controls, were correlated with lung weight. Compared with controls, the attenuation was significantly increased in the anterior and posterior regions at both levels in animals with pulmonary damage, but not in the mid regions. There was a statistically significant correlation between increasing attenuation and increasing lung weight. A significant difference was found between damaged and control lungs regarding the microscopic grade of interstitial oedema, alveolar oedema and fibrin. Histograms of attenuation values in computed tomograms might be of value in detecting alveolar oedema. It is concluded that computed chest tomography is a good method for detection pulmonary oedema at an early stage of experimental microembolism in the rat.

Computed chest tomography in rats with pulmonary damage due to microembolism

International Nuclear Information System (INIS)

Wegener, T.; Wegenius, G.; Hemmingsson, A.; Jung, B.; Saldeen, T.; Uppsala Univ.; Uppsala Univ.; Uppsala Univ.

1986-01-01

Computed chest tomography was performed in 13 rats with pulmonary damage due to microembolism, caused by injection of thrombin (500 NIH/kg body weight) and tranexamic acid, a fibrinolytic inhibitor (200 mg/kg body weight), and in 9 control rats. The purpose of the investigation was to perform attenuation measurements at two levels of the right lung, each with three regions of interest (anterior, mid and posterior). Alterations in attenuation, compared with controls, were correlated with lung weight. Compared with controls, the attenuation was significantly increased in the anterior and posterior regions at both levels in animals with pulmonary damage, but not in the mid regions. There was a statistically significant correlation between increasing attenuation and increasing lung weight. A significant difference was found between damaged and control lungs regarding the microscopic grade of interstitial oedema, alveolar oedema and fibrin. Histograms of attenuation values in computed tomograms might be of value in detecting alveolar oedema. It is concluded that computed chest tomography is a good method for detection pulmonary oedema at an early stage of experimental microembolism in the rat. (orig.)

Pulmonary arterial pressure and right ventricular dilatation independently determine tricuspid valve insufficiency severity in pre-capillary pulmonary hypertension.

Science.gov (United States)

De Meester, Pieter; Van De Bruaene, Alexander; Delcroix, Marion; Belmans, Ann; Herijgers, Paul; Voigt, Jens-Uwe; Budts, Werner

2012-11-01

Elevated pulmonary artery systolic pressure (PASP) causes functional tricuspid valve insufficiency (TI). However, the differential contribution of pressure load and right ventricular (RV) dilatation is not well established. The study aim was to evaluate both variables in relation to TI. A cross-sectional study was performed of consecutive transthoracic echocardiographic studies of patients with pre-capillary pulmonary hypertension (PH). Both, demographic data and echocardiographic RV parameters were reviewed. TI was graded semi-quantitatively with color Doppler flow imaging. Trend analyses for TI severity (TI grade 0/4, 1/4, 2/4, 3/4, or 4/4) were performed. A proportional odds logistic regression analysis was carried out to identify independent predictors of TI severity. Eighty-one patients (56 females, 25 males; mean age 60 +/- 15 years) with pre-capillary PH were evaluated. Patients with more severe TI had a significantly lower body mass index, a lower mean systemic blood pressure, a shorter pulmonary acceleration time, a higher tricuspid regurgitant gradient, and a more dilated right ventricle. From the echocardiographic parameters, RV dilatation (p = 0.0143) and the tricuspid regurgitant gradient (p = 0.0026) were independently related to the degree of TI. In patients with pre-capillary PH, PASP and RV dilatation were both related to the increasing severity of TI. When focusing on TI to improve the prognosis of patients with pre-capillary PH, both PASP and RV dimensions should be taken into consideration.

Dynamic 99mTc-DTPA radioaerosol lung scanning for the evaluation of alveolar-capillary barrier permeability

International Nuclear Information System (INIS)

Maini, C.L.; Marchetti, L.; Bonetti, M.G.; Giordano, A.; Pistelli, R.; Antonelli Incalzi, R.

1987-01-01

Pulmonary clearance of small droplet 99m Tc-DTPA radioaerosol was studied in 100 patients (12 normal subjects, N; 10 asymptomatic healthy smoker, FA; 31 patients with interstitial lung diseases, IP; 47 patients with chronic obstructive lung disease, BPCO). The first seven minutes of clearance were described with the function At=Ao*exp(-K*t) and the time constant K was considered representative of the 99m Tc-DTPA clearance rate and hence of the alveolar-capillary barrier permeability. Groups FA, IP and BPCO showed a significant (p 99m Tc-DTPA dynamic lung scanning is an easy, non-invasive method to assess derangements of alveolar-capillary barrier permeability secondary to epithelial damage; 2) permeability increase is a very early effect of cigarette smoke damafe to the epithelium; 3) other mechanisms of epithelial injury are present in diffuse lung disease; 4) while the clinical role of this new pathophysiological test is not yet clear, it is likely that it may become a very early marker of pulmonary epithelial damage in diffuse lung disease

Distracción osteogénica alveolar como método de aumento del reborde alveolar Alveolar osteogenic distraction as method to increase the alveolar ridge

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Denia Morales Navarro

2011-03-01

Full Text Available La distracción osteogénica alveolar, como proceso biológico de neoformación de hueso alveolar, nos motivó a la realización de la presente revisión bibliográfica, con el objetivo enfatizar en el análisis de las variables: antecedentes históricos en Cuba, clasificación de los distractores, fases de la distracción (latencia, distracción y consolidación, indicaciones, contraindicaciones, ventajas, desventajas y complicaciones. Se realizó una revisión bibliográfica mediante la consulta de bases de datos de los sistemas referativos, como MEDLINE y PubMed con la utilización de descriptores "alveolar distraction" y "osteogenic distraction". Se consultaron las fuentes bibliográficas publicadas fundamentalmente en los últimos 5 años, lo que reveló que esta técnica es una excelente alternativa para la formación de huesos y tejidos blandos en zonas de atrofia alveolar, que consta de tres etapas: latencia, distracción y consolidación; un método previsible y con bajas tasas de reabsorción ósea en comparación con otras técnicas de aumento del reborde alveolar. Tiene su principal indicación en la terapia de implantes al proveer volumen óseo. Debemos individualizar cada caso y usar el método más adecuado según las características clínicas y personales del paciente. Una adecuada selección de los casos y una mejor comprensión de la técnica son los puntales para lograr exitosos resultados mediante la distracción osteogénica alveolar. En Cuba se ha aplicado poco la distracción alveolar, por lo que ha sido necesario ampliar los estudios sobre esta temática.The alveolar osteogenic distraction, as a biological process of alveolar bone neoformation, motivates us to make the bibliographic review whose objective was to emphasize in analysis the following variables: historical backgrounds in Cuba, distraction classification, distraction phases (latency, distraction and consolidation, indications, contraindications, advantages

Serum Pentraxin 3 and hs-CRP Levels in Children with Severe Pulmonary Hypertension

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Cemşit Karakurt

2014-09-01

Full Text Available Background: Pulmonary arterial hypertension secondary to untreated left-to-right shunt defects leads to increased pulmonary blood flow, endothelial dysfunction, increased pulmonary vascular resistance, vascular remodelling, neointimal and plexiform lesions. Some recent studies have shown that inflammation has an important role in the pathophysiology of pulmonary arterial hypertension. Aims: The aim of this study is to evaluate serum pentraxin 3 and high sensitive (hs-C reactive protein (hs-CRP levels in children with severe pulmonary arterial hypertension (PAH secondary to untreated congenital heart defects and evaluate the role of inflammation in pulmonary hypertension. Study Design: Cross sectional study. Methods: After ethics committee approval and receiving consent from parents, there were 31 children were selected for the study with severe PAH, mostly with a left-to-right shunt, who had been assessed by cardiac catheterisation and were taking specific pulmonary vasodilators. The control group consisted of 39 age and gender matched healthy children. After recording data about all the patients including age, gender, weight, haemodynamic studies and vasodilator testing, a physical examination was done for all subjects. Blood was taken from patients and the control group using peripheral veins to analyse serum Pentraxin 3, N-terminal pro-Brain Natriuretic Peptide (NT-ProBNP and hs-CRP levels. Serum Pentraxin-3 levels were measured by enzyme linked immunosorbent assay (ELISA and expressed as ng/mL. Serum hs-CRP levels were measured with an immunonephelometric method and expressed as mg/dL. The serum concentration of NT-proBNP was determined by a chemiluminescent immunumetric assay and expressed as pg/mL. Results: Serum Pentraxin- 3 levels were determined to be 1.28±2.12 (0.12-11.43 in the PAH group (group 1 and 0.40±0.72 (0.07-3.45 in group 2. There was a statistically significant difference between the two groups (p<0.01. Serum hs-CRP levels

Murine iPSC-Derived Macrophages as a Tool for Disease Modeling of Hereditary Pulmonary Alveolar Proteinosis due to Csf2rb Deficiency

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Adele Mucci

2016-08-01

Full Text Available Induced pluripotent stem cells (iPSCs represent an innovative source for the standardized in vitro generation of macrophages (Mφ. We here describe a robust and efficient protocol to obtain mature and functional Mφ from healthy as well as disease-specific murine iPSCs. With regard to morphology, surface phenotype, and function, our iPSC-derived Mφ (iPSC-Mφ closely resemble their counterparts generated in vitro from bone marrow cells. Moreover, when we investigated the feasibility of our differentiation system to serve as a model for rare congenital diseases associated with Mφ malfunction, we were able to faithfully recapitulate the pathognomonic defects in GM-CSF signaling and Mφ function present in hereditary pulmonary alveolar proteinosis (herPAP. Thus, our studies may help to overcome the limitations placed on research into certain rare disease entities by the lack of an adequate supply of disease-specific primary cells, and may aid the development of novel therapeutic approaches for herPAP patients.

Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury.

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Hasan, Djo; Blankman, Paul; Nieman, Gary F

2017-09-01

Severe pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high ATP levels despite the conversion to adenosine. Above a certain level, extracellular ATP molecules act as danger-associated molecular patterns (DAMPs) and activate the pro-inflammatory response of the innate immunity through purinergic receptors on the surface of the immune cells. This results in lung tissue inflammation, capillary leakage, interstitial and alveolar oedema and lung injury reducing the production of surfactant by the damaged AT II cells and deactivating the surfactant function by the concomitant extravasated serum proteins through capillary leakage followed by a substantial increase in alveolar surface tension and alveolar collapse. The resulting inhomogeneous ventilation of the lungs is an important mechanism in the development of ventilation-induced lung injury. The high levels of extracellular ATP and the upregulation of ecto-enzymes and soluble enzymes that hydrolyse ATP to adenosine (CD39 and CD73) increase the extracellular adenosine levels that inhibit the innate and adaptive immune responses rendering the host susceptible to infection by invading microorganisms. Moreover, high levels of extracellular adenosine increase the expression, the production and the activation of pro-fibrotic proteins (such as TGF-β, α-SMA, etc.) followed by the establishment of lung fibrosis.

Salmeterol improves fluid clearance from alveolar-capillary membrane in COPD patients: a pilot study.

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Di Marco, Fabiano; Guazzi, Marco; Sferrazza Papa, Giuseppe Francesco; Vicenzi, Marco; Santus, Pierachille; Busatto, Paolo; Piffer, Federico; Blasi, Francesco; Centanni, Stefano

2012-02-01

The cardiovascular component associated with chronic obstructive pulmonary disease (COPD) plays a major role in disease prognosis, accounting for 25% of the deaths. Experimental and initial clinical data suggest that beta-adrenergic agonists accelerate fluid clearance from the alveolar airspace, with potentially positive effects on cardiogenic and noncardiogenic pulmonary oedema. This pilot study investigated the acute effects of the long-acting beta-2 agonist, salmeterol, on alveolar fluid clearance after rapid saline intravenous infusion by evaluating diffusive and mechanical lung properties. Ten COPD and 10 healthy subjects were treated with salmeterol or placebo 4 h before the patient's mechanical and diffusive lung properties were measured during four non consecutive days, just before and after a rapid saline infusion, or during a similar period without an infusion. In both COPD and healthy subjects, rapid saline infusion with placebo or salmeterol premedication lead to a significant decrease in diffusion capacity for carbon monoxide (DLCO) and forced expiratory volume in 1 s (FEV1). Nonetheless, salmeterol pretreatment lead to a significantly reduced gas exchange impairment caused by saline infusion (-64% of DLCO reduction compared with placebo), whereas it did not affect changes in FEV1. In the control setting with no infusion, we found no significant change in either DLCO or mechanical properties of the lung. Salmeterol appears to provide a protective effect, not related to bronchodilation, against an acute alveolar fluid clearance challenge secondary to lung fluid overload in COPD patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pulmonary toxicity of well-dispersed titanium dioxide nanoparticles following intratracheal instillation

International Nuclear Information System (INIS)

Yoshiura, Yukiko; Izumi, Hiroto; Oyabu, Takako; Hashiba, Masayoshi; Kambara, Tatsunori; Mizuguchi, Yohei; Lee, Byeong Woo; Okada, Takami; Tomonaga, Taisuke; Myojo, Toshihiko; Yamamoto, Kazuhiro; Kitajima, Shinichi; Horie, Masanori; Kuroda, Etsushi; Morimoto, Yasuo

2015-01-01

In order to investigate the pulmonary toxicity of titanium dioxide (TiO 2 ) nanoparticles, we performed an intratracheal instillation study with rats of well-dispersed TiO 2 nanoparticles and examined the pulmonary inflammation and histopathological changes in the lung. Wistar Hannover rats were intratracheally administered 0.2 mg (0.66 mg/kg) and 1.0 mg (3.3 mg/kg) of well-dispersed TiO 2 nanoparticles (P90; diameter of agglomerates: 25 nm), then the pulmonary inflammation responses were examined from 3 days to 6 months after the instillation, and the pathological features were examined up to 24 months. Transient inflammation and the upregulation of chemokines in the broncho-alveolar lavage fluid were observed for 1 month. No respiratory tumors or severe fibrosis were observed during the recovery time. These data suggest that transient inflammation induced by TiO 2 may not lead to chronic, irreversible legions in the lung, and that TiO 2 nanoparticles may not have a high potential for lung disorder

Pulmonary toxicity of well-dispersed titanium dioxide nanoparticles following intratracheal instillation

Energy Technology Data Exchange (ETDEWEB)

Yoshiura, Yukiko, E-mail: y-yoshiura@med.uoeh-u.ac.jp; Izumi, Hiroto [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan); Oyabu, Takako [University of Occupational and Environmental Health, Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences (Japan); Hashiba, Masayoshi; Kambara, Tatsunori [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan); Mizuguchi, Yohei; Lee, Byeong Woo; Okada, Takami [University of Occupational and Environmental Health, Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences (Japan); Tomonaga, Taisuke [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan); Myojo, Toshihiko [University of Occupational and Environmental Health, Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences (Japan); Yamamoto, Kazuhiro [National Institute of Advanced Industrial Science and Technology (AIST) (Japan); Kitajima, Shinichi [National Sanatorium Hoshizuka Keiaien (Japan); Horie, Masanori [National Institute of Advanced Industrial Science and Technology (AIST), Health Research Institute (HRI) (Japan); Kuroda, Etsushi [Osaka University, Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (Japan); Morimoto, Yasuo [University of Occupational and Environmental Health, Department of Occupational Pneumology, Institute of Industrial Ecological Science (Japan)

2015-06-15

In order to investigate the pulmonary toxicity of titanium dioxide (TiO{sub 2}) nanoparticles, we performed an intratracheal instillation study with rats of well-dispersed TiO{sub 2} nanoparticles and examined the pulmonary inflammation and histopathological changes in the lung. Wistar Hannover rats were intratracheally administered 0.2 mg (0.66 mg/kg) and 1.0 mg (3.3 mg/kg) of well-dispersed TiO{sub 2} nanoparticles (P90; diameter of agglomerates: 25 nm), then the pulmonary inflammation responses were examined from 3 days to 6 months after the instillation, and the pathological features were examined up to 24 months. Transient inflammation and the upregulation of chemokines in the broncho-alveolar lavage fluid were observed for 1 month. No respiratory tumors or severe fibrosis were observed during the recovery time. These data suggest that transient inflammation induced by TiO{sub 2} may not lead to chronic, irreversible legions in the lung, and that TiO{sub 2} nanoparticles may not have a high potential for lung disorder.

Surgical outcome of severe pulmonary arterial hypertension secondary to left-to-right shunt lesions

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Cha Gon Lee

2010-02-01

Full Text Available Purpose : Despite recent advances in pulmonary hypertension management and surgery, appropriate guidelines remain to be developed for operability in congenital heart disease with pulmonary artery hypertension (PAH. Our aim was to evaluate clinical outcomes of patients with severe PAH who underwent surgical closure of left-to-right shunt lesions (LRSL on the basis of pulmonary reactivity. Methods : We retrospectively reviewed 21 patients who underwent surgical closure of LRSL with severe PAH (?#248; Wood unit from January 1995 to April 2009. The median age at operation was 26 years. Atrial septal defect, ventricular septal defect (VSD, VSD and patent ductus arteriosus (PDA, and PDA was present in 11, 4, 4, and 2 patients, respectively. Results : Operability was based on vasoreactivity of PAH. Of the 21 patients, 5 showed response to pulmonary vasodilator therapy and 8 showed vasoreactivity after balloon occlusion of defects. The remaining 8 patients were considered operable because of significant left-to-right shunt (Qp/Qs ?#241;.5. Five patients underwent total closure of defects and 16 were left with small residual shunts. The median follow-up duration was 32 months. There was no significant postoperative mortality or morbidity. Systolic pulmonary artery pressure (PAP decreased in all but 2 patients. All patients except 1 showed improvement of New York Heart Association functional class. Conclusion : Closure of LRSL in patients with severe PAH on the basis of pulmonary vasoreactivity seems reasonable. PAP and clinical symptoms improved in most patients. Further research is needed for the evaluation of long-term results.

Quantitation and renewal of alveolar and bronchiolar cell populations of rat lungs. Changes during some pathological processes

International Nuclear Information System (INIS)

Fritsch, Paul.

1979-02-01

The various cells of alveolar and bronchiolar tissues of rat lungs were studied qualitatively and quantitatively. In physiological conditions, the renewal rate of the cell populations is low and the frequency of the various cell types is constant. This stability, especially at the level of the alveolar tissue, was also found during the latency period and the development of radiation-induced lung cancers. A particular cellular population was demonstrated: marginated leukocyte pool at the level of the pulmonary circulation. This pool was different both qualitatively and quantitatively from the leukocytes of the systemic circulation and, in physiological conditions, behaved as a cellular reservoir of monocytes chiefly re-distributed according to the body needs. In pathological conditions, its fast migration contributed to the defence of the alveolar medium. A quantitative study of the renewal of alveolar macrophages showed that under 1 p. cent of the marginated leukocyte pool is used daily to keep up this population. This fraction undergoes a maturation stage by cellular division within the endoalveolar medium. In some pathological conditions, this division can be completely inhibited [fr

Validation of two-dimensional and three-dimensional measurements of subpleural alveolar size parameters by optical coherence tomography

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Unglert, Carolin I.; Warger, William C.; Hostens, Jeroen; Namati, Eman; Birngruber, Reginald; Bouma, Brett E.; Tearney, Guillermo J.

2012-12-01

Optical coherence tomography (OCT) has been increasingly used for imaging pulmonary alveoli. Only a few studies, however, have quantified individual alveolar areas, and the validity of alveolar volumes represented within OCT images has not been shown. To validate quantitative measurements of alveoli from OCT images, we compared the cross-sectional area, perimeter, volume, and surface area of matched subpleural alveoli from microcomputed tomography (micro-CT) and OCT images of fixed air-filled swine samples. The relative change in size between different alveoli was extremely well correlated (r>0.9, Pvolume), and 25% (surface area) on average. We hypothesized that the differences resulted from refraction at the tissue-air interfaces and developed a ray-tracing model that approximates the reconstructed alveolar size within OCT images. Using this model and OCT measurements of the refractive index for lung tissue (1.41 for fresh, 1.53 for fixed), we derived equations to obtain absolute size measurements of superellipse and circular alveoli with the use of predictive correction factors. These methods and results should enable the quantification of alveolar sizes from OCT images in vivo.

Alveolar macrophages and type I IFN in airway homeostasis and immunity.

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Divangahi, Maziar; King, Irah L; Pernet, Erwan

2015-05-01

Globally, respiratory infections cause more than 4 million deaths per year, with influenza and tuberculosis (TB) in particular being major causes of mortality and morbidity. Although immune cell activation is critical for killing respiratory pathogens, this response must be tightly regulated to effectively control and eliminate invading microorganisms while minimizing immunopathology and maintaining pulmonary function. The distinct microenvironment of the lung is constantly patrolled by alveolar macrophages (Mφ), which are essential for tissue homeostasis, early pathogen recognition, initiation of the local immune response, and resolution of inflammation. Here, we focus on recent advances that have provided insight into the relation between pulmonary Mφ, type I interferon (IFN) signaling, and the delicate balance between protective and pathological immune responses in the lung. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pathology and pathophysiology of pulmonary manifestations in leptospirosis

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Marisa Dolhnikoff

Full Text Available Leptospirosis is a re-emerging zoonosis occurring as large outbreaks throughout the world caused by Leptospira interrogans. The incidence of pulmonary involvement in leptospirosis has been reported to be increasing in the last years, affecting up to 70% of the patients. Alveolar hemorrhage presented as dyspnea and hemoptysis is the main pulmonary manifestation. The emergence of massive hemoptysis and acute respiratory distress syndrome has characterized the recent changes reported in the clinical patterns of leptospirosis. The pulmonary involvement has been emerged as a serious life threat, becoming the main cause of death due to leptospirosis in some countries. In this review we present the main clinical and pathological manifestations of pulmonary involvement in leptospirosis, with special focus on recent data concerning the pathophysiological mechanisms underlying lung injury.

The CT appearances of delayed amniotic fluid clearance from the lungs in an infant with absent pulmonary valve and congenital lobar emphysema

International Nuclear Information System (INIS)

Fink, A. Michelle; Edis, Brian; Massie, John

2005-01-01

Congenital lobar emphysema (CLE) is a cause of severe neonatal respiratory distress. Overexpansion of the affected pulmonary lobe in the fetus is due to narrowing of the airway, with a resultant 'ball-valve' effect. At birth, there may be delayed clearance of fetal lung fluid. Early chest radiographs show opacification of the hyperexpanded lobe. The CT findings in the immediate neonatal period have not been previously reported. We describe the imaging in a neonate with tetralogy of Fallot and absent pulmonary valve with secondary CLE. CT demonstrates the hyperexpanded lobe with initial thickening of the interlobular septa and alveolar ground glass attenuation, with subsequent clearing. This resorption of fetal lung fluid via the pulmonary interstitium should not be confused with interstitial lung disease. (orig.)

The CT appearances of delayed amniotic fluid clearance from the lungs in an infant with absent pulmonary valve and congenital lobar emphysema

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Fink, A. Michelle [Royal Children' s Hospital, Department of Medical Imaging, Parkville, Victoria (Australia); University of Melbourne, Melbourne, Victoria (Australia); Edis, Brian [Royal Children' s Hospital, Department of Cardiology, Parkville, Victoria (Australia); Massie, John [University of Melbourne, Melbourne, Victoria (Australia); Royal Children' s Hospital, Department of Respiratory Medicine, Parkville, Victoria (Australia); Murdoch Children' s Research Institute, Melbourne, Victoria (Australia)

2005-09-01

Congenital lobar emphysema (CLE) is a cause of severe neonatal respiratory distress. Overexpansion of the affected pulmonary lobe in the fetus is due to narrowing of the airway, with a resultant 'ball-valve' effect. At birth, there may be delayed clearance of fetal lung fluid. Early chest radiographs show opacification of the hyperexpanded lobe. The CT findings in the immediate neonatal period have not been previously reported. We describe the imaging in a neonate with tetralogy of Fallot and absent pulmonary valve with secondary CLE. CT demonstrates the hyperexpanded lobe with initial thickening of the interlobular septa and alveolar ground glass attenuation, with subsequent clearing. This resorption of fetal lung fluid via the pulmonary interstitium should not be confused with interstitial lung disease. (orig.)

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)

The contribution of intrapulmonary shunts to the alveolar-to-arterial oxygen difference during exercise is very small

DEFF Research Database (Denmark)

Vogiatzis, Ioannis; Zakynthinos, Spyros; Boushel, Robert

2008-01-01

Exercise is well known to cause arterial PO2 to fall and the alveolar-arterial PO2 difference(Aa PO2 ) to increase. Until recently, the physiological basis for this was considered to be mostly ventilation/perfusion ((.)VA/(.)Q) inequality and alveolar-capillary diffusion limitation. Recently......, arterio-venous shunting through dilated pulmonary blood vessels has been proposed to explain a significant part of the Aa PO2 during exercise. To test this hypothesis we determined venous admixture during 5 min of near-maximal, constant-load, exercise in hypoxia (in inspired O2 fraction, FIO2 , 0...... venous admixture, Aa PO2 and hypoxaemia during heavy exercise....

Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation.

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Moazed, Farzad; Burnham, Ellen L; Vandivier, R William; O'Kane, Cecilia M; Shyamsundar, Murali; Hamid, Umar; Abbott, Jason; Thickett, David R; Matthay, Michael A; McAuley, Daniel F; Calfee, Carolyn S

2016-12-01

Cigarette smoke exposure is associated with an increased risk of the acute respiratory distress syndrome (ARDS); however, the mechanisms underlying this relationship remain largely unknown. To assess pathways of lung injury and inflammation in smokers and non-smokers with and without lipopolysaccharide (LPS) inhalation using established biomarkers. We measured plasma and bronchoalveolar lavage (BAL) biomarkers of inflammation and lung injury in smokers and non-smokers in two distinct cohorts of healthy volunteers, one unstimulated (n=20) and one undergoing 50 μg LPS inhalation (n=30). After LPS inhalation, cigarette smokers had increased alveolar-capillary membrane permeability as measured by BAL total protein, compared with non-smokers (median 274 vs 208 μg/mL, p=0.04). Smokers had exaggerated inflammation compared with non-smokers, with increased BAL interleukin-1β (p=0.002), neutrophils (p=0.02), plasma interleukin-8 (p=0.003), and plasma matrix metalloproteinase-8 (p=0.006). Alveolar epithelial injury after LPS was more severe in smokers than non-smokers, with increased plasma (p=0.04) and decreased BAL (p=0.02) surfactant protein D. Finally, smokers had decreased BAL vascular endothelial growth factor (VEGF) (p<0.0001) with increased soluble VEGF receptor-1 (p=0.0001). Cigarette smoke exposure may predispose to ARDS through an abnormal response to a 'second hit,' with increased alveolar-capillary membrane permeability, exaggerated inflammation, increased epithelial injury and endothelial dysfunction. LPS inhalation may serve as a useful experimental model for evaluation of the acute pulmonary effects of existing and new tobacco products. 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/.

Hormonal regulation of alveolarization: structure-function correlation

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Godinez Marye H

2006-03-01

Full Text Available Abstract Background Dexamethasone (Dex limits and all-trans-retinoic acid (RA promotes alveolarization. While structural changes resulting from such hormonal exposures are known, their functional consequences are unclear. Methods Neonatal rats were treated with Dex and/or RA during the first two weeks of life or were given RA after previous exposure to Dex. Morphology was assessed by light microscopy and radial alveolar counts. Function was evaluated by plethysmography at d13, pressure volume curves at d30, and exercise swim testing and arterial blood gases at both d15 and d30. Results Dex-treated animals had simplified lung architecture without secondary septation. Animals given RA alone had smaller, more numerous alveoli. Concomitant treatment with Dex + RA prevented the Dex-induced changes in septation. While the results of exposure to Dex + RA were sustained, the effects of RA alone were reversed two weeks after treatment was stopped. At d13, Dex-treated animals had increased lung volume, respiratory rate, tidal volume, and minute ventilation. On d15, both RA- and Dex-treated animals had hypercarbia and low arterial pH. By d30, the RA-treated animals resolved this respiratory acidosis, but Dex-treated animals continued to demonstrate blood gas and lung volume abnormalities. Concomitant RA treatment improved respiratory acidosis, but failed to normalize Dex-induced changes in pulmonary function and lung volumes. No differences in exercise tolerance were noted at either d15 or d30. RA treatment after the period of alveolarization also corrected the effects of earlier Dex exposure, but the structural changes due to RA alone were again lost two weeks after treatment. Conclusion We conclude that both RA- and corticosteroid-treatments are associated with respiratory acidosis at d15. While RA alone-induced changes in structure andrespiratory function are reversed, Dex-treated animals continue to demonstrate increased respiratory rate, minute

Chronic obstructive pulmonary disease

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V K Vijayan

2013-01-01

Full Text Available The global prevalence of physiologically defined chronic obstructive pulmonary disease (COPD in adults aged >40 yr is approximately 9-10 per cent. Recently, the Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis in Adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent. The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors. Pathological changes in COPD are observed in central airways, small airways and alveolar space. The proposed pathogenesis of COPD includes proteinase-antiproteinase hypothesis, immunological mechanisms, oxidant-antioxidant balance, systemic inflammation, apoptosis and ineffective repair. Airflow limitation in COPD is defined as a postbronchodilator FEV1 (forced expiratory volume in 1 sec to FVC (forced vital capacity ratio <0.70. COPD is characterized by an accelerated decline in FEV1. Co morbidities associated with COPD are cardiovascular disorders (coronary artery disease and chronic heart failure, hypertension, metabolic diseases (diabetes mellitus, metabolic syndrome and obesity, bone disease (osteoporosis and osteopenia, stroke, lung cancer, cachexia, skeletal muscle weakness, anaemia, depression and cognitive decline. The assessment of COPD is required to determine the severity of the disease, its impact on the health status and the risk of future events (e.g., exacerbations, hospital admissions or death and this is essential to guide therapy. COPD is treated with inhaled bronchodilators, inhaled corticosteroids, oral theophylline and oral phosphodiesterase-4 inhibitor. Non pharmacological treatment of COPD includes smoking cessation, pulmonary rehabilitation and nutritional support. Lung volume reduction surgery and lung transplantation are advised in selected severe patients. Global strategy for the diagnosis, management and prevention of Chronic Obstructive Pulmonary Disease

Effect of glutathione aerosol on oxidant-antioxidant imbalance in idiopathic pulmonary fibrosis.

Science.gov (United States)

Borok, Z; Buhl, R; Grimes, G J; Bokser, A D; Hubbard, R C; Holroyd, K J; Roum, J H; Czerski, D B; Cantin, A M; Crystal, R G

1991-07-27

Idiopathic pulmonary fibrosis (IPF) is characterised by alveolar inflammation, exaggerated release of oxidants, and subnormal concentrations of the antioxidant glutathione in respiratory epithelial lining fluid (ELF). Glutathione (600 mg twice daily for 3 days) was given by aerosol to 10 patients with IPF. Total ELF glutathione rose transiently, ELF oxidised glutathione concentrations increased, and there was a decrease in spontaneous superoxide anion release by alveolar macrophages. Thus, glutathione by aerosol could be a means of reversing the oxidant-antioxidant imbalance in IPF.

Radiological diagnosis of pulmonary edema in chronic renal failure

International Nuclear Information System (INIS)

Tret'yakov, A.E.

1983-01-01

Pulmonary edema has been revealed in 132 patients (51.6 %) during radiologic examination of 256 patients with chronic renal failure. The performance of anterio-posterior chest radiographs was in most cases necessary and quite sufficient for making diagnostic conclusions. Follow up study of patients with pulmonary edema and analysis of radiologic picture of the alterations permitted physicians to distinguish approximately 3 stages of the process development, which transit from one into another. Stage 1 involves early disorders and prodromes of pulmonary edema; Stage 2 interstitial lung edema; Stage 3 alveolar edema. The circulation enforcement of the upper lobar vessels has been the main feature of stage 1. Radiogramometry provided additional information for the pulmonary edema diagnosis. For instance, cardioradiometric data are useful for pulmonary edema diagnosis and evidence in favour of its close connection with heart disorders

Continuous inhaled iloprost in a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension.

Science.gov (United States)

Dykes, John C; Torres, Marilyn; Alexander, Plato J

2016-03-01

This report describes the case of a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension stabilised in the post-operative period with continuous iloprost nebulisation. To our knowledge, this is the first documented method of treating post-operative severe pulmonary arterial hypertension with continuous inhaled iloprost in a patient with complex CHD. We found this method of delivering the drug very effective in stabilising haemodynamic swings in the setting of severe pulmonary arterial hypertension.

[Association of atypical pulmonary TB, polyserositis, severe leukopenia and panniculitis. Case report].

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Mihălţan, F; Lupu, A; Ungureanu, D; Halic, G; Badea, C; Marcu, C

2001-01-01

Many reports have associated tuberculosis with haematological abnormalities. These reports suggest that severe pulmonary tuberculosis, if associated with reduced tissue cellular reaction, may cause blood discrasias. Anemia was present in 32 percent of patients. Leucopenia with neutropenia and lymphopenia was observed in 15 percent in patients with very severe clinical tuberculosis. Active tuberculosis was associated with significant reductions in absolute numbers of total T, T4 and B lymphocytes, but there were no significant differences in total T8 counts. T4 lymphopenia causes reversal of T4/T8 ratio. Also, many histopathologic diagnosis of panniculitis have been reported in tuberculosis patients--the incidence of panniculitis caused by tuberculosis was 8.2%. We present a case of secondary pulmonary tuberculosis with atypically Rx changes, associated with polyserositis and severe leucopenia, which debuted with a panniculitis.

Severe pulmonary hypertension associated with the acute motor sensory axonal neuropathy subtype of Guillain-Barré syndrome.

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Rooney, Kris A; Thomas, Neal J

2010-01-01

To evaluate pulmonary hypertension associated with acute motor sensory axonal neuropathy subtype of Guillain-Barré syndrome. Guillain-Barré syndrome consists of a group of autoimmune disorders that generally manifest as symmetric, progressive, ascending paralysis. There are five subtypes of Guillain-Barré syndrome, and autonomic involvement has been described in all subtypes, including cardiovascular, vasomotor, or pseudomotor dysfunction of both the sympathetic and parasympathetic systems. Case report. Tertiary care pediatric intensive care unit. Three-yr-old female patient. None. Serial measurements of pulmonary artery pressure. We report the case of a young girl with acute motor sensory axonal neuropathy who presented with severe cardiovascular collapse secondary to severe pulmonary hypertension. In this patient, multiple factors may have played a role in the development of pulmonary hypertension including autonomic dysfunction, hypoventilation, and immobility as a risk for thrombosis and pulmonary emboli. It is possible that many other individuals suffering from severe forms of Guillain-Barré syndrome, especially those with significant autonomic dysfunction, may actually have undiagnosed and therefore untreated pulmonary hypertension. Therefore, it is recommended that clinicians caring for critically ill children with Guillain-Barré syndrome have a high index of suspicion for pulmonary hypertension and consider echocardiography if there are clinical signs of this potentially fatal process.

Alveolar epithelial permeability in bronchial asthma in children

International Nuclear Information System (INIS)

Oishi, Takuji

1993-01-01

To evaluate alveolar epithelial permeability (k ep ) in children with bronchial asthma, 99m Tc-DTPA (diethylene triamine penta acetate) aerosol lung inhalation scintigraphies were performed. There was no correlation between the k ep value and the severity of asthma. On the other hand, out of 10 cases which had no aerosol deposition defect in the lung field, 4 showed high k ep values on the whole lung field and 7 had high k ep value areas, particularly apparent in the upper lung field. These results suggest that even when the central airway lesions are mild, severe damage exists in the alveolar region of the peripheral airway. (author)

Loss of Dignity in Severe Chronic Obstructive Pulmonary Disease.

Science.gov (United States)

Solomon, Brahm K; Wilson, Keith G; Henderson, Peter R; Poulin, Patricia A; Kowal, John; McKim, Douglas A

2016-03-01

The maintenance of dignity is an important concept in palliative care, and the loss of dignity is a significant concern among patients with advanced cancer. The goals of this study were to examine whether loss of dignity is also a concern for patients receiving interdisciplinary rehabilitation for Stage III or IV chronic obstructive pulmonary disease. We examined the prevalence and correlates of loss of dignity and determined whether it improves with treatment. Inpatients underwent a structured interview inquiry around their sense of dignity and completed measures of pulmonary, physical, and psychological function at admission (n = 195) and discharge (n = 162). Loss of dignity was identified as a prominent ongoing concern for 13% of patients. It was correlated with measures of depression and anxiety sensitivity, but not with pulmonary capacity or functional performance. A robust improvement in loss of dignity was demonstrated, with 88% of those who reported a significant problem at admission no longer reporting one at discharge. The prevalence of a problematic loss of dignity among patients with severe chronic obstructive pulmonary disease is at least as high as among those receiving palliative cancer care. Loss of dignity may represent a concern among people with medical illnesses more broadly, and not just in the context of "death with dignity" at the end of life. Furthermore, interdisciplinary care may help to restore a sense of dignity to those individuals who are able to participate in rehabilitation. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Pulmonary edema and lung injury after severe laryngospasm

International Nuclear Information System (INIS)

Saddiqi, R.; Khalique, K.

2006-01-01

A young male with no pre-operative medical illness underwent corrective surgery for a deviated nasal septum under general anesthesia. At the end of surgery, patient was extubated but went into severe laryngospasm that did not improve with gentle Intermittent Positive Pressure Ventilation (IPPV) and small dose of Suxamethonium. As the situation worsened and patient developed severe bradycardia and de-saturation, re-intubation was done that revealed pink froth in the endotracheal tube. His portable chest X-ray was suggestive of non-cardiogenic pulmonary edema. With an overnight supportive treatment, using mechanical ventilation with Positive End- Expiratory Pressure (PEEP), morphine infusion and frusemide, patient improved and was subsequently weaned off from ventilator. (author)

Disease activity of idiopathic pulmonary fibrosis -value of high resolution CT-

International Nuclear Information System (INIS)

Lee, Jin Seong; Im, Jung Gi; Han, Man Chung; Kim, Chu Wan; Suh, Jin Suk

1991-01-01

Idiopathic pulmonary fibrosis (IPF) has characteristic clinical and pathologic features. In patients with uniform intra-alveolar cellularity, the process is often referred to as desquamative interstitial pneumonia. When alveolar septal fibrosis predominate, the process is known as usual interstitial pneumonia. Recently most investigators believe that desquamative interstitial pneumonia is the early stage and usual interstitial pneumonia is the late stage of the same disease process. The lone-term survival and the best response to treatment with corticosteroids is found in patients with marked disease activity and little fibrosis. Since disease activity is reflected by interstitial and intraalveolar cellularity, activity of idiopathic pulmonary fibrosis might result in opacification of air spaces on CT scans. There was no significant difference in estimating the visual HRCT scores of active area between two observers (p>0.05). Activity score of HRCT scan correlated significantly with improvement of DLCO/VA after corticosteroids treatment

Disease activity of idiopathic pulmonary fibrosis -value of high resolution CT-

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Lee, Jin Seong; Im, Jung Gi; Han, Man Chung; Kim, Chu Wan; Suh, Jin Suk [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1991-01-15

Idiopathic pulmonary fibrosis (IPF) has characteristic clinical and pathologic features. In patients with uniform intra-alveolar cellularity, the process is often referred to as desquamative interstitial pneumonia. When alveolar septal fibrosis predominate, the process is known as usual interstitial pneumonia. Recently most investigators believe that desquamative interstitial pneumonia is the early stage and usual interstitial pneumonia is the late stage of the same disease process. The lone-term survival and the best response to treatment with corticosteroids is found in patients with marked disease activity and little fibrosis. Since disease activity is reflected by interstitial and intraalveolar cellularity, activity of idiopathic pulmonary fibrosis might result in opacification of air spaces on CT scans. There was no significant difference in estimating the visual HRCT scores of active area between two observers (p>0.05). Activity score of HRCT scan correlated significantly with improvement of DLCO/VA after corticosteroids treatment.

Quantitative CT analysis of small pulmonary vessels in lymphangioleiomyomatosis

International Nuclear Information System (INIS)

Ando, Katsutoshi; Tobino, Kazunori; Kurihara, Masatoshi; Kataoka, Hideyuki; Doi, Tokuhide; Hoshika, Yoshito; Takahashi, Kazuhisa; Seyama, Kuniaki

2012-01-01

Backgrounds: Lymphangioleiomyomatosis (LAM) is a destructive lung disease that share clinical, physiologic, and radiologic features with chronic obstructive pulmonary disease (COPD). This study aims to identify those features that are unique to LAM by using quantitative CT analysis. Methods: We measured total cross-sectional areas of small pulmonary vessels (CSA) less than 5 mm 2 and 5–10 mm 2 and calculated percentages of those lung areas (%CSA), respectively, in 50 LAM and 42 COPD patients. The extent of cystic destruction (LAA%) and mean parenchymal CT value were also calculated and correlated with pulmonary function. Results: The diffusing capacity for carbon monoxide/alveolar volume (DL CO /VA %predicted) was similar for both groups (LAM, 44.4 ± 19.8% vs. COPD, 45.7 ± 16.0%, p = 0.763), but less tissue damage occurred in LAM than COPD (LAA% 21.7 ± 16.3% vs. 29.3 ± 17.0; p CO /VA %predicted, %CSA and mean parenchymal CT value were still greater for LAM than COPD (p < 0.05). Conclusions: Quantitative CT analysis revealing a correlation between cystic destruction and CSA in COPD but not LAM indicates that this approach successfully reflects different mechanisms governing the two pathologic courses. Such determinations of small pulmonary vessel density may serve to differentiate LAM from COPD even in patients with severe lung destruction.

Dynamic thermal performance of alveolar brick construction system

International Nuclear Information System (INIS)

Gracia, A. de; Castell, A.; Medrano, M.; Cabeza, L.F.

2011-01-01

Highlights: → Even though U-value does not measure thermal inertia, it is the commonly used parameter. → The thermal performance analysis of buildings must include the evaluation of transient parameters. → Transient parameters of alveolar brick constructive system show good agreement with its low energy consumption. -- Abstract: Alveolar bricks are being introduced in building sector due to the simplicity of their construction system and to the elimination of the insulation material. Nevertheless, it is not clear if this new system is energetically efficient and which is its thermal behaviour. This paper presents an experimental and theoretical study to evaluate the thermal behaviour of the alveolar brick construction system, compared with a traditional Mediterranean brick system with insulation. The experimental study consists of measuring the thermal performance of four real house-like cubicles. The thermal transmittance in steady-state, also known as U-value, is calculated theoretically and experimentally for each cubicle, presenting the insulated cubicles as the best construction system, with differences around 45% in comparison to the alveolar one. On the other hand, experimental results show significantly smaller differences on the energy consumption between the alveolar and insulated construction systems during summer period (around 13% higher for the alveolar cubicle). These values demonstrate the high thermal efficiency of the alveolar system. In addition, the lack of agreement between the measured energy consumption and the calculated U-values, guides the authors to analyze the thermal inertia of the different building components. Therefore, several transient parameters, extracted from the heat transfer matrix and from experimental data, are also evaluated. It can be concluded that the alveolar brick construction system presents higher thermal inertia than the insulated one, justifying the low measured energy consumption.

Three-Dimensional Volumetric Changes in Severely Resorbed Alveolar Sockets After Ridge Augmentation with Bovine-Derived Xenograft and Resorbable Barrier: A Preliminary Study on CBCT Imaging.

Science.gov (United States)

Manavella, Valeria; Romano, Federica; Corano, Lisa; Bignardi, Cristina; Aimetti, Mario

The primary aim of the study was to describe a novel technique to evaluate volumetric hard tissue dimensional changes after ridge augmentation procedures. The secondary aim was to apply this newly developed measuring method to compromised alveolar sockets grafted with a slowly resorbing biomaterial covered with a collagen membrane. Eleven patients (6 men and 5 women, mean age 52.7 ± 8.3 years) requiring extraction of one hopeless tooth for severe periodontitis in the maxillary anterior area were consecutively treated with a ridge augmentation procedure. All experimental sockets showed advanced buccal bone plate deficiency and were grafted with deproteinized bovine bone mineral with 10% collagen covered with a collagen membrane. Sockets healed by secondary intention. Three-dimensional volumetric alveolar bone changes were calculated by superimposing cone beam computed tomography scans obtained before and 12 months after the augmentation procedure. After 12 months, the alveolar mineralized tissue filled 91.20% ± 7.96% of the maximum volume for regeneration. The augmentation procedure appeared not only to compensate for bone remodeling in most alveolar regions but also to repair a significant portion of the buccal wall. The most significant ridge width changes occurred 1 mm apical to the bone crest (2.33 ± 1.46 mm, P socket volume. A ridge preservation technique performed with collagenated bovine bone and a collagen membrane was able to improve ridge shape and dimensions in compromised alveolar sockets.

Muc1 deficiency exacerbates pulmonary fibrosis in a mouse model of silicosis.

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Kato, Kosuke; Zemskova, Marina A; Hanss, Alec D; Kim, Marianne M; Summer, Ross; Kim, Kwang Chul

2017-11-25

MUC1 (MUC in human and Muc in animals) is a membrane-tethered mucin expressed on the apical surface of lung epithelial cells. However, in the lungs of patients with interstitial lung disease, MUC1 is aberrantly expressed in hyperplastic alveolar type II epithelial (ATII) cells and alveolar macrophages (AM), and elevated levels of extracellular MUC1 are found in bronchoalveolar lavage (BAL) fluid and the serum of these patients. While pro-fibrotic effects of extracellular MUC1 have recently been described in cultured fibroblasts, the contribution of MUC1 to the pathobiology of pulmonary fibrosis is unknown. In this study, we hypothesized that MUC1 deficiency would reduce susceptibility to pulmonary fibrosis in a mouse model of silicosis. We employed human MUC1 transgenic mice, Muc1 deficient mice and wild-type mice on C57BL/6 background in these studies. Some mice received a one-time dose of crystalline silica instilled into their oropharynx in order to induce pulmonary fibrosis and assess the effects of Muc1 deficiency on fibrotic and inflammatory responses in the lung. As previously described in other mouse models of pulmonary fibrosis, we found that extracellular MUC1 levels were markedly increased in whole lung tissues, BALF and serum of human MUC1 transgenic mice after silica. We also detected an increase in total MUC1 levels in the lungs of these mice, indicating that production as well as release contributed to elevated levels after lung injury. Immunohistochemical staining revealed that increased MUC1 expression was mostly confined to ATII cells and AMs in areas of fibrotic remodeling, illustrating a pattern similar to the expression of MUC1 in human fibrotic lung tissues. However, contrary to our hypothesis, we found that Muc1 deficiency resulted in a worsening of fibrotic remodeling in the mouse lung as judged by an increase in number of silicotic nodules, an increase in lung collagen deposition and an increase in the severity of pulmonary inflammation

[Cleft lip, alveolar and palate sequelae. Proposal of new alveolar score by the Alveolar Cleft Score (ACS) classification].

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Molé, C; Simon, E

2015-06-01

The management of cleft lip, alveolar and palate sequelae remains problematic today. To optimize it, we tried to establish a new clinical index for diagnostic and prognostic purposes. Seven tissue indicators, that we consider to be important in the management of alveolar sequelae, are listed by assigning them individual scores. The final score, obtained by adding together the individual scores, can take a low, high or maximum value. We propose a new classification (ACS: Alveolar Cleft Score) that guides the therapeutic team to a prognosis approach, in terms of the recommended surgical and prosthetic reconstruction, the type of medical care required, and the preventive and supportive therapy to establish. Current studies are often only based on a standard radiological evaluation of the alveolar bone height at the cleft site. However, the gingival, the osseous and the cellular areas bordering the alveolar cleft sequelae induce many clinical parameters, which should be reflected in the morphological diagnosis, to better direct the surgical indications and the future prosthetic requirements, and to best maintain successful long term aesthetic and functional results. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Relationship between plasma matrix metalloproteinase levels, pulmonary function, bronchodilator response, and emphysema severity.

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Koo, Hyeon-Kyoung; Hong, Yoonki; Lim, Myoung Nam; Yim, Jae-Joon; Kim, Woo Jin

2016-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the airway and lung. A protease-antiprotease imbalance has been suggested as a possible pathogenic mechanism for COPD. We evaluated the relationship between matrix metalloproteinase (MMP) levels and COPD severity. Plasma levels of MMP-1, MMP-8, MMP-9, and MMP-12 were measured in 57 COPD patients and 36 normal controls. The relationship between MMP levels and lung function, emphysema index, bronchial wall thickness, pulmonary artery pressure, and quality of life was examined using general linear regression analyses. There were significant associations of MMP-1 with bronchodilator reversibility and of MMP-8 and MMP-9 with lung function. Also, MMP-1, MMP-8, and MMP-9 levels were correlated with the emphysema index, independent of lung function. However, MMP-12 was not associated with lung function or emphysema severity. Associations between MMP levels and bronchial wall thickness, pulmonary artery pressure, and quality of life were not statistically significant. Plasma levels of MMP-1, MMP-8, and MMP-9 are associated with COPD severity and can be used as a biomarker to better understand the characteristics of COPD patients.

Lung inhalation scintigraphy with radioactive aerosols in several pulmonary diseases. Cintigrafia de ventialacao pulmonar por aerosol em diversas patologias pulmonares

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Martins, L R; Marioni Filho, H [Instituto Dante Pazzanese de Cardiologia, Sao Paulo, SP (Brazil); Romaldini, H; Uehara, C; Alonso, G [Escola Paulista de Medicina, Sao Paulo, SP (Brazil)

1983-01-01

The pulmonary ventilation scintigraphy with 99m Tc diethylene-triamine-pentaacetate (99mTc-DTPA) delivered through a new nebulizer system when analyzed together with the classic lung perfusion scintigraphy with 99mTc-labeled albumin macroaggregates (99mTcMAA) is a very important diagnostic tool in several pulmonary diseases. Several aspects of the lung ventilation-perfusion scintigraphy are studied in 15 people with no lung disease, smokers and nonsmokers. The findings with the lung ventilation-perfusion scintigraphy are also discussed in 34 patients with several pulmonary diseases: lung cancer, chronic obstructive lung disease, policystic pulmonary disease, and pulmonary embolims. The authors concluded that the procedure is a valuable diagnostic tool in several pulmonary diseases, especially because good lung images are obtained, no side effects were detected, the technique is ease and low cost, and it brings new informations, not available with other diagnostic methods. (author).

Perinatal hypoxia increases susceptibility to high-altitude polycythemia and attendant pulmonary vascular dysfunction.

Science.gov (United States)

Julian, Colleen Glyde; Gonzales, Marcelino; Rodriguez, Armando; Bellido, Diva; Salmon, Carlos Salinas; Ladenburger, Anne; Reardon, Lindsay; Vargas, Enrique; Moore, Lorna G

2015-08-15

Perinatal exposures exert a profound influence on physiological function, including developmental processes vital for efficient pulmonary gas transfer throughout the lifespan. We extend the concept of developmental programming to chronic mountain sickness (CMS), a debilitating syndrome marked by polycythemia, ventilatory impairment, and pulmonary hypertension that affects ∼10% of male high-altitude residents. We hypothesized that adverse perinatal oxygenation caused abnormalities of ventilatory and/or pulmonary vascular function that increased susceptibility to CMS in adulthood. Subjects were 67 male high-altitude (3,600-4,100 m) residents aged 18-25 yr with excessive erythrocytosis (EE, Hb concentration ≥18.3 g/dl), a preclinical form of CMS, and 66 controls identified from a community-based survey (n = 981). EE subjects not only had higher Hb concentrations and erythrocyte counts, but also lower alveolar ventilation, impaired pulmonary diffusion capacity, higher systolic pulmonary artery pressure, lower pulmonary artery acceleration time, and more frequent right ventricular hypertrophy, than controls. Compared with controls, EE subjects were more often born to mothers experiencing hypertensive complications of pregnancy and hypoxia during the perinatal period, with each increasing the risk of developing EE (odds ratio = 5.25, P = 0.05 and odds ratio = 6.44, P = 0.04, respectively) after other factors known to influence EE status were taken into account. Adverse perinatal oxygenation is associated with increased susceptibility to EE accompanied by modest abnormalities of the pulmonary circulation that are independent of increased blood viscosity. The association between perinatal hypoxia and EE may be due to disrupted alveolarization and microvascular development, leading to impaired gas exchange and/or pulmonary hypertension. Copyright © 2015 the American Physiological Society.

Leptospirosis-Associated Severe Pulmonary Hemorrhagic Syndrome with Lower Back Pain as an Initial Symptom

DEFF Research Database (Denmark)

Søndergaard, Mads Madsen; tursunovic, Amela; Thye-Roenn, Peter

2016-01-01

BACKGROUND Leptospirosis is a zoonosis transmitted through urine of infected animals. Symptoms range from mild influenza-like symptoms to severe pulmonary hemorrhagic syndrome (SPHS); the latter are often fatal. The serogroup distribution in Denmark has changed from 1988 to 2012, with Icterohaemo......BACKGROUND Leptospirosis is a zoonosis transmitted through urine of infected animals. Symptoms range from mild influenza-like symptoms to severe pulmonary hemorrhagic syndrome (SPHS); the latter are often fatal. The serogroup distribution in Denmark has changed from 1988 to 2012......, the patient died a few hours after hospital admission....

Acinus-on-a-chip: a microfluidic platform for pulmonary acinar flows.

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Fishler, Rami; Mulligan, Molly K; Sznitman, Josué

2013-11-15

Convective respiratory flows in the pulmonary acinus and their influence on the fate of inhaled particles are typically studied using computational fluid dynamics (CFD) or scaled-up experimental models. However, experiments that replicate several generations of the acinar tree while featuring cyclic wall motion have not yet been realized. Moreover, current experiments generally capture only flow dynamics, without inhaled particle dynamics, due to difficulties in simultaneously matching flow and particle dynamics. In an effort to overcome these limitations, we introduce a novel microfluidic device mimicking acinar flow characteristics directly at the alveolar scale. The model features an anatomically-inspired geometry that expands and contracts periodically with five dichotomously branching airway generations lined with alveolar-like cavities. We use micro-particle image velocimetry with a glycerol solution as the carrying fluid to quantitatively characterize detailed flow patterns within the device and reveal experimentally for the first time a gradual transition of alveolar flow patterns along the acinar tree from recirculating to radial streamlines, in support of hypothesized predictions from past CFD simulations. The current measurements show that our microfluidic system captures the underlying characteristics of the acinar flow environment, including Reynolds and Womersley numbers as well as cyclic wall displacements and alveolar flow patterns at a realistic length scale. With the use of air as the carrying fluid, our miniaturized platform is anticipated to capture both particle and flow dynamics and serve in the near future as a promising in vitro tool for investigating the mechanisms of particle deposition deep in the lung. © 2013 Elsevier Ltd. All rights reserved.

Upfront triple combination therapy-induced pulmonary edema in a case of pulmonary arterial hypertension associated with Sjogren's syndrome

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Kimikazu Takeuchi

Full Text Available Clinical efficacy of combination therapy using vasodilators for pulmonary arterial hypertension (PAH is well established. However, information on its safety are limited. We experienced a case of primary Sjogren's syndrome associated with PAH where the patient developed pulmonary edema immediately after the introduction of upfront triple combination therapy. Although the combination therapy successfully stabilized her pre-shock state, multiple ground glass opacities (GGO emerged. We aborted the dose escalation of epoprostenol and initiated continuous furosemide infusion and noninvasive positive pressure ventilation (NPPV, but this did not prevent an exacerbation of pulmonary edema. Chest computed tomography showing diffuse alveolar infiltrates without inter-lobular septal thickening suggests the pulmonary edema was unlikely due to cardiogenic pulmonary edema and pulmonary venous occlusive disease. Acute respiratory distress syndrome was also denied from no remarkable inflammatory sign and negative results of drug-induced lymphocyte stimulation tests (DLST. We diagnosed the etiological mechanism as pulmonary vasodilator-induced trans-capillary fluid leakage. Following steroid pulse therapy dramatically improved GGO. We realized that overmuch dose escalation of epoprostenol on the top of dual upfront combination poses the risk of pulmonary edema. Steroid pulse therapy might be effective in cases of vasodilator-induced pulmonary edema in Sjogren's syndrome associated with PAH. Keywords: Steroid therapy, Ground glass opacity, Inter-lobular septal thickening, Epoprostenol, Acute respiratory distress syndrome, Trans-capillary fluid leakage

A new method for noninvasive measurement of pulmonary gas exchange using expired gas.

Science.gov (United States)

West, John B; Prisk, G Kim

2018-01-01

Measurement of the gas exchange efficiency of the lung is often required in the practice of pulmonary medicine and in other settings. The traditional standard is the values of the PO2, PCO2, and pH of arterial blood. However arterial puncture requires technical expertise, is invasive, uncomfortable for the patient, and expensive. Here we describe how the composition of expired gas can be used in conjunction with pulse oximetry to obtain useful measures of gas exchange efficiency. The new procedure is noninvasive, well tolerated by the patient, and takes only a few minutes. It could be particularly useful when repeated measurements of pulmonary gas exchange are required. One product of the procedure is the difference between the PO2 of end-tidal alveolar gas and the calculated PO2 of arterial blood. This measurement is related to the classical alveolar-arterial PO2 difference based on ideal alveolar gas. However that traditional index is heavily influenced by lung units with low ventilation-perfusion ratios, whereas the new index has a broader physiological basis because it includes contributions from the whole lung. Copyright © 2017 Elsevier B.V. All rights reserved.

Lung Fibroblasts, Aging, and Idiopathic Pulmonary Fibrosis.

Science.gov (United States)

Pardo, Annie; Selman, Moisés

2016-12-01

Idiopathic pulmonary fibrosis (IPF) is an aging-associated, progressive, and irreversible lung disease of unknown etiology, elusive pathogenesis, and very limited therapeutic options. The hallmarks of IPF are aberrant activation of alveolar epithelial cells and accumulation of fibroblasts and myofibroblasts along with excessive production of extracellular matrix. The linkage of aging with this disorder is uncertain, but a number of changes associated with aging, including telomere attrition, cell senescence, and mitochondrial dysfunction, have been revealed in IPF lungs. Also, aging seems to confer a profibrotic phenotype upon fibroblasts and to increase the severity of the fibrogenic response in non-IPF fibrotic lung disorders. Better knowledge of the pathophysiological mechanisms linking aging to IPF will advance understanding of its pathogenesis and may provide new therapeutic windows to treatment of this devastating disease.

The Effects of Synthetic Cannabinoids on Alveolar-Arterial Oxygen Gradient

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Egemen Kucuk

2016-09-01

Full Text Available Aim: Synthetic cannabinoids are chemicals that produce several marijuana-like effects in humans. Aim of this study is to investigate the effects of synthetic cannabinoids on to alveolar-arterial oxygen gradient. Material and Method: A total of 112 patients, who admitted directly to emergency clinic with synthetic cannabinoid usage, were determined between February 2014 and August 2014. Blood gases of 41 patients were determined as arterial blood gases on room air, and included in to study. Patients were evaluated according to age, sex, decade, partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, pH, bicarbonate, metabolic status, age consistent expected alveolar-arterial oxygen gradient and calculated alveolar-arterial oxygen gradient. Results: Synthetic cannabinoid using was higher in males, mean age of patients was 23.32±6.14 years. Number of patients in the third decade were significantly higher than the other decades. The calculated alveolar-arterial oxygen gradient value of patients was significantly higher than age consistent expected alveolar-arterial oxygen gradient value. Respiratory acidosis, was significantly higher than the other types of the metabolic disorders. The best cutoff point for calculated alveolar-arterial oxygen gradient was 12.70, with sensitivity of 90% and specifity of 85%. Area under curve was 0.70 for calculated alveolar-arterial oxygen gradient. Discussion: The value of alveolar-arterial oxygen gradient has been increased due to synthetic cannabinoid usage. This can be used as a supportive parameter in the diagnosis of synthetic cannabinoid usage.

Activated alveolar macrophage and lymphocyte alveolitis in extrathoracic sarcoidosis without radiological mediastinopulmonary involvement

International Nuclear Information System (INIS)

Wallaert, B.; Ramon, P.; Fournier, E.C.; Prin, L.; Tonnel, A.B.; Voisin, C.

1986-01-01

Cellular characteristics of BAL were investigated in 18 patients with proved extrathoracic sarcoidosis (that is, sarcoidosis that affected the skin, eyes, parotid glands, stomach, nose, kidneys, or meninges) without clinical or radiological mediastinopulmonary involvement. Computed tomography of the thorax was performed on five patients: four patients were normal, and one had enlarged lymph nodes (these enlargements were not detectable on the patient's chest roentgenogram). The results of pulmonary function tests were normal in all patients. The total BAL cell count did not differ significantly between controls and patients. Abnormal percentages of alveolar lymphocytes (from 18 to 87%) were noted in 15 out of 18 patients. SACE levels were normal in 15 patients. No pulmonary gallium uptake was detected. The chemiluminescence of AM's, whether spontaneous or PMA induced, was increased in five out of seven patients. The percentages of T3+ lymphocytes in sarcoidosis patients did not significantly differ from those in controls. The T4+:T8+ ratio was normal in four patients and slightly increased in one. Follow-up of patients showed that alveolar lymphocytosis is as lasting as extrathoracic involvement. Our data demonstrate increased percentages of lymphocytes and activated AM's in the BAL of patients with extrathoracic sarcoidosis. This may be due to the initial involvement of the respiratory tract in extrathoracic sarcoidosis or to the diffusion of activated macrophages and lymphocytes from an extrathoracic site into the lung

Correction of Pulmonary Oxygenizing Dysfunction in the Early Activation of Cardiosurgical Patients

Directory of Open Access Journals (Sweden)

I. A. Kozlov

2009-01-01

Full Text Available Objective: to justify a comprehensive approach to preventing and correcting pulmonary oxygenizing dysfunction requiring prolonged artificial ventilation in patients operated on under extracorporeal circulation for coronary heart disease. Subjects and methods. One hundred and twenty-three patients aged 55±0.6 years were examined. The study excluded patients with a complicated course of operations (perioperative myocardial infarction, acute cardiovascular insufficiency, hemorrhage, and long extracorporeal circulation. Stimulating spirometry was initiated 2 days before surgery. An alveolar opening maneuver was performed using a continuous dynamic thoracopulmonary compliance monitoring. The parameters of lung oxygenizing function and biomechanics were analyzed. Results. In 78% of the patients, preoperative inspiratory lung capacity was 5—30% lower than the age-related normal values. After extracorporeal circulation, pulmonary oxygenizing dysfunction was diagnosed in 40.9% of cases; at the same time PaO2/FiO2 was associated with an intrapulmonary shunt fraction (Qs/St (r=-0.53; p=0.002 and Qs/Qt was related to static thoracopulmonary compliance (Cst (r=-0.39; p=0.03. Preoperative stimulating spirometry provided a considerable increase in intraoperative PaO2/FiO2 values (p<0.05; improved Cst and decreased Qs/Qt. After extracorporeal circulation, the incidence of pulmonary oxygenizing dysfunction was decreased by more than twice (p<0.05. Patients with relative arterial hypoxemia showed a noticeable relationship to the magnitudes of a reduction in Cst and a rise in Qs/Qt (r=0.72; p=0.008, which served as the basis for applying the alveolar opening maneuver. This type of lung support corrected arterial hypoxemia in 67% of cases. Conclusion. In car-diosurgical patients with coronary heart disease, effective prophylaxis and correction of relative arterial hypoxemia caused by the interrelated impairments of pulmonary biomechanical properties and

Molecular characterization of the porcine surfactant, pulmonary-associated protein C gene

DEFF Research Database (Denmark)

Cirera, S.; Nygård, A.B.; Jensen, H.E.

2006-01-01

The surfactant, pulmonary-associated protein C (SFTPC) is a peptide secreted by the alveolar type II pneumocytes of the lung. We have characterized the porcine SFTPC gene at genomic, transcriptional, and protein levels. The porcine SFTPC is a single-copy gene on pig chromosome 14. Two transcripts...

Protection from pulmonary tissue damage associated with infection of cynomolgus macaques by highly pathogenic avian influenza virus (H5N1) by low dose natural human IFN-α administered to the buccal mucosa.

Science.gov (United States)

Strayer, David R; Carter, William A; Stouch, Bruce C; Stittelaar, Koert J; Thoolen, Robert J M M; Osterhaus, Albert D M E; Mitchell, William M

2014-10-01

Using an established nonhuman primate model for H5N1 highly pathogenic influenza virus infection in humans, we have been able to demonstrate the prophylactic mitigation of the pulmonary damage characteristic of human fatal cases from primary influenza virus pneumonia with a low dose oral formulation of a commercially available parenteral natural human interferon alpha (Alferon N Injection®). At the highest oral dose (62.5IU/kg body weight) used there was a marked reduction in the alveolar inflammatory response with minor evidence of alveolar and interstitial edema in contrast to the hemorrhage and inflammatory response observed in the alveoli of control animals. The mitigation of severe damage to the lower pulmonary airway was observed without a parallel reduction in viral titers. Clinical trial data will be necessary to establish its prophylactic human efficacy for highly pathogenic influenza viruses. Copyright © 2014. Published by Elsevier B.V.

Autochthonous human alveolar echinococcosis in a Hungarian patient.

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Dezsényi, Balázs; Strausz, Tamás; Makrai, Zita; Csomor, Judit; Danka, József; Kern, Peter; Rezza, Giovanni; Barth, Thomas F E; Casulli, Adriano

2017-02-01

Alveolar echinococcosis is a zoonotic parasitic disease causing a severe clinical condition and is known as the most deadly of all helminth infections. Moreover, this disease is also an increasing concern in Northern and Eastern Europe due to its spread in the wildlife animal host. An asymptomatic 70-year-old woman from south-western Hungary was diagnosed with multiple liver lesions. Imaging techniques (ultrasound, computed tomography and magnetic resonance imaging), serology (ELISA, indirect hemagglutination and Western blot), and conventional staining methods (hematoxylin-eosin and periodic acid-Schiff) were used for the detection of the disease. A histopathological re-evaluation of formalin-fixed paraffin block by immunohistochemical staining with the monoclonal antibody Em2G11 definitively confirmed the diagnosis of alveolar echinococcosis. To our knowledge, this is the first confirmed autochthonous case of human alveolar echinococcosis in Hungary. To what extent diagnostic difficulties may contribute to underestimate this zoonosis in Eastern Europe is unknown. Differential diagnosis with alveolar echinococcosis should be considered for patients with multiple, tumor-like cystic lesions of the liver, in countries where this parasite is emerging.

Clearance of 99mTc-DTPA and experimentally increased alveolar surfactant content

International Nuclear Information System (INIS)

Bos, J.A.H.; Wollmer, P.; Bakker, W.; Hannappel, E.; Lachmann, B.

1992-01-01

The authors measured clearance of 99m Tc-labeled diethylenetriamine pentaacetic acid ( 99m Tc-DTPA) in rabbits with experimentally increased alveolar surfactant content. In one group of animals, surfactant production was increased by treatment with ambroxol, and another group of animals was treated with tracheal instillation of natural surfactant. A group of untreated control animals and animals treated with instillation of saline were also studied. Clearance was measured during standard conditions of mechanical ventilation and during ventilation with large tidal volumes. In ambroxol- and surfactant-treated groups, clearance rate was reduced compared with untreated control animals. In contrast, clearance rate increased after saline instillation. The differences were observed at both modes of ventilation. The findings indicate that the pulmonary surfactant system is a rate-limiting factor for the clearance of 99m Tc-DTPA and that the volume dependence of clearance is not explained by stretching of the alveolar wall only. 28 refs., 2 figs., 1 tab

Sphingosine 1-Phosphate-Induced ICAM-1 Expression via NADPH Oxidase/ROS-Dependent NF-κB Cascade on Human Pulmonary Alveolar Epithelial Cells

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Lin, Chih-Chung; Yang, Chien-Chung; Cho, Rou-Ling; Wang, Chen-Yu; Hsiao, Li-Der; Yang, Chuen-Mao

2016-01-01

The intercellular adhesion molecule-1 (ICAM-1) expression is frequently correlated with the lung inflammation. In lung injury, sphingosine-1-phosphate (S1P, bioactive sphingolipid metabolite), participate gene regulation of adhesion molecule in inflammation progression and aggravate tissue damage. To investigate the transduction mechanisms of the S1P in pulmonary epithelium, we demonstrated that exposure of HPAEpiCs (human pulmonary alveolar epithelial cells) to S1P significantly induces ICAM-1 expression leading to increase monocyte adhesion on the surface of HPAEpiCs. These phenomena were effectively attenuated by pretreatments with series of inhibitors such as Rottlerin (PKCδ), PF431396 (PYK2), diphenyleneiodonium chloride (DPI), apocynin (NADPH oxidase), Edaravone (ROS), and Bay11-7082 (NF-κB). Consistently, knockdown with siRNA transfection of PKCδ, PYK2, p47phox, and p65 exhibited the same results. Pretreatment with both Gq-coupled receptor antagonist (GPA2A) and Gi/o-coupled receptor antagonist (GPA2) also blocked the upregulation of ICAM-1 protein and mRNA induced by S1P. We observed that S1P induced PYK2 activation via a Gq-coupled receptor/PKCδ-dependent pathway. In addition, S1P induced NADPH oxidase activation and intracellular ROS generation, which were also reduced by Rottlerin or PF431396. We demonstrated that S1P induced NF-κB p65 phosphorylation and nuclear translocation in HPAEpiCs. Activated NF-κB was blocked by Rottlerin, PF431396, APO, DPI, or Edaravone. Besides, the results of monocyte adhesion assay indicated that S1P-induced ICAM-1 expression on HPAEpiCs can enhance the monocyte attachments. In the S1P-treated mice, we found that the levels of ICAM-1 protein and mRNA in the lung fractions, the pulmonary hematoma and leukocyte count in bronchoalveolar lavage fluid were enhanced through a PKCδ/PYK2/NADPH oxidase/ROS/NF-κB signaling pathway. We concluded that S1P-accelerated lung damage is due to the ICAM-1 induction associated with

Fibrosis of Two: Epithelial Cell-Fibroblast Interactions in Pulmonary Fibrosis

Science.gov (United States)

Sakai, Norihiko; Tager, Andrew M.

2013-01-01

Idiopathic pulmonary fibrosis (IPF) is characterized by the progressive and ultimately fatal accumulation of fibroblasts and extracellular matrix in the lung that distorts its architecture and compromises its function. IPF is now thought to result from wound-healing processes that, although initiated to protect the host from injurious environmental stimuli, lead to pathological fibrosis due to these processes becoming aberrant or over-exuberant. Although the environmental stimuli that trigger IPF remain to be identified, recent evidence suggests that they initially injure the alveolar epithelium. Repetitive cycles of epithelial injury and resultant alveolar epithelial cell death provoke the migration, proliferation, activation and myofibroblast differentiation of fibroblasts, causing the accumulation of these cells and the extracellular matrix that they synthesize. In turn, these activated fibroblasts induce further alveolar epithelial cell injury and death, thereby creating a vicious cycle of pro-fibrotic epithelial cell-fibroblast interactions. Though other cell types certainly make important contributions, we focus here on the “pas de deux” (steps of two), or perhaps more appropriate to IPF pathogenesis, the “folie à deux” (madness of two) of epithelial cells and fibroblasts that drives the progression of pulmonary fibrosis. We describe the signaling molecules that mediate the interactions of these cell types in their “fibrosis of two”, including transforming growth factor-β, connective tissue growth factor, sonic hedgehog, prostaglandin E2, angiotensin II and reactive oxygen species. PMID:23499992

Injurious mechanical ventilation in the normal lung causes a progressive pathologic change in dynamic alveolar mechanics.

Science.gov (United States)

Pavone, Lucio A; Albert, Scott; Carney, David; Gatto, Louis A; Halter, Jeffrey M; Nieman, Gary F

2007-01-01

lung volume with each breath will, in time, lead to unstable alveoli and pulmonary damage. Reducing the change in lung volume by increasing the PEEP, even with high inflation pressure, prevents alveolar instability and reduces injury. We speculate that ventilation with large changes in lung volume over time results in surfactant deactivation, which leads to alveolar instability.

The Biophysical Function of Pulmonary Surfactant

OpenAIRE

Rugonyi, Sandra; Biswas, Samares C.; Hall, Stephen B.

2008-01-01

Pulmonary surfactant lowers surface tension in the lungs. Physiological studies indicate two key aspects of this function: that the surfactant film forms rapidly; and that when compressed by the shrinking alveolar area during exhalation, the film reduces surface tension to very low values. These observations suggest that surfactant vesicles adsorb quickly, and that during compression, the adsorbed film resists the tendency to collapse from the interface to form a three-dimensional bulk phase....

Perfusion lung scintigraphy in primary pulmonary hypertension

International Nuclear Information System (INIS)

Ogawa, Yoji; Nishimura, Tsunehiko; Kumita, Shin-ichirou; Hayashida, Kohei; Uehara, Toshiisa; Shimonagata, Tsuyoshi; Ohno, Akira

1991-01-01

Fifteen cases with primary pulmonary hypertension (PPH) were classified into two groups by using the perfusion lung scan pattern. Eight cases had multiple, small, ill-defined defects (mottled pattern), and remaining seven cases had no mottled pattern. These two groups were compared with mean pulmonary arterial pressure (mean PAP), right ventricular ejection fraction (RVEF), blood gas at room air (PaO 2 ), and alveolar-arterial O 2 difference (A-aDo 2 ). The cases with mottled pattern showed a significant increase in mean PAP. There were no significant differences in RVEF, PaO 2 , and A-aDo 2 , between the groups. The survival rate of the patients with mottled pattern was significantly lower than that without mottled pattern (p<0.05). We concluded that perfusion lung scan is very useful for evaluation of the prognosis in primary pulmonary hypertension. (author)

Reduced baroreflex sensitivity and pulmonary dysfunction in alcoholic cirrhosis: effect of hyperoxia

DEFF Research Database (Denmark)

Møller, Søren; Iversen, Jens S; Krag, Aleksander

2010-01-01

matched controls underwent hemodynamic and pulmonary investigations. BRS was assessed by cross-spectral analysis of variabilities between blood pressure and heart rate time series. A 100% oxygen test was performed with the assessment of arterial oxygen tensions (Pa(O(2))) and alveolar-arterial oxygen...

Graves' disease presenting as right heart failure with severe pulmonary hypertension

OpenAIRE

Furqan Mohd Akram Khan; Anannya Mukherji; Shekhar T. Nabar; Ashwini G

2016-01-01

We report a patient who presented to our institution with clinical features of right sided heart failure and hyperthyroidism. Diagnosis of grave's disease induced reversible severe pulmonary hypertension leading to severe tricuspid regurgitation and right sided heart failure was made after all the common causes were ruled out using the biochemical and radiological investigations and review of literature. Graves disease is a common cause hyperthyroidism, is an immune system disorder that resul...

Dysfunction of pulmonary surfactant mediated by phospholipid oxidation is cholesterol-dependent.

Science.gov (United States)

Al-Saiedy, Mustafa; Pratt, Ryan; Lai, Patrick; Kerek, Evan; Joyce, Heidi; Prenner, Elmar; Green, Francis; Ling, Chang-Chun; Veldhuizen, Ruud; Ghandorah, Salim; Amrein, Matthias

2018-04-01

Pulmonary surfactant forms a cohesive film at the alveolar air-lung interface, lowering surface tension, and thus reducing the work of breathing and preventing atelectasis. Surfactant function becomes impaired during inflammation due to degradation of the surfactant lipids and proteins by free radicals. In this study, we examine the role of reactive nitrogen (RNS) and oxygen (ROS) species on surfactant function with and without physiological cholesterol levels (5-10%). Surface activity was assessed in vitro in a captive bubble surfactometer (CBS). Surfactant chemistry, monolayer fluidity and thermodynamic behavior were also recorded before and after oxidation. We report that physiologic amounts of cholesterol combined with oxidation results in severe impairment of surfactant function. We also show that surfactant polyunsaturated phospholipids are the most susceptible to oxidative alteration. Membrane thermodynamic experiments showed significant surfactant film stiffening after free radical exposure in the presence of cholesterol. These results point to a previously unappreciated role for cholesterol in amplifying defects in surface activity caused by oxidation of pulmonary surfactant, a finding that may have implications for treating several lung diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

Persistent Tachypnea and Alveolar Hemorrhage in an Infant: An Unexpected Etiology

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John Bishara

2016-01-01

Full Text Available Persistent tachypnea and failure to thrive during infancy have a broad differential diagnosis which includes pulmonary and cardiovascular disorders. Diffuse alveolar hemorrhage (DAH is a rare entity in children. DAH requires an extensive work-up as certain conditions may need chronic therapy. Cardiovascular disorders are included in the etiology of DAH. We present a case of an 8-month-old female with a moderate, restrictive patent ductus arteriosus (PDA admitted to the hospital with respiratory distress and failure to thrive. An extensive work-up into tachypnea including multiple echocardiograms did not find an etiology. Open lung biopsy was performed and consistent with pulmonary hypertension. After closure of the PDA, patient’s tachypnea improved, and she was discharged home with periodic follow-up showing a growing, thriving child. When an infant presents with tachypnea, a respiratory viral illness is often a common cause. The diagnosis of persistent tachypnea requires further investigation. Echocardiography, although readily available, may not always be sensitive in detecting clinically significant pulmonary hypertension. A clinician must have a heightened index of suspicion to proceed in evaluating for causes of tachypnea with a nonrespiratory etiology.

Proteinase-activated receptor 4 stimulation-induced epithelial-mesenchymal transition in alveolar epithelial cells

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Araki Hiromasa

2007-04-01

Full Text Available Abstract Background Proteinase-activated receptors (PARs; PAR1–4 that can be activated by serine proteinases such as thrombin and neutrophil catepsin G are known to contribute to the pathogenesis of various pulmonary diseases including fibrosis. Among these PARs, especially PAR4, a newly identified subtype, is highly expressed in the lung. Here, we examined whether PAR4 stimulation plays a role in the formation of fibrotic response in the lung, through alveolar epithelial-mesenchymal transition (EMT which contributes to the increase in myofibroblast population. Methods EMT was assessed by measuring the changes in each specific cell markers, E-cadherin for epithelial cell, α-smooth muscle actin (α-SMA for myofibroblast, using primary cultured mouse alveolar epithelial cells and human lung carcinoma-derived alveolar epithelial cell line (A549 cells. Results Stimulation of PAR with thrombin (1 U/ml or a synthetic PAR4 agonist peptide (AYPGKF-NH2, 100 μM for 72 h induced morphological changes from cobblestone-like structure to elongated shape in primary cultured alveolar epithelial cells and A549 cells. In immunocytochemical analyses of these cells, such PAR4 stimulation decreased E-cadherin-like immunoreactivity and increased α-SMA-like immunoreactivity, as observed with a typical EMT-inducer, tumor growth factor-β (TGF-β. Western blot analyses of PAR4-stimulated A549 cells also showed similar changes in expression of these EMT-related marker proteins. Such PAR4-mediated changes were attenuated by inhibitors of epidermal growth factor receptor (EGFR kinase and Src. PAR4-mediated morphological changes in primary cultured alveolar epithelial cells were reduced in the presence of these inhibitors. PAR4 stimulation increased tyrosine phosphorylated EGFR or tyrosine phosphorylated Src level in A549 cells, and the former response being inhibited by Src inhibitor. Conclusion PAR4 stimulation of alveolar epithelial cells induced epithelial

Pulmonary manifestations of malaria : recognition and management.

Science.gov (United States)

Taylor, Walter R J; Cañon, Viviam; White, Nicholas J

2006-01-01

Lung involvement in malaria has been recognized for more than 200 hundred years, yet our knowledge of its pathogenesis and management is limited. Pulmonary edema is the most severe form of lung involvement. Increased alveolar capillary permeability leading to intravascular fluid loss into the lungs is the main pathophysiologic mechanism. This defines malaria as another cause of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).Pulmonary edema has been described most often in non-immune individuals with Plasmodium falciparum infections as part of a severe systemic illness or as the main feature of acute malaria. P.vivax and P.ovale have also rarely caused pulmonary edema.Clinically, patients usually present with acute breathlessness that can rapidly progress to respiratory failure either at disease presentation or, interestingly, after treatment when clinical improvement is taking place and the parasitemia is falling. Pregnant women are particularly prone to developing pulmonary edema. Optimal management of malaria-induced ALI/ARDS includes early recognition and diagnosis. Malaria must always be suspected in a returning traveler or a visitor from a malaria-endemic country with an acute febrile illness. Slide microscopy and/or the use of rapid antigen tests are standard diagnostic tools. Malaria must be treated with effective drugs, but current choices are few: e.g. parenteral artemisinins, intravenous quinine or quinidine (in the US only). A recent trial in adults has shown that intravenous artesunate reduces severe malaria mortality by a third compared with adults treated with intravenous quinine. Respiratory compromise should be managed on its merits and may require mechanical ventilation.Patients should be managed in an intensive care unit and particular attention should be paid to the energetic management of other severe malaria complications, notably coma and acute renal failure. ALI/ARDS may also be related to a coincidental bacterial

Clinical assessment of transcatheter closure of patent ductus arteriosus with severe pulmonary hypertention using Amplatzer occluder

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Xiumin, Han; Xianyang, Zhu; Yuwei, Zhang; Yan, Jin; Dong' an, Deng; Chanju, Hou; Wei, Quan [Shenyang General Hospital, PLA, Shenyang (China)

2004-04-01

Objective: To evaluate the application of transcatheter closure of patent ductus arteriosus (PDA) with severe pulmonary hypertention using the Amplatzer occluder device. Methods: Fifty-one cases of PDA with severe pulmonary hypertention were treated by transcatheter closure with Amplatzer occluder. Patients mean age was 9.4 years (ranging 3 months to 60 years) and the mean weight was (18.7 {+-} 13.8) kg (ranging 5.0 to 65.0 kg). The mean PDA diameter at its narrowest segment was (7.0 {+-} 2.4) (ranging 3.0 to 15.0) mm. The achievement of permanent transcatheter closure was decided according to the change of the pulmonary arterial pressure, aortic pressure and oxygen saturation. Results: The devices were successfully placed in all patients except one failure owing to the resistance of pulmonary hypertention. The systolic pulmonary pressure decreased from (84.7 {+-} 13.5) (range 70 to 137) to mmHg to (46.1 {+-} 14.9) (24 to 109) mmHg, and the mean pulmonary pressure decreased from (65.0 {+-} 11.5) (42 to 97) mmHg to (31.3 {+-} 11.6) (14 to 69) mmHg. Complete angiographic closure was seen 10 minutes after the device deployment in 30 out of 50 patients (60%), while trivial to small leak was present in 20 (40%). Complete echocardiographic closure was demonstrated in 49 out of 50 patients (98%) at 10 min, and 100% at 6-month follow-up in all patients. There were no PDA recanalization and migration of devices after the complete occlusion during following up. Conclusion: Transcatheter closure of patent ductus arteriosus with severe pulmonary hypertention by using the Amplatzer occluder is a safe and effective interventional method with excellent short-term and middle-term results. (authors)

Clinical assessment of transcatheter closure of patent ductus arteriosus with severe pulmonary hypertention using Amplatzer occluder

International Nuclear Information System (INIS)

Han Xiumin; Zhu Xianyang; Zhang Yuwei; Jin Yan; Deng Dong'an; Hou Chanju; Quan Wei

2004-01-01

Objective: To evaluate the application of transcatheter closure of patent ductus arteriosus (PDA) with severe pulmonary hypertention using the Amplatzer occluder device. Methods: Fifty-one cases of PDA with severe pulmonary hypertention were treated by transcatheter closure with Amplatzer occluder. Patients mean age was 9.4 years (ranging 3 months to 60 years) and the mean weight was (18.7 ± 13.8) kg (ranging 5.0 to 65.0 kg). The mean PDA diameter at its narrowest segment was (7.0 ± 2.4) (ranging 3.0 to 15.0) mm. The achievement of permanent transcatheter closure was decided according to the change of the pulmonary arterial pressure, aortic pressure and oxygen saturation. Results: The devices were successfully placed in all patients except one failure owing to the resistance of pulmonary hypertention. The systolic pulmonary pressure decreased from (84.7 ± 13.5) (range 70 to 137) to mmHg to (46.1 ± 14.9) (24 to 109) mmHg, and the mean pulmonary pressure decreased from (65.0 ± 11.5) (42 to 97) mmHg to (31.3 ± 11.6) (14 to 69) mmHg. Complete angiographic closure was seen 10 minutes after the device deployment in 30 out of 50 patients (60%), while trivial to small leak was present in 20 (40%). Complete echocardiographic closure was demonstrated in 49 out of 50 patients (98%) at 10 min, and 100% at 6-month follow-up in all patients. There were no PDA recanalization and migration of devices after the complete occlusion during following up. Conclusion: Transcatheter closure of patent ductus arteriosus with severe pulmonary hypertention by using the Amplatzer occluder is a safe and effective interventional method with excellent short-term and middle-term results. (authors)

Estrogen exposure, obesity and thyroid disease in women with severe pulmonary hypertension

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Sweeney Lori

2009-09-01

Full Text Available Abstract Severe pulmonary hypertension is a lethal group of disorders which preferentially afflicts women. It appears that in recent years the patient profile has shifted towards older, obese, and postmenopausal women, suggesting that endocrine factors may be important. Several studies have revealed an increased prevalence of thyroid disease in these patients, but no studies have evaluated for a coexistence of endocrine factors. In particular, no studies have attempted to evaluate for concurrent thyroid disease, obesity and long-term estrogen exposure in patients. 88 patients attending the Pulmonary Hypertension Association 8th International meeting completed a questionnaire and were interviewed. Information was collected regarding reproductive history, height, weight, and previous diagnosis of thyroid disease. 46% met criteria for obesity. 41% reported a diagnosis of thyroid disease. 81% of women reported prior use of hormone therapy. 70% reported greater than 10 years of exogenous hormone use. 74% of female patients reported two or more of potentially disease modifying endocrine factors (obesity, thyroid disease or estrogen therapy. The coexistent high prevalence in our cohort of exogenous estrogen exposure, thyroid disease and obesity suggests that an interaction of multiple endocrine factors might contribute to the pathogenesis of pulmonary hypertension and may represent epigenetic modifiers in genetically-susceptible individuals.

Subcutaneous emphysema in cavitary pulmonary tuberculosis without pneumothorax or pneumomediastinum

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Ramakant Dixit

2012-01-01

Full Text Available Extra-alveolar air in the form of subcutaneous tissue emphysema is observed in a variety of clinical settings. Spontaneous subcutaneous emphysema in the absence of pneumothorax or pneumomediastinum is very rare. We report a case of spontaneous subcutaneous emphysema secondary to cavitary pulmonary tuberculosis in the absence of pneumothorax or pneumomediastinum.

Matrix Remodeling in Pulmonary Fibrosis and Emphysema

Science.gov (United States)

O’Reilly, Philip; Antony, Veena B.; Gaggar, Amit

2016-01-01

Pulmonary fibrosis and emphysema are chronic lung diseases characterized by a progressive decline in lung function, resulting in significant morbidity and mortality. A hallmark of these diseases is recurrent or persistent alveolar epithelial injury, typically caused by common environmental exposures such as cigarette smoke. We propose that critical determinants of the outcome of the injury-repair processes that result in fibrosis versus emphysema are mesenchymal cell fate and associated extracellular matrix dynamics. In this review, we explore the concept that regulation of mesenchymal cells under the influence of soluble factors, in particular transforming growth factor-β1, and the extracellular matrix determine the divergent tissue remodeling responses seen in pulmonary fibrosis and emphysema. PMID:26741177

Monitoring pulmonary function with superimposed pulmonary gas exchange curves from standard analyzers.

Science.gov (United States)

Zar, Harvey A; Noe, Frances E; Szalados, James E; Goodrich, Michael D; Busby, Michael G

2002-01-01

A repetitive graphic display of the single breath pulmonary function can indicate changes in cardiac and pulmonary physiology brought on by clinical events. Parallel advances in computer technology and monitoring make real-time, single breath pulmonary function clinically practicable. We describe a system built from a commercially available airway gas monitor and off the shelf computer and data-acquisition hardware. Analog data for gas flow rate, O2, and CO2 concentrations are introduced into a computer through an analog-to-digital conversion board. Oxygen uptake (VO2) and carbon dioxide output (VCO2) are calculated for each breath. Inspired minus expired concentrations for O2 and CO2 are displayed simultaneously with the expired gas flow rate curve for each breath. Dead-space and alveolar ventilation are calculated for each breath and readily appreciated from the display. Graphs illustrating the function of the system are presented for the following clinical scenarios; upper airway obstruction, bronchospasm, bronchopleural fistula, pulmonary perfusion changes and inadequate oxygen delivery. This paper describes a real-time, single breath pulmonary monitoring system that displays three parameters graphed against time: expired flow rate, oxygen uptake and carbon dioxide production. This system allows for early and rapid recognition of treatable conditions that may lead to adverse events without any additional patient measurements or invasive procedures. Monitoring systems similar to the one described in this paper may lead to a higher level of patient safety without any additional patient risk.

Reexpansion Pulmonary Edema following Laparoscopy-Assisted Distal Gastrectomy for a Patient with Early Gastric Cancer: A Case Report

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Kazuhito Yajima

2012-01-01

Full Text Available We report here a case of reexpansion pulmonary edema following laparoscopy-assisted distal gastrectomy (LADG for early gastric cancer. A 57-year-old Japanese woman with no preoperative comorbidity was diagnosed with early gastric cancer. The patient underwent LADG using the pneumoperitoneum method. During surgery, the patient was unintentionally subjected to single-lung ventilation for approximately 247 minutes due to intratracheal tube dislocation. One hour after surgery, she developed severe dyspnea and produced a large amount of pink frothy sputum. Chest radiography results showed diffuse ground-glass attenuation and alveolar consolidation in both lungs without cardiomegaly. A diagnosis of pulmonary edema was made, and the patient was immediately intubated and received ventilatory support with high positive end-expiratory pressure. The patient gradually recovered and was weaned from the ventilatory support on the third postoperative day. This case shows that single-lung ventilation may be a risk factor for reexpansion pulmonary edema during laparoscopic surgery with pneumoperitoneum.

Severity of Anxiety Disorders in Patients with Chronic Obstructive Pulmonary Disease

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Mitra Safa

2015-10-01

Full Text Available Objective: Patients with chronic physical diseases sometimes show increased loss of function; such patients need more care. Anxiety is a well-known symptom that is prevalent among chronic obstructive pulmonary disease patients that can prolong and increase the risk of hospitalization. The purpose of this study was to evaluate the severity of anxiety in the mentioned patients and to examine the presence of symptoms and appropriate treatment strategies to understand the role of psychological functions in physical patients.Methods: This was a cross sectional study conducted in Masih Daneshvari Hospital. One hundred forty- three patients entered into the project by accessible method and signed the informed consent; they filled demographic information and Hamilton anxiety and depression questionnaires. Data were analyzed by SPSS-16 .Results: Of the participants, 68% were above 60 years of age; 78% were male; 89% were married; and 38% were self-employed. Also, among the participants, 51% were illiterate; 72% had history of smoking; 46% had history of substance abuse; and 49% had moderate to severe anxiety disorder. Moreover, of the patients with severe anxiety, 41.3% had severe muscle spasms; and severe sleeplessness was found in 38.5% of those with severe anxiety disorder. Severe anxiety related symptoms were found in 20.3% of the patients with severe anxiety disorder. Depressed mood was found in 27.3% of the patients with severe anxiety disorder. Severe physical and muscular signs were found in 35.7% of those with severe anxiety disorder .Conclusion: According to our findings, many chronic diseases such as chronic obstructive pulmonary disease may contain anxiety and depression which result in vulnerability. Therefore, evaluation of anxiety in such patients is of importance for alleviating the disease.

[Diagnosis of pulmonary hemorrhage of the newborn infants using lung ultrasonography].

Science.gov (United States)

Liu, J; Fu, W; Chen, S W; Wang, Y

2017-01-02

Objective: To investigate the accuracy and reliability of lung ultrasound in diagnosis of pulmonary hemorrhage of the newborn infants. Method: From January 2014 to May 2016, 142 neonates from the Army General Hospital of the Chinese PLA were enrolled in the study. They were divided into two groups: a study group of 42 neonates, who were diagnosed with pulmonary hemorrhage according to their medical history, clinical manifestations and chest X-ray findings, and a control group of 100 neonates with no lung disease. All subjects underwent bedside lung ultrasound in a quiet state in a supine, lateral or prone posture, performed by a single experienced physician. The ultrasound findings were compared between the two groups.Fisher's exact test was uesd for comparison between two groups. Result: The lung ultrasound main findings associated with pulmonary hemorrhage included: (1) Shred sign: which was seen in 40 patients(95%). (2) Lung consolidation with air bronchograms: which were seen in 35 patients(83%). (3) Pleural effusion: which was seen in 34 infants(81%), pleurocentesis confirmed that the fluid was really bleeding.(4)Atelectasis: which was seen in 14 cases(33%). (5) Pleural line abnormalities and disappearing A-lines with an incidence of 100%. (6) Alveolar-interstitial syndrome: 5 patients(12%)had the main manifestations of alveolar-interstitial syndrome. The above signs were not seen in normal controls (all P hemorrhage, which is suitable for routine application for the diagnosis of pulmonary hemorrhage in the neonatal intensive care unit.

Pulmonary berylliosis. Experimental induction. Early detection

International Nuclear Information System (INIS)

Andre, Stephane

1984-01-01

This research thesis reports the study of the biological reactivity of industrial and environmental aerosols, notably beryllium powder aerosols. In order to study beryllium toxicity under its metal form, and the dose-effect relationship and the suspected carcinogen effect, a pulmonary berylliosis has been experimentally induced in rat and monkey. In order to develop means of rapid detection of exposure and sensitisation to beryllium, the author studied early pathological cellular mechanisms occurring during a pulmonary granulomatosis. Quantitative and qualitative modifications have been searched for, more particularly at the level of endo-alveolar cellular populations of macrophages and lymphocytes. The study has also been extended to the sensitisation of lymphocytes with respect to beryllium. After some generalities about beryllium (properties, sources, uses, exposure sources), and an overview of its toxicity (epidemiology, pathologies, experiments, biological mechanisms, detoxification), the author reports the introduction of a chronic pulmonary berylliosis into animals, discusses the various noticed pathologies and their analysis, and reports in situ and in vitro studies [fr

Transcatheter closure of patent ductus arteriosus with severe pulmonary arterial hypertension in adults

International Nuclear Information System (INIS)

Zhao Shihua; Yan Chaowu; Jiang Shiliang; Xu Zhongying; Huang Lianjun; Ling Jian; Zheng Hong; Wang Cheng; Hu Haibo; Wu Wenhui; Li Shiguo; Dai Ruping

2006-01-01

Objective: To evaluate the effect of self-expandable occluder on closure of patent ductus arteriosus (PDA) with severe pulmonary arterial hypertension (PH) in adults. Methods: Twenty-eight adult patients underwent transcatheter closure of PDA at a mean age of (31.3±11.6) years [(18-58) years]. Either Amplatzer duct occluder or domestic device was used in the present study. X-ray, EKG and UCG were repeated in one day, one month, three months, and six months. Results: Twenty of the 28 patients had successful occlusion, and the other 8 patients were given up. In the successful group, the narrowest diameter of PDA was (10.4±2.7) mm [(6-16) mm], the diameter of selected occluder was (15.6±3.2)mm [(10-20) mm] at the end of pulmonary artery. Systemic artery oxygen saturation (SAsat) before and after oxygen inhalation was (93.5±1.8)%, (98.2±1.8)%, respectively (P<0.01). Systolic pulmonary arterial pressure decreased significantly after trial occlusion from (95.5± 24.l) mm Hg to (56.3±18.3) mm Hg (P<0.01); Mean pulmonary arterial pressures decreased significantly from (70.8±18.2) mm Hg to (41.0±13.8 )mm Hg (P<0. 01), too. Six months later UCG showed that the dimensions of left atrium, left ventricle and pulmonary artery attenuated significantly with one exception; X rays showed decreased pulmonary vascularity or cardiac size as well [cardio-thoracic ratio: (59.2±6.6)% vs (54.2±3.3)%, P<0.01]. In given up group, four patients were defined as Eisenmenger syndromes with differential cyanosis. They presented with elevated systolic pulmonary arterial pressure [(110.3±13.9) mm Hg vs (139.5±20.0)mm Hg, P<0.01], or decreased systolic aortic pressure[(116.0±20.2)mm Hg vs (106.3±16.9) mm Hg, P<0.05]after occlusion. The others included two cases with large residual shunt, and two cases with worsening of symptoms. Conclusions: Transcatheter closure of PDA with reversible severe PH is feasible, effective and safe in adults. (authors)

Transcatheter closure of patent ductus arteriosus with severe pulmonary arterial hypertension in adults

Energy Technology Data Exchange (ETDEWEB)

Shihua, Zhao; Chaowu, Yan; Shiliang, Jiang; Zhongying, Xu; Lianjun, Huang; Jian, Ling; Hong, Zheng; Cheng, Wang; Haibo, Hu; Wenhui, Wu; Shiguo, Li; Ruping, Dai [Department of Radiology, Cardiovascular Inst. and Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing Union Medical College, Beijing (China)

2006-11-15

Objective: To evaluate the effect of self-expandable occluder on closure of patent ductus arteriosus (PDA) with severe pulmonary arterial hypertension (PH) in adults. Methods: Twenty-eight adult patients underwent transcatheter closure of PDA at a mean age of (31.3{+-}11.6) years [(18-58) years]. Either Amplatzer duct occluder or domestic device was used in the present study. X-ray, EKG and UCG were repeated in one day, one month, three months, and six months. Results: Twenty of the 28 patients had successful occlusion, and the other 8 patients were given up. In the successful group, the narrowest diameter of PDA was (10.4{+-}2.7) mm [(6-16) mm], the diameter of selected occluder was (15.6{+-}3.2)mm [(10-20) mm] at the end of pulmonary artery. Systemic artery oxygen saturation (SAsat) before and after oxygen inhalation was (93.5{+-}1.8)%, (98.2{+-}1.8)%, respectively (P<0.01). Systolic pulmonary arterial pressure decreased significantly after trial occlusion from (95.5{+-} 24.l) mm Hg to (56.3{+-}18.3) mm Hg (P<0.01); Mean pulmonary arterial pressures decreased significantly from (70.8{+-}18.2) mm Hg to (41.0{+-}13.8 )mm Hg (P<0. 01), too. Six months later UCG showed that the dimensions of left atrium, left ventricle and pulmonary artery attenuated significantly with one exception; X rays showed decreased pulmonary vascularity or cardiac size as well [cardio-thoracic ratio: (59.2{+-}6.6)% vs (54.2{+-}3.3)%, P<0.01]. In given up group, four patients were defined as Eisenmenger syndromes with differential cyanosis. They presented with elevated systolic pulmonary arterial pressure [(110.3{+-}13.9) mm Hg vs (139.5{+-}20.0)mm Hg, P<0.01], or decreased systolic aortic pressure[(116.0{+-}20.2)mm Hg vs (106.3{+-}16.9) mm Hg, P<0.05]after occlusion. The others included two cases with large residual shunt, and two cases with worsening of symptoms. Conclusions: Transcatheter closure of PDA with reversible severe PH is feasible, effective and safe in adults. (authors)

[The clinical effect of root amputation in the treatment of periodontal/alveolar abscess].

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Tan, Baochun; Wu, Wenlei; Sun, Weibin; Xiao, Jianping

2012-06-01

To study the clinical effect of root amputation in the treatment of periodontal/alveolar abscess teeth with one severe lesion root. 30 periodontal/alveolar abscess teeth with one severe lesion root were chosen in the study. After root canal treatment, supragingival scaling, subgingival scaling and root planning, occlusal adjustment were done. Then the teeth were treated by root amputation. The clinical effect was evaluated 3 months, 6 months and 1 year after surgery. One year after surgery, 27 of 30 teeth were successful, 1 mandibular molar occurred root fracture, 1 mandibular molar was removed because of tooth loosening secondary to periodontal damage. 1 patient lost. Root amputation is an effective solution of periodontal/alveolar abscess.

Association of Body Mass Index with Asthma Severity and Pulmonary Function among Asthmatic Children

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Rasuol Nasiri Kalmarzi

2016-09-01

Full Text Available Background Asthma is a chronic inflammatory disease in respiratory system and obesity is another inflammatory disease which incidence rate is increasing. Although, many studies have been conducted on severity of asthma and its relationship with obesity, but different results have been obtained. This study aimed to determine a relationship between asthma severity, Body Mass Index (BMI and pulmonary function in Kurdistan province, Iran. Materials and Methods: In this cross sectional study 90 asthmatic patients referred to referral hospital in Kurdistan, North West of Iran, were selected by simple random method. BMI was calculated by dividing weight by height.Pulmonary Function Test (PFT and bronchial-stimulation-test were used for confirmation and investigation of asthma severity. Data were analyzed using SPSS-15 and Chi-square and spearman correlation coefficient tests. Results: Relationship between BMI and severity of asthma (mild, medium and severe was evaluated, there was a relationship and positive relationship between them (P

Sex-specific cardiopulmonary exercise testing indices to estimate the severity of inoperable chronic thromboembolic pulmonary hypertension

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Chen TX

2018-01-01

Full Text Available Tian-Xiang Chen,1 Bigyan Pudasaini,1 Jian Guo,2 Su-Gang Gong,1 Rong Jiang,1 Lan Wang,1 Qin-Hua Zhao,1 Wen-Hui Wu,1 Ping Yuan,1 Jin-Ming Liu1 1Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China; 2Department of Pulmonary Function Test, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China Background: Sex differences in chronic thromboembolic pulmonary hypertension (CTEPH have been revealed in few studies. Although right heart catheterization (RHC is the gold standard for clinical diagnosis and assessment of prognosis in pulmonary hypertension (PH, cardiopulmonary exercise testing (CPET has been a more widely used assessment of functional capacity, disease severity, prognosis, and treatment response in PH. We hypothesized that the “sex-specific” CPET indices could estimate the severity of inoperable CTEPH.Methods: Data were retrieved for 33 male (age, mean ± standard deviation [SD] =62.5±13.4 years and 40 female (age, mean ± SD =56.3±11.8 years patients with stable CTEPH who underwent both RHC and CPET at Shanghai Pulmonary Hospital from February 2010 to February 2016. Univariate and forward/backward multiple stepwise regression analysis was performed to assess the predictive value of CPET indices to hemodynamic parameters. Event-free survival was estimated using the Kaplan–Meier method and analyzed with the log-rank test. Cox proportional hazards models were performed to determine the independent event-free survival predictors.Results: Numerous CPET parameters were different between male and female patients with CTEPH and the control group. There were no significant differences in both clinical variables and RHC parameters between male and female patients with CTEPH. O2 pulse, workload, minute ventilation (VE, and end-tidal partial pressure of O2 (PETO2 at anaerobic threshold, as well as peak O2 pulse, workload, VE, and nadir

Fusariosis as solitary pulmonary nodule

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Moreno, Nelson; Saavedra R, Alfredo; Sanchez Edgar A

2008-01-01

Invasive fungal infections are common cause of morbidity and mortality in immunocompromised patients. Of these the most frequents are: aspergillosis and Fusariosis, both grouped under the term Hyalohyphomycosis. One of the organs most commonly affected is the lung.Unfortunately the clinical manifestations as cough, pain and bleeding pleuritic such are none specific. The chest Rx may show since alveolar infiltration, or nodular lesions until cavitaciones. This is the first report on Colombia of a single pulmonary nodule by Fusarium fungi in an immunocompetent patient.

Isolated pulmonary vasculitis: case report and literature review.

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Riancho-Zarrabeitia, Leyre; Zurbano, Felipe; Gómez-Román, Javier; Martínez-Meñaca, Amaya; López, Marta; Hernández, Miguel A; Pina, Trinitario; González-Gay, Miguel A

2015-04-01

Single-organ vasculitis has been reported to affect the skin, kidneys, central nervous system, peripheral nerves, genitourinary tract, calf muscles, aorta, coronary arteries, retina, or gastrointestinal tract. However, isolated pulmonary vasculitis is a very rare entity. Our aims were to describe a case of localized pulmonary vasculitis affecting medium-sized vessels and review the literature. A patient with localized pulmonary vasculitis affecting medium-sized vessels that presented as pulmonary arterial hypertension is described. A MEDLINE database search of cases with localized pulmonary vasculitis was also conducted. A 30-year-old man presented with pulmonary hypertension due to isolated pulmonary medium-sized vessel vasculitis that was confirmed histologically. Initially he responded to corticosteroids and vasodilator treatment, but therapy eventually lost efficacy. Treatment with rituximab was not effective, and as the clinical situation worsened, lung transplant was performed. Isolated large pulmonary vessel disease, often related to Takayasu disease or giant cell arteritis, may present as pulmonary artery hypertension, thus mimicking chronic thromboembolic disease. Medium- and small-vessel pulmonary vasculitis usually develops in the context of a systemic disease. Some cases of isolated small-vessel vasculitis have been reported presenting as diffuse alveolar hemorrhage. In contrast, our case developed pulmonary artery hypertension secondary to medium-sized vessels vasculitis. To our knowledge, this is the first case of lung transplantation in isolated pulmonary vasculitis. Pulmonary isolated vasculitis is a rare cause of pulmonary hypertension but it must be taken into consideration after more common disorders are excluded. Copyright © 2014 Elsevier Inc. All rights reserved.

Hemorragia alveolar como complicación del uso de trombolíticos Alveolar hemorrhage as a complication of thrombolytic therapy

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Alejandra González

2011-12-01

Full Text Available La trombolisis se usa como estrategia de reperfusión coronaria en el infarto agudo de miocardio. El sangrado es su principal complicación; la mayoría ocurre en los sitios de accesos venosos y es leve, pero también pueden presentarse hemorragia gastrointestinal, retroperitoneal, genitourinaria, pulmonar y a nivel del sistema nervioso central, episodios estos generalmente de mayor gravedad y a veces fatales. Se describe aquí el caso de un paciente que recibió terapia trombolítica con estreptoquinasa como tratamiento por un infarto de miocardio, y que posteriormente desarrolló insuficiencia respiratoria aguda, infiltrados pulmonares bilaterales, caída del hematocrito y aumento de la difusión de monóxido de carbono, cuadro compatible con diagnóstico de hemorragia alveolar.Coronary thrombolysis is used as a strategy for coronary reperfusion for acute myocardial infarction. Bleeding is the main complication described. Although most of these events occur at sites of vascular access and are mild, in some cases gastrointestinal, retroperitoneal, genitourinary, lung and central nervous system bleeding may occur. These episodes are usually serious and sometimes fatal. The following report describes the case of a patient who received thrombolytic therapy with streptokinase as a treatment for myocardial infarction. Subsequently he developed acute respiratory failure, bilateral pulmonary infiltrates and fall of hematocrit compatible with diagnosis of alveolar hemorrhage.

Cystic Fibrosis Transmembrane Conductance Regulator Potentiation as a Therapeutic Strategy for Pulmonary Edema: A Proof-of-Concept Study in Pigs.

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Li, Xiaopeng; Vargas Buonfiglio, Luis G; Adam, Ryan J; Stoltz, David A; Zabner, Joseph; Comellas, Alejandro P

2017-12-01

To determine the feasibility of using a cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770/Kalydeco, Vertex Pharmaceuticals, Boston, MA), as a therapeutic strategy for treating pulmonary edema. Prospective laboratory animal investigation. Animal research laboratory. Newborn and 3 days to 1 week old pigs. Hydrostatic pulmonary edema was induced in pigs by acute volume overload. Ivacaftor was nebulized into the lung immediately after volume overload. Grams of water per grams of dry lung tissue were determined in the lungs harvested 1 hour after volume overload. Ivacaftor significantly improved alveolar liquid clearance in isolated pig lung lobes ex vivo and reduced edema in a volume overload in vivo pig model of hydrostatic pulmonary edema. To model hydrostatic pressure-induced edema in vitro, we developed a method of applied pressure to the basolateral surface of alveolar epithelia. Elevated hydrostatic pressure resulted in decreased cystic fibrosis transmembrane conductance regulator activity and liquid absorption, an effect which was partially reversed by cystic fibrosis transmembrane conductance regulator potentiation with ivacaftor. Cystic fibrosis transmembrane conductance regulator potentiation by ivacaftor is a novel therapeutic approach for pulmonary edema.

Negative pressure pulmonary edema revisited: Pathophysiology and review of management

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Balu Bhaskar

2011-01-01

Full Text Available Negative pressure pulmonary edema (NPPE is a dangerous and potentially fatal condition with a multifactorial pathogenesis. Frequently, NPPE is a manifestation of upper airway obstruction, the large negative intrathoracic pressure generated by forced inspiration against an obstructed airway is thought to be the principal mechanism involved. This negative pressure leads to an increase in pulmonary vascular volume and pulmonary capillary transmural pressure, creating a risk of disruption of the alveolar-capillary membrane. The early detection of the signs of this syndrome is vital to the treatment and to patient outcome. The purpose of this review is to highlight the available literature on NPPE, while probing the pathophysiological mechanisms relevant in both the development of this condition and that involved in its resolution.

Severe pulmonary compromise in an immunocompetent patient with acute disseminated toxoplasmosis: A Case Report

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Salinas, Jorge; Pino, Luis; Lopez Consuelo

2008-01-01

Introduction: The acute toxoplasmosis in the immunocompetent patient, unlike of the positive HIV patient, it is characterizes for prolonged fever, lymph node and nonspecific infectious symptoms, generally with benign course and without systemic commitment. This pathology acquired a very importance in the pregnancy people, where the primary infection can to derivates in the congenital transmission of the illness with irreversible sequels in newborn. Nevertheless, the travel of the people to inhospitable woodsy areas, and the contact with wild-type strain of toxoplasma gondii, to be permitted a new expression of the illness in the immunocompetent patient, with pulmonary, cardiovascular and central nervous system manifestations. They are a high risk for the patient life's. In this study, one case of severe pulmonary commitment for toxoplasma gondii in immunocompetent patient is review; he is admitted to Internal Medicine Service of the Militar Central Hospital's in Bogota. He has a favorable evolution and adequate survival. Objective: To describe the clinical characteristics and follow-up of one patient with severe pulmonary commitment caused by toxoplasma gondii. Design: Case report. Materials and methods: The clinical records of the one patient who was hospitalized in the Militar Central Hospital's in Bogota was reviewed and described. Afterwards, the existing literature on Acute toxoplasmosis in immunocompetent patient was reviewed in PubMed, MD consult and OVID databases. Conclusions: The toxoplasma gondii infection's in immunocompetent patient generally has a benign course without systemic manifestations; nevertheless, the exposure to wild-type strain can to be related with severe pulmonary commitment.

Nonhomogeneous immunostaining of hyaline membranes in different manifestations of diffuse alveolar damage Imunomarcação não homogênea das membranas hialinas na sindrome da angustia respiratório do adulto pulmonar, extrapulmonar e idiopática

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André Peres e Serra

2006-01-01

Full Text Available PURPOSE: To determine the nature of hyaline membranes in different manifestations of diffuse alveolar damage, [pulmonary and extrapulmonary acute respiratory distress syndrome], and idiopathic [acute interstitial pneumonia]. MATERIALS AND METHODS: Pulmonary specimens were obtained from 17 patients with acute respiratory distress syndrome and 9 patients with acute interstitial pneumonia. They were separated into 3 different groups: (a pulmonary diffuse alveolar damage (pDAD (n = 8, consisting only of pneumonia cases; (b extrapulmonary diffuse alveolar damage (expDAI (n = 9, consisting of sepsis and septic shock cases; and (c idiopathic diffuse alveolar damage (iDAD (n = 9, consisting of idiopathic cases (acute interstitial pneumonia. Hyaline membranes, the hallmark of the diffuse alveolar damage histological pattern, were examined using various kinds of antibodies. The antibodies used were against surfactant apoprotein-A (SP-A, cytokeratin 7 (CK7, cytokeratin 8 (CK8, alpha smooth muscle actin (a-SMA, cytokeratin AE1/AE3 (AE1/AE3, and factor VIII-related antigen (factor VIII. RESULTS: Pulmonary diffuse alveolar damage showed the largest quantity of hyaline membranes (12.65% ± 3.24%, while extrapulmonary diffuse alveolar damage (9.52% ± 3.64% and idiopathic diffuse alveolar damage (7.34% ± 2.11% showed intermediate and lower amounts, respectively, with the difference being statistically significant between pulmonary and idiopathic diffuse alveolar damage (P OBJETIVO: Determinar a natureza da membrana hialina nas diferentes manifestações do dano alveolar difuso [pulmonar e extrapulmonar síndrome do desconforto respiratório] e idiopático [pneumonia intersticial aguda]. MATERIAIS E MÉTODOS: Espécimes pulmonares foram obtidos de 17 pacientes com SDRA e 9 pacientes com pneumonia intersticial aguda e separados em três diferentes grupos: (a dano alveolar difuso pulmonar (DADp (n=8 constituído por casos de pneumonia, (b dano alveolar difuso

Validation of the 2nd Generation Proteasome Inhibitor Oprozomib for Local Therapy of Pulmonary Fibrosis.

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Nora Semren

Full Text Available Proteasome inhibition has been shown to prevent development of fibrosis in several organs including the lung. However, effects of proteasome inhibitors on lung fibrosis are controversial and cytotoxic side effects of the overall inhibition of proteasomal protein degradation cannot be excluded. Therefore, we hypothesized that local lung-specific application of a novel, selective proteasome inhibitor, oprozomib (OZ, provides antifibrotic effects without systemic toxicity in a mouse model of lung fibrosis. Oprozomib was first tested on the human alveolar epithelial cancer cell line A549 and in primary mouse alveolar epithelial type II cells regarding its cytotoxic effects on alveolar epithelial cells and compared to the FDA approved proteasome inhibitor bortezomib (BZ. OZ was less toxic than BZ and provided high selectivity for the chymotrypsin-like active site of the proteasome. In primary mouse lung fibroblasts, OZ showed significant anti-fibrotic effects, i.e. reduction of collagen I and α smooth muscle actin expression, in the absence of cytotoxicity. When applied locally into the lungs of healthy mice via instillation, OZ was well tolerated and effectively reduced proteasome activity in the lungs. In bleomycin challenged mice, however, locally applied OZ resulted in accelerated weight loss and increased mortality of treated mice. Further, OZ failed to reduce fibrosis in these mice. While upon systemic application OZ was well tolerated in healthy mice, it rather augmented instead of attenuated fibrotic remodelling of the lung in bleomycin challenged mice. To conclude, low toxicity and antifibrotic effects of OZ in pulmonary fibroblasts could not be confirmed for pulmonary fibrosis of bleomycin-treated mice. In light of these data, the use of proteasome inhibitors as therapeutic agents for the treatment of fibrotic lung diseases should thus be considered with caution.

Severe pulmonary hypertension in a young patient with end-stage renal disease on chronic hemodialysis

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Sharma, Satyavan; Kirpalani, Ashok L; Kulkarni, Amit

2010-01-01

Severe pulmonary hypertension in a teenager with end-stage renal disease on chronic hemodialysis via arteriovenous access is reported. Clinical presentation included persistent volume overload and pericardial effusion. Serial hemodynamic data obtained at cardiac catheterization confirmed the diagnosis. In addition, detailed biochemical and imaging data (echo- Doppler, computed tomography of chest, computed tomographic pulmonary angiography, VQ lung scan, etc.) were obtained to find out the mechanism. The exact cause of pulmonary hypertension remains unclear, and a multi- factorial mechanism is postulated. This rare case is presented to highlight the role of aggressive dialysis, pericardiocentesis, and use of sildenafil and bosentan in the management

Achondroplasia-hypochondroplasia complex and abnormal pulmonary anatomy.

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Bober, Michael B; Taylor, Megan; Heinle, Robert; Mackenzie, William

2012-09-01

Achondroplasia and hypochondroplasia are two of the most common forms of skeletal dysplasia. They are both caused by activating mutations in FGFR3 and are inherited in an autosomal dominant manner. Our patient was born to parents with presumed achondroplasia, and found on prenatal testing to have p.G380R and p.N540K FGFR3 mutations. In addition to having typical problems associated with both achondroplasia and hypochondroplasia, our patient had several atypical findings including: abnormal lobulation of the lungs with respiratory insufficiency, C1 stenosis, and hypoglycemia following a Nissen fundoplication. After his reflux and aspiration were treated, the persistence of the tachypnea and increased respiratory effort indicated this was not the primary source of the respiratory distress. Our subsequent hypothesis was that primary restrictive lung disease was the cause of his respiratory distress. A closer examination of his chest circumference did not support this conclusion either. Following his death, an autopsy found the right lung had 2 lobes while the left lung had 3 lobes. A literature review demonstrates that other children with achondroplasia-hypochondroplasia complex have been described with abnormal pulmonary function and infants with thanatophoric dysplasia have similar abnormal pulmonary anatomy. We hypothesize that there may be a primary pulmonary phenotype associated with FGFR3-opathies, unrelated to chest size which leads to the consistent finding of increased respiratory signs and symptoms in these children. Further observation of respiratory status, combined with the macroscopic and microscopic analysis of pulmonary branching anatomy and alveolar structure in this patient population will be important to explore this hypothesis. Copyright © 2012 Wiley Periodicals, Inc.

Transforming growth factor. beta. sub 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis

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Broekelmann, T.J.; Limper, A.H.; McDonald, J.A. (Washington Univ., St. Louis, MO (United States)); Colby, T.V. (Mayo Clinic, Rochester, MN (United States))

1991-08-01

Idiopathic pulmonary fibrosis is an inexorably fatal disorder characterized by connective tissue deposition within the terminal air spaces resulting in loss of lung function and eventual respiratory failure. Previously, the authors demonstrated that foci of activated fibroblasts expressing high levels of fibronectin, procollagen, and smooth muscle actin and thus resembling those found in healing wounds are responsible for the connective tissue deposition and scarring in idiopathic pulmonary fibrosis. Using in situ hybridization and immunohistochemistry, they now demonstrate the presence of transforming growth factor {beta}{sub 1} (TGF-{beta}{sub 1}), a potent profibrotic cytokine, in the foci containing these activated fibroblasts. These results suggest that matrix-associated TGF-{beta}{sub 1} may serve as a stimulus for the persistent expression of connective tissue genes. One potential source of the TGF-{beta}{sub 1} is the alveolar macrophage, and they demonstrate the expression of abundant TGF-{beta}{sub 1} mRNA in alveolar macrophages in lung tissue from patients with idiopathic pulmonary fibrosis.

Severe idiopathic pulmonary fibrosis: what can be done?

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Antonella Caminati

2017-09-01

Full Text Available Idiopathic pulmonary fibrosis (IPF remains a challenging disease to manage. Two drugs are now available that can slow disease progression in patients with mild-to-moderate IPF. This means that early diagnosis is mandatory, because there are no proven effective therapies for severe IPF. This lack of proven therapies may be at least partially due to the fact that severe IPF patients are usually not enrolled in randomised, prospective, multicentre, international trials. Clinical observation experiences and preliminary results of long-term, open-label extensions of clinical trials suggest that both pirfenidone and nintedanib may also slow or decrease progression in patients with severe IPF. However, data are sparse and obtained from a relatively small number of patients. Lung transplantation should be taken into account early and discussed with patients, when indicated. Rehabilitative strategies are important and effective supportive therapies. The needs of patients with severe IPF are similar to those of patients with an advanced neoplastic disease. Palliative care and psychological support play an important role in the relief of symptoms of anxiety and depression. Accordingly, these therapeutic approaches should start early in IPF patients.

Quantitative CT analysis of small pulmonary vessels in lymphangioleiomyomatosis

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Ando, Katsutoshi, E-mail: kando@juntendo.ac.jp [Department of Internal Medicine, Division of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421 (Japan); The Study Group of Pneumothorax and Cystic Lung Diseases, 4-8-1 Seta, Setagaya-Ku, Tokyo 158-0095 (Japan); Tobino, Kazunori [Department of Respiratory Medicine, Iizuka Hospital, 3-83 Yoshio-Machi, Iizuka-City, Fukuoka 820-8505 (Japan); The Study Group of Pneumothorax and Cystic Lung Diseases, 4-8-1 Seta, Setagaya-Ku, Tokyo 158-0095 (Japan); Kurihara, Masatoshi; Kataoka, Hideyuki [Pneumothorax Center, Nissan Tamagawa Hospital, 4-8-1 Seta, Setagaya-Ku, Tokyo 158-0095 (Japan); The Study Group of Pneumothorax and Cystic Lung Diseases, 4-8-1 Seta, Setagaya-Ku, Tokyo 158-0095 (Japan); Doi, Tokuhide [Fukuoka Clinic, 7-18-11 Umeda, Adachi-Ku, Tokyo 123-0851 (Japan); Hoshika, Yoshito [Department of Internal Medicine, Division of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421 (Japan); The Study Group of Pneumothorax and Cystic Lung Diseases, 4-8-1 Seta, Setagaya-Ku, Tokyo 158-0095 (Japan); Takahashi, Kazuhisa [Department of Internal Medicine, Division of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421 (Japan); Seyama, Kuniaki [Department of Internal Medicine, Division of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421 (Japan); The Study Group of Pneumothorax and Cystic Lung Diseases, 4-8-1 Seta, Setagaya-Ku, Tokyo 158-0095 (Japan)

2012-12-15

Backgrounds: Lymphangioleiomyomatosis (LAM) is a destructive lung disease that share clinical, physiologic, and radiologic features with chronic obstructive pulmonary disease (COPD). This study aims to identify those features that are unique to LAM by using quantitative CT analysis. Methods: We measured total cross-sectional areas of small pulmonary vessels (CSA) less than 5 mm{sup 2} and 5–10 mm{sup 2} and calculated percentages of those lung areas (%CSA), respectively, in 50 LAM and 42 COPD patients. The extent of cystic destruction (LAA%) and mean parenchymal CT value were also calculated and correlated with pulmonary function. Results: The diffusing capacity for carbon monoxide/alveolar volume (DL{sub CO}/VA %predicted) was similar for both groups (LAM, 44.4 ± 19.8% vs. COPD, 45.7 ± 16.0%, p = 0.763), but less tissue damage occurred in LAM than COPD (LAA% 21.7 ± 16.3% vs. 29.3 ± 17.0; p < 0.05). Pulmonary function correlated negatively with LAA% (p < 0.001) in both groups, yet the correlation with %CSA was significant only in COPD (p < 0.001). When the same analysis was conducted in two groups with equal levels of LAA% and DL{sub CO}/VA %predicted, %CSA and mean parenchymal CT value were still greater for LAM than COPD (p < 0.05). Conclusions: Quantitative CT analysis revealing a correlation between cystic destruction and CSA in COPD but not LAM indicates that this approach successfully reflects different mechanisms governing the two pathologic courses. Such determinations of small pulmonary vessel density may serve to differentiate LAM from COPD even in patients with severe lung destruction.

Cultured alveolar epithelial cells from septic rats mimic in vivo septic lung.

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Taylor S Cohen

2010-06-01

Full Text Available Sepsis results in the formation of pulmonary edema by increasing in epithelial permeability. Therefore we hypothesized that alveolar epithelial cells isolated from septic animals develop tight junctions with different protein composition and reduced barrier function relative to alveolar epithelial cells from healthy animals. Male rats (200-300 g were sacrificed 24 hours after cecal ligation and double puncture (2CLP or sham surgery. Alveolar epithelial cells were isolated and plated on fibronectin-coated flexible membranes or permeable, non-flexible transwell substrates. After a 5 day culture period, cells were either lysed for western analysis of tight junction protein expressin (claudin 3, 4, 5, 7, 8, and 18, occludin, ZO-1, and JAM-A and MAPk (JNK, ERK, an p38 signaling activation, or barrier function was examined by measuring transepithelial resistance (TER or the flux of two molecular tracers (5 and 20 A. Inhibitors of JNK (SP600125, 20 microM and ERK (U0126, 10 microM were used to determine the role of these pathways in sepsis induced epithelial barrier dysfunction. Expression of claudin 4, claudin 18, and occludin was significantly lower, and activation of JNK and ERK signaling pathways was significantly increased in 2CLP monolayers, relative to sham monolayers. Transepithelial resistance of the 2CLP monolayers was reduced significantly compared to sham (769 and 1234 ohm-cm(2, respectively, however no significant difference in the flux of either tracer was observed. Inhibition of ERK, not JNK, significantly increased TER and expression of claudin 4 in 2CLP monolayers, and prevented significant differences in claudin 18 expression between 2CLP and sham monolayers. We conclude that alveolar epithelial cells isolated from septic animals form confluent monolayers with impaired barrier function compared to healthy monolayers, and inhibition of ERK signaling partially reverses differences between these monolayers. This model provides a unique

Reversal of echocardiographic right-sided heart pathology in a dog with severe pulmonary hypertension: a case report

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McMahon P

2015-06-01

Full Text Available Peggy McMahon,1 Carley Saelinger 2  1Emergency and Critical Care Department, 2Cardiology Department, Animal Specialty and Emergency Center, Los Angeles, CA, USA Abstract: Pathologic right-sided heart changes are a common echocardiographic finding in patients with pulmonary hypertension (PH. Canines with PH may have right heart pathology documented via echocardiographic color Doppler interrogation including tricuspid valve regurgitation, pulmonic valve insufficiency, elevated pulmonary arterial systolic pressure, elevated pulmonary arterial diastolic pressure, and alterations in ejection profiles. Two-dimensional echocardiographic findings may include right ventricular hypertrophy, interventricular septal flattening, paradoxical interventricular septal motion, pulmonary artery dilation, and potentially abnormal left heart dimensions. In veterinary medicine, much confidence is given to the measurement of pulmonary arterial systolic pressure estimated from tricuspid valve regurgitation to grade the severity of PH and monitor its improvement with little emphasis placed on the integration of two-dimensional echocardiographic right and left heart pathology in conjunction with Doppler findings. To the authors’ knowledge, marked improvement and/or resolution of echocardiographic-documented right heart pathology have not been previously reported in the veterinary literature. This case report documents profound echocardiographic improvement of right-sided heart disease in a dog with severe PH. Keywords: canine, pulmonary hypertension, tricuspid valve regurgitation, right heart hypertrophy, sildenafil  

Successful Tricuspid Valve Replacement in a Patient with Severe Pulmonary Arterial Hypertension and Preserved Right Ventricular Systolic Function

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Jamil A. Aboulhosn

2009-01-01

Full Text Available A 56-year-old patient with severe pulmonary hypertension developed severe tricuspid regurgitation, right-sided heart failure, and congestive hepatopathy. She was transferred for possible lung transplant and/or tricuspid valve surgery. Clinical and echocardiographic assessment provided confidence that acute tricuspid valve failure was responsible for the decompensation and that tricuspid valve replacement despite pulmonary hypertension could be performed.

Diallylsulfide attenuates excessive collagen production and apoptosis in a rat model of bleomycin induced pulmonary fibrosis through the involvement of protease activated receptor-2

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Kalayarasan, Srinivasan, E-mail: kalaivasanbio@gmail.com; Sriram, Narayanan; Soumyakrishnan, Syamala; Sudhandiran, Ganapasam, E-mail: sudhandiran@yahoo.com

2013-09-01

Pulmonary fibrosis (PF) can be a devastating lung disease. It is primarily caused by inflammation leading to severe damage of the alveolar epithelial cells. The pathophysiology of PF is not yet been clearly defined, but studying lung parenchymal injury by involving reactive oxygen species (ROS) through the activation of protease activated receptor-2 (PAR-2) may provide promising results. PAR-2 is a G-protein coupled receptor is known to play an important role in the development of PF. In this study, we investigated the inhibitory role of diallylsulfide (DAS) against ROS mediated activation of PAR-2 and collagen production accompanied by epithelial cell apoptosis. Bleomycin induced ROS levels may prompt to induce the expression of PAR-2 as well as extracellular matrix proteins (ECM), such as MMP 2 and 9, collagen specific proteins HSP-47, α-SMA, and cytokines IL-6, and IL-8RA. Importantly DAS treatment effectively decreased the expression of all these proteins. The inhibitory effect of DAS on profibrotic molecules is mediated by blocking the ROS level. To identify apoptotic signaling as a mediator of PF induction, we performed apoptotic protein expression, DNA fragmentation analysis and ultrastructural details of the lung tissue were performed. DAS treatment restored all these changes to near normalcy. In conclusion, treatment of PF bearing rats with DAS results in amelioration of the ROS production, PAR-2 activation, ECM production, collagen synthesis and alveolar epithelial cell apoptosis during bleomycin induction. We attained the first evidence that treatment of DAS decreases the ROS levels and may provide a potential therapeutic effect attenuating bleomycin induced PF. - Highlights: • DAS inhibits PAR-2 activity; bleomycin stimulates PAR-2 activity. • Increase in PAR-2 activity is correlated with pulmonary fibrosis • DAS reduces pro-inflammatory activity linked to facilitating pulmonary fibrosis. • DAS inhibits apoptosis of alveolar epithelial cells.

Diallylsulfide attenuates excessive collagen production and apoptosis in a rat model of bleomycin induced pulmonary fibrosis through the involvement of protease activated receptor-2

International Nuclear Information System (INIS)

Kalayarasan, Srinivasan; Sriram, Narayanan; Soumyakrishnan, Syamala; Sudhandiran, Ganapasam

2013-01-01

Pulmonary fibrosis (PF) can be a devastating lung disease. It is primarily caused by inflammation leading to severe damage of the alveolar epithelial cells. The pathophysiology of PF is not yet been clearly defined, but studying lung parenchymal injury by involving reactive oxygen species (ROS) through the activation of protease activated receptor-2 (PAR-2) may provide promising results. PAR-2 is a G-protein coupled receptor is known to play an important role in the development of PF. In this study, we investigated the inhibitory role of diallylsulfide (DAS) against ROS mediated activation of PAR-2 and collagen production accompanied by epithelial cell apoptosis. Bleomycin induced ROS levels may prompt to induce the expression of PAR-2 as well as extracellular matrix proteins (ECM), such as MMP 2 and 9, collagen specific proteins HSP-47, α-SMA, and cytokines IL-6, and IL-8RA. Importantly DAS treatment effectively decreased the expression of all these proteins. The inhibitory effect of DAS on profibrotic molecules is mediated by blocking the ROS level. To identify apoptotic signaling as a mediator of PF induction, we performed apoptotic protein expression, DNA fragmentation analysis and ultrastructural details of the lung tissue were performed. DAS treatment restored all these changes to near normalcy. In conclusion, treatment of PF bearing rats with DAS results in amelioration of the ROS production, PAR-2 activation, ECM production, collagen synthesis and alveolar epithelial cell apoptosis during bleomycin induction. We attained the first evidence that treatment of DAS decreases the ROS levels and may provide a potential therapeutic effect attenuating bleomycin induced PF. - Highlights: • DAS inhibits PAR-2 activity; bleomycin stimulates PAR-2 activity. • Increase in PAR-2 activity is correlated with pulmonary fibrosis • DAS reduces pro-inflammatory activity linked to facilitating pulmonary fibrosis. • DAS inhibits apoptosis of alveolar epithelial cells

A study on quantifying COPD severity by combining pulmonary function tests and CT image analysis

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Nimura, Yukitaka; Kitasaka, Takayuki; Honma, Hirotoshi; Takabatake, Hirotsugu; Mori, Masaki; Natori, Hiroshi; Mori, Kensaku

2011-03-01

This paper describes a novel method that can evaluate chronic obstructive pulmonary disease (COPD) severity by combining measurements of pulmonary function tests and measurements obtained from CT image analysis. There is no cure for COPD. However, with regular medical care and consistent patient compliance with treatments and lifestyle changes, the symptoms of COPD can be minimized and progression of the disease can be slowed. Therefore, many diagnosis methods based on CT image analysis have been proposed for quantifying COPD. Most of diagnosis methods for COPD extract the lesions as low-attenuation areas (LAA) by thresholding and evaluate the COPD severity by calculating the LAA in the lung (LAA%). However, COPD is usually the result of a combination of two conditions, emphysema and chronic obstructive bronchitis. Therefore, the previous methods based on only LAA% do not work well. The proposed method utilizes both of information including the measurements of pulmonary function tests and the results of the chest CT image analysis to evaluate the COPD severity. In this paper, we utilize a multi-class AdaBoost to combine both of information and classify the COPD severity into five stages automatically. The experimental results revealed that the accuracy rate of the proposed method was 88.9% (resubstitution scheme) and 64.4% (leave-one-out scheme).

Alveolar epithelial type II cells induce T cell tolerance to specific antigen

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Lo, Bernice; Hansen, Søren; Evans, Kathy

2008-01-01

The lungs face the immunologic challenge of rapidly eliminating inhaled pathogens while maintaining tolerance to innocuous Ags. A break in this immune homeostasis may result in pulmonary inflammatory diseases, such as allergies or asthma. The observation that alveolar epithelial type II cells (Type...... II) constitutively express the class II MHC led us to hypothesize that Type II cells play a role in the adaptive immune response. Because Type II cells do not express detectable levels of the costimulatory molecules CD80 and CD86, we propose that Type II cells suppress activation of naive T cells...

Redistribution of Extracellular Superoxide Dismutase Causes Neonatal Pulmonary Vascular Remodeling and PH but Protects Against Experimental Bronchopulmonary Dysplasia

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Laurie G. Sherlock

2018-03-01

Full Text Available Background: A naturally occurring single nucleotide polymorphism (SNP, (R213G, in extracellular superoxide dismutase (SOD3, decreases SOD3 matrix binding affinity. Humans and mature mice expressing the R213G SNP exhibit increased cardiovascular disease but decreased lung disease. The impact of this SNP on the neonatal lung at baseline or with injury is unknown. Methods: Wild type and homozygous R213G mice were injected with intraperitoneal bleomycin or phosphate buffered saline (PBS three times weekly for three weeks and tissue harvested at 22 days of life. Vascular and alveolar development were evaluated by morphometric analysis and immunostaining of lung sections. Pulmonary hypertension (PH was assessed by right ventricular hypertrophy (RVH. Lung protein expression for superoxide dismutase (SOD isoforms, catalase, vascular endothelial growth factor receptor 2 (VEGFR2, endothelial nitric oxide synthase (eNOS and guanosine triphosphate cyclohydrolase-1 (GTPCH-1 was evaluated by western blot. SOD activity and SOD3 expression were measured in serum. Results: In R213G mice, SOD3 lung protein expression decreased, serum SOD3 protein expression and SOD serum activity increased compared to wild type (WT mice. Under control conditions, R213G mice developed pulmonary vascular remodeling (decreased vessel density and increased medial wall thickness and PH; alveolar development was similar between strains. After bleomycin injury, in contrast to WT, R213G mice were protected from impaired alveolar development and their vascular abnormalities and PH did not worsen. Bleomycin decreased VEGFR2 and GTPCH-1 only in WT mice. Conclusion: R213G neonatal mice demonstrate impaired vascular development and PH at baseline without alveolar simplification, yet are protected from bleomycin induced lung injury and worsening of pulmonary vascular remodeling and PH. These results show that vessel bound SOD3 is essential in normal pulmonary vascular development, and

Dynamic /sup 99m/Tc-DTPA radioaerosol lung scanning for the evaluation of alveolar-capillary barrier permeability

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Maini, C L; Marchetti, L; Bonetti, M G; Giordano, A; Pistelli, R; Antonelli Incalzi, R

1987-01-01

Pulmonary clearance of small droplet /sup 99m/Tc-DTPA radioaerosol was studied in 100 patients (12 normal subjects, N; 10 asymptomatic healthy smoker, FA; 31 patients with interstitial lung diseases, IP; 47 patients with chronic obstructive lung disease, BPCO). The first seven minutes of clearance were described with the function At=Ao*exp(-K*t) and the time constant K was considered representative of the /sup 99m/Tc-DTPA clearance rate and hence of the alveolar-capillary barrier permeability. Groups FA, IP and BPCO showed a significant (p<0.05) or a highly significant (p<0.01) increase in permeability when compared to group N. No correlation was found between permeability and bronchial obstraction tests. The following conclusions were drawn: 1) /sup 99m/Tc-DTPA dynamic lung scanning is an easy, non-invasive method to assess derangements of alveolar-capillary barrier permeability secondary to epithelial damage; 2) permeability increase is a very early effect of cigarette smoke damafe to the epithelium; 3) other mechanisms of epithelial injury are present in diffuse lung disease; 4) while the clinical role of this new pathophysiological test is not yet clear, it is likely that it may become a very early marker of pulmonary epithelial damage in diffuse lung disease. 35 refs.

Inhaled Diesel Emissions Generated with Cerium Oxide Nanoparticle Fuel Additive Induce Adverse Pulmonary and Systemic Effects

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Snow, Samantha J.; McGee, John; Miller, Desinia B.; Bass, Virginia; Schladweiler, Mette C.; Thomas, Ronald F.; Krantz, Todd; King, Charly; Ledbetter, Allen D.; Richards, Judy; Weinstein, Jason P.; Conner, Teri; Willis, Robert; Linak, William P.; Nash, David; Wood, Charles E.; Elmore, Susan A.; Morrison, James P.; Johnson, Crystal L.; Gilmour, Matthew Ian; Kodavanti, Urmila P.

2014-01-01

Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe > DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration- and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF γ-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe. PMID:25239632

Cell therapy with bone marrow mononuclear cells in elastase-induced pulmonary emphysema.

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Longhini-Dos-Santos, Nathalia; Barbosa-de-Oliveira, Valter Abraão; Kozma, Rodrigo Heras; Faria, Carolina Arruda de; Stessuk, Talita; Frei, Fernando; Ribeiro-Paes, João Tadeu

2013-04-01

Emphysema is characterized by destruction of alveolar walls with loss of gas exchange surface and consequent progressive dyspnea. This study aimed to evaluate the efficiency of cell therapy with bone marrow mononuclear cells (BMMC) in an animal model of elastase-induced pulmonary emphysema. Emphysema was induced in C57Bl/J6 female mice by intranasal instillation of elastase. After 21 days, the mice received bone marrow mononuclear cells from EGFP male mice with C57Bl/J6 background. The groups were assessed by comparison and statistically significant differences (p pulmonary emphysema.

Alterações histopatológicas pulmonares em pacientes com insuficiência respiratória aguda: um estudo em autopsias Pulmonary histopathological alterations in patients with acute respiratory failure: an autopsy study

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Alexandre de Matos Soeiro

2008-02-01

Full Text Available OBJETIVOS: Apresentar alterações histopatológicas pulmonares encontradas em autopsias de pacientes falecidos por insuficiência respiratória aguda (IRA e verificar se doenças de base e específicos fatores de risco associados aumentam a incidência dessas alterações. MÉTODOS: Foram revisados laudos finais de autopsias e selecionadas 3.030 autopsias de pacientes > 1 ano de idade, com infiltrado pulmonar radiológico, portadores de doença de base e fatores de risco associados, que morreram por alterações pulmonares decorrentes de IRA. RESULTADOS: As principais alterações histopatológicas pulmonares causadoras de morte imediata foram: dano alveolar difuso (DAD; edema pulmonar; pneumonia intersticial linfocítica (PIL e hemorragia alveolar. As principais doenças de base encontradas foram: AIDS; broncopneumonia; sepse; cirrose hepática; tromboembolismo pulmonar; infarto agudo do miocárdio (IAM; acidente vascular cerebral; tuberculose; câncer; insuficiência renal crônica e leucemia. Os principais fatores de risco associados foram: idade > 50 anos; hipertensão arterial; insuficiência cardíaca congestiva; doença pulmonar obstrutiva crônica e diabetes mellitus. Pacientes com esses fatores de risco e AIDS apresentaram alta probabilidade de desenvolver PIL; pacientes com esses mesmos fatores, de desenvolver DAD, se portadores de sepse ou cirrose hepática; pacientes com tromboembolismo e os mesmos fatores de risco, de desenvolver hemorragia alveolar; pacientes com esses fatores de risco e IAM, de desenvolver edema pulmonar. CONCLUSÕES: Os achados pulmonares em pacientes com óbito por IRA apresentaram quatro padrões histopatológicos: DAD, edema pulmonar, PIL e hemorragia alveolar. Doenças de base e específicos fatores de risco associados correlacionaram-se positivamente com determinados padrões histopatológicos detectados à autópsia.OBJECTIVE: To present the pulmonary histopathological alterations found in the autopsies of

A syndrome of severe idiopathic pulmonary parenchymal disease with pulmonary hypertension in Pekingese

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Köster LS

2016-02-01

Full Text Available Liza S Köster,1 Robert M Kirberger2 1Section of Medicine, Department of Clinical Sciences, Integrative Mammalian Research (IMR Center, Ross University School of Veterinary Medicine (RUSVM, Basseterre, St Kitts, West Indies; 2Diagnostic Imaging Section, Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa Abstract: This paper describes 35 Pekingese dogs with a syndrome characterized by dyspnea, cyanosis, episodic syncope, soft pulmonary “Velcro” crackles, pulmonary hypertension (PH, and computed tomography and radiographic changes consistent with pulmonary parenchymal disease. The medical data base was searched with the criteria “Pekingese” and “syncope” or “dyspnea” or “tachypnea” or “pulmonary hypertension”, over a 36-month period. Inclusion criteria were echocardiographic changes consistent with noninvasive diagnosis of PH, either subjectively by B-mode or objectively by Doppler. Dogs were excluded (n=106 if there were insufficient or poor-quality radiographic or echocardiographic records or if diseases other than chronic pulmonary disease were found to be the etiology. The records of 35 dogs met these criteria and presented with a respiratory crises preceded by a history of chronic exercise intolerance and episodic syncope. The average age was 14.5 years (range: 7–19 years, with 21 males and 14 females. Most of the dogs had an interstitial lung pattern with radiographic evidence of right heart enlargement. There was a 77% (n=27 mortality and a median survival of 60 days (interquartile range: 9–210 days. This study highlights a cor pulmonale syndrome from PH due to chronic pulmonary parenchymal disease, with a grave prognosis, in middle-aged to geriatric population of Hong Kong Pekingese. Keywords: computed tomography, interstitial lung disease, dog, syncope

Analysis of volatile compounds in exhaled breath condensate in patients with severe pulmonary arterial hypertension.

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Mansoor, J K; Schelegle, Edward S; Davis, Cristina E; Walby, William F; Zhao, Weixiang; Aksenov, Alexander A; Pasamontes, Alberto; Figueroa, Jennifer; Allen, Roblee

2014-01-01

An important challenge to pulmonary arterial hypertension (PAH) diagnosis and treatment is early detection of occult pulmonary vascular pathology. Symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression to advanced states of disease. There is a significant need to develop new markers for early disease detection and management of PAH. Exhaled breath condensate (EBC) samples were compared from 30 age-matched normal healthy individuals and 27 New York Heart Association functional class III and IV idiopathic pulmonary arterial hypertenion (IPAH) patients, a subgroup of PAH. Volatile organic compounds (VOC) in EBC samples were analyzed using gas chromatography/mass spectrometry (GC/MS). Individual peaks in GC profiles were identified in both groups and correlated with pulmonary hemodynamic and clinical endpoints in the IPAH group. Additionally, GC/MS data were analyzed using autoregression followed by partial least squares regression (AR/PLSR) analysis to discriminate between the IPAH and control groups. After correcting for medicaitons, there were 62 unique compounds in the control group, 32 unique compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by-peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds significantly correlated with pulmonary hemodynamic variables important in IPAH diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable metabolic signature for IPAH patients. These findings indicate the utility of EBC VOC analysis to discriminate between severe IPAH and a healthy population; additionally, we identified potential novel biomarkers that correlated with IPAH pulmonary hemodynamic variables that may be important in screening for less severe forms IPAH.

Analysis of volatile compounds in exhaled breath condensate in patients with severe pulmonary arterial hypertension.

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J K Mansoor

Full Text Available BACKGROUND: An important challenge to pulmonary arterial hypertension (PAH diagnosis and treatment is early detection of occult pulmonary vascular pathology. Symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression to advanced states of disease. There is a significant need to develop new markers for early disease detection and management of PAH. METHODOLGY AND FINDINGS: Exhaled breath condensate (EBC samples were compared from 30 age-matched normal healthy individuals and 27 New York Heart Association functional class III and IV idiopathic pulmonary arterial hypertenion (IPAH patients, a subgroup of PAH. Volatile organic compounds (VOC in EBC samples were analyzed using gas chromatography/mass spectrometry (GC/MS. Individual peaks in GC profiles were identified in both groups and correlated with pulmonary hemodynamic and clinical endpoints in the IPAH group. Additionally, GC/MS data were analyzed using autoregression followed by partial least squares regression (AR/PLSR analysis to discriminate between the IPAH and control groups. After correcting for medicaitons, there were 62 unique compounds in the control group, 32 unique compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by-peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds significantly correlated with pulmonary hemodynamic variables important in IPAH diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable metabolic signature for IPAH patients. CONCLUSIONS: These findings indicate the utility of EBC VOC analysis to discriminate between severe IPAH and a healthy population; additionally, we identified potential novel biomarkers that correlated with IPAH pulmonary hemodynamic variables that may be important in screening for less severe forms IPAH.

Distinct changes in pulmonary surfactant homeostasis in common beta-chain-and GM-CSF-deficient mice

NARCIS (Netherlands)

Reed, JA; Ikegami, M; Robb, L; Begley, CG; Ross, G; Whitsett, JA

Pulmonary alveolar proteinosis (PAP) is caused by inactivation of either granulocyte-macrophage colony-stimulating factor (GMCSF) or GM receptor common beta-chain (beta(c)) genes in mice [GM(-/-), beta(c)(-/-)], demonstrating a critical role of GM-CSF signaling in surfactant homeostasis. To

Type II congenital pulmonary airway malformation associated with intralobar pulmonary sequestration: report of a case and review of classification criteria.

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Mastrogiulio, M G; Barone, A; Disanto, M G; Ginori, A; Ambrosio, M R; Carbone, S F; Spina, D

2016-03-01

Pulmonary congenital abnormalities are rare disorders including congenital pulmonary airway malformations (CPAM) and pulmonary sequestration (PS). CPAM is a lesion characterized by the presence of anomalous bronchiolar or acinar structures, variable in size, either cystic or not cystic. PS is generally defined as nonfunctioning lung tissue that is not in normal continuity with the tracheobronchial tree and that derives its blood supply from systemic vessels. We describe a case of a baby girl with a very rare association between CPAM type 2 and intralobar pulmonary sequestration (IPS) focusing on the cystic lesions typical of CPAM and on the lymphatic and blood vessels. The cells lining the cysts often were positive for D2-40 (oncofetal protein M2A). Lymphatic endothelial cells, positive for D2-40, were widely present in the lung parenchyma and dilated lymphatic vessels were present also in the inter-alveolar septa. Moreover, we discuss the pathogenesis of CPAM and its classification criteria. © Copyright Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.

[Toxicity of chongqing acid fogwater on rabbit alveolar macrophages in vitro].

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Shu, W Q; Zhuo, J B

1992-07-01

We collected acid fogwater on a fogday and observed its toxic effects on rabbits' pulmonary alveolar macrophages (AM) in vitro. The fogwater was diluted into 4 concentrations: 1, 1/10, 1/100, and 1/1000 of the original fogwater and the exposure time was 12 hours. The results showed that both the AM's viability and the phagocytic capacity were depressed significantly, but the AM's lysosomal enzyme--acid phosphatase activity was found to be stimulated to increase. All these changes were directly correlated with the degree of pollution of the fogwater. Of these three toxicity indices, the most sensitive one was the change of AM's phagocytic capacity.

Over-expression of thymosin β4 in granulomatous lung tissue with active pulmonary tuberculosis.

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Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun; Yoo, Young-Bin; Chun, Bong-Kwon; Oak, Chul-Ho; Cha, Hee-Jae

2014-05-01

Recent studies have shown that thymosin β4 (Tβ4) stimulates angiogenesis by inducing vascular endothelial growth factor (VEGF) expression and stabilizing hypoxia inducible factor-1α (HIF-1α) protein. Pulmonary tuberculosis (TB), a type of granulomatous disease, is accompanied by intense angiogenesis and VEGF levels have been reported to be elevated in serum or tissue inflamed by pulmonary tuberculosis. We investigated the expression of Tβ4 in granulomatous lung tissues at various stages of active pulmonary tuberculosis, and we also examined the expression patterns of VEGF and HIF-1α to compare their Tβ4 expression patterns in patients' tissues and in the tissue microarray of TB patients. Tβ4 was highly expressed in both granulomas and surrounding lymphocytes in nascent granulomatous lung tissue, but was expressed only surrounding tissues of necrotic or caseous necrotic regions. The expression pattern of HIF-1α was similar to that of Tβ4. VEGF was expressed in both granulomas and blood vessels surrounding granulomas. The expression pattern of VEGF co-localized with CD31 (platelet endothelial cell adhesion molecule, PECAM-1), a blood endothelial cell marker, and partially co-localized with Tβ4. However, the expression of Tβ4 did not co-localize with alveolar macrophages. Stained alveolar macrophages were present surrounding regions of granuloma highly expressing Tβ4. We also analyzed mRNA expression in the sputum of 10 normal and 19 pulmonary TB patients. Expression of Tβ4 was significantly higher in patients with pulmonary tuberculosis than in normal controls. These data suggest that Tβ4 is highly expressed in granulomatous lung tissue with active pulmonary TB and is associated with HIF-1α- and VEGF-mediated inflammation and angiogenesis. Furthermore, the expression of Tβ4 in the sputum of pulmonary tuberculosis patients can be used as a potential marker for diagnosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

TRPA1 channels: expression in non-neuronal murine lung tissues and dispensability for hyperoxia-induced alveolar epithelial hyperplasia.

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Kannler, Martina; Lüling, Robin; Yildirim, Ali Önder; Gudermann, Thomas; Steinritz, Dirk; Dietrich, Alexander

2018-05-12

Transient receptor potential A1 (TRPA1) channels were originally characterized in neuronal tissues but also identified in lung epithelium by staining with fluorescently coupled TRPA1 antibodies. Its exact function in non-neuronal tissues, however, is elusive. TRPA1 is activated in vitro by hypoxia and hyperoxia and is therefore a promising TRP candidate for sensing hyperoxia in pulmonary epithelial cells and for inducing alveolar epithelial hyperplasia. Here, we isolated tracheal, bronchial, and alveolar epithelial cells and show low but detectable TRPA1 mRNA levels in all these cells as well as TRPA1 protein by Western blotting in alveolar type II (AT II) cells. We quantified changes in intracellular Ca 2+ ([Ca 2+ ] i ) levels induced by application of hyperoxic solutions in primary tracheal epithelial, bronchial epithelial, and AT II cells isolated from wild-type (WT) and TRPA1-deficient (TRPA1-/-) mouse lungs. In all cell types, we detected hyperoxia-induced rises in [Ca 2+ ] i levels, which were not significantly different in TRPA1-deficient cells compared to WT cells. We also tested TRPA1 function in a mouse model for hyperoxia-induced alveolar epithelial hyperplasia. A characteristic significant increase in thickening of alveolar tissues was detected in mouse lungs after exposure to hyperoxia, but not in normoxic WT and TRPA1-/- controls. Quantification of changes in lung morphology in hyperoxic WT and TRPA1-/- mice, however, again revealed no significant changes. Therefore, TRPA1 expression does neither appear to be a key player for hyperoxia-induced changes in [Ca 2+ ] i levels in primary lung epithelial cells, nor being essential for the development of hyperoxia-induced alveolar epithelial hyperplasia.

Effects of altitude and exercise on pulmonary capillary integrity: evidence for subclinical high-altitude pulmonary edema.

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Eldridge, Marlowe W; Braun, Ruedi K; Yoneda, Ken Y; Walby, William F

2006-03-01

Strenuous exercise may be a significant contributing factor for development of high-altitude pulmonary edema, particularly at low or moderate altitudes. Thus we investigated the effects of heavy cycle ergometer exercise (90% maximal effort) under hypoxic conditions in which the combined effects of a marked increase in pulmonary blood flow and nonuniform hypoxic pulmonary vasoconstriction could add significantly to augment the mechanical stress on the pulmonary microcirculation. We postulated that intense exercise at altitude would result in an augmented permeability edema. We recruited eight endurance athletes and examined their bronchoalveolar lavage fluid (BALF) for red blood cells (RBCs), protein, inflammatory cells, and soluble mediators at 2 and 26 h after intense exercise under normoxic and hypoxic conditions. After heavy exercise, under all conditions, the athletes developed a permeability edema with high BALF RBC and protein concentrations in the absence of inflammation. We found that exercise at altitude (3,810 m) caused significantly greater leakage of RBCs [9.2 (SD 3.1)x10(4) cells/ml] into the alveolar space than that seen with normoxic exercise [5.4 (SD 1.2)x10(4) cells/ml]. At altitude, the 26-h postexercise BALF revealed significantly higher RBC and protein concentrations, suggesting an ongoing capillary leak. Interestingly, the BALF profiles following exercise at altitude are similar to that of early high-altitude pulmonary edema. These findings suggest that pulmonary capillary disruption occurs with intense exercise in healthy humans and that hypoxia augments the mechanical stresses on the pulmonary microcirculation.

[Percutaneous closure of ductus arteriosus and muscular ventricular defect with amplatzer occluder in a patient with severe pulmonary hypertension].

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García-Montes, José Antonio; Zabal Cerdeira, Carlos; Calderón-Colmenero, Juan; Espínola, Nilda; Fernández de la Reguera, Guillermo; Buendía Hernández, Alfonso

2005-01-01

Surgical treatment of multiple muscular ventricular septal defects with associated lesions and severe pulmonary hypertension has a high morbility and mortality. Closure of these defects by the Amplatzer muscular VSD occluder is an alternative to surgery, avoiding the need of cardiopulmonary bypass. We present the case of a 38 year-old woman with signs of heart failure in NYHA functional class IV, with two muscular ventricular septal defects, patent ductus arteriosus and severe pulmonary hypertension, that were treated with three Amplatzer muscular VSD occluders, with significant reduction of pulmonary pressure and functional class improvement.

Bone graft healing in alveolar osteoplasty in patients with unilateral lip, alveolar process, and palate clefts.

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Rychlik, Dariusz; Wójcicki, Piotr

2012-01-01

Secondary osteoplasty by means of autogenic spongy bone grafting is the most common procedure used in the reconstruction of the continuity of the maxillary alveolar process. The aim of the study was to analyze retrospectively the effect of certain factors on the course of the bone graft healing process in patients with unilateral complete clefts of the lip, alveolar process, and palate. The investigations involved 62 children aged 8 to 14 years (mean age, 11 years) with unilateral complete cleft of the lip, alveolar process, and palate operated on at the Clinic of Plastic Surgery in Polanica Zdrój from November 2007 to April 2009. All the procedures consisted in the reconstruction of the maxillary alveolar process by means of autogenic spongy bone grafting from the iliac bone. The analysis was performed on the basis of computed tomography scans presenting maxillary alveolar processes in the horizontal cross-sectional planes performed on the second or third postoperative day and after 6 months. They were used as the basis for the measurement of the volume and density (condensation) of the bone graft, the surface of its adhesion to the maxillary alveolar bone, and the volume and density of the healed bone. The following correlation coefficients were determined: between the adhesion surface of the bone to the alveolar bone and the volume of the healed bone, between the adhesion surface of the bone to the alveolar bone and the density of the healed bone, and between the density of the graft and the volume of the healed bone. Increasing the surface of the graft adhesion to the bone ridges of the alveolar cleft contributes to increased volume of the healed bone and slows down the increase in its density (on 6-month follow-up). Crushing of the bone graft increases its resorption and reduces volume of the healed bone.

Pathogenesis of pulmonary emphysema – cellular and molecular events

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Antonio Di Petta

2010-06-01

Full Text Available Pulmonary emphysema is a chronic obstructive disease, resulting fromimportant alterations in the whole distal structure of terminal bronchioles, either by enlargement of air spaces or by destruction of the alveolar wall, leading to loss of respiratory surface, decreased elastic recoil and lung hyperinflation. For many years, the hypothesis of protease-antiprotease unbalance prevailed as the central theme in the pathogenesis of pulmonary emphysema. According to this hypothesis, the release of active proteolytic enzymes, produced mainly by neutrophils and macrophages, degrades the extracellular matrix, affecting the integrity of its components, especially collagen and elastic fibers. However, new concepts involving cellular and molecular events were proposed, including oxidative stress, cell apoptosis, cellular senescence and failed lung tissue repair. The aim of this review paper was to evaluate the cellular and molecular mechanisms seen in the pathogenesis of pulmonary emphysema.

[Clinical effect of high-frequency oscillatory ventilation combined with pulmonary surfactant in treatment of neonatal severe meconium aspiration syndrome complicated by pulmonary hemorrhage].

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Huang, Jing; Lin, Xin-Zhu; Zheng, Zhi

2016-11-01

To study the clinical effect and safety of high-frequency oscillatory ventilation (HFOV) combined with pulmonary surfactant (PS) in the treatment of neonatal severe meconium aspiration syndrome (MAS) complicated by neonatal pulmonary hemorrhage (NPH). A total of 48 children with severe MAS complicated by NPH were enrolled, and a retrospective analysis was performed for the clinical effects of HFOV+PS (trial group, 25 children) and HFOV alone (control group, 23 children). The blood gas parameters, oxygenation index (OI), PaO 2 /FiO 2 (P/F) value, duration of pulmonary hemorrhage, ventilation time, length of hospital stay, incidence of complications, and outcome were compared between the two groups. At 6, 12, 24, and 48 hours after treatment, the trial group had significantly better PaO 2 , OI, and P/F value than the control group (Phemorrhage (P0.05). HFOV combined with PS can better improve oxygenation function and shorten the duration of NPH and ventilation time. Meanwhile, it does not increase the incidence of adverse events. Therefore, it is a safe and effective therapy.

Swimming-induced pulmonary oedema an uncommon condition diagnosed with POCUS ultrasound.

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Alonso, Joaquín Valle; Chowdhury, Motiur; Borakati, Raju; Gankande, Upali

2017-12-01

Swimming Induced Pulmonary Edema, or SIPE, is an emerging condition occurring in otherwise healthy individuals during surface swimming or diving that is characterized by cough, dyspnea, hemoptysis, and hypoxemia. It is typically found in those who spend time in cold water exercise with heavy swimming and surface swimming, such as civilian training for iron Man, triathalon, and military training. We report the case of a highly trained young female swimmer in excellent cardiopulmonary health, who developed acute alveolar pulmonary oedema in an open water swimming training diagnosed in the emergency department using POCUS ultrasound. Copyright © 2017 Elsevier Inc. All rights reserved.

The prognostic value of pulmonary embolism severity index in acute pulmonary embolism: a meta-analysis

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Zhou Xiao-Yu

2012-12-01

Full Text Available Abstract Background Prognostic assessment is important for the management of patients with acute pulmonary embolism (APE. Pulmonary Embolism Severity Index (PESI and simple PESI (sPESI are new emerged prognostic assessment tools for APE. The aim of this meta-analysis is to assess the accuracy of the PESI and the sPESI to predict prognostic outcomes (all-cause and PE-related mortality, serious adverse events in APE patients, and compare between these two PESIs. Methods MEDLINE and EMBASE database were searched up to June 2012 using the terms “Pulmonary Embolism Severity Index” and “pulmonary embolism”. Summary odds ratio (OR with 95% confidence intervals (CIs for prognostic outcomes in low risk PESI versus high risk PESI were calculated. Summary receiver operating characteristic curve (SROC used to estimate overall predicting accuracies of prognostic outcomes. Results Twenty-one studies were included in this meta-analysis. The results showed low-risk PESI was significantly associated with lower all-cause mortality (OR 0.13; 95% CI 0.12 to 0.15, PE-related mortality (OR 0.09; 95% CI 0.05 to 0.17 and serious adverse events (OR 0.34; 95% CI 0.29 to 0.41, with no homogeneity across studies. In sPESI subgroup, the OR of all-cause mortality, PE-related mortality, and serious adverse events was 0.10 (95% CI 0.08 to 0.14, 0.09 (95% CI 0.03 to 0.26 and 0.40 (95% CI 0.31 to 0.51, respectively; while in PESI subgroup, the OR was 0.14 (95% CI 0.13 to 0.16, 0.09 (95% CI 0.04 to 0.21, and 0.30 (95% CI 0.23 to 0.38, respectively. For accuracy analysis, the pooled sensitivity, the pooled specificity, and the overall weighted AUC for PESI predicting all-cause mortality was 0.909 (95% CI: 0.900 to 0.916, 0.411 (95% CI: 0.407 to 0.415, and 0.7853±0.0058, respectively; for PE-related mortality, it was 0.953 (95% CI: 0.913 to 0.978, 0.374 (95% CI: 0.360 to 0.388, and 0.8218±0.0349, respectively; for serious adverse events, it was 0.821 (95% CI: 0.795 to 0

PULMONARY LESIONS CAUSED BY THE LUNGWORM (DIDELPHOSTRONGYLUS HAYESI) IN THE OPOSSUM (DIDELPHIS VIRGINIANA) IN COLIMA, MEXICO.

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López-Crespo, Rubén A; López-Mayagoitia, Alfonso; Ramírez-Romero, Rafael; Martínez-Burnes, Julio; Prado-Rebolledo, Omar F; García-Márquez, Luis J

2017-06-01

Didelphostrongylus hayesi is an important and prevalent pulmonary nematode in the opossum ( Didelphis virginiana ). An in-depth description of the pulmonary lesions caused by this nematode is lacking. The objective of this investigation was to make a detailed account of the gross, subgross, and microscopic changes that occur in the lungs of opossums naturally infected with D. hayesi. Forty-four opossums trapped in the state of Colima, Mexico, were euthanized by an overdose of barbiturates. Following a postmortem examination, the right lung was cut from the main bronchi and placed in a Petri dish containing a saline solution for the detection and identification of live parasites. The left lung was fixed and cut serially for subgross microscopic examination and sections of lung were cut and stained for histopathologic examination. The most remarkable gross change in parasitized lungs was a poorly collapsible pulmonary parenchyma and mild emphysema. The right lung tested positive for lungworms on gross examination in 20/44, and 11/44 (25%) of the left lungs showed tan nodules on the pleural surface. Microscopically, the bronchi of 20/44 animals harbored adult and larval stages of D. hayesi (left lung), the same 20 opossums from which nematodes were grossly evident at necropsy (right lung). Adults and larvae were present in bronchi, bronchioles, and alveoli mixed with desquamated cells and many eosinophils, and to a lesser extent neutrophils, alveolar macrophages, and giant cells. Bronchi and bronchioles exhibited goblet cell hyperplasia and metaplasia respectively, and infiltration of lymphoplasmacytic cells in the interstitium and lamina propria. The tan nodules consisted of focal alveolar endogenous lipidosis, which likely resulted from parasitic airway obstruction. The lungs of 3/20 parasitized opossums also showed alveolar bronchiolization (Lambertosis). The absence of Eucoleus aerophilus or bacterial pneumonia incriminates D. hayesi as the putative cause of

Histopathological Study of Cyclosporine Pulmonary Toxicity in Rats

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Said Said Elshama

2016-01-01

Full Text Available Cyclosporine is considered one of the common worldwide immunosuppressive drugs that are used for allograft rejection prevention. However, articles that address adverse effects of cyclosporine use on the vital organs such as lung are still few. This study aims to investigate pulmonary toxic effect of cyclosporine in rats by assessment of pulmonary histopathological changes using light and electron microscope examination. Sixty male adult albino rats were divided into three groups; each group consists of twenty rats. The first received physiological saline while the second and third groups received 25 and 40 mg/kg/day of cyclosporine, respectively, by gastric gavage for forty-five days. Cyclosporine reduced the lung and body weight with shrinkage or pyknotic nucleus of pneumocyte type II, degeneration of alveoli and interalveolar septum beside microvilli on the alveolar surface, emphysema, inflammatory cellular infiltration, pulmonary blood vessels congestion, and increase of fibrous tissues in the interstitial tissues and around alveoli with negative Periodic Acid-Schiff staining. Prolonged use of cyclosporine induced pulmonary ultrastructural and histopathological changes with the lung and body weight reduction depending on its dose.

The α and Δ isoforms of CREB1 are required to maintain normal pulmonary vascular resistance.

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Lili Li

Full Text Available Chronic hypoxia causes pulmonary hypertension associated with structural alterations in pulmonary vessels and sustained vasoconstriction. The transcriptional mechanisms responsible for these distinctive changes are unclear. We have previously reported that CREB1 is activated in the lung in response to alveolar hypoxia but not in other organs. To directly investigate the role of α and Δ isoforms of CREB1 in the regulation of pulmonary vascular resistance we examined the responses of mice in which these isoforms of CREB1 had been inactivated by gene mutation, leaving only the β isoform intact (CREB(αΔ mice. Here we report that expression of CREB regulated genes was altered in the lungs of CREB(αΔ mice. CREB(αΔ mice had greater pulmonary vascular resistance than wild types, both basally in normoxia and following exposure to hypoxic conditions for three weeks. There was no difference in rho kinase mediated vasoconstriction between CREB(αΔ and wild type mice. Stereological analysis of pulmonary vascular structure showed characteristic wall thickening and lumen reduction in hypoxic wild-type mice, with similar changes observed in CREB(αΔ. CREB(αΔ mice had larger lungs with reduced epithelial surface density suggesting increased pulmonary compliance. These findings show that α and Δ isoforms of CREB1 regulate homeostatic gene expression in the lung and that normal activity of these isoforms is essential to maintain low pulmonary vascular resistance in both normoxic and hypoxic conditions and to maintain the normal alveolar structure. Interventions that enhance the actions of α and Δ isoforms of CREB1 warrant further investigation in hypoxic lung diseases.

Altered Pulmonary Lymphatic Development in Infants with Chronic Lung Disease

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McNellis, Emily M.; Mabry, Sherry M.; Taboada, Eugenio; Ekekezie, Ikechukwu I.

2014-01-01

Pulmonary lymphatic development in chronic lung disease (CLD) has not been investigated, and anatomy of lymphatics in human infant lungs is not well defined. Hypothesis. Pulmonary lymphatic hypoplasia is present in CLD. Method. Autopsy lung tissues of eighteen subjects gestational ages 22 to 40 weeks with and without history of respiratory morbidity were stained with monoclonal antipodoplanin and reviewed under light microscopy. Percentage of parenchyma podoplanin stained at the acinar level was determined using computerized image analysis; 9 CLD and 4 control subjects gestational ages 27 to 36 weeks were suitable for the analysis. Results. Distinct, lymphatic-specific staining with respect to other vascular structures was appreciated in all gestations. Infants with and without respiratory morbidity had comparable lymphatic distribution which extended to the alveolar ductal level. Podoplanin staining per parenchyma was increased and statistically significant in the CLD group versus controls at the alveolar ductal level (0.06% ± 0.02% versus 0.04% ± 0.01%, 95% CI −0.04% to −0.002%, P CLD. It is suggested that the findings, by expanding current knowledge of CLD pathology, may offer insight into the development of more effective therapies to tackle CLD. PMID:24527433

Noninvasive measurement of mean alveolar carbon dioxide tension and Bohr's dead space during tidal breathing.

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Koulouris, N G; Latsi, P; Dimitroulis, J; Jordanoglou, B; Gaga, M; Jordanoglou, J

2001-06-01

The lack of methodology for measuring the alveolar carbon dioxide tension (PA,CO2) has forced investigators to make several assumptions, such as that PA,CO2 is equal to end-tidal (PET,CO2) and arterial CO2 tension (Pa,CO2). The present study measured the mean PA,CO2 and Bohr's dead space ratio (Bohr's dead space/tidal volume (VD,Bohr/VT)) during tidal breathing. The method used is a new, simple and noninvasive technique, based on the analysis of the expired CO2 volume per breath (VCO2) versus the exhaled VT. This curve was analysed in 21 normal, healthy subjects and 35 chronic obstructive pulmonary disease (COPD) patients breathing tidally through a mouthpiece apparatus in the sitting position. It is shown that: 1) PA,CO2 is similar to Pa,CO2 in normal subjects, whilst it is significantly lower than Pa,CO2 in COPD patients; 2) PA,CO2 is significantly higher than PET,CO2 in all subjects, especially in COPD patients; 3) VD,Bohr/VT is increased in COPD patients as compared to normal subjects; and 4) VD,Bohr/VT is lower than the "physiological" dead space ratio (VD,phys/VT) in COPD patients. It is concluded that the expired carbon dioxide versus tidal volume curve is a useful tool for research and clinical work, because it permits the noninvasive and accurate measurement of Bohr's dead space and mean alveolar carbon dioxide tension accurately during spontaneous breathing.

Idiopathic Pulmonary Hemosiderosis in a Young Adult Patient: A Rare Case

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Abhishek Agarwal

2018-01-01

Full Text Available Idiopathic pulmonary hemosiderosis (IPH is often an ignored and rare cause of diffuse alveolar hemorrhage (DAH. It is characterized by triad of hemoptysis, anemia, and alveolar opacity on radiology. It is a diagnosis of exclusion, established after ruling out other causes of DAH such as Goodpasture’s syndrome, large vessel vasculitis, small vessel vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA (Wegener’s granulomatosis, Churg–Strauss syndrome, microscopic polyangiitis, immune complex-related vasculitis (collagen vascular diseases, Henoch–Schönlein purpura, mixed cryoglobulinemia drug reactions, anticoagulation and thrombocytopenia. Though it is a disease primarily affecting children, we hereby report a case of IPH in an adult patient who responded dramatically to oral corticosteroid.

Detection of alveolar epithelial injury by 99mTc-DTPA radioaerosol inhalation lung scan following blunt chest trauma

International Nuclear Information System (INIS)

Okudan, B.; Han, S.; Baldemir, M.; Yildiz, M.

2004-01-01

DTPA clearance rate is a reliable index of alveolar epithelial permeability, and is a highly sensitive marker of pulmonary epithelial damage, even of mild degree. In this study, 99m Tc-DTPA aerosol inhalation scintigraphy was used to assess the pulmonary epithelial membrane permeability and to investigate the possible application of this permeability value as an indicator of early alveolar or interstitial changes in patients with blunt chest trauma. A total of 26 patients was chest trauma (4 female, 22 male, 31-80 yrs, mean age; 53±13 yrs) who were referred to the emergency department in our hospital participated in this study. Technetium-99m diethylene triamine pentaacetic acid (DTPA) aerosol inhalation scintigraphy was performed on the first and thirtieth days after trauma. Clearance half times (T 1/2 ) were calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was calculated on the first-minute image. On the first day, mean T 1/2 value of the whole lung was 63±19 minutes (min), and thirtieth day mean T 1/2 value was 67±21 min. On the first day, mean PI values of the lung and 30th day mean PI value were 0.60±0.05, and 0.63 ±0.05, respectively. Significant changes were observed in radioaerosol clearance and penetration indices. Following chest trauma, clearance of 99m Tc-DTPA increased owing to breakdown of the alveolar-capillary barrier. This increase in the epithelial permeability of the lung appears to be an early manifestation of lung disease that may lead to efficient therapy in the early phase. (author)

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

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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

Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

International Nuclear Information System (INIS)

Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G.; Castiglione, F.; Vanzi, E.; Bottoncetti, A.; Pupi, A.

2011-01-01

Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation

Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

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Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G. [Radiotherapy Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy); Castiglione, F. [Department of Human Pathology and Oncology, University of Florence, Firenze (Italy); Vanzi, E.; Bottoncetti, A.; Pupi, A. [Nuclear Medicine Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy)

2011-10-15

Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation

Enhanced rifampicin delivery to alveolar macrophages by solid lipid nanoparticles

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Chuan Junlan [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China); Li Yanzhen [Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery Technology and Pharmacokinetics (China); Yang Likai; Sun Xun [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China); Zhang Qiang [Peking University, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences (China); Gong Tao, E-mail: gongtaoy@126.com; Zhang Zhirong, E-mail: zrzzl@vip.sina.com [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China)

2013-05-15

The present study aimed at developing a drug delivery system targeting the densest site of tuberculosis infection, the alveolar macrophages (AMs). Rifampicin (RFP)-loaded solid lipid nanoparticles (RFP-SLNs) with an average size of 829.6 {+-} 16.1 nm were prepared by a modified lipid film hydration method. The cytotoxicity of RFP-SLNs to AMs and alveolar epithelial type II cells (AECs) was examined using MTT assays. The viability of AMs and AECs was above 80 % after treatment with RFP-SLNs, which showed low toxicity to both AMs and AECs. Confocal Laser Scanning Microscopy was employed to observe the interaction between RFP-SLNs and both AMs and AECs. After incubating the cells with RFP-SLNs for 2 h, the fluorescent intensity in AMs was more and remained longer (from 0.5 to 12 h) when compared with that in AECs (from 0.5 to 8 h). In vitro uptake characteristics of RFP-SLNs in AMs and AECs were also investigated by detection of intracellular RFP by High performance liquid chromatography. Results showed that RFP-SLNs delivered markedly higher RFP into AMs (691.7 ng/mg in cultured AMs, 662.6 ng/mg in primary AMs) than that into AECs (319.2 ng/mg in cultured AECs, 287.2 ng/mg in primary AECs). Subsequently, in vivo delivery efficiency and the selectivity of RFP-SLNs were further verified in Sprague-Dawley rats. Under pulmonary administration of RFP-SLNs, the amount of RFP in AMs was significantly higher than that in AECs at each time point. Our results demonstrated that solid lipid nanoparticles are a promising strategy for the delivery of rifampicin to alveolar macrophages selectively.

Pulmonary gas exchange impairment following tourniquet deflation: a prospective, single-blind clinical trial.

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Lin, Lina; Wang, Liangrong; Bai, Yu; Zheng, Liupu; Zhao, Xiyue; Xiong, Xiangqing; Jin, Lida; Ji, Wei; Wang, Wantie

2010-06-09

The tourniquet has been considered as a recognized cause of limb ischemia/reperfusion injury in orthopedic surgery resulting in a transient neutrophil, monocyte activation, and enhanced neutrophil transendothelial migration with potential remote tissue injury. This study investigated the effect of unilateral tourniquet application within a safe time limit on pulmonary function and the roles of lipid peroxidation and systemic inflammatory response. Thirty patients undergoing unilateral lower extremity surgery with or without tourniquet were equally divided into a control group with no tourniquet (Group C) and a tourniquet (Group T). Arterial partial pressure of oxygen (P(a)O(2)), arterial-alveolar oxygen tension ratio (a/A ratio), alveolar-arterial oxygen difference (A-aDO(2)) and respiratory index, plasma malondialdehyde, serum interleukin (IL) -6 and IL-8 levels were measured immediately before and 1 hour after tourniquet inflation/operation beginning, 0.5, 2, 6, and 24 hours after tourniquet deflation/operation ending. The results represented no significant changes in Group C with regard to either blood gas variables or levels of circulating mediators, while blood gas variable changes of greater A-aDO(2) and respiratory index and lower PaO2 and a/A ratio were shown at 6 hours following tourniquet deflation. The levels of malondialdehyde, IL-6, and IL-8 were increased over baseline values from 2 to 24 hours following tourniquet deflation in Group T. We concluded that tourniquet application within a safe time limit may cause pulmonary gas exchange impairment several hours after tourniquet deflation, where lipid peroxidation and systemic inflammatory response may be involved. Copyright 2010, SLACK Incorporated.

Pulmonary dysfunction in advanced liver disease: frequent occurrence of an abnormal diffusing capacity

International Nuclear Information System (INIS)

Hourani, J.M.; Bellamy, P.E.; Tashkin, D.P.; Batra, P.; Simmons, M.S.

1991-01-01

Abnormalities in pulmonary function have been reported in association with chronic liver disease of varied etiology. The aim of this study was to better define the frequency and nature of these abnormalities in patients who were being evaluated for liver transplantation. We performed a battery of pulmonary function tests and chest radiographs in 116 consecutive patients (50 men, 66 women; aged 19 to 70 years, mean 44.6 years) with severe advanced liver disease who were hospitalized specifically for evaluation for possible orthotopic liver transplantation and were able to perform technically satisfactory tests. In 17 patients, quantitative whole-body technetium-99m macroaggregated albumin perfusion scanning was also performed for assessment of possible right-to-left shunting through intrapulmonary vascular dilatations. The most commonly affected test of lung function was the single-breath diffusing capacity for carbon monoxide (DLCO), which was abnormal in 48%, 45%, and 71% of patients who never smoked, former smokers, and current smokers, respectively. Ventilatory restriction was noted in 25% of all patients, airflow obstruction (reduced ratio of forced expiratory volume in 1 second to forced vital expiratory volume in 1 second to forced vital capacity) in only 3%, and a widened alveolar-arterial oxygen gradient in 45%. Diffusion impairment was accompanied by a restrictive defect in only 35% of the patients and by an abnormally widened alveolar-arterial oxygen gradient in 60%. When diffusion impairment was accompanied by an oxygenation defect, it was also associated with a significantly increased right-to-left shunt fraction (mean 24.9%) assessed from quantitative whole-body perfusion imaging

Distinct Roles of Wnt/β-Catenin Signaling in the Pathogenesis of Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis

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Shi, Juan; Li, Feng; Luo, Meihui; Wei, Jun

2017-01-01

Wnt signaling pathways are tightly controlled under a physiological condition, under which they play key roles in many biological functions, including cell fate specification and tissue regeneration. Increasing lines of evidence recently demonstrated that a dysregulated activation of Wnt signaling, particularly the Wnt/β-catenin signaling, was involved in the pathogenesis of chronic pulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). In this respect, Wnt signaling interacts with other cellular signaling pathways to regulate the initiation and pathogenic procedures of airway inflammation and remodeling, pulmonary myofibroblast proliferation, epithelial-to-mesenchymal transition (EMT), and development of emphysema. Intriguingly, Wnt/β-catenin signaling is activated in IPF; an inhibition of this signaling leads to an alleviation of pulmonary inflammation and fibrosis in experimental models. Conversely, Wnt/β-catenin signaling is inactivated in COPD tissues, and its reactivation results in an amelioration of airspace enlargement with a restored alveolar epithelial structure and function in emphysema models. These studies thus imply distinct mechanisms of Wnt/β-catenin signaling in the pathogenesis of these two chronic pulmonary diseases, indicating potential targets for COPD and IPF treatments. This review article aims to summarize the involvement and pathogenic roles of Wnt signaling pathways in the COPD and IPF, with a focus on the implication of Wnt/β-catenin signaling as underlying mechanisms and therapeutic targets in these two incurable diseases. PMID:28588349

Gerbode defect following endocarditis and misinterpreted as severe pulmonary arterial hypertension

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Allajbeu Iris

2010-09-01

Full Text Available Abstract A Gerbode -type defect is a ventricular septal defect communicating directly between the left ventricle and right atrium. It is usually congenital, but rarely is acquired, as a complication of endocarditis. This can be anatomically possible because the normal tricuspid valve is more apically displaced than the mitral valve. However, identification of an actual communication is often extremely difficult, so a careful and meticulous echocardiogram should be done in order to prevent echocardiographic misinterpretation of this defect as pulmonary arterial hypertension. The large systolic pressure gradient between the left ventricle and the right atrium would expectedly result in a high velocity systolic Doppler flow signal in right atrium and it can be sometimes mistakably diagnosed as tricuspid regurgitant jet simulating pulmonary arterial hypertension. We present a rare case of young woman, with endocarditis who presented with severe pulmonary arterial hypertension. The preoperative diagnosis of left ventricle to right atrial communication (acquired Gerbode defect was suspected initially by echocardiogram and confirmed at the time of the surgery. A point of interest, apart from the diagnostic problem, was the explanation for its mechanism and presentation. The probability of a bacterial etiology of the defect is high in this case.

Diffuse alveolar hemorrhage in a patient with acute poststreptococcal glomerulonephritis caused by impetigo.

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Yoshida, Masahiro; Yamakawa, Hideaki; Yabe, Masami; Ishikawa, Takeo; Takagi, Masamichi; Matsumoto, Kei; Hamaguchi, Akihiko; Ogura, Makoto; Kuwano, Kazuyoshi

2015-01-01

We herein report a case of pulmonary renal syndrome with nephritis in a 17-year-old boy with diffuse alveolar hemorrhage (DAH) associated with acute poststreptococcal glomerulonephritis (APSGN). The patient exhibited hemoptysis two weeks after developing impetigo, and DAH was diagnosed on bronchoscopy. Respiratory failure progressed, and high-dose methylprednisolone therapy was administered; the respiratory failure regressed immediately after the onset of therapy. Streptococcus pyogenes was detected in an impetigo culture, and, together with the results of the renal biopsy, a diagnosis of APSGN was made. This case demonstrates the effects of high-dose methylprednisolone therapy in improving respiratory failure.

Effect of implanted radioactive 125I seeds on normal tissue structures of bronchus, esophagus, pulmonary artery, pulmonary vein and alveolus in dogs

International Nuclear Information System (INIS)

Qi Liangchen; Han Zhenguo; Yang Bin; Heersitai

2008-01-01

Objective: To investigate the effect of implanted radioactive 125 I seeds on normal tissue structures of bronchus, esophagus, pulmonary artery, pulmonary vein and alveolus in dogs. Methods: Nine healthy male dogs weighing 17-21 kg were randomly divided into three groups: 30 d, 60 d experimental groups and control group. Radioactive 125 I seeds (3.7 x 10 7 Bg, 1.0 mCi) were implanted into the sides of bronchus, esophagus, pulmonary artery, pulmonary vein respectively, the samples of bronchus, esophagus, pulmonary artery, pulmonary vein were taken 30 and 60 d after transplantation, HE staining was used to observe the pathologic changes of the tissues under light microscope. Results: The damages of normal bronchus, esophagus, pulmonary artery, pulmonary vein and alveolus after radioactive 125 I seeds implantation in 30 d group were weaker than those in control group and 60 d group, there were no complications such as perforation, hemorrhage, necrosis, etc. Histopathological score indicated that the scores of bronchus, esophagus and alveolar in 30 d group and 60 d group were higher than those in control group (P 0.05); there was no significant difference in histopathological score of pulmonary vein among all groups (P>0.05). Conclusion: The implanted radioactive 125 I seeds can damage all kinds of tissues at different degrees, but this kind of damage is reversible, the dog may repair the damage through its own repair ability, its clinical application is safe. (authors)

Static and dynamic hyperinflation during severe acute exacerbations of chronic obstructive pulmonary disease

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van Geffen WH

2018-04-01

Full Text Available Wouter H van Geffen,1,2 Huib AM Kerstjens2 1Department of Respiratory Medicine, Medical Centre Leeuwarden, Leeuwarden, the Netherlands; 2Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands Background: Static hyperinflation is known to be increased during moderate acute exacerbations of chronic obstructive pulmonary disease (COPD (AECOPD, but few data exist in patients with severe exacerbations of COPD. The role of dynamic hyperinflation during exacerbations is unclear. Methods: In a prospective, observational cohort study, we recruited patients admitted to hospital for AECOPD. The following measurements were performed upon admission and again after resolution (stable state at least 42 days later: inspiratory capacity (IC, body plethysmography, dynamic hyperinflation by metronome-paced IC measurement, health-related quality of life and dyspnea. Results: Forty COPD patients were included of whom 28 attended follow-up. The IC was low at admission (2.05±0.11 L and increased again during resolution by 15.6%±23.1% or 0.28±0.08 L (mean ± standard error of the mean, p<0.01. Testing of metronome-paced changes in IC was feasible, and it decreased by 0.74±0.06 L at admission, similarly to at stable state. Clinical COPD Questionnaire score was 3.7±0.2 at admission and improved by 1.7±0.2 points (p<0.01, and the Borg dyspnea score improved by 2.2±0.5 points from 4.4±0.4 at admission (p<0.01. Conclusion: Static hyperinflation is increased during severe AECOPD requiring hospitalization compared with stable state. We could measure metronome-paced dynamic hyperinflation during severe AECOPD but found no increase. Keywords: COPD, exacerbations of COPD, static hyperinflation, dynamic hyperinflation, severe acute exacerbations of COPD, COPD exacerbation, chronic obstructive pulmonary disease

Pulmonary endarterectomy outputs in chronic thromboembolic pulmonary hypertension.

Science.gov (United States)

López Gude, María Jesús; Pérez de la Sota, Enrique; Pérez Vela, Jose Luís; Centeno Rodríguez, Jorge; Muñoz Guijosa, Christian; Velázquez, María Teresa; Alonso Chaterina, Sergio; Hernández González, Ignacio; Escribano Subías, Pilar; Cortina Romero, José María

2017-07-07

Pulmonary thromboendarterectomy surgery is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension; extremely high pulmonary vascular resistance constitutes a risk factor for hospital mortality. The objective of this study was to analyze the immediate and long-term results of the surgical treatment of chronic thromboembolic pulmonary hypertension in patients with very severe pulmonary hypertension. Since February 1996, we performed 160 pulmonary thromboendarterectomies. We divided the patient population in 2 groups: group 1, which included 40 patients with pulmonary vascular resistance≥1090dyn/sec/cm -5 , and group 2, which included the remaining 120 patients. Hospital mortality (15 vs. 2.5%), reperfusion pulmonary edema (33 vs. 14%) and heart failure (23 vs. 3.3%) were all higher in group 1; however, after one year of follow-up, there were no significant differences in the clinical, hemodynamic and echocardiographic conditions of both groups. Survival rate after 5 years was 77% in group 1 and 92% in group 2 (P=.033). After the learning curve including the 46 first patients, there was no difference in hospital mortality (3.8 vs. 2.3%) or survival rate after 5 years (96.2% in group 1 and 96.2% in group 2). Pulmonary thromboendarterectomy is linked to significantly higher morbidity and mortality rates in patients with severe chronic thromboembolic pulmonary hypertension. Nevertheless, these patients benefit the same from the procedure in the mid-/long-term. In our experience, after the learning curve, this surgery is safe in severe pulmonary hypertension and no level of pulmonary vascular resistance should be an absolute counter-indication for this surgery. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Comparison between the radiological manifestations of thoracic involvement in collagen vascular diseases and idiopathic pulmonary fibrosis

International Nuclear Information System (INIS)

Kirova, G.; Rashkov, R.; Georgiev, O.

2002-01-01

The purpose of the study is to compare the presentation and distribution of lung abnormalities seen in Collagen Vascular Diseases (CVD) with those specifics for Idiopathic Pulmonary Fibrosis (IPF). The HRCT scans of 92 patients fulfilling the ARA criteria's for the diagnosis of four different CVD were reviewed and compared with those of 18 patients with IPF. The presentations of three main patterns of lung disease were assessed into the both groups. In order to find out the trend distribution in each disease, the grade and severity of presentation for the main abnormalities were assessed, using a scoring system.The incidence of reticular lung abnormalities for the group of IPF is 100 % versus 57.3 % for the CVD (p<0.0009). At the same time CVD, except for PSS, had a low incidence of reticular diseases (37 %). The incidence of alveolar abnormalities in CVD (57.3 %) were similar as these in IPF (66.6 %) (p=NS). The severity of the disease was greatest in IPF and PSS without significant difference between them. Nevertheless of uniform character of the abnormalities in the rest of CVD, they were presented with lesser degree and severity. The main abnormalities, seen in pulmonary parenchyma in patients with IPF and CVD were similar but with different grade, severity and distribution. (authors)

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

The Role of Oxidative Stress in Severity of Obstructive Pulmonary Complications in Sputum of Sulfur Mustard-Injured Patients

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Javad Heydari

2017-09-01

Full Text Available Background: Sulfur mustard (SM is a strong bifunctional alkylating agent that causes delayed complications in organs such as lung. Oxidative stress plays a pivotal role in the pathogenesis and progression of many pulmonary diseases. The aim of this study was to investigate the oxidative stress in sputum of SM exposed patients with mild, moderate and severe pulmonary dysfunction and assessing their relationship with pulmonary function. Methods: In this cross–sectional study, oxidative stress biomarkers in sputum were examined on 26 patients with SM-induced bronchiolitis obliterans (9 mild, 14 moderate and 3 severe and 12 matched healthy controls referred to Baqiyatallah Hospital, Tehran between October 2015 and April 2016. Results: Sputum superoxide dismutase, catalase and glutathione S-transferase activities and malondialdehyde level in moderate and severe groups were significantly higher than in the control group (P=0.002, P=0.004, P=0.014 and P=0.009, respectively. Glutathione (GSH level in moderate (22.29%, P=0.025 and severe (45.07%, P=0.004 groups were significantly lower than the control. A decreased in GSH level in severe (41.7% groups was observed as compared with the mild group. Pearson analysis revealed strong correlations between disease severity and oxidative stress biomarkers in sputum of patients with moderate and severe injuries. Conclusions: Oxidative stress is involved in the pathogenesis of patients with moderate and severe pulmonary dysfunction following SM exposure. The presence of enhanced oxidative stress relates to the decline lung function and the progression of the disease. Sputum induction in SM-injured patients can be used to the assessment of the antioxidant status of bronchial secretions.

Role of the inflammasome in chronic obstructive pulmonary disease (COPD).

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Colarusso, Chiara; Terlizzi, Michela; Molino, Antonio; Pinto, Aldo; Sorrentino, Rosalinda

2017-10-10

Inflammation is central to the development of chronic obstructive pulmonary disease (COPD), a pulmonary disorder characterized by chronic bronchitis, chronic airway obstruction, emphysema, associated to progressive and irreversible decline of lung function. Emerging genetic and pharmacological evidence suggests that IL-1-like cytokines are highly detected in the sputum and broncho-alveolar lavage (BAL) of COPD patients, implying the involvement of the multiprotein complex inflammasome. So far, scientific evidence has focused on nucleotide-binding oligomerization domain-like receptors protein 3 (NLRP3) inflammasome, a specialized inflammatory signaling platform that governs the maturation and secretion of IL-1-like cytokines through the regulation of caspase-1-dependent proteolytic processing. Some studies revealed that it is involved during airway inflammation typical of COPD. Based on the influence of cigarette smoke in various respiratory diseases, including COPD, in this view we report its effects in inflammatory and immune responses in COPD mouse models and in human subjects affected by COPD. In sharp contrast to what reported on experimental and clinical studies, randomized clinical trials show that indirect inflammasome inhibitors did not have any beneficial effect in moderate to severe COPD patients.

Immunohistochemical and morphometric evaluation of COX 1 and COX-2 in the remodeled lung in idiopathic pulmonary fibrosis and systemic sclerosis

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Edwin Roger Parra

2013-12-01

Full Text Available OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc and idiopathic pulmonary fibrosis (IPF patients, correlating that expression with patient survival.METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP in SSc patients and usual interstitial pneumonia (UIP in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival.RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP, and low COX-1 expression in alveolar septa.CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that.

Emphysema distribution and annual changes in pulmonary function in male patients with chronic obstructive pulmonary disease

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Tanabe Naoya

2012-04-01

Full Text Available Abstract Background The progression of chronic obstructive pulmonary disease (COPD considerably varies among patients. Those with emphysema identified by quantitative computed tomography (CT are associated with the rapid progression assessed by forced expiratory volume in one second (FEV1. However, whether the rate of the decline in lung function is independently affected by the regional distribution or the severity of emphysema in the whole lung is unclear. Methods We followed up 131 male patients with COPD for a median of 3.7 years. We measured wall area percent (WA% in right apical segmental bronchus, total lung volume, percent low attenuation volume (LAV%, and the standard deviation (SD of LAV% values from CT images of 10 isovolumetric partitions (SD-LAV as an index of cranial-caudal emphysema heterogeneity. Annual changes in FEV1 were then determined using a random coefficient model and relative contribution of baseline clinical parameters, pulmonary function, and CT indexes including LAV%, SD-LAV, and WA% to annual changes in FEV1 were examined. Results The mean (SD annual change in FEV1 was −44.4 (10.8 mL. Multivariate random coefficient model showed that higher baseline FEV1, higher LAV%, current smoking, and lower SD-LAV independently contributed to an excessive decline in FEV1, whereas ratio of residual volume to total lung capacity, ratio of diffusing capacity to alveolar ventilation, and WA% did not, after adjusting for age, height, weight, and ratio of CT-measured total lung volume to physiologically-measured total lung capacity. Conclusions A more homogeneous distribution of emphysema contributed to an accelerated decline in FEV1 independently of baseline pulmonary function, whole-lung emphysema severity, and smoking status. In addition to whole-lung analysis of emphysema, CT assessment of the cranial-caudal distribution of emphysema might be useful for predicting rapid, progressive disease and for developing a targeted

Fulminant Invasive Pulmonary Aspergillosis After a Near-Drowning Accident in an Immunocompetent Patient.

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Ratermann, Kelley L; Ereshefsky, Benjamin J; Fleishaker, Elise L; Thornton, Alice C; Buch, Ketan P; Martin, Craig A

2014-09-01

To report on invasive aspergillosis infection in an immunocompetent adult after a near-drowning event, which allowed this pathogen to easily gain access to the human respiratory system and result in rapid, severe infection. A 51-year-old female developed severe pneumonia after a near-drowning accident. Two days after admission, a bronchial alveolar lavage (BAL) was performed and was positive for Aspergillus fumigatus. After a 30-day hospital course, multiple antifungals, and various routes of administration, the patient expired. Pneumonia is particularly common because of the aspiration of contaminated water. Whereas pneumococci, staphylococci, and Gram-negative bacteria are all common pathogens for this type of infection, fungi such as Aspergillus spp can also be involved and may be life threatening. Typically, these cases are reported in individuals with an immunodeficiency such as from receipt of myelosuppressive chemotherapy, bone marrow transplants, or lung transplants. Despite initiation of an appropriate empirical antifungal regimen, the rapid recovery of A fumigatus from pulmonary alveolar lavage and BAL samples as well as extremely elevated levels of galactomannan and (1→3)-β-D glucan may have indicated an invasive fungal infection (IFI). IFIs are uncommon in immunocompetent adults, but in the event of a near-drowning accident, environmental fungi can gain access to the human respiratory system and result in rapid, severe infection. Based on this case and the others described, it appears that near-drowning patients need an early initial evaluation for IFI. © The Author(s) 2014.

The optimization of iloprost inhalation under moderate flow of oxygen therapy in severe pulmonary arterial hypertension.

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Nakayama, Kazuhiko; Emoto, Noriaki; Tamada, Naoki; Okano, Mitsumasa; Shinkura, Yuto; Yanaka, Kenichi; Onishi, Hiroyuki; Hiraishi, Mana; Yamada, Shinichiro; Tanaka, Hidekazu; Shinke, Toshiro; Hirata, Ken-Ichi

2018-01-01

Inhaled iloprost efficiently improves pulmonary hemodynamics, exercise capacity, and quality of life in patients with pulmonary arterial hypertension (PAH). However, the process of inhalation is laborious for patients suffering from resting dyspnea. We describe a 75-year-old man with idiopathic PAH and a low gas transfer. Investigations excluded significant parenchymal lung disease and airflow obstruction (presuming FEV1/FVC ration > 70%). The patient struggled to complete iloprost inhalation due to severe dyspnea and hypoxemia. As such, we optimized the methods of oxygen supply from the nasal cannula to the trans-inhalator during the inhalation. We successfully shortened the inhalation duration that effectively reduced the laborious efforts required of patients. We also recorded pulmonary hemodynamics during inhalation of nebulized iloprost. This revealed significant hemodynamic improvement immediately following inhalation but hemodynamics returned to baseline within 2 hours. We hope that this optimization will enable patients with severe PAH to undergo iloprost inhalation.

Cystic Pulmonary Metastasis in a Patient with Scalp Angiosarcoma: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Kim, Ah Yeong; Lee, Kyung Soo; Han, Jong Ho; Kim, Ho Joong; Kim, Kwhan Mien; Baek, Chung Hwan [Samsugn Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2011-08-15

It has been well known that angiosarcoma (AS), particularly scalp AS, metastasizes to the lungs with multiple air-filled cystic lesions on chest computed tomography scans. Pneumothorax, due to cystic lesion rupture into the pleural space, is frequent;however, we do not exactly know how rapidly the metastatic lesions spread to the lungs or what the exact pathogenetic mechanism for cystic metastasis is. According to our experience, the speed of disease progression in pulmonary metastasis is relatively fast and the entire lungs may be involved within two or three months. The infiltrating spindle cell tumors in the alveolar walls are tethering the adjacent alveolar spaces in order to form a dilated air-filled cystic lesion.

Extramedullary pulmonary hematopoiesis causing pulmonary hypertension and severe tricuspid regurgitation detected by 99m technetium sulfur colloid bone marrow scan and single-photon emission computed tomography/CT

International Nuclear Information System (INIS)

Ali, Syed Zama; Clarke, Michael John; Kannivelu, Anbalagan; Chinchure, Dinesh; Srinivasan, Sivasubramanian

2014-01-01

Extramedullary pulmonary hematopoiesis is a rare entity with a limited number of case reports in the available literature only. We report the case of a 66-year-old man with known primary myelofibrosis, in whom a 99m technetium sulfur colloid bone marrow scan with single-photon emission computed tomography (SPECT)/CT revealed a pulmonary hematopoiesis as the cause of pulmonary hypertension and severe tricuspid regurgitation. To the best of our knowledge, this is the first description of 99m technetium sulfur colloid SPECT/CT imaging in this rare condition.

Propilthiouracil-induced diffuse pulmonary hemorrhage: a case report with the clinical and radiologic findings

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Cho, Young Jun; Kim, Joung Sook; Kim, Ji Young; Choi, Soo Jeon [Sanggye Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of)

2007-05-15

Propylthiouracil (PTU) is a drug that's used to manage hyperthyroidism and it can, on rare occasions, induce antineutrophil cytoplasmic antibody-associated vasculitis that involved multiple organ systems and it can also cause extremely rare isolated or diffuse pulmonary hemorrhage. We report here on a case of a patient who develop diffuse pulmonary hemorrhage after she had been taking PTU for five years. The patient is a 33-year-old woman who presented with hemoptysis. Simple chest radiographs and the chest CT showed bilateral ground-glass opacity, consolidation and pulmonary arterial hypertension. The bronchoalveolar lavage fluid revealed alveolar hemorrhage. The laboratory values showed increased perinuclear-antineutrophil cytoplasmic antibody ({rho} - ANCA) and anti-peroxidase antibody titers.

Proteinosis alveolar pulmonar

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Concepción Sánchez Infante

2011-12-01

Full Text Available La proteinosis alveolar pulmonar es una enfermedad respiratoria crónica, caracterizada por alteración en el metabolismo del surfactante, lo que determina su acumulación anormal en el espacio alveolar. Es una enfermedad extremadamente rara. Se han reportado solamente 500 casos en la literatura. Se describió por primera vez en 1958. Se presenta un caso de proteinosis alveolar pulmonar en un lactante de 2 meses, con desnutrición proteico energética, que ingresa por dificultad respiratoria e hipoxemia, y, con imágenes radiológicas de tipo retículo-nodulillar, en vidrio deslustrado, en el cual se plantea inicialmente el diagnóstico de bronconeumonía. Ante la evolución desfavorable y no respuesta al tratamiento, se realizó un estudio para descartar enfermedades pulmonares crónicas. El paciente fallece y se confirma el diagnóstico por anatomía patológica. Se realiza una revisión del tema.

Pulmonary effects of inhaled limonene ozone reaction products in elderly rats.

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Sunil, Vasanthi R; Laumbach, Robert J; Patel, Kinal J; Turpin, Barbara J; Lim, Ho-Jin; Kipen, Howard M; Laskin, Jeffrey D; Laskin, Debra L

2007-07-15

d-Limonene is an unsaturated volatile organic chemical found in cleaning products, air fresheners and soaps. It is oxidized by ozone to secondary organic aerosols consisting of aldehydes, acids, oxidants and fine and ultra fine particles. The lung irritant effects of these limonene ozone reaction products (LOP) were investigated. Female F344 rats (2- and 18-month-old) were exposed for 3 h to air or LOP formed by reacting 6 ppm d-limonene and 0.8 ppm ozone. BAL fluid, lung tissue and cells were analyzed 0 h and 20 h later. Inhalation of LOP increased TNF-alpha, cyclooxygenase-2, and superoxide dismutase in alveolar macrophages (AM) and Type II cells. Responses of older animals were attenuated when compared to younger animals. LOP also decreased p38 MAP kinase in AM from both younger and older animals. In contrast, while LOP increased p44/42 MAP kinase in AM from younger rats, expression decreased in AM and Type II cells from older animals. NF-kappaB and C/EBP activity also increased in AM from younger animals following LOP exposure but decreased or was unaffected in Type II cells. Whereas in younger animals LOP caused endothelial cell hypertrophy, perivascular and pleural edema and thickening of alveolar septal walls, in lungs from older animals, patchy accumulation of fluid within septal walls in alveolar sacs and subtle pleural edema were noted. LOP are pulmonary irritants inducing distinct inflammatory responses in younger and older animals. This may contribute to the differential sensitivity of these populations to pulmonary irritants.

Pulmonary effects of inhaled limonene ozone reaction products in elderly rats

International Nuclear Information System (INIS)

Sunil, Vasanthi R.; Laumbach, Robert J.; Patel, Kinal J.; Turpin, Barbara J.; Lim, Ho-Jin; Kipen, Howard M.; Laskin, Jeffrey D.; Laskin, Debra L.

2007-01-01

d-Limonene is an unsaturated volatile organic chemical found in cleaning products, air fresheners and soaps. It is oxidized by ozone to secondary organic aerosols consisting of aldehydes, acids, oxidants and fine and ultra fine particles. The lung irritant effects of these limonene ozone reaction products (LOP) were investigated. Female F344 rats (2- and 18-month-old) were exposed for 3 h to air or LOP formed by reacting 6 ppm d-limonene and 0.8 ppm ozone. BAL fluid, lung tissue and cells were analyzed 0 h and 20 h later. Inhalation of LOP increased TNF-α, cyclooxygenase-2, and superoxide dismutase in alveolar macrophages (AM) and Type II cells. Responses of older animals were attenuated when compared to younger animals. LOP also decreased p38 MAP kinase in AM from both younger and older animals. In contrast, while LOP increased p44/42 MAP kinase in AM from younger rats, expression decreased in AM and Type II cells from older animals. NF-κB and C/EBP activity also increased in AM from younger animals following LOP exposure but decreased or was unaffected in Type II cells. Whereas in younger animals LOP caused endothelial cell hypertrophy, perivascular and pleural edema and thickening of alveolar septal walls, in lungs from older animals, patchy accumulation of fluid within septal walls in alveolar sacs and subtle pleural edema were noted. LOP are pulmonary irritants inducing distinct inflammatory responses in younger and older animals. This may contribute to the differential sensitivity of these populations to pulmonary irritants

Grainyhead-like 2 (GRHL2) distribution reveals novel pathophysiological differences between human idiopathic pulmonary fibrosis and mouse models of pulmonary fibrosis

Science.gov (United States)

Mahavadi, Poornima; Sasikumar, Satish; Cushing, Leah; Hyland, Tessa; Rosser, Ann E.; Riccardi, Daniela; Lu, Jining; Kalin, Tanya V.; Kalinichenko, Vladimir V.; Guenther, Andreas; Ramirez, Maria I.; Pardo, Annie; Selman, Moisés; Warburton, David

2013-01-01

Chronic injury of alveolar lung epithelium leads to epithelial disintegrity in idiopathic pulmonary fibrosis (IPF). We had reported earlier that Grhl2, a transcriptional factor, maintains alveolar epithelial cell integrity by directly regulating components of adherens and tight junctions and thus hypothesized an important role of GRHL2 in pathogenesis of IPF. Comparison of GRHL2 distribution at different stages of human lung development showed its abundance in developing lung epithelium and in adult lung epithelium. However, GRHL2 is detected in normal human lung mesenchyme only at early fetal stage (week 9). Similar mesenchymal reexpression of GRHL2 was also observed in IPF. Immunofluorescence analysis in serial sections from three IPF patients revealed at least two subsets of alveolar epithelial cells (AEC), based on differential GRHL2 expression and the converse fluorescence intensities for epithelial vs. mesenchymal markers. Grhl2 was not detected in mesenchyme in intraperitoneal bleomycin-induced injury as well as in spontaneously occurring fibrosis in double-mutant HPS1 and HPS2 mice, whereas in contrast in a radiation-induced fibrosis model, with forced Forkhead box M1 (Foxm1) expression, an overlap of Grhl2 with a mesenchymal marker was observed in fibrotic regions. Grhl2's role in alveolar epithelial cell plasticity was confirmed by altered Grhl2 gene expression analysis in IPF and further validated by in vitro manipulation of its expression in alveolar epithelial cell lines. Our findings reveal important pathophysiological differences between human IPF and specific mouse models of fibrosis and support a crucial role of GRHL2 in epithelial activation in lung fibrosis and perhaps also in epithelial plasticity. PMID:24375798

Effects of a Pulmonary Rehabilitation Program for Several Asthme. Case Presentation

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Gómez V

2012-05-01

Full Text Available Objective: to present the effectiveness of pulmonary rehabilitation programs in the treatment of a patient with asthma. Case: this is the case of a young Caucasian girl —17 years old— with severe asthma diagnosis, with symptoms since she was eight years old, 10th grade student. She was referred to the program of Pulmonary Rehabilitation after three hospitalizations during the last year due to asthmatic crises, dyspnoea in activities of daily living, and intolerance to physical exercise. In the initial evaluation, a patient with non-controlled asthma was found; she was receiving short-acting medication admitting that she was not complying with regular use and with a prescribed dose of the pharmacological treatment and that she ignored the importance of this commitment for optimal evolution. The patient expressed concern about the progressive deterioration at her respiratory and functional level during the last year and her fear and anxiety for not being able to breathe during activities befitting her age. One month after receiving bronchodilators and long-acting steroids permanently and complying with recommendations about regular use and adequate inhalatory technique, the patient was included in a three-timesa-week program of pulmonary rehabilitation during eight weeks for upper and lower extremity endurance and resistance training. This intervention showed significant changes in the patient at functional level and a greater social participation.

Radiotherapy and pulmonary fibrosis

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Sone, S; Miyata, Y; Tachiiri, H [Osaka Univ. (Japan). Faculty of Medicine

1975-04-01

Clinical findings of radiation pneumonitis and pulmonary fibrosis were outlined, and the relationship between occurence of these disorders and radiotherapy, clinical findings and X-ray picture were studied. Standard radiation dose as cell lethal response of carcinoma of the lung were 4,500 to 5,500 rad in 4 to 5.5 weeks in undifferentiated carcinoma, 6,000 to 7,000 rad in 6 to 7 weeks in squamous cell carcinoma, 7,000 to 9,000 rad in 7 to 9 weeks in adenocarcinoma, 4,500 to 5,000 rad in 4 to 5 weeks in the large sized cancer of the esophagus, 6,500 to 7,000 rad in 5 to 7 weeks in the small sized cancer of the esophagus, and irradiation of these amount of dose caused hazards in pulmonary function. Pathological and clinical findings of pulmonary hazards within 6 month period after irradiation, factors causing them and changes in X-ray pictures before and after irradiation were observed and discussed in clinical cases: the case of breast cancer in which 3,000 R/6 times/18 days of 5.5 MeV Liniac electron was irradiated to the chest wall, and the case of pulmonary cancer in which 5,000 rad/25 times/34 days of 6 MeV Liniac X-ray was irradiated in opposite 2 ports radiation beam treatment. The former revealed alveolar lesion and interlobular pleuritis at 4 month later, and remarkable lesion of pulmonary fibrosis was followed at 9 month after radiotherapy. The later developed radiation pneumonitis 1 month after radiotherapy, of which lesion extended to the upper part by 3 months later, and cancer recurred 6.5 month later.

Modeling pulmonary fibrosis by abnormal expression of telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia

International Nuclear Information System (INIS)

Parra, E.R.; Pincelli, M.S.; Teodoro, W.R.; Velosa, A.P.P.; Martins, V.; Rangel, M.P.; Barbas-Filho, J.V.; Capelozzi, V.L.

2014-01-01

Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis

Modeling pulmonary fibrosis by abnormal expression of telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia

Energy Technology Data Exchange (ETDEWEB)

Parra, E.R.; Pincelli, M.S. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Teodoro, W.R.; Velosa, A.P.P. [Disciplina de Reumatologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Martins, V.; Rangel, M.P.; Barbas-Filho, J.V.; Capelozzi, V.L. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

2014-06-04

Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis.

Nostril Base Augmentation Effect of Alveolar Bone Graft

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Woojin Lee

2013-09-01

Full Text Available Background The aims of alveolar bone grafting are closure of the fistula, stabilization ofthe maxillary arch, support for the roots of the teeth adjacent to the cleft on each side.We observed nostril base augmentation in patients with alveolar clefts after alveolar bonegrafting. The purpose of this study was to evaluate the nostril base augmentation effect ofsecondary alveolar bone grafting in patients with unilateral alveolar cleft.Methods Records of 15 children with alveolar clefts who underwent secondary alveolar bonegrafting with autogenous iliac cancellous bone between March of 2011 and May of 2012 werereviewed. Preoperative and postoperative worm’s-eye view photographs and reconstructedthree-dimensional computed tomography (CT scans were used for photogrammetry. Thedepression of the nostril base and thickness of the philtrum on the cleft side were measuredin comparison to the normal side. The depression of the cleft side pyriform aperture wasmeasured in comparison to the normal side on reconstructed three-dimensional CT.Results Significant changes were seen in the nostril base (P=0.005, the philtrum length(P=0.013, and the angle (P=0.006. The CT measurements showed significant changes in thepyriform aperture (P<0.001 and the angle (P<0.001.Conclusions An alveolar bone graft not only fills the gap in the alveolar process but alsoaugments the nostril base after surgery. In this study, only an alveolar bone graft was performedto prevent bias from other procedures. Nostril base augmentation can be achieved byperforming alveolar bone grafts in children, in whom invasive methods are not advised.

A multislice single breath-hold scheme for imaging alveolar oxygen tension in humans.

Science.gov (United States)

Hamedani, Hooman; Kadlecek, Stephen J; Emami, Kiarash; Kuzma, Nicholas N; Xu, Yinan; Xin, Yi; Mongkolwisetwara, Puttisarn; Rajaei, Jennia; Barulic, Amy; Wilson Miller, G; Rossman, Milton; Ishii, Masaru; Rizi, Rahim R

2012-05-01

Reliable, noninvasive, and high-resolution imaging of alveolar partial pressure of oxygen (p(A)O(2)) is a potentially valuable tool in the early diagnosis of pulmonary diseases. Several techniques have been proposed for regional measurement of p(A)O(2) based on the increased depolarization rate of hyperpolarized (3) He. In this study, we explore one such technique by applying a multislice p(A)O(2) -imaging scheme that uses interleaved-slice ordering to utilize interslice time-delays more efficiently. This approach addresses the low spatial resolution and long breath-hold requirements of earlier techniques, allowing p(A)O(2) measurements to be made over the entire human lung in 10-15 s with a typical resolution of 8.3 × 8.3 × 15.6 mm(3). PO(2) measurements in a glass syringe phantom were in agreement with independent gas analysis within 4.7 ± 4.1% (R = 0.9993). The technique is demonstrated in four human subjects (healthy nonsmoker, healthy former smoker, healthy smoker, and patient with COPD), each imaged six times on 3 different days during a 2-week span. Two independent measurements were performed in each session, consisting of 12 coronal slices. The overall p(A)O(2) mean across all subjects was 95.9 ± 12.2 Torr and correlated well with end-tidal O(2) (R = 0.805, P < 0.0001). The alveolar O(2) uptake rate was consistent with the expected range of 1-2 Torr/s. Repeatable visual features were observed in p(A)O(2) maps over different days, as were characteristic differences among the subjects and gravity-dependent effects. Copyright © 2011 Wiley Periodicals, Inc.

Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.

Science.gov (United States)

Hamid, U; Krasnodembskaya, A; Fitzgerald, M; Shyamsundar, M; Kissenpfennig, A; Scott, C; Lefrancais, E; Looney, M R; Verghis, R; Scott, J; Simpson, A J; McNamee, J; McAuley, D F; O'Kane, C M

2017-11-01

Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin's antiplatelet and immunomodulatory effects may be beneficial in ARDS. To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Healthy volunteers were randomised to receive placebo or aspirin 75  or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 µg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the

3D-CT evaluation of secondary alveolar bone grafts in alveolar clefts

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Naitoh, Hiroshi; Nishimura, Yoshihiko [Kyoto Univ. (Japan). Graduate School of Medicine; Yamawaki, Yoshiroh [Kyoto Katsura Hospital (Japan); Morimoto, Naoki [Kobe City General Hospital (Japan)

2002-07-01

From 1994 to 2000, we treated 116 patients with cleft alveolus by secondary alveolar bone grafts, and 48 of them were evaluated morphologically with 3D-CT. The frequency of successful bony bridging was significantly higher in the group whose grafts were completely enveloped (including the anterior alveolar ridge) with a mucoperiosteal flap. The frequency was also significantly higher in the group who underwent bone grafts at the age of 13 or less, and canine eruptions did not influence the ratio. Some cases showed such an improved growth pattern of grafted bone that the shape of the affected maxilla resembled that of the normal side, after long-term follow-up observations. The growth increment was remarkable in anterior maxillary height. Orthodontic management guides the canine or incisor into the reconstructed area of the previous cleft. We surmise that the new occlusal position puts pressure on the grafted bone and promotes further osteogenesis. These findings show that it is important to produce sufficient bony bridge to guide the canine or incisor, not the volume of grafted bone, in secondary alveolar bone grafts. Long-term follow-up observation, after more than 2-3 years, is also necessary to evaluate secondary alveolar bone grafts. (author)

Evaluation of the concentration of marbofloxacin in alveolar macrophages and pulmonary epithelial lining fluid after administration in dogs.

Science.gov (United States)

Boothe, Harry W; Jones, Sarah A; Wilkie, W Scott; Boeckh, Albert; Stenstrom, Kristol K; Boothe, Dawn M

2005-10-01

To determine concentrations of marbofloxacin in alveolar macrophages (AMs) and epithelial lining fluid (ELF) and compare those concentrations with plasma concentrations in healthy dogs. 12 adult mixed-breed and purebred hounds. 10 dogs received orally administered marbofloxacin at a dosage of 2.75 mg/kg every 24 hours for 5 days. Two dogs served as nontreated controls. Fiberoptic bronchoscopy and bronchoalveolar lavage procedures were performed while dogs were anesthetized with propofol, approximately 6 hours after the fifth dose. The concentrations of marbofloxacin in plasma and bronchoalveolar fluid (cell and supernatant fractions) were determined by use of high-performance liquid chromatography with detection of fluorescence. Mean +/- SD plasma marbofloxacin concentrations 2 and 6 hours after the fifth dose were 2.36 +/- 0.52 microg/mL and 1.81 +/- 0.21 microg/mL, respectively. Mean +/- SD marbofloxacin concentration 6 hours after the fifth dose in AMs (37.43 +/- 24.61 microg/mL) was significantly greater than that in plasma (1.81 +/- 0.21 microg/mL) and ELF (0.82 +/- 0.34 microg/mL), resulting in a mean AM concentration-to-plasma concentration ratio of 20.4, a mean AM:ELF ratio of 60.8, and a mean ELF-to-plasma ratio of 0.46. Marbofloxacin was not detected in any samples from control dogs. Marbofloxacin concentrations in AMs were greater than the mean inhibitory concentrations of major bacterial pathogens in dogs. Results indicated that marbofloxacin accumulates in AMs at concentrations exceeding those reached in plasma and ELF The accumulation of marbofloxacin in AMs may facilitate treatment for susceptible intracellular pathogens or infections associated with pulmonary macrophage infiltration.

Ablation of the Leptin receptor in Myeloid Cells Impairs Pulmonary Clearance of Streptococcus Pneumoniae and Alveolar Macrophage Bactericidal Function.

Science.gov (United States)

Mancuso, Peter; Curtis, Jeffrey L; Freeman, Christine M; Peters-Golden, Marc; Weinberg, Jason B; Myers, Martin G

2018-03-22

Leptin is a pleiotropic hormone produced by white adipose tissue that regulates appetite and many physiologic functions including the immune response to infection. Genetic leptin deficiency in humans and mice impairs host defenses against respiratory tract infections. Since leptin deficiency is associated with obesity and other metabolic abnormalities, we generated mice that lack the leptin receptor (LepRb) in cells of the myeloid linage (LysM-LepRb-KO) to evaluate its impact in lean metabolically normal mice in a murine model of pneumococcal pneumonia. We observed higher lung and spleen bacterial burdens in LysM-LepRb-KO mice following an intratracheal challenge with S. pneumoniae. Although numbers of leukocytes recovered from bronchoalveolar lavage fluid did not differ between groups, we did observe higher levels of pulmonary IL-13 and TNFα in LysM-LepRb-KO mice 48 h post-infection. Phagocytosis and killing of ingested S. pneumoniae were also impaired in alveolar macrophages (AM)s from LysM-LepRb-KO mice in vitro, and was associated with reduced LTB4 and enhanced PGE2 synthesis in vitro. Pretreatment of AMs with LTB4 and the cyclooxygenase inhibitor, indomethacin, restored phagocytosis but not bacterial killing in vitro. These results, confirm our previous observations in leptin-deficient (ob/ob) and fasted mice, and demonstrate that decreased leptin action, as opposed to metabolic irregularities associated with obesity or starvation, are responsible for the defective host defense against pneumococcal pneumonia. They also provide novel targets for therapeutic intervention in humans with bacterial pneumonia.

Oral Rehabilitation of Adult Edentulous Siblings Severely Lacking Alveolar Bone Due to Ectodermal Dysplasia: A Report of 2 Clinical Cases and a Literature Review.

Science.gov (United States)

Wu, Yiqun; Zhang, Chenping; Squarize, Cristiane H; Zou, Duohong

2015-09-01

The oral conditions of adult edentulous patients with ectodermal dysplasia (ED) often lead to decreased physical and psychological health, and the negative effects can become as extreme as social and psychological isolation. However, restoring oral function of adult edentulous patients with ED using zygomatic implants (ZIs) or conventional implants (CIs) remains challenging for dentists because of the severe atrophy of these patients' alveolar ridges. This report describes 2 cases of adult edentulous siblings with ED; they exhibited severe alveolar bone atrophy and were treated with ZIs and CIs as bases to augment the bone in their anterior jaws. For these patients, bone augmentation was completed with an autogenous fibular graft. Although there was mild evidence of bone graft resorption in the maxilla, the bone augmentation procedures were successful in the 2 patients. Effective osseointegration of the implants was obtained. After placement, the functional and esthetic results of the oral rehabilitation were acceptable. More importantly, restoration of the patients' oral function enhanced their self-confidence and self-esteem. Therefore, restoring oral function in adult patients with ED and edentulous jaws using ZIs and CIs as the bases for bone augmentation is an effective approach. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

The study of the lung accumulation of I-123 IMP by the broncho-alveolar lavage

International Nuclear Information System (INIS)

Itasaka, Miyoko; Ikeda, Hideki; Yakuwa, Naoshi; Kato, Shuichi; Takahashi, Keiji; Yasui, Shoji

1989-01-01

We studied the accumulated portion and the movement of I-123 IMP in the lung. Ten subjects were studied. They were four patients with fibrosing lung disease, two with lung cancer, and four with other lung disease. They underwent the broncho-alveolar lavage (BAL) for the diagnosis of their diseases. l.5 mCi of I-123 IMP was injected into the ante-cubital vein. The BAL examination was carried out about 40 minutes after the injection of I-123 IMP. The subjects' blood was sampled at the same time. The total BAL liquid (BAL-T) was divided into the fluid component (BAL-F) and the cell component (BAL-C) by centrifugation. The radioactivities in BAL-T, BAL-F, BAL-C, and serum (B-S) were measured by the well-counter. The average of BAL-T/B-S, BAL-F/B-S and BAL-C/B-S were 6.86, 4.26 and 2.71 respectively. It was confirmed that I-123 IMP was transported from the pulmonary capillary to the alveolar space and was taken up by the alveolar cells. It was considered that the analysis of the I-123 IMP release from the lung showed not only the endothelial cell uptake function but also the interstitial and material cells' amine transport and uptake function. (author)

Athletes and Sedentary Individuals: An Intergroup Comparison Utilizing a Pulmonary Function Ratio Obtained During Submaximal Exercise.

Science.gov (United States)

Maud, Peter J.

A pulmonary function ratio describing oxygen extraction from alveolar ventilation was used for an intergroup comparison between three groups of athletes (rugby, basketball, and football players) and one group of sedentary subjects during steady-state submaximal exercise. The ratio and its component parts are determined from only three gas…

Invasive pulmonary aspergillosis in patients with decompensated cirrhosis: case series

Directory of Open Access Journals (Sweden)

Poynard Thierry

2007-01-01

Full Text Available Abstract Background Opportunistic invasive fungal infections are increasingly frequent in intensive care patients. Their clinical spectrum goes beyond the patients with malignancies, and for example invasive pulmonary aspergillosis has recently been described in critically ill patients without such condition. Liver failure has been suspected to be a risk factor for aspergillosis. Case presentation We describe three cases of adult respiratory distress syndrome with sepsis, shock and multiple organ failure in patients with severe liver failure among whom two had positive Aspergillus antigenemia and one had a positive Aspergillus serology. In all cases bronchoalveolar lavage fluid was positive for Aspergillus fumigatus. Outcome was fatal in all cases despite treatment with voriconazole and agressive symptomatic treatment. Conclusion Invasive aspergillosis should be among rapidly raised hypothesis in cirrhotic patients developing acute respiratory symptoms and alveolar opacities.

Adenoviral transfer of HSP-70 into pulmonary epithelium ameliorates experimental acute respiratory distress syndrome.

Science.gov (United States)

Weiss, Yoram G; Maloyan, Alina; Tazelaar, John; Raj, Nichelle; Deutschman, Clifford S

2002-09-01

The acute respiratory distress syndrome (ARDS) provokes three pathologic processes: unchecked inflammation, interstitial/alveolar protein accumulation, and destruction of pulmonary epithelial cells. The highly conserved heat shock protein HSP-70 can limit all three responses but is not appropriately expressed in the lungs after cecal ligation and double puncture (2CLP), a clinically relevant model of ARDS. We hypothesize that restoring expression of HSP-70 using adenovirus-mediated gene therapy will limit pulmonary pathology following 2CLP. We administered a vector containing the porcine HSP-70 cDNA driven by a CMV promoter (AdHSP) into the lungs of rats subjected to 2CLP or sham operation. Administration of AdHSP after either sham operation or 2CLP increased HSP-70 protein expression in lung tissue, as determined by immunohistochemistry and Western blot hybridization. Administration of AdHSP significantly attenuated interstitial and alveolar edema and protein exudation and dramatically decreased neutrophil accumulation, relative to a control adenovirus. CLP-associated mortality at 48 hours was reduced by half. Modulation of HSP-70 production reduces pathologic changes and may improve outcome in experimental ARDS.

Relationship of distraction rate with inferior alveolar nerve degeneration-regeneration shift

Directory of Open Access Journals (Sweden)

Ying-hua Zhao

2018-01-01

Full Text Available Distraction osteogenesis is an important technique for the treatment of maxillofacial abnormities and defects. However, distraction osteogenesis may cause the injury of the inferior alveolar nerve. The relationship between distraction rate and nerve degeneration-regeneration shift remains poorly understood. In this study, 24 rabbits were randomly divided into four groups. To establish the rabbit mandibular distraction osteogenesis model, the mandibles of rabbits in distraction osteogenesis groups were subjected to continuous osteogenesis distraction at a rate of 1.0, 1.5 and 2.0 mm/d, respectively, by controlling rounds of screwing each day in the distractors. In the sham group, mandible osteotomy was performed without distraction. Pin-prick test with a 10 g blunt pin on the labium, histological and histomorphometric analyses with methylene blue staining, Bodian's silver staining, transmission electron microscopy and myelinated fiber density of inferior alveolar nerve cross-sections were performed to assess inferior alveolar nerve conditions. At 28 days after model establishment, in the pin-prick test, the inferior alveolar nerve showed no response in the labium to a pin pricks in the 2 mm/d group, indicating a severe dysfunction. Histological and histomorphometric analyses indicated that the inferior alveolar nerve suffered more degeneration and injuries at a high distraction rate (2 mm/d. Importantly, the nerve regeneration, indicated by newborn Schwann cells and axons, was more abundant in 1.0 and 1.5 mm/d groups than in 2.0 mm/d group. We concluded that the distraction rate was strongly associated with the inferior alveolar nerve function, and the distraction rates of 1.0 and 1.5 mm/d had regenerative effects on the inferior alveolar nerve. This study provides an experimental basis for the relationship between distraction rate and nerve degeneration-regeneration shift during distraction osteogenesis, and may facilitate reducing nerve

Extramedullary pulmonary hematopoiesis causing pulmonary hypertension and severe tricuspid regurgitation detected by {sup 99m} technetium sulfur colloid bone marrow scan and single-photon emission computed tomography/CT

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Ali, Syed Zama; Clarke, Michael John; Kannivelu, Anbalagan; Chinchure, Dinesh; Srinivasan, Sivasubramanian [Dept. of Diagnostic Radiology, Khoo Teck Puat Hospital, Singapore (Singapore)

2014-06-15

Extramedullary pulmonary hematopoiesis is a rare entity with a limited number of case reports in the available literature only. We report the case of a 66-year-old man with known primary myelofibrosis, in whom a {sup 99m}technetium sulfur colloid bone marrow scan with single-photon emission computed tomography (SPECT)/CT revealed a pulmonary hematopoiesis as the cause of pulmonary hypertension and severe tricuspid regurgitation. To the best of our knowledge, this is the first description of {sup 99m} technetium sulfur colloid SPECT/CT imaging in this rare condition.

Bronchoalveolar lavage fluid from normal rats stimulates DNA synthesis in rat alveolar type II cells

International Nuclear Information System (INIS)

Leslie, C.C.; McCormick-Shannon, K.; Mason, R.J.

1989-01-01

Proliferation of alveolar type II cells after lung injury is important for the restoration of the alveolar epithelium. Bronchoalveolar lavage fluid (BALF) may represent an important source of growth factors for alveolar type II cells. To test this possibility, BALF fluid was collected from normal rats, concentrated 10-fold by Amicon filtration, and tested for its ability to stimulate DNA synthesis in rat alveolar type II cells in primary culture. BALF induced a dose-dependent increase in type II cell DNA synthesis resulting in a 6-fold increase in [3H]thymidine incorporation. Similar doses also stimulated [3H]thymidine incorporation into rat lung fibroblasts by 6- to 8-fold. Removal of pulmonary surface active material by centrifugation did not significantly reduce the stimulatory activity of BALF for type II cells. The stimulation of type II cell DNA synthesis by BALF was reduced by 100% after heating at 100 degrees C for 10 min, and by approximately 80% after reduction with dithiothreitol, and after trypsin treatment. Dialysis of BALF against 1 N acetic acid resulted in a 27% reduction in stimulatory activity. The effect of BALF in promoting type II cell DNA synthesis was more pronounced when tested in the presence of serum, although serum itself has very little effect on type II cell DNA synthesis. When BALF was tested in combination with other substances that stimulate type II cell DNA synthesis (cholera toxin, insulin, epidermal growth factor, and acidic fibroblast growth factor), additive effects or greater were observed. When BALF was chromatographed over Sephadex G150, the activity eluted with an apparent molecular weight of 100 kDa

Reconstruction of supracrestal alveolar bone lost as a result of severe chronic periodontitis. Five-year outcome: case report.

Science.gov (United States)

Kotschy, Peter; Laky, Markus

2006-10-01

This patient presented with generalized severe chronic periodontitis. Conventional periodontal therapy would have left her compromised esthetically and anatomically, with growing interdental "black triangles." This prompted the authors to try to reconstruct the maxillary alveolar bone that had been lost in the previous three decades because of untreated periodontitis. To maintain the level and quality of the gingival margin, open flap surgery was performed in the maxilla soon after scaling and root planing. To gain access to the roots and bone surfaces, a flap was raised by intrasulcular incisions and the modified and simplified papilla preservation technique. After debridement, the root surfaces were conditioned and enamel matrix proteins were applied. Bovine bone mineral was placed in the infrabony defects and supracrestally (buccally, lingually, and interdentally) to help regenerate the lost alveolar bone. In addition, the defects around the maxillary anterior teeth were covered with a membrane. To prevent shrinkage of the gingiva, suspensory sutures were placed on the right central incisor and both left incisors so that the anterior flap would be positioned approximately 3 mm coronally. After surgery, the patient was advised to apply 1% chlorhexidine gel twice a day and to avoid brushing the surgical site for 4 weeks. Professional maintenance care was administered twice a week for 2 months and the patient was instructed to maintain a liquid diet for 4 weeks. The treatment outcome was evaluated clinically and radiographically at regular intervals for 5 years postsurgically. Periodontal conditions were stable and fulfilled the patient's desire to eliminate the pockets without compromising esthetics, particularly in the maxillary anterior.

Prognostic Value of C-Reactive Protein, Leukocytes, and Vitamin D in Severe Chronic Obstructive Pulmonary Disease

DEFF Research Database (Denmark)

Moberg, Mia; Vestbo, Jørgen; Martinez, Gerd

2014-01-01

Inflammatory biomarkers predict mortality and hospitalisation in chronic obstructive pulmonary disease (COPD). Yet, it remains uncertain if biomarkers in addition to reflecting disease severity add new prognostic information on severe COPD. We investigated if leukocytes, C-reactive protein (CRP......), and vitamin D were independent predictors of mortality and hospitalisation after adjusting for disease severity with an integrative index, the i-BODE index. In total, 423 patients participating in a pulmonary rehabilitation programme, with a mean value of FEV1 of 38% of predicted, were included. Mean followup...... was 45 months. During the follow-up period, 149 deaths (35%) were observed and 330 patients (78.0%) had at least one acute hospitalisation; 244 patients (57.7%) had at least one hospitalisation due to an exacerbation of COPD. In the analysis (Cox proportional hazards model) fully adjusted for age, sex...

Oxygen-enhanced MRI for patients with connective tissue diseases: Comparison with thin-section CT of capability for pulmonary functional and disease severity assessment

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Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.jp [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Nishio, Mizuho [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Koyama, Hisanobu [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Yoshikawa, Takeshi; Matsumoto, Sumiaki [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Seki, Shinichiro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Tsubakimoto, Maho [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nakagami-Gun, Okinawa (Japan); Sugimura, Kazuro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan)

2014-02-15

Purpose: To prospectively and directly compare oxygen-enhanced (O{sub 2}-enhanced) MRI with thin-section CT for pulmonary functional loss and disease severity assessment in connective tissue disease (CTD) patients with interstitial lung disease (ILD). Materials and methods: Thin-section CT, O{sub 2}-enhanced MRI, pulmonary function test and serum KL-6 were administered to 36 CTD patients with ILD (23 men, 13 women; mean age: 63.9 years) and nine CTD patients without ILD (six men, and three women; mean age: 62.0 years). A relative-enhancement ratio (RER) map was generated from O{sub 2}-enhanced MRI and mean relative enhancement ratio (MRER) for each subject was calculated from all ROI measurements. CT-assessed disease severity was evaluated with a visual scoring system from each of the thin-section CT data. MRER and CT-assessed disease severities of CTD patients with and without ILD were then statistically compared. To assess capability for pulmonary functional loss and disease severity assessment in CTD patients, correlations of MRER and CT-assessed disease severity with pulmonary functional parameters and serum KL-6 in all subjects were statistically determined. Results: MRER and CT-assessed disease severity showed significant differences between CTD patients with (MRER: 0.15 ± 0.08, CT-assessed disease severity: 13.0 ± 7.4%) and without ILD (MRER: 0.25 ± 0.06, p = 0.0011; CT-assessed disease severity: 1.6 ± 1.6%, p < 0.0001). MRER and CT-assessed disease severity correlated significantly with pulmonary functional parameters and serum KL-6 in all subjects (0.61 ≤ r ≤ 0.79, p < 0.05). Conclusion: O{sub 2}-enhanced MRI was found to be as useful as thin-section CT for pulmonary functional loss and disease severity assessment of CTD patients with ILD.

Oxygen-enhanced MRI for patients with connective tissue diseases: Comparison with thin-section CT of capability for pulmonary functional and disease severity assessment

International Nuclear Information System (INIS)

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Seki, Shinichiro; Tsubakimoto, Maho; Sugimura, Kazuro

2014-01-01

Purpose: To prospectively and directly compare oxygen-enhanced (O 2 -enhanced) MRI with thin-section CT for pulmonary functional loss and disease severity assessment in connective tissue disease (CTD) patients with interstitial lung disease (ILD). Materials and methods: Thin-section CT, O 2 -enhanced MRI, pulmonary function test and serum KL-6 were administered to 36 CTD patients with ILD (23 men, 13 women; mean age: 63.9 years) and nine CTD patients without ILD (six men, and three women; mean age: 62.0 years). A relative-enhancement ratio (RER) map was generated from O 2 -enhanced MRI and mean relative enhancement ratio (MRER) for each subject was calculated from all ROI measurements. CT-assessed disease severity was evaluated with a visual scoring system from each of the thin-section CT data. MRER and CT-assessed disease severities of CTD patients with and without ILD were then statistically compared. To assess capability for pulmonary functional loss and disease severity assessment in CTD patients, correlations of MRER and CT-assessed disease severity with pulmonary functional parameters and serum KL-6 in all subjects were statistically determined. Results: MRER and CT-assessed disease severity showed significant differences between CTD patients with (MRER: 0.15 ± 0.08, CT-assessed disease severity: 13.0 ± 7.4%) and without ILD (MRER: 0.25 ± 0.06, p = 0.0011; CT-assessed disease severity: 1.6 ± 1.6%, p < 0.0001). MRER and CT-assessed disease severity correlated significantly with pulmonary functional parameters and serum KL-6 in all subjects (0.61 ≤ r ≤ 0.79, p < 0.05). Conclusion: O 2 -enhanced MRI was found to be as useful as thin-section CT for pulmonary functional loss and disease severity assessment of CTD patients with ILD

Distracción osteogénica alveolar como método de aumento del reborde alveolar

Directory of Open Access Journals (Sweden)

Denia Morales Navarro

2011-03-01

Full Text Available La distracción osteogénica alveolar, como proceso biológico de neoformación de hueso alveolar, nos motivó a la realización de la presente revisión bibliográfica, con el objetivo enfatizar en el análisis de las variables: antecedentes históricos en Cuba, clasificación de los distractores, fases de la distracción (latencia, distracción y consolidación, indicaciones, contraindicaciones, ventajas, desventajas y complicaciones. Se realizó una revisión bibliográfica mediante la consulta de bases de datos de los sistemas referativos, como MEDLINE y PubMed con la utilización de descriptores "alveolar distraction" y "osteogenic distraction". Se consultaron las fuentes bibliográficas publicadas fundamentalmente en los últimos 5 años, lo que reveló que esta técnica es una excelente alternativa para la formación de huesos y tejidos blandos en zonas de atrofia alveolar, que consta de tres etapas: latencia, distracción y consolidación; un método previsible y con bajas tasas de reabsorción ósea en comparación con otras técnicas de aumento del reborde alveolar. Tiene su principal indicación en la terapia de implantes al proveer volumen óseo. Debemos individualizar cada caso y usar el método más adecuado según las características clínicas y personales del paciente. Una adecuada selección de los casos y una mejor comprensión de la técnica son los puntales para lograr exitosos resultados mediante la distracción osteogénica alveolar. En Cuba se ha aplicado poco la distracción alveolar, por lo que ha sido necesario ampliar los estudios sobre esta temática.

Assessment of Alveolar Bone Status in Middle Aged Chinese (40-59 Years) with Chronic Periodontitis--Using CBCT.

Science.gov (United States)

Zhao, Haijiao; Li, Chen; Lin, Li; Pan, Yaping; Wang, Hongyan; Zhao, Jian; Tan, Lisi; Pan, Chunling; Song, Jia; Zhang, Dongmei

2015-01-01

This study used con-beam computed tomography (CBCT) to investigate the prevalence and severity of alveolar bone loss in middle-aged (40-59 years) Chinese with chronic periodontitis. The study group comprised 145 dentate individuals aged 40 to 59 years residing in China who suffered from chronic periodontitis. CBCT and the application of NNT software were used to examine the level and location of alveolar bone loss. The study revealed that 40-59 year old patients with chronic periodontitis had severe bone loss. At 5,286 sites (34.7%), alveolar bone loss was mild; severe alveolar bone loss was found at 5,978 sites (39.2%). A comparison of bone loss in different jaws revealed that the area with the highest degree of bone loss was on the lingual side of the maxillary molar (56.3 ± 7.2%), and that the area with the lowest degree was primarily on the lingual side of the mandibular canine (27.5 ± 6.3%). There was a lower degree of alveolar bone loss in males than females. Differences were observed when comparing the incidence of bone loss between males and females (P chronic periodontitis, the highest degrees of bone loss in the incisors, premolars, and molars were on the lingual side, mesial side and lingual side, respectively. Menopause in females and smoking may affect the level of bone loss.

A New, Noninvasive Method of Measuring Impaired Pulmonary Gas Exchange in Lung Disease: An Outpatient Study.

Science.gov (United States)

West, John B; Crouch, Daniel R; Fine, Janelle M; Makadia, Dipen; Wang, Daniel L; Prisk, G Kim

2018-02-13

It would be valuable to have a noninvasive method of measuring impaired pulmonary gas exchange in patients with lung disease and thus reduce the need for repeated arterial punctures. This study reports the results of using a new test in a group of outpatients attending a pulmonary clinic. Inspired and expired partial pressure of oxygen (PO 2 ) and Pco 2 are continually measured by small, rapidly responding analyzers. The arterial PO 2 is calculated from the oximeter blood oxygen saturation level and the oxygen dissociation curve. The PO 2 difference between the end-tidal gas and the calculated arterial value is called the oxygen deficit. Studies on 17 patients with a variety of pulmonary diseases are reported. The mean ± SE oxygen deficit was 48.7 ± 3.1 mm Hg. This finding can be contrasted with a mean oxygen deficit of 4.0 ± 0.88 mm Hg in a group of 31 normal subjects who were previously studied (P gas in determining ventilation-perfusion ratio inequality. This factor is largely ignored in the classic index of impaired pulmonary gas exchange using the ideal alveolar PO 2 to calculate the alveolar-arterial oxygen gradient. The results previously reported in normal subjects and the present studies suggest that this new noninvasive test will be valuable in assessing abnormal gas exchange in the clinical setting. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Modulation pf pulmonary surfactant secretion from alveolar type II cells by cytoplasmic free calcium ([Ca2+]/sub i/)

International Nuclear Information System (INIS)

Sano, K.; Voelker, D.R.; Mason, R.J.

1986-01-01

Ca 2+ is regulator of a variety of cellular functions including exocytosis. TPA and terbutaline have been shown to stimulate surfactant secretion from alveolar type II cells. The authors examined changes in [Ca 2+ ]/sub i/ and surfactant secretion by secretagogues in primary culture of alveolar type II cells. Cells were isolated from adult rats and were cultured for 24 h with 3 H-choline to label phosphatidylcholine. Percent secretion was determined by counting the lipids of cells and medium; cytotoxicity was excluded by measuring lactate dehydrogenase as cells and medium. [Ca 2+ ]/sub i/ was determined by measuring quin2 fluroescence of cells cultured on a glass coverslip. Ionomycin increased secretion as well as [Ca 2+ ] in dose dependent manner at the concentration from 25 to 400 nM. Ionomycin (50 nM) increased terbutaline-induced secretion in a synergistic manner but only increased TPA-induced secretion in an additive manner. Terbutaline mobilized [Ca 2+ ]/sub i/ from intracellular stores and increased [Ca 2+ ]/sub i/ by 20% from a basal level of 140 nM. TPA itself did not change [Ca 2+ ]/sub i/ but inhibited the effect of terbutaline on [Ca 2+ ]/sub i/. Loading of quin2 in the absence of extracellular calcium lowered [Ca 2+ ]/sub i/ from 143 nM to 31 nM. Lowering [Ca 2+ ]/sub i/ inhibited TPA- or terbutaline-induced secretion by 22% and 40% respectively. These results indicate that [Ca 2+ ]/sub i/ effects cAMp-induced secretion more than protein kinase C-mediated secretion in alveolar type II cells

[PREVENTION AND CORRECTION OF PULMONARY COMPLICATIONS FOR SEVERE ACUTE PANCREATITIS].

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Fedorkiv, M B

2015-06-01

Increased of proinflammatory cytokines levels, including interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) on severe acute pancreatitis causes vasodilatation, increased permeability of the wall, accumulation of fluid in lung tissue and pleural sinuses. Transudate from acute parapancreatyc clusters of hot liquid and abdomen falls into the chest cavity through microscopic defects in the diaphragm due to the formation of pathological pleural-peritoneal connections or the relevant pressure gradient between the abdominal and pleural cavities. Remediation and removal of acute parapancreatyc clusters combined with the use of a multicomponent drug infusion therapy Cytoflavin provide a reduction in the frequency of pulmonary complications of acute pancreatitis from 48.3 to 31.0%. Use of the drug Cytoflavin reduces the severity of endogenous intoxication and mortality from acute lung injury from 12.9 to 6.1%.

Decreased proteasomal function accelerates cigarette smoke-induced pulmonary emphysema in mice.

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Yamada, Yosuke; Tomaru, Utano; Ishizu, Akihiro; Ito, Tomoki; Kiuchi, Takayuki; Ono, Ayako; Miyajima, Syota; Nagai, Katsura; Higashi, Tsunehito; Matsuno, Yoshihiro; Dosaka-Akita, Hirotoshi; Nishimura, Masaharu; Miwa, Soichi; Kasahara, Masanori

2015-06-01

Chronic obstructive pulmonary disease (COPD) is a disease common in elderly people, characterized by progressive destruction of lung parenchyma and chronic inflammation of the airways. The pathogenesis of COPD remains unclear, but recent studies suggest that oxidative stress-induced apoptosis in alveolar cells contributes to emphysematous lung destruction. The proteasome is a multicatalytic enzyme complex that plays a critical role in proteostasis by rapidly destroying misfolded and modified proteins generated by oxidative and other stresses. Proteasome activity decreases with aging in many organs including lungs, and an age-related decline in proteasomal function has been implicated in various age-related pathologies. However, the role of the proteasome system in the pathogenesis of COPD has not been investigated. Recently, we have established a transgenic (Tg) mouse model with decreased proteasomal chymotrypsin-like activity, showing age-related phenotypes. Using this model, we demonstrate here that decreased proteasomal function accelerates cigarette smoke (CS)-induced pulmonary emphysema. CS-exposed Tg mice showed remarkable airspace enlargement and increased foci of inflammation compared with wild-type controls. Importantly, apoptotic cells were found in the alveolar walls of the affected lungs. Impaired proteasomal activity also enhanced apoptosis in cigarette smoke extract (CSE)-exposed fibroblastic cells derived from mice and humans in vitro. Notably, aggresome formation and prominent nuclear translocation of apoptosis-inducing factor were observed in CSE-exposed fibroblastic cells isolated from Tg mice. Collective evidence suggests that CS exposure and impaired proteasomal activity coordinately enhance apoptotic cell death in the alveolar walls that may be involved in the development and progression of emphysema in susceptible individuals such as the elderly.

Fatigue and multidimensional disease severity in chronic obstructive pulmonary disease

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Inal-Ince Deniz

2010-06-01

Full Text Available Abstract Background and aims Fatigue is associated with longitudinal ratings of health in patients with chronic obstructive pulmonary disease (COPD. Although the degree of airflow obstruction is often used to grade disease severity in patients with COPD, multidimensional grading systems have recently been developed. The aim of this study was to investigate the relationship between perceived and actual fatigue level and multidimensional disease severity in patients with COPD. Materials and methods Twenty-two patients with COPD (aged 52-74 years took part in the study. Multidimensional disease severity was measured using the SAFE and BODE indices. Perceived fatigue was assessed using the Fatigue Severity Scale (FSS and the Fatigue Impact Scale (FIS. Peripheral muscle endurance was evaluated using the number of sit-ups, squats, and modified push-ups that each patient could do. Results Thirteen patients (59% had severe fatigue, and their St George's Respiratory Questionnaire scores were significantly higher (p Conclusions Peripheral muscle endurance and fatigue perception in patients with COPD was related to multidimensional disease severity measured with both the SAFE and BODE indices. Improvements in perceived and actual fatigue levels may positively affect multidimensional disease severity and health status in COPD patients. Further research is needed to investigate the effects of fatigue perception and exercise training on patients with different stages of multidimensional COPD severity.

Echocardiographic evaluation of heart in chronic obstructive pulmonary disease patient and its co-relation with the severity of disease

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N K Gupta

2011-01-01

Full Text Available Background: Chronic obstructive pulmonary disease (COPD has considerable effects on cardiac functions, including those of the right ventricle, left ventricle, and pulmonary blood vessels. Most of the increased mortality associated with COPD is due to cardiac involvement. Echocardiography provides a rapid, noninvasive, portable, and accurate method to evaluate the cardiac changes. Aims: To assess the cardiac changes secondary to COPD by echocardiography and to find out the correlation between echocardiographic findings and severity of COPD, if there is any. Materials and Methods: A total 40 of patients of COPD were selected and staged by pulmonary function test (PFT and evaluated by echocardiography. Results: On echocardiographic evaluation of COPD, 50% cases had normal echocardiographic parameters. Measurable tricuspid regurgitation (TR was observed in 27/40 cases (67.5%. Pulmonary hypertension (PH, which is defined as systolic pulmonary arterial pressure (sPAP > 30 mmHg was observed in 17/27 (63% cases in which prevalence of mild, moderate, and severe PH were 10/17 (58.82%, 4/17 (23.53%, and 3/17 (17.65%, respectively. The frequencies of PH in mild, moderate, severe, and very severe COPD were 16.67%, 54.55%, 60.00%, and 83.33%, respectively. Right atrial pressure was 10 mmHg in 82.5% cases and 15 mmHg in 17.5% cases. Cor pulmonale was observed in 7/17 (41.17% cases; 7.50% cases had left ventricle (LV systolic dysfunction and 47.5% cases had evidence of LV diastolic dysfunction defined as A ≥ E (peak mitral flow velocity of the early rapid filling wave (E, peak velocity of the late filling wave caused by atrial contraction (A on mitral valve tracing. Left ventricle hypertrophy was found in 22.5% cases. Conclusion : Prevalence of PH has a linear relationship with severity of COPD and severe PH is almost associated with cor pulmonale. Echocardiography helps in early detection of cardiac complications in COPD cases giving time for early

Gas Exchange and Mechanical Properties of the Lung in Miners with Severe Concomitant Injury

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V. V. Moroz

2007-01-01

Full Text Available Objective: to study the specific features of pulmonary gas exchange and mechanical properties in various manifestations of respiratory failure in miners with severe concomitant injury, who have a service length of 10 years or more, in order to optimize respiratory support.Subjects and methods. Pulmonary gas exchange and mechanical properties were studied over time in the presence of respiratory failure (acute lung injury/acute respiratory distress syndrome in 34 miners and 36 victims (a control group with severe concomitant injury who had no underground service length. Both groups were matched in age, severity and nature of traumatic lesions and surgical interventions. Pulmonary gas exchange and mechanical properties were evaluated by the following indices: oxygen fraction in an inspired gas mixture; hemoglobin saturation and partial arterial blood oxygen and carbon dioxide tension with the alveolar-arterial gradient being calculated by the oxygen level; oxygenation index; intrapulmonary shunting; statistical compliance and airways resistance.Results. The studies demonstrated that the miners, as compared with the controls, had more pronounced gas exchange changes within 5—7 post-traumatic days; later on (days 7—9 the above differences were undetectable. Impaired pulmonary mechanical properties in the miners persisted throughout the study while in the control group, their recovery started just on day 3. The course of respiratory failure in the miners was attributable to the baseline external respiratory function. Their respiratory support was performed during 14.5±1.4 days versus 9.5±1.9 days in the controls. In the miners, the mean bed-days at an intensive care unit were 18.5±2.2 whereas in the controls those were 12.3±2.1.Conclusion. More significant impairments of pulmonary gas exchange and mechanical properties are seen in the miners due to the background changes in external respiratory function in the development of respiratory

Relationship between CT visual score and lung volume which is measured by helium dilution method and body plethysmographic method in patients with pulmonary emphysema

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Toyoshima, Hideo; Ishibashi, Masayoshi; Senju, Syoji; Tanaka, Hideki; Aritomi, Takamichi; Watanabe, Kentaro; Yoshida, Minoru

1997-01-01

We examined the relationship between CT visual score and pulmonary function studies in patients with pulmonary emphysema. Lung volume was measured using helium dilution method and body plethysmographic method. Although airflow obstruction and overinflation measured by helium dilution method did not correlate with CT visual score, CO diffusing capacity per alveolar volume (DL CO /V A ) showed significant negative correlation with CT visual score (r=-0.49, p CO /V A reflect pathologic change in pulmonary emphysema. Further, both helium dilution method and body plethysmographic method are required to evaluate lung volume of pulmonary emphysema because of its ventilatory unevenness. (author)

Small-animal dark-field radiography for pulmonary emphysema evaluation

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Yaroshenko, Andre; Meinel, Felix G.; Hellbach, Katharina; Bech, Martin; Velroyen, Astrid; Müller, Mark; Bamberg, Fabian; Nikolaou, Konstantin; Reiser, Maximilian F.; Yildirim, Ali Ã.-.; Eickelberg, Oliver; Pfeiffer, Franz

2014-03-01

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide and emphysema is one of its main components. The disorder is characterized by irreversible destruction of the alveolar walls and enlargement of distal airspaces. Despite the severe changes in the lung tissue morphology, conventional chest radiographs have only a limited sensitivity for the detection of mild to moderate emphysema. X-ray dark-field is an imaging modality that can significantly increase the visibility of lung tissue on radiographic images. The dark-field signal is generated by coherent, small-angle scattering of x-rays on the air-tissue interfaces in the lung. Therefore, morphological changes in the lung can be clearly visualized on dark-field images. This is demonstrated by a preclinical study with a small-animal emphysema model. To generate a murine model of pulmonary emphysema, a female C57BL/6N mouse was treated with a single orotracheal application of porcine pancreatic elastase (80 U/kg body weight) dissolved in phosphate-buffered saline (PBS). Control mouse received PBS. The mice were imaged using a small-animal dark-field scanner. While conventional x-ray transmission radiography images revealed only subtle indirect signs of the pulmonary disorder, the difference between healthy and emphysematous lungs could be clearly directly visualized on the dark-field images. The dose applied to the animals is compatible with longitudinal studies. The imaging results correlate well with histology. The results of this study reveal the high potential of dark-field radiography for clinical lung imaging.

Polarized light microscopy reveals physiological and drug-induced changes in surfactant membrane assembly in alveolar type II pneumocytes.

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Haller, Thomas; Cerrada, Alejandro; Pfaller, Kristian; Braubach, Peter; Felder, Edward

2018-05-01

In alveolar type II (AT II) cells, pulmonary surfactant (PS) is synthetized, stored and exocytosed from lamellar bodies (LBs), specialized large secretory organelles. By applying polarization microscopy (PM), we confirm a specific optical anisotropy of LBs, which indicates a liquid-crystalline mesophase of the stored surfactant phospholipids (PL) and an unusual case of a radiation-symmetric, spherocrystalline organelle. Evidence is shown that the degree of anisotropy is dependent on the amount of lipid layers and their degree of hydration, but unaffected by acutely modulating vital cell parameters like intravesicular pH or cellular energy supply. In contrast, physiological factors that perturb this structure include osmotic cell volume changes and LB exocytosis. In addition, we found two pharmaceuticals, Amiodarone and Ambroxol, both of which severely affect the liquid-crystalline order. Our study shows that PM is an easy, very sensitive, but foremost non-invasive and label-free method able to collect important structural information of PS assembly in live AT II cells which otherwise would be accessible by destructive or labor intense techniques only. This may open new approaches to dynamically investigate LB biosynthesis - the incorporation, folding and packing of lipid membranes - or the initiation of pathological states that manifest in altered LB structures. Due to the observed drug effects, we further suggest that PM provides an appropriate way to study unspecific drug interactions with alveolar cells and even drug-membrane interactions in general. Copyright © 2018 Elsevier B.V. All rights reserved.

Pulmonary CT findings in acute mercury vapour exposure

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Hashimoto, Manabu; Sato, Kimihiko; Heianna, Jyouiti; Hirano, Yoshinori; Omachi, Kohiti; Izumi, Jyunichi; Watarai, Jiro

2001-01-01

AIM: We describe the pulmonary computed tomography (CT) findings in acute mercury poisoning. MATERIALS AND METHODS: Initial (n= 8) and follow-up (n= 6) chest CT examinations in eight patients exposed to mercury vapour while cutting pipes in a sulphuric acid plant were reviewed. Of the eight patients, two were asymptomatic and had normal CT results, two were asymptomatic but had abnormalities on CT, and four had both acute symptoms and positive CT results. The patients were all men whose ages ranged from 37 to 54 years (mean, 49 years). RESULTS: Poorly defined nodules were present in five of six patients with positive CT findings, present alone in two patients or as part of a mixed pattern in three. They were random in distribution. Alveolar consolidation (n= 3) and areas of ground-glass opacity (n= 4) were observed and were more prominent in the most severely affected patients with the highest blood and urine level of mercury, predominantly in the upper and/or middle zone. These abnormal findings on CT resolved with (n= 1) or without (n= 5) steroid therapy. Pathological findings (n= 1) demonstrated acute interstitial changes predominantly with oedema. CONCLUSION: We report CT findings in eight patients acutely exposed to mercury vapour. The pulmonary injury was reversible on CT in these cases. Hashimoto, M. (2001)

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

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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

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)

Contribution of pulmonary emphysema to functional impairment in patients with severe chronic obstructive pulmonary disease. A high-resolution CT study

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Zompatori, M.; Fasano, L.; Battista, G.

1999-01-01

The purpose of the paper is to investigate whether high-resolution CT (HRCT) can detect the subjects with massive emphysematous destruction in a group of patients with severe chronic obstructive pulmonary disease (COPD) and therefor be of help in selecting the candidates to surgical lung volume reduction. Have been examined 40 former smokers with severe COPD (FEV 1 ≤40% of the predicted value, with no major improvement after inhalation of bronchodilators). The emphysema extent score was significantly correlated with the hematocrit value and Tiffeneau index (p 1 was significantly correlated with emphysema extent (p [it

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

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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.

Lung lecithin synthesis in Syrian hamster lung: effect of pulmonary lavage

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Henderson, R.F.

1976-01-01

A single pulmonary lavage in the Syrian hamster stimulated the synthesis of both the surface-active dipalmitoyl lecithin and its proposed precursor, the unsaturated lecithins. The rate of breakdown of the two types of lung lecithin did not appear to be greatly affected by the lavage. The data were consistent with the view that alveolar lecithins are secreted by the tissue into the alveoli and that unsaturated lecithins are the precursors of dipalmitoyl lecithin

Nicardipine-induced acute pulmonary edema: a rare but severe complication of tocolysis.

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Serena, Claire; Begot, Emmanuelle; Cros, Jérôme; Hodler, Charles; Fedou, Anne Laure; Nathan-Denizot, Nathalie; Clavel, Marc

2014-01-01

We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU) each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative.

Nicardipine-Induced Acute Pulmonary Edema: A Rare but Severe Complication of Tocolysis

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Claire Serena