WorldWideScience

Sample records for chronic airway lung

  1. Patient-Specific Airway Wall Remodeling in Chronic Lung Disease.

    Science.gov (United States)

    Eskandari, Mona; Kuschner, Ware G; Kuhl, Ellen

    2015-10-01

    Chronic lung disease affects more than a quarter of the adult population; yet, the mechanics of the airways are poorly understood. The pathophysiology of chronic lung disease is commonly characterized by mucosal growth and smooth muscle contraction of the airways, which initiate an inward folding of the mucosal layer and progressive airflow obstruction. Since the degree of obstruction is closely correlated with the number of folds, mucosal folding has been extensively studied in idealized circular cross sections. However, airflow obstruction has never been studied in real airway geometries; the behavior of imperfect, non-cylindrical, continuously branching airways remains unknown. Here we model the effects of chronic lung disease using the nonlinear field theories of mechanics supplemented by the theory of finite growth. We perform finite element analysis of patient-specific Y-branch segments created from magnetic resonance images. We demonstrate that the mucosal folding pattern is insensitive to the specific airway geometry, but that it critically depends on the mucosal and submucosal stiffness, thickness, and loading mechanism. Our results suggests that patient-specific airway models with inherent geometric imperfections are more sensitive to obstruction than idealized circular models. Our models help to explain the pathophysiology of airway obstruction in chronic lung disease and hold promise to improve the diagnostics and treatment of asthma, bronchitis, chronic obstructive pulmonary disease, and respiratory failure. PMID:25821112

  2. Hemodynamic effects of nasal continuous positive airway pressure in preterm infants with evolving chronic lung disease, a crossover randomized trial.

    Science.gov (United States)

    Beker, Friederike; Rogerson, Sheryle R; Hooper, Stuart B; Sehgal, Arvind; Davis, Peter G

    2015-02-01

    Previous studies suggest that high airway pressure may compromise cardiac output. We investigated the effect of 3 nasal continuous positive airway pressure levels on cardiac output in preterm infants with evolving chronic lung disease. We found that brief changes in continuous positive airway pressure did not affect cardiac output. PMID:25454930

  3. Noninvasive Investigations for the Early Detection of Chronic Airways Dysfunction Following Lung Transplantation

    OpenAIRE

    Cook, Richard C.; Guy Fradet; Nestor L Muller; Daniel F Worsley; David Ostrow; Levy, Robert D

    2003-01-01

    BACKGROUND: The diagnosis of chronic rejection after lung transplantation is limited by the lack of a reliable test to detect airways disease early.OBJECTIVES: To determine whether maximum midexpiratory flow (MMEF), or changes on high resolution computed tomography (HRCT) or ventilation/perfusion lung (V/Q) scans are sensitive and specific for early detection of bronchiolitis obliterans syndrome (BOS; forced expiratory volume in 1 s [FEV1] less than 80% post-transplant baseline) by evaluating...

  4. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde Marie; Pedersen, Jesper Holst; Dirksen, Asger; Petersen, Jens; De Bruijne, Marleen

    2013-01-01

    airway distensibility, defined as the ratio of relative change in lumen diameter to the relative change in total lung volume (TLV) divided by predicted total lung capacity (pTLC) . Methods – We included 1900 participants from the Danish Lung Cancer Screening Trial (DLCST); all randomized to annual low......-dose CT for a period of 5 years (table 1). Images were reconstructed both with high contrast resolution (3 mm, kernel C) for emphysema analysis and with high spatial resolution (1 mm, kernel D) for airway analysis. Images were analysed by in-house developed software designed to segment lungs and localize......), 10-20% (mild), 20%-30% (moderate) or >30% (severe). Spirometry was performed annually and participants were divided into severity groups according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Data were analysed in a mixed effects regression model with log(airway lumen...

  5. The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation.

    Science.gov (United States)

    Grabiec, Aleksander M; Hussell, Tracy

    2016-07-01

    Acute and chronic inflammatory responses in the lung are associated with the accumulation of large quantities of immune and structural cells undergoing apoptosis, which need to be engulfed by phagocytes in a process called 'efferocytosis'. Apoptotic cell recognition and removal from the lung is mediated predominantly by airway macrophages, though immature dendritic cells and non-professional phagocytes, such as epithelial cells and mesenchymal cells, can also display this function. Efficient clearance of apoptotic cells from the airways is essential for successful resolution of inflammation and the return to lung homeostasis. Disruption of this process leads to secondary necrosis of accumulating apoptotic cells, release of necrotic cell debris and subsequent uncontrolled inflammatory activation of the innate immune system by the released 'damage associated molecular patterns' (DAMPS). To control the duration of the immune response and prevent autoimmune reactions, anti-inflammatory signalling cascades are initiated in the phagocyte upon apoptotic cell uptake, mediated by a range of receptors that recognise specific phospholipids or proteins externalised on, or secreted by, the apoptotic cell. However, prolonged activation of apoptotic cell recognition receptors, such as the family of receptor tyrosine kinases Tyro3, Axl and MerTK (TAM), may delay or prevent inflammatory responses to subsequent infections. In this review, we will discuss recent advances in our understanding of the mechanism controlling apoptotic cell recognition and removal from the lung in homeostasis and during inflammation, the contribution of defective efferocytosis to chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease, asthma and cystic fibrosis, and implications of the signals triggered by apoptotic cells in the susceptibility to pulmonary microbial infections. PMID:26957481

  6. Airway oxidative stress in chronic cough

    OpenAIRE

    Koskela, Heikki O; Purokivi, Minna K

    2013-01-01

    Background The mechanisms of chronic cough are unclear. Many reactive oxygen species affect airway sensory C-fibres which are capable to induce cough. Several chronic lung diseases are characterised by cough and oxidative stress. In asthma, an association between the cough severity and airway oxidative stress has been demonstrated. The present study was conducted to investigate whether airway oxidative stress is associated with chronic cough in subjects without chronic lung diseases. Methods ...

  7. The Effects of Tumstatin on Vascularity, Airway Inflammation and Lung Function in an Experimental Sheep Model of Chronic Asthma

    Science.gov (United States)

    Van der Velden, Joanne; Harkness, Louise M.; Barker, Donna M.; Barcham, Garry J.; Ugalde, Cathryn L.; Koumoundouros, Emmanuel; Bao, Heidi; Organ, Louise A.; Tokanovic, Ana; Burgess, Janette K.; Snibson, Kenneth J.

    2016-01-01

    Tumstatin, a protein fragment of the alpha-3 chain of Collagen IV, is known to be significantly reduced in the airways of asthmatics. Further, there is evidence that suggests a link between the relatively low level of tumstatin and the induction of angiogenesis and inflammation in allergic airway disease. Here, we show that the intra-segmental administration of tumstatin can impede the development of vascular remodelling and allergic inflammatory responses that are induced in a segmental challenge model of experimental asthma in sheep. In particular, the administration of tumstatin to lung segments chronically exposed to house dust mite (HDM) resulted in a significant reduction of airway small blood vessels in the diameter range 10+–20 μm compared to controls. In tumstatin treated lung segments after HDM challenge, the number of eosinophils was significantly reduced in parenchymal and airway wall tissues, as well as in the bronchoalveolar lavage fluid. The expression of VEGF in airway smooth muscle was also significantly reduced in tumstatin-treated segments compared to control saline-treated segments. Allergic lung function responses were not attenuated by tumstatin administration in this model. The data are consistent with the concept that tumstatin can act to suppress vascular remodelling and inflammation in allergic airway disease. PMID:27199164

  8. The Effects of Tumstatin on Vascularity, Airway Inflammation and Lung Function in an Experimental Sheep Model of Chronic Asthma.

    Science.gov (United States)

    Van der Velden, Joanne; Harkness, Louise M; Barker, Donna M; Barcham, Garry J; Ugalde, Cathryn L; Koumoundouros, Emmanuel; Bao, Heidi; Organ, Louise A; Tokanovic, Ana; Burgess, Janette K; Snibson, Kenneth J

    2016-01-01

    Tumstatin, a protein fragment of the alpha-3 chain of Collagen IV, is known to be significantly reduced in the airways of asthmatics. Further, there is evidence that suggests a link between the relatively low level of tumstatin and the induction of angiogenesis and inflammation in allergic airway disease. Here, we show that the intra-segmental administration of tumstatin can impede the development of vascular remodelling and allergic inflammatory responses that are induced in a segmental challenge model of experimental asthma in sheep. In particular, the administration of tumstatin to lung segments chronically exposed to house dust mite (HDM) resulted in a significant reduction of airway small blood vessels in the diameter range 10(+)-20 μm compared to controls. In tumstatin treated lung segments after HDM challenge, the number of eosinophils was significantly reduced in parenchymal and airway wall tissues, as well as in the bronchoalveolar lavage fluid. The expression of VEGF in airway smooth muscle was also significantly reduced in tumstatin-treated segments compared to control saline-treated segments. Allergic lung function responses were not attenuated by tumstatin administration in this model. The data are consistent with the concept that tumstatin can act to suppress vascular remodelling and inflammation in allergic airway disease. PMID:27199164

  9. Sub-chronic lung inflammation after airway exposures to Bacillus thuringiensis biopesticides in mice

    DEFF Research Database (Denmark)

    Barfod, Kenneth K; Poulsen, Steen Seier; Hammer, Maria;

    2010-01-01

    The aim of the present study was to assess possible health effects of airway exposures to Bacillus thuringiensis (Bt) based biopesticides in mice. Endpoints were lung inflammation evaluated by presence of inflammatory cells in bronchoalveolar lavage fluid (BALF), clearance of bacteria from the lung...

  10. Effect of lung volume on airway luminal area assessed by computed tomography in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Kenta Kambara

    Full Text Available BACKGROUND: Although airway luminal area (Ai is affected by lung volume (LV, how is not precisely understood. We hypothesized that the effect of LV on Ai would differ by airway generation, lung lobe, and chronic obstructive pulmonary disease (COPD severity. METHODS: Sixty-seven subjects (15 at risk, 18, 20, and 14 for COPD stages 1, 2, and 3 underwent pulmonary function tests and computed tomography scans at full inspiration and expiration (at functional residual capacity. LV and eight selected identical airways were measured in the right lung. Ai was measured at the mid-portion of the 3(rd, the segmental bronchus, to 6(th generation of the airways, leading to 32 measurements per subject. RESULTS: The ratio of expiratory to inspiratory LV (LV E/I ratio and Ai (Ai E/I ratio was defined for evaluation of changes. The LV E/I ratio increased as COPD severity progressed. As the LV E/I ratio was smaller, the Ai E/I ratio was smaller at any generation among the subjects. Overall, the Ai E/I ratios were significantly smaller at the 5(th (61.5% and 6(th generations (63.4% and than at the 3(rd generation (73.6%, p<0.001 for each, and also significantly lower in the lower lobe than in the upper or middle lobe (p<0.001 for each. And, the Ai E/I ratio decreased as COPD severity progressed only when the ratio was corrected by the LV E/I ratio (at risk v.s. stage 3 p<0.001, stage 1 v.s. stage 3 p<0.05. CONCLUSIONS: From full inspiration to expiration, the airway luminal area shrinks more at the distal airways compared with the proximal airways and in the lower lobe compared with the other lobes. Generally, the airways shrink more as COPD severity progresses, but this phenomenon becomes apparent only when lung volume change from inspiration to expiration is taken into account.

  11. A Dynamic Bronchial Airway Gene Expression Signature of Chronic Obstructive Pulmonary Disease and Lung Function Impairment

    NARCIS (Netherlands)

    Steiling, Katrina; van den Berge, Maarten; Hijazi, Kahkeshan; Florido, Roberta; Campbell, Joshua; Liu, Gang; Xiao, Ji; Zhang, Xiaohui; Duclos, Grant; Drizik, Eduard; Si, Huiqing; Perdomo, Catalina; Dumont, Charles; Coxson, Harvey O.; Alekseyev, Yuriy O.; Sin, Don; Pare, Peter; Hogg, James C.; McWilliams, Annette; Hiemstra, Pieter S.; Sterk, Peter J.; Timens, Wim; Chang, Jeffrey T.; Sebastiani, Paola; O'Connor, George T.; Bild, Andrea H.; Postma, Dirkje S.; Lam, Stephen; Spira, Avrum; Lenburg, Marc E.

    2013-01-01

    Rationale Molecular phenotyping of chronic obstructive pulmonary disease (COPD) has been impeded in part by the difficulty in obtaining lung tissue samples from individuals with impaired lung function. Objectives: We sought to determine whether COPD-associated processes are reflected in gene express

  12. The effect of increased lung volume in chronic obstructive pulmonary disease on upper airway obstruction during sleep.

    Science.gov (United States)

    Biselli, Paolo; Grossman, Peter R; Kirkness, Jason P; Patil, Susheel P; Smith, Philip L; Schwartz, Alan R; Schneider, Hartmut

    2015-08-01

    Patients with chronic obstructive pulmonary disease (COPD) exhibit increases in lung volume due to expiratory airflow limitation. Increases in lung volumes may affect upper airway patency and compensatory responses to inspiratory flow limitation (IFL) during sleep. We hypothesized that COPD patients have less collapsible airways inversely proportional to their lung volumes, and that the presence of expiratory airflow limitation limits duty cycle responses to defend ventilation in the presence of IFL. We enrolled 18 COPD patients and 18 controls, matched by age, body mass index, sex, and obstructive sleep apnea disease severity. Sleep studies, including quantitative assessment of airflow at various nasal pressure levels, were conducted to determine upper airway mechanical properties [passive critical closing pressure (Pcrit)] and for quantifying respiratory timing responses to experimentally induced IFL. COPD patients had lower passive Pcrit than their matched controls (COPD: -2.8 ± 0.9 cmH2O; controls: -0.5 ± 0.5 cmH2O, P = 0.03), and there was an inverse relationship of subject's functional residual capacity and passive Pcrit (-1.7 cmH2O/l increase in functional residual capacity, r(2) = 0.27, P = 0.002). In response to IFL, inspiratory duty cycle increased more (P = 0.03) in COPD patients (0.40 to 0.54) than in controls (0.41 to 0.51) and led to a marked reduction in expiratory time from 2.5 to 1.5 s (P hyperinflation due to a marked reduction in expiratory time. PMID:26048975

  13. Interpretation of bronchodilator response in patients with obstructive airways disease. The Dutch Chronic Non-Specific Lung Disease (CNSLD) Study Group.

    OpenAIRE

    Brand, P L; Quanjer, P. H.; Postma, D. S.; Kerstjens, H.A.; Koëter, G. H.; Dekhuijzen, P. N.; Sluiter, H J

    1992-01-01

    BACKGROUND: There is no agreement on how a bronchodilator response should be expressed. Ideally, the index used should be able to distinguish asthma from chronic obstructive lung disease and be independent of initial FEV1. METHODS: Two hundred and seventy four adults (aged 18-60 years) outpatients with obstructive airways disease were studied. Patients were divided into syndrome groups on the basis of a standardised history: asthma (n = 99), asthmatic bronchitis (n = 88), and chronic obstruct...

  14. Could prominent airway-centered fibroblast foci in lung biopsies predict underlying chronic microaspiration in idiopathic pulmonary fibrosis patients?

    Science.gov (United States)

    Bois, Melanie C; Hu, Xiaowen; Ryu, Jay H; Yi, Eunhee S

    2016-07-01

    Chronic occult aspiration of small droplets (microaspiration) due to gastroesophageal reflux disease (GERD) and/or hiatal hernia is postulated to be a contributing factor in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Usual interstitial pneumonia (UIP) is the histopathologic correlate of IPF. We hypothesized that chronic microaspiration may manifest as prominent airway-centered fibroblastic foci (FFs) in IPF. UIP cases diagnosed by wedge biopsies over a 6-year period (2006-2011) were identified and scored (1-3) for the prominence of airway-centered FFs by 2 authors blinded for clinical history. Relevant clinical information was obtained. Thirty-seven patients (22 men) were diagnosed with IPF by multidisciplinary approach. Thirteen cases (35.1%) demonstrated high airway-centered FF score (score 3). Twenty (54.1%) patients carried a clinical diagnosis of GERD, and 3 patients (8.1%) had hiatal hernia. High airway-centered FF score was significantly associated with hiatal hernia diagnosis (P=.037) but not with a diagnosis of GERD or the use of proton pump inhibitors/histamine-2 receptor antagonists. High airway-centered FF score was associated with airway-centered acute inflammation (P=.028) and peribronchiolar granulomas (P=.042). In summary, IPF cases with hiatal hernia were more likely to have a prominent airway-centered FF. Given the strong association between hiatal hernia and GERD and their risk for developing chronic microaspiration, the prominent airway-centered FF in UIP might predict the presence of chronic microaspiration, acknowledging that GERD and proton pump inhibitor/histamine-2 receptor antagonist use failed to demonstrate a significant association. Larger studies are warranted for further investigation. PMID:26980038

  15. Impulse oscillometry in COPD: identification of measurements related to airway obstruction, airway conductance and lung volumes

    DEFF Research Database (Denmark)

    Kolsum, Umme; Borrill, Zoë; Roy, Kay; Starkey, Cerys; Vestbo, Jørgen; Houghton, Catherine; Singh, Dave

    2008-01-01

    BACKGROUND: Impulse oscillometry system (IOS) assesses pulmonary resistance and reactance. We set out to investigate which IOS measurements are related to airflow obstruction, airway conductance and lung volumes in chronic obstructive pulmonary disease (COPD). METHODS: Ninety-four COPD patients...

  16. Dysfunctional lung anatomy and small airways degeneration in COPD

    Directory of Open Access Journals (Sweden)

    Burgel PR

    2013-01-01

    Full Text Available Clémence Martin, Justine Frija, Pierre-Régis BurgelDepartment of Respiratory Medicine, Cochin Hospital, AP-HP and Université Paris Descartes, Sorbonne Paris Cité, Paris, FranceAbstract: Chronic obstructive pulmonary disease (COPD is characterized by incompletely reversible airflow obstruction. Direct measurement of airways resistance using invasive techniques has revealed that the site of obstruction is located in the small conducting airways, ie, bronchioles with a diameter < 2 mm. Anatomical changes in these airways include structural abnormalities of the conducting airways (eg, peribronchiolar fibrosis, mucus plugging and loss of alveolar attachments due to emphysema, which result in destabilization of these airways related to reduced elastic recoil. The relative contribution of structural abnormalities in small conducting airways and emphysema has been a matter of much debate. The present article reviews anatomical changes and inflammatory mechanisms in small conducting airways and in the adjacent lung parenchyma, with a special focus on recent anatomical and imaging data suggesting that the initial event takes place in the small conducting airways and results in a dramatic reduction in the number of airways, together with a reduction in the cross-sectional area of remaining airways. Implications of these findings for the development of novel therapies are briefly discussed.Keywords: emphysema, small airways disease, airway mucus, innate immunity, adaptive immunity

  17. PPARγ as a Potential Target to Treat Airway Mucus Hypersecretion in Chronic Airway Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Yongchun Shen

    2012-01-01

    Full Text Available Airway mucus hypersecretion (AMH is a key pathophysiological feature of chronic airway inflammatory diseases such as bronchial asthma, cystic fibrosis, and chronic obstructive pulmonary disease. AMH contributes to the pathogenesis of chronic airway inflammatory diseases, and it is associated with reduced lung function and high rates of hospitalization and mortality. It has been suggested that AMH should be a target in the treatment of chronic airway inflammatory diseases. Recent evidence suggests that a key regulator of airway inflammation, hyperresponsiveness, and remodeling is peroxisome proliferator-activated receptor gamma (PPARγ, a ligand-activated transcription factor that regulates adipocyte differentiation and lipid metabolism. PPARγ is expressed in structural, immune, and inflammatory cells in the lung. PPARγ is involved in mucin production, and PPARγ agonists can inhibit mucin synthesis both in vitro and in vivo. These findings suggest that PPARγ is a novel target in the treatment of AMH and that further work on this transcription factor may lead to new therapies for chronic airway inflammatory diseases.

  18. Airway vascular reactivity and vascularisation in human chronic airway disease

    NARCIS (Netherlands)

    Bailey, Simon R; Boustany, Sarah; Burgess, Janette K; Hirst, Stuart J; Sharma, Hari S; Simcock, David E; Suravaram, Padmini R; Weckmann, Markus

    2009-01-01

    Altered bronchial vascular reactivity and remodelling including angiogenesis are documented features of asthma and other chronic inflammatory airway diseases. Expansion of the bronchial vasculature under these conditions involves both functional (vasodilation, hyperperfusion, increased microvascular

  19. Association between lung function and airway wall density

    Science.gov (United States)

    Leader, J. Ken; Zheng, Bin; Fuhrman, Carl R.; Tedrow, John; Park, Sang C.; Tan, Jun; Pu, Jiantao; Drescher, John M.; Gur, David; Sciurba, Frank C.

    2009-02-01

    Computed tomography (CT) examination is often used to quantify the relation between lung function and airway remodeling in chronic obstructive pulmonary disease (COPD). In this preliminary study, we examined the association between lung function and airway wall computed attenuation ("density") in 200 COPD screening subjects. Percent predicted FVC (FVC%), percent predicted FEV1 (FEV1%), and the ratio of FEV1 to FVC as a percentage (FEV1/FVC%) were measured post-bronchodilator. The apical bronchus of the right upper lobe was manually selected from CT examinations for evaluation. Total airway area, lumen area, wall area, lumen perimeter and wall area as fraction of the total airway area were computed. Mean HU (meanHU) and maximum HU (maxHU) values were computed across pixels assigned membership in the wall and with a HU value greater than -550. The Pearson correlation coefficients (PCC) between FVC%, FEV1%, and FEV1/FVC% and meanHU were -0.221 (p = 0.002), -0.175 (p = 0.014), and -0.110 (p = 0.123), respectively. The PCCs for maxHU were only significant for FVC%. The correlations between lung function and the airway morphometry parameters were slightly stronger compared to airway wall density. MeanHU was significantly correlated with wall area (PCC = 0.720), airway area (0.498) and wall area percent (0.611). This preliminary work demonstrates that airway wall density is associated with lung function. Although the correlations in our study were weaker than a recent study, airway wall density initially appears to be an important parameter in quantitative CT analysis of COPD.

  20. Azithromycin and the Treatment of Lymphocytic Airway Inflammation After Lung Transplantation

    OpenAIRE

    Vos, Rein; Verleden, S. E.; Ruttens, D.; Vandermeulen, E; Bellon, H.; Neyrinck, A.; Van Raemdonck, D. E.; Yserbyt, J.; Dupont, L J; Verbeken, E.K.; Moelants, E.; Mortier, A.; Proost, P.; Schols, D; Cox, B.

    2014-01-01

    Lymphocytic airway inflammation is a major risk factor for chronic lung allograft dysfunction, for which there is no established treatment. We investigated whether azithromycin could control lymphocytic airway inflammation and improve allograft function. Fifteen lung transplant recipients demonstrating acute allograft dysfunction due to isolated lymphocytic airway inflammation were prospectively treated with azithromycin for at least 6 months (NCT01109160). Spirometry (FVC, FEV1, FEF25-75, Ti...

  1. Anastomotic Airway Complications after Lung Transplantation

    OpenAIRE

    Cho, Eun Na; Haam, Suk Jin; Kim, Song Yee; Chang, Yoon Soo; Paik, Hyo Chae

    2015-01-01

    Purpose Anastomotic airway complications are a major cause of morbidity and mortality after lung transplantation (LTx). In this study, the authors identified types and clinical outcomes of airway complications after LTx. Materials and Methods All bronchial anastomotic complications were analyzed in a total of 94 LTx cases involving 90 recipients who underwent surgery between July 2006 and May 2014. Fifteen LTx cases (14 recipients) with incomplete medical records for fiberoptic bronchoscopy (...

  2. Influence of Chronic Sinusitis and Nasal Polyp on the Lower Airway of Subjects Without Lower Airway Diseases

    OpenAIRE

    Lee, Suh-Young; Yoon, Soon Ho; Song, Woo-Jung; Lee, So-Hee; Kang, Hye-Ryun; Kim, Sun-Sin; Cho, Sang-Heon

    2014-01-01

    Purpose Upper and lower respiratory tract pathologies are believed to be interrelated; however, the impact of upper airway inflammation on lung function in subjects without lung disease has not been evaluated. This study investigated the association of CT finding suggesting chronic sinusitis and lung function in healthy subjects without lung disease. Methods This was a retrospective study of prospectively collected data from 284 subjects who underwent a pulmonary function test, bronchial prov...

  3. Clinical significance of epithelial mesenchymal transition (EMT) in chronic obstructive pulmonary disease (COPD): potential target for prevention of airway fibrosis and lung cancer

    OpenAIRE

    Sohal, Sukhwinder Singh; Mahmood, Malik Quasir; Walters, Eugene Haydn

    2014-01-01

    Unfortunately, the research effort directed into chronic obstructive pulmonary disease (COPD) has been disproportionately weak compared to its social importance, and indeed it is the least researched of all common chronic conditions. Tobacco smoking is the major etiological factor. Only 25% of smokers will develop “classic” COPD; in these vulnerable individuals the progression of airways disease to symptomatic COPD occurs over two or more decades. We know surprisingly little about the pathobi...

  4. Mast cells in airway diseases and interstitial lung disease.

    Science.gov (United States)

    Cruse, Glenn; Bradding, Peter

    2016-05-01

    Mast cells are major effector cells of inflammation and there is strong evidence that mast cells play a significant role in asthma pathophysiology. There is also a growing body of evidence that mast cells contribute to other inflammatory and fibrotic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. This review discusses the role that mast cells play in airway diseases and highlights how mast cell microlocalisation within specific lung compartments and their cellular interactions are likely to be critical for their effector function in disease. PMID:25959386

  5. Airway inflammation in severe chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    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

  6. Endoluminal bronchial valves: a replacement for lung volume reduction surgery (LVRS) in chronic obstructive airways disease (COAD)?

    International Nuclear Information System (INIS)

    Full text: The benefit of LVRS in COAD is controversial because of a high complication rate. A potentially effective less invasive method may be endoluminal placement of one-way valves to block air entry and thus collapse affected lung zones. Our study assessed the physiological effects of this procedure. Three patients with severe COAD suitable for LVRS, underwent this procedure to both upper lobe main bronchi. Assessment included pre-and post-operative Tc-99m Technegas and quantitative Tc-99m macroaggregated albumin (MAA) studies, and also measurement of regional ventilation dynamics using Xe-133, ( 80 seconds wash-in / equilibration and a 3.5 minutes wash-out phase). The index of wash-in was Xe-133 counts at 20 sees /Xe-133 counts at 80 seconds. In all 6 treated upper lobes in patients with COAD substantial ventilation and perfusion persisted, and no radiographic collapse occurred. % perfusion to upper lung zones fell slightly from 27+12% to 21+8% (mean +SD): (P<0.05). The decreased wash-in index to the treated lobes shows a significant effect of the endoluminal valve. The increased washout rate from the lower lobes suggests therapeutic benefit. However preserved volume, ventilation and perfusion in the treated lobes suggest continuing aeration via interlobar ventilatory connections with the untreated lobes. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  7. Effect of mesenchymal stem cells on inhibiting airway remodeling and airway inflammation in chronic asthma.

    Science.gov (United States)

    Ge, Xiahui; Bai, Chong; Yang, Jianming; Lou, Guoliang; Li, Qiang; Chen, Ruohua

    2013-07-01

    Previous studies proved that bone marrow-derived mesenchymal stem cells (BMSCs) could improve a variety of immune-mediated disease by its immunomodulatory properties. In this study, we investigated the effect on airway remodeling and airway inflammation by administrating BMSCs in chronic asthmatic mice. Forty-eight female BALB/c mice were randomly distributed into PBS group, BMSCs treatment group, BMSCs control group, and asthmatic group. The levels of cytokine and immunoglobulin in serum and bronchoalveolar lavage fluid were detected by enzyme-linked immunosorbent assay. The number of CD4(+) CD25(+) regulatory T cells and morphometric analysis was determined by flow cytometry, hematoxylin-eosin, immunofluorescence staining, periodic-acid Schiff, and masson staining, respectively. We found that airway remodeling and airway inflammation were evident in asthmatic mice. Moreover, low level of IL-12 and high levels of IL-13, IL-4, OVA-specific IgG1, IgE, and IgG2a and the fewer number of CD4(+) CD25(+) regulatory T cells were present in asthmatic group. However, transplantation of BMSCs significantly decreased airway inflammation and airway remodeling and level of IL-4, OVA-specific IgE, and OVA-specific IgG1, but elevated level of IL-12 and the number of CD4 + CD25 + regulatory T cells in asthma (P cells in asthma, but not contribution to lung regeneration. PMID:23334934

  8. Mesenchymal stem cells suppress lung inflammation and airway remodeling in chronic asthma rat model via PI3K/Akt signaling pathway

    OpenAIRE

    Lin, Hai-Yan; Xu, Lei; Xie, Shuan-shuan; Yu, Fei; Hu, Hai-Yang; Song, Xiao-lian; Wang, Chang-Hui

    2015-01-01

    Background: Mesenchymal stem cells (MSCs) came out to attract wide attention and had become one of the hotspots of most diseases’ research in decades. But at present, the mechanisms of how MSCs work on chronic asthma remain undefined. Our study aims at verifying whether MSCs play a role in preventing inflammation and airway remodeling via PI3K/AKT signaling pathway in the chronic asthma rats model. Methods: First, an ovalbumin (OVA)-induced asthma model was built. MSCs were administered to ov...

  9. Lung and vascular function during chronic severe pulmonary ischemia

    OpenAIRE

    Elizabeth M Wagner; Jenkins, John; Perino, Maria Grazia; Sukkar, Adlah; Mitzner, Wayne

    2010-01-01

    Bronchial vascular angiogenesis takes place in a variety of lung inflammatory conditions such as asthma, cystic fibrosis, lung cancer, and chronic pulmonary thromboembolic disease. However, it is unclear whether neovascularization is predominantly appropriate and preserves lung tissue or whether it contributes further to lung pathology through edema formation and inflammation. In the present study we examined airway and lung parenchymal function 14 days after left pulmonary artery ligation. I...

  10. Mesenchymal stem cells and serelaxin synergistically abrogate established airway fibrosis in an experimental model of chronic allergic airways disease.

    Science.gov (United States)

    Royce, Simon G; Shen, Matthew; Patel, Krupesh P; Huuskes, Brooke M; Ricardo, Sharon D; Samuel, Chrishan S

    2015-11-01

    This study determined if the anti-fibrotic drug, serelaxin (RLN), could augment human bone marrow-derived mesenchymal stem cell (MSC)-mediated reversal of airway remodeling and airway hyperresponsiveness (AHR) associated with chronic allergic airways disease (AAD/asthma). Female Balb/c mice subjected to the 9-week model of ovalbumin (OVA)-induced chronic AAD were either untreated or treated with MSCs alone, RLN alone or both combined from weeks 9-11. Changes in airway inflammation (AI), epithelial thickness, goblet cell metaplasia, transforming growth factor (TGF)-β1 expression, myofibroblast differentiation, subepithelial and total lung collagen deposition, matrix metalloproteinase (MMP) expression, and AHR were then assessed. MSCs alone modestly reversed OVA-induced subepithelial and total collagen deposition, and increased MMP-9 levels above that induced by OVA alone (all p<0.05 vs OVA group). RLN alone more broadly reversed OVA-induced epithelial thickening, TGF-β1 expression, myofibroblast differentiation, airway fibrosis and AHR (all p<0.05 vs OVA group). Combination treatment further reversed OVA-induced AI and airway/lung fibrosis compared to either treatment alone (all p<0.05 vs either treatment alone), and further increased MMP-9 levels. RLN appeared to enhance the therapeutic effects of MSCs in a chronic disease setting; most likely a consequence of the ability of RLN to limit TGF-β1-induced matrix synthesis complemented by the MMP-promoting effects of MSCs. PMID:26426509

  11. Th17 Responses in Chronic Allergic Airway Inflammation Abrogate Regulatory T cell-mediated Tolerance and Contribute to Airway Remodeling

    OpenAIRE

    Zhao, Jingyue; Lloyd, Clare M.; Noble, Alistair

    2012-01-01

    The role of Th17 responses in airway remodeling in asthma is currently unknown. We demonstrate that both parenteral and mucosal allergen sensitization followed by allergen inhalation leads to Th17-biased lung immune responses. Unlike Th17 cells generated in vitro, lung Th17 cells did not produce TNF-α or IL-22. Eosinophilia predominated in acute inflammation while neutrophilia and IL-17 increased in chronic disease. Allergen-induced tolerance involved Foxp3, Helios and GARP expressing regulat...

  12. Airflow, transport and regional deposition of aerosol particles during chronic bronchitis of human central airways.

    Science.gov (United States)

    Farkhadnia, Fouad; Gorji, Tahereh B; Gorji-Bandpy, Mofid

    2016-03-01

    In the present study, the effects of airway blockage in chronic bronchitis disease on the flow patterns and transport/deposition of micro-particles in a human symmetric triple bifurcation lung airway model, i.e., Weibel's generations G3-G6 was investigated. A computational fluid and particle dynamics model was implemented, validated and applied in order to evaluate the airflow and particle transport/deposition in central airways. Three breathing patterns, i.e., resting, light activity and moderate exercise, were considered. Using Lagrangian approach for particle tracking and random particle injection, an unsteady particle tracking method was performed to simulate the transport and deposition of micron-sized aerosol particles in human central airways. Assuming laminar, quasi-steady, three-dimensional air flow and spherical non-interacting particles in sequentially bifurcating rigid airways, airflow patterns and particle transport/deposition in healthy and chronic bronchitis (CB) affected airways were evaluated and compared. Comparison of deposition efficiency (DE) of aerosols in healthy and occluded airways showed that at the same flow rates DE values are typically larger in occluded airways. While in healthy airways, particles deposit mainly around the carinal ridges and flow dividers-due to direct inertial impaction, in CB affected airways they deposit mainly on the tubular surfaces of blocked airways because of gravitational sedimentation. PMID:26541595

  13. Novel therapeutic strategies for lung disorders associated with airway remodelling and fibrosis.

    Science.gov (United States)

    Royce, Simon G; Moodley, Yuben; Samuel, Chrishan S

    2014-03-01

    Inflammatory cell infiltration, cytokine release, epithelial damage, airway/lung remodelling and fibrosis are central features of inflammatory lung disorders, which include asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome and idiopathic pulmonary fibrosis. Although the lung has some ability to repair itself from acute injury, in the presence of ongoing pathological stimuli and/or insults that lead to chronic disease, it no longer retains the capacity to heal, resulting in fibrosis, the final common pathway that causes an irreversible loss of lung function. Despite inflammation, genetic predisposition/factors, epithelial-mesenchymal transition and mechanotransduction being able to independently contribute to airway remodelling and fibrosis, current therapies for inflammatory lung diseases are limited by their ability to only target the inflammatory component of the disease without having any marked effects on remodelling (epithelial damage and fibrosis) that can cause lung dysfunction independently of inflammation. Furthermore, as subsets of patients suffering from these diseases are resistant to currently available therapies (such as corticosteroids), novel therapeutic approaches are required to combat all aspects of disease pathology. This review discusses emerging therapeutic approaches, such as trefoil factors, relaxin, histone deacetylase inhibitors and stem cells, amongst others that have been able to target airway inflammation and airway remodelling while improving related lung dysfunction. A better understanding of the mode of action of these therapies and their possible combined effects may lead to the identification of their clinical potential in the setting of lung disease, either as adjunct or alternative therapies to currently available treatments. PMID:24513131

  14. Spirometric abnormalities associated with chronic bronchitis, asthma, and airway hyperresponsiveness among boilermaker construction workers

    Energy Technology Data Exchange (ETDEWEB)

    Hauser, R.; Eisen, E,A,; Pothier, L,; Lewis, D,; Bledsoe, T,; Christiani, D.C. [Harvard University, Boston, MA (United States). School of Public Health

    2002-06-01

    In a 2-year longitudinal study of boilermaker construction workers, authors found a significant association between working at oil-fired, coal-fired, and gas-fired industries during the past year and reduced lung function. In the present study, authors investigated whether chronic bronchitis, asthma, or baseline methacholine airway responsiveness can explain the heterogeneity in lung function response to boilermaker work. Exposure was assessed with a work history questionnaire. Spirometry was performed annually to assess lung function. A generalized estimating equation approach was used to account for the repeated-measures design. One hundred eighteen boilermakers participated in the study. Self-reported history of chronic bronchitis and asthma were associated with a larger FEV1 reduction in response to workplace exposure at coal-fired and gas-fired industries. Although a high prevalence (39%) of airway hyperresponsiveness (provocative concentration of methacholine causing a 20% fall in FEVI of {lt} 8 mg/mL) among boilermakers was found, there was no consistent pattern of effect modification by airway responsiveness. Conclusions: Although chronic bronchitis and asthma were associated with a greater loss in lung function in response to hours worked as a boilermaker, and therefore they acted as effect modifiers of the exposure-lung function relationship, airway hyperresponsiveness did not. However, the high prevalence of airway hyperresponsiveness found in the cohort may be a primary consequence of long-term workplace exposure among boilermakers.

  15. On the Role of Mechanics in Chronic Lung Disease

    Directory of Open Access Journals (Sweden)

    Mona Eskandari

    2013-12-01

    Full Text Available Progressive airflow obstruction is a classical hallmark of chronic lung disease, affecting more than one fourth of the adult population. As the disease progresses, the inner layer of the airway wall grows, folds inwards, and narrows the lumen. The critical failure conditions for airway folding have been studied intensely for idealized circular cross-sections. However, the role of airway branching during this process is unknown. Here, we show that the geometry of the bronchial tree plays a crucial role in chronic airway obstruction and that critical failure conditions vary significantly along a branching airway segment. We perform systematic parametric studies for varying airway cross-sections using a computational model for mucosal thickening based on the theory of finite growth. Our simulations indicate that smaller airways are at a higher risk of narrowing than larger airways and that regions away from a branch narrow more drastically than regions close to a branch. These results agree with clinical observations and could help explain the underlying mechanisms of progressive airway obstruction. Understanding growth-induced instabilities in constrained geometries has immediate biomedical applications beyond asthma and chronic bronchitis in the diagnostics and treatment of chronic gastritis, obstructive sleep apnea and breast cancer.

  16. Role of Airway Recruitment and Derecruitment in Lung Injury

    OpenAIRE

    Ghadiali, S. N.; Huang, Y.

    2011-01-01

    The mechanical forces generated during the ventilation of patients with acute lung injury causes significant lung damage and inflammation. Low-volume ventilation protocols are commonly used to prevent stretch-related injury that occurs at high lung volumes. However, the cyclic closure and reopening of pulmonary airways at low lung volumes, i.e., derecruitment and recruitment, also causes significant lung damage and inflammation. In this review, we provide an overview of how biomedical enginee...

  17. Effects of lung inflation on airway heterogeneity during histaminergic bronchoconstriction.

    Science.gov (United States)

    Kaczka, David W; Mitzner, Wayne; Brown, Robert H

    2013-09-01

    Lung inflation has been shown to dilate airways by altering the mechanical equilibrium between opposing airway and parenchymal forces. However, it is not known how heterogeneously such dilation occurs throughout the airway tree. In six anesthetized dogs, we measured the diameters of five to six central airway segments using high-resolution computed tomography, along with respiratory input impedance (Zrs) during generalized aerosol histamine challenge, and local histamine challenge in which the agonist was instilled directly onto the epithelia of the imaged central airways. Airway diameters and Zrs were measured at 12 and 25 cmH2O. The Zrs spectra were fitted with a model that incorporated continuous distributions of airway resistances. Airway heterogeneity was quantified using the coefficient of variation for predefined airway distribution functions. Significant reductions in average central airway diameter were observed at 12 cmH2O for both aerosolized and local challenges, along with significant increases upon inflation to 25 cmH2O. No significant differences were observed for the coefficient of variation of airway diameters under any condition. Significant increases in effective airway resistance as measured by Zrs were observed only for the aerosolized challenge at 12 cmH2O, which was completely reversed upon inflation. We conclude that the lung periphery may be the most dominant contributor to increases in airway resistance and tissue elastance during bronchoconstriction induced by aerosolized histamine. However, isolated constriction of only a few central airway segments may also affect tissue stiffness via interdependence with their surrounding parenchyma. PMID:23813528

  18. Mesenchymal stem cells and serelaxin synergistically abrogate established airway fibrosis in an experimental model of chronic allergic airways disease

    Directory of Open Access Journals (Sweden)

    Simon G. Royce

    2015-11-01

    Full Text Available This study determined if the anti-fibrotic drug, serelaxin (RLN, could augment human bone marrow-derived mesenchymal stem cell (MSC-mediated reversal of airway remodeling and airway hyperresponsiveness (AHR associated with chronic allergic airways disease (AAD/asthma. Female Balb/c mice subjected to the 9-week model of ovalbumin (OVA-induced chronic AAD were either untreated or treated with MSCs alone, RLN alone or both combined from weeks 9–11. Changes in airway inflammation (AI, epithelial thickness, goblet cell metaplasia, transforming growth factor (TGF-β1 expression, myofibroblast differentiation, subepithelial and total lung collagen deposition, matrix metalloproteinase (MMP expression, and AHR were then assessed. MSCs alone modestly reversed OVA-induced subepithelial and total collagen deposition, and increased MMP-9 levels above that induced by OVA alone (all p < 0.05 vs OVA group. RLN alone more broadly reversed OVA-induced epithelial thickening, TGF-β1 expression, myofibroblast differentiation, airway fibrosis and AHR (all p < 0.05 vs OVA group. Combination treatment further reversed OVA-induced AI and airway/lung fibrosis compared to either treatment alone (all p < 0.05 vs either treatment alone, and further increased MMP-9 levels. RLN appeared to enhance the therapeutic effects of MSCs in a chronic disease setting; most likely a consequence of the ability of RLN to limit TGF-β1-induced matrix synthesis complemented by the MMP-promoting effects of MSCs.

  19. Lung cysts in chronic paracoccidioidomycosis

    Directory of Open Access Journals (Sweden)

    Andre Nathan Costa

    2013-06-01

    Full Text Available On HRCT scans, lung cysts are characterized by rounded areas of low attenuation in the lung parenchyma and a well-defined interface with the normal adjacent lung. The most common cystic lung diseases are lymphangioleiomyomatosis, Langerhans cell histiocytosis, and lymphocytic interstitial pneumonia. In a retrospective analysis of the HRCT findings in 50 patients diagnosed with chronic paracoccidioidomycosis, we found lung cysts in 5 cases (10%, indicating that patients with paracoccidioidomycosis can present with lung cysts on HRCT scans. Therefore, paracoccidioidomycosis should be included in the differential diagnosis of cystic lung diseases.

  20. Airway and lung parenchyma morphology during the respiratory cycle

    OpenAIRE

    Escolar Castellón, J.de D.; Escolar, M.A.; Blasco, J; Ros, L.H.

    2007-01-01

    Objective: Describe the morphological changes that take place in the lung parenchyma and in the airways during the respiratory cycle with a view to establishing a relationship between them. Subjects: Adult Wistar rats. Interventions: The lungs were fixed at seven different points in the respiratory cycle: Inflation, 10 and 20 cm. transpulmonary pressure, total lung capacity. Deflation, 20, 15, 10 and 0 cm transpulmonary pressure. Measurements: The lungs were pr...

  1. A PAF receptor antagonist inhibits acute airway inflammation and late-phase responses but not chronic airway inflammation and hyperresponsiveness in a primate model of asthma

    Directory of Open Access Journals (Sweden)

    R. H. Gundel

    1992-01-01

    Full Text Available We have examined the effects of a PAF receptor antagonist, WEB 2170, on several indices of acute and chronic airway inflammation and associated changes in lung function in a primate model of allergic asthma. A single oral administration WEB 2170 provided dose related inhibition of the release of leukotriene C4 (LTC4 and prostaglandin D2 (PGD2 recovered and quantified in bronchoalveolar lavage (BAL fluid obtained during the acute phase response to inhaled antigen. In addition, oral WEB 2170 treatment in dual responder primates blocked the acute influx of neutrophils into the airways as well as the associated late-phase airway obstruction occurring 6 h after antigen inhalation. In contrast, a multiple dosing regime with WEB 2170 (once a day for 7 consecutive days failed to reduce the chronic airway inflammation (eosinophilic and associated airway hyperresponsiveness to inhaled methacholine that is characteristic of dual responder monkeys. Thus, we conclude that the generation of PAF following antigen inhalation contributes to the development of lipid mediators, acute airway inflammation and associated late-phase airway obstruction in dual responder primates; however, PAF does not play a significant role in the maintenance of chronic airway inflammation and associated airway hyperresponsiveness in this primate model.

  2. CT analysis of peripheral airway and lung lesions of patients with asthma and COPD

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Takayuki; Tanaka, Hiroshi; Sahara, Shin; Ohnishi, Tetsuro; Abe, Shosaku [Sapporo Medical Univ. (Japan). School of Medicine; Koba, Hiroyuki [Teinekeijinkai Hospital, Sapporo (Japan); Ueno, Kan [Hitachi Medico Technology Corp., Tokyo (Japan)

    2002-12-01

    We compared peripheral airway and lung parenchyma images among patients with asthma, chronic obstructive pulmonary disease (COPD) and healthy controls using high-resolution CT images taken by a multidetector-row CT scanner (Aquillion, Toshiba, Japan). CT images were saved as digital image and communication (DICOM) files and %low attenuation area (LAA) (<-960 Hounsfield Unit) was calculated with the imaging software. %LAA was significantly increased in patients with COPD (p<0.0001) and smokers with stable asthma (p<0.01) as compared with healthy controls. In stable asthma, mucous plugging in the airway sometime appeared, while during asthma exacerbation small nodules and mosaic pattern of peripheral lung field appeared. Since smoker's patients with asthma have hyper-secretion of sputum due to smoking, mucous plugging and airway inflammation may easily occur and consequently air trapping may increase. In the future, image diagnosis of peripheral airway should develop for early detection of airway diseases as a non-invasive examination. On the other hand, micro focus X-ray computed tomography system (Hitachi Medico Technology Co., Japan) can display CT images closely similar to the pictures of microscopic findings and it will be a useful tool to analyze radiologic-pathologic correlations of peripheral airways and lung parenchyma. (author)

  3. CT analysis of peripheral airway and lung lesions of patients with asthma and COPD

    International Nuclear Information System (INIS)

    We compared peripheral airway and lung parenchyma images among patients with asthma, chronic obstructive pulmonary disease (COPD) and healthy controls using high-resolution CT images taken by a multidetector-row CT scanner (Aquillion, Toshiba, Japan). CT images were saved as digital image and communication (DICOM) files and %low attenuation area (LAA) (<-960 Hounsfield Unit) was calculated with the imaging software. %LAA was significantly increased in patients with COPD (p<0.0001) and smokers with stable asthma (p<0.01) as compared with healthy controls. In stable asthma, mucous plugging in the airway sometime appeared, while during asthma exacerbation small nodules and mosaic pattern of peripheral lung field appeared. Since smoker's patients with asthma have hyper-secretion of sputum due to smoking, mucous plugging and airway inflammation may easily occur and consequently air trapping may increase. In the future, image diagnosis of peripheral airway should develop for early detection of airway diseases as a non-invasive examination. On the other hand, micro focus X-ray computed tomography system (Hitachi Medico Technology Co., Japan) can display CT images closely similar to the pictures of microscopic findings and it will be a useful tool to analyze radiologic-pathologic correlations of peripheral airways and lung parenchyma. (author)

  4. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease

    OpenAIRE

    George, Leena; Brightling, Christopher E.

    2016-01-01

    The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 10–40% of patients with COPD. Consistently in both asthma and COPD a...

  5. The effects of in utero vitamin D deficiency on airway smooth muscle mass and lung function.

    Science.gov (United States)

    Foong, Rachel E; Bosco, Anthony; Jones, Anya C; Gout, Alex; Gorman, Shelley; Hart, Prue H; Zosky, Graeme R

    2015-11-01

    We have previously demonstrated increased airway smooth muscle (ASM) mass and airway hyperresponsiveness in whole-life vitamin D-deficient female mice. In this study, we aimed to uncover the molecular mechanisms contributing to altered lung structure and function. RNA was extracted from lung tissue of whole-life vitamin D-deficient and -replete female mice, and gene expression patterns were profiled by RNA sequencing. The data showed that genes involved in embryonic organ development, pattern formation, branching morphogenesis, Wingless/Int signaling, and inflammation were differentially expressed in vitamin D-deficient mice. Network analysis suggested that differentially expressed genes were connected by the hubs matrix metallopeptidase 9; NF-κ light polypeptide gene enhancer in B cells inhibitor, α; epidermal growth factor receptor; and E1A binding protein p300. Given our findings that developmental pathways may be altered, we investigated if the timing of vitamin D exposure (in utero vs. postnatal) had an impact on lung health outcomes. Gene expression was measured in in utero or postnatal vitamin D-deficient mice, as well as whole-life vitamin D-deficient and -replete mice at 8 weeks of age. Baseline lung function, airway hyperresponsiveness, and airway inflammation were measured and lungs fixed for lung structure assessment using stereological methods and quantification of ASM mass. In utero vitamin D deficiency was sufficient to increase ASM mass and baseline airway resistance and alter lung structure. There were increased neutrophils but decreased lymphocytes in bronchoalveolar lavage. Expression of inflammatory molecules S100A9 and S100A8 was mainly increased in postnatal vitamin D-deficient mice. These observations suggest that in utero vitamin D deficiency can alter lung structure and function and increase inflammation, contributing to symptoms in chronic diseases, such as asthma. PMID:25867172

  6. What does airway resistance tell us about lung function?

    Science.gov (United States)

    Kaminsky, David A

    2012-01-01

    Spirometry is considered the primary method to detect the air flow limitation associated with obstructive lung disease. However, air flow limitation is the end-result of many factors that contribute to obstructive lung disease. One of these factors is increased airway resistance. Airway resistance is traditionally measured by relating air flow and driving pressure using body plethysmography, thus deriving airway resistance (R(aw)), specific airway resistance (sR(aw)), and specific airway conductance (sG(aw)). Other methods to measure airway resistance include the forced oscillation technique (FOT), which allows calculation of respiratory system resistance (R(RS)) and reactance (X(RS)), and the interrupter technique, which allows calculation of interrupter resistance (R(int)). An advantage of these other methods is that they may be easier to perform than spirometry, making them particularly suited to patients who cannot perform spirometry, such as young children, patients with neuromuscular disorders, or patients on mechanical ventilation. Since spirometry also requires a deep inhalation, which can alter airway resistance, these alternative methods may provide more sensitive measures of airway resistance. Furthermore, the FOT provides unique information about lung mechanics that is not available from analysis using spirometry, body plethysmography, or the interrupter technique. However, it is unclear whether any of these measures of airway resistance contribute clinically important information to the traditional measures derived from spirometry (FEV(1), FVC, and FEV(1)/FVC). The purpose of this paper is to review the physiology and methodology of these measures of airway resistance, and then focus on their clinical utility in relation to each other and to spirometry. PMID:22222128

  7. Airway Inflammation in Chronic Rhinosinusitis with Nasal Polyps and Asthma: The United Airways Concept Further Supported

    DEFF Research Database (Denmark)

    Håkansson, Kåre; Bachert, Claus; Konge, Lars;

    2015-01-01

    Background It has been established that patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have co-existing asthma. Objective We aimed to test two hypotheses: (i) upper and lower airway inflammation in CRSwNP is uniform in agreement with the united airways concept; and (ii...

  8. Dynamics of Surfactant Liquid Plugs at Bifurcating Lung Airway Models

    Science.gov (United States)

    Tavana, Hossein

    2013-11-01

    A surfactant liquid plug forms in the trachea during surfactant replacement therapy (SRT) of premature babies. Under air pressure, the plug propagates downstream and continuously divides into smaller daughter plugs at continuously branching lung airways. Propagating plugs deposit a thin film on airway walls to reduce surface tension and facilitate breathing. The effectiveness of SRT greatly depends on the final distribution of instilled surfactant within airways. To understand this process, we investigate dynamics of splitting of surfactant plugs in engineered bifurcating airway models. A liquid plug is instilled in the parent tube to propagate and split at the bifurcation. A split ratio, R, is defined as the ratio of daughter plug lengths in the top and bottom daughter airway tubes and studied as a function of the 3D orientation of airways and different flow conditions. For a given Capillary number (Ca), orienting airways farther away from a horizontal position reduced R due to the flow of a larger volume into the gravitationally favored daughter airway. At each orientation, R increased with 0.0005 surfactant distribution in airways and develop effective SRT strategies.

  9. Chronic obstructive pulmonary disease

    Science.gov (United States)

    ... airways disease; Chronic obstructive lung disease; Chronic bronchitis; Emphysema; Bronchitis - chronic ... a protein called alpha-1 antitrypsin can develop emphysema. Other risk factors for COPD are: Exposure to ...

  10. Investigation of airway inflammation and asthma by repeated bronchoalveolar lavage combined with measurements of airway and lung tissue mechanics in individual rats.

    OpenAIRE

    dr Bánfi Andrea

    2011-01-01

    Acute and chronic airway inflammations are the main pathogenetic features of numerous pulmonary diseases. There are several methods studying the pathomechanisms of inflammatory respiratory diseases. To asses the severity of lung diseases, the bronchoalveolar lavage (BAL) and lung function tests are the most current diagnostic methods in the experimental and human pulmonology. However, repetition of BAL procedures and assessments of respiratory mechanic parameters in small rodents (mice and ra...

  11. Covered Bronchial Stent Insertion to Manage Airway Obstruction with Hemoptysis Caused by Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sae Ah; Kim, Do Hyeong [Dankook University College of Medicine, Dankook University Hospital, Cheonan (Korea, Republic of); Jen, Gyeong Sik [Bundang CHA General Hospital, CHA University, Seongnam (Korea, Republic of)

    2012-07-15

    Malignant airway obstruction and hemoptysis are common in lung cancer patients. Recently, airway stent is commonly used to preserve airway in malignant airway obstruction. Hemoptysis can be managed through various methods including conservative treatment, endobronchial tamponade, bronchoscopic intervention, embolization and surgery. In our case studies, we sought to investigate the effectiveness of airway stents for re-opening the airway as well as tamponade effects in four patients with malignant airway obstruction and bleeding caused by tumors or lymph node invasions.

  12. Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling.

    Science.gov (United States)

    Johnson, Jill R; Wiley, Ryan E; Fattouh, Ramzi; Swirski, Filip K; Gajewska, Beata U; Coyle, Anthony J; Gutierrez-Ramos, José-Carlos; Ellis, Russ; Inman, Mark D; Jordana, Manel

    2004-02-01

    It is now fully appreciated that asthma is a disease of a chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses to continuous antigen exposure, mice were exposed to either house dust mite extract (HDM) or ovalbumin intranasally for five consecutive days, followed by 2 days of rest, for up to seven consecutive weeks. Continuous exposure to HDM, unlike ovalbumin, elicited severe and persistent eosinophilic airway inflammation. Flow cytometric analysis demonstrated an accumulation of CD4+ lymphocytes in the lung with elevated expression of inducible costimulator a marker of T cell activation, and of T1/ST2, a marker of helper T Type 2 effector cells. We also detected increased and sustained production of helper T cell Type 2-associated cytokines by splenocytes of HDM-exposed mice on in vitro HDM recall. Histologic analysis of the lung showed evidence of airway remodeling in mice exposed to HDM, with goblet cell hyperplasia, collagen deposition, and peribronchial accumulation of contractile tissue. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. Finally, these responses were studied for up to 9 weeks after cessation of HDM exposure. We observed that whereas airway inflammation resolved fully, the remodeling changes did not resolve and airway hyperreactivity resolved only partly. PMID:14597485

  13. Chronic continuous positive airway pressure (CPAP) reduces airway reactivity in vivo in an allergen-induced rabbit model of asthma

    OpenAIRE

    Xue, Z.; Yu, Y.; Gao, H.; Gunst, S.J.; Tepper, R.S.

    2011-01-01

    Previous studies have demonstrated that chronic mechanical strain produced by continuous positive airway pressure (CPAP) reduces in vivo airway reactivity in rabbits and ferrets. For CPAP to potentially have a therapeutic benefit for asthmatic subjects, the reduction in airway responsiveness would need to persist for 12–24 h after its discontinuation, require application for only part of the day, and be effective in the presence of atopic airway inflammation. In the present study, airway resp...

  14. Volumetric capnography for the evaluation of chronic airways diseases

    Directory of Open Access Journals (Sweden)

    Veronez L

    2014-09-01

    Full Text Available Liliani de Fátima Veronez,1 Monica Corso Pereira,2 Silvia Maria Doria da Silva,2 Luisa Affi Barcaui,2 Eduardo Mello De Capitani,2 Marcos Mello Moreira,2 Ilma Aparecida Paschoalz2 1Department of Physical Therapy, University of Votuporanga (Educational Foundation of Votuporanga, Votuporanga, 2Department of Internal Medicine, School of Medical Sciences, State University of Campinas (UNICAMP, Campinas, Sao Paulo, BrazilBackground: Obstructive lung diseases of different etiologies present with progressive peripheral airway involvement. The peripheral airways, known as the silent lung zone, are not adequately evaluated with conventional function tests. The principle of gas washout has been used to detect pulmonary ventilation inhomogeneity and to estimate the location of the underlying disease process. Volumetric capnography (VC analyzes the pattern of CO2 elimination as a function of expired volume.Objective: To measure normalized phase 3 slopes with VC in patients with non-cystic fibrosis bronchiectasis (NCB and in bronchitic patients with chronic obstructive pulmonary disease (COPD in order to compare the slopes obtained for the groups.Methods: NCB and severe COPD were enrolled sequentially from an outpatient clinic (Hospital of the State University of Campinas. A control group was established for the NCB group, paired by sex and age. All subjects performed spirometry, VC, and the 6-Minute Walk Test (6MWT. Two comparisons were made: NCB group versus its control group, and NCB group versus COPD group. The project was approved by the ethical committee of the institution. Statistical tests used were Wilcoxon or Student’s t-test; P<0.05 was considered to be a statistically significant difference.Results: Concerning the NCB group (N=20 versus the control group (N=20, significant differences were found in body mass index and in several functional variables (spirometric, VC, 6MWT with worse results observed in the NCB group. In the comparison between

  15. Unmet needs in severe chronic upper airway disease (SCUAD).

    Science.gov (United States)

    Bousquet, Jean; Bachert, Claus; Canonica, Giorgio W; Casale, Thomas B; Cruz, Alvaro A; Lockey, Richard J; Zuberbier, Torsten

    2009-09-01

    Although the majority of patients with chronic upper airway diseases have controlled symptoms during treatment, many patients have severe chronic upper airway diseases (SCUADs). SCUAD defines those patients whose symptoms are inadequately controlled despite adequate (ie, effective, safe, and acceptable) pharmacologic treatment based on guidelines. These patients have impaired quality of life, social functioning, sleep, and school/work performance. Severe uncontrolled allergic rhinitis, nonallergic rhinitis, chronic rhinosinusitis, aspirin-exacerbated respiratory diseases, or occupational airway diseases are defined as SCUADs. Pediatric SCUADs are still unclear. In developing countries SCUADs exist, but risk factors can differ from those seen in developed countries. Comorbidities are common in patients with SCUADs and might increase their severity. The present document is the position of a group of experts considering that SCUADs should be considered differently from mild chronic upper airway diseases. It reviews the state of the art, highlighting gaps in our knowledge, and proposes several areas for a better understanding, prevention, and management of SCUADs. This document can also serve to optimize the pharmacoeconomic evaluation of SCUADs by means of comparison with mild chronic upper airway diseases. PMID:19660803

  16. A plasminogen activator inhibitor-1 inhibitor reduces airway remodeling in a murine model of chronic asthma.

    Science.gov (United States)

    Lee, Sun H; Eren, Mesut; Vaughan, Douglas E; Schleimer, Robert P; Cho, Seong H

    2012-06-01

    We previously reported that plasminogen activator inhibitor (PAI)-1 deficiency prevents collagen deposition in the airways of ovalbumin (OVA)-challenged mice. In this study, we explored the therapeutic utility of blocking PAI-1 in preventing airway remodeling, using a specific PAI-1 inhibitor, tiplaxtinin. C57BL/6J mice were immunized with intraperitoneal injections of OVA on Days 0, 3, and 6. Starting on Day 11, mice were challenged with phosphate-buffered saline or OVA by nebulization three times per week for 4 weeks. Tiplaxtinin was mixed with chow and administered orally from 1 day before the phosphate-buffered saline or OVA challenge. Lung tissues were harvested after challenge and characterized histologically for infiltrating inflammatory cells, mucus-secreting goblet cells, and collagen deposition. Airway hyperresponsiveness was measured using whole-body plethysmography. Tiplaxtinin treatment significantly decreased levels of PAI-1 activity in bronchoalveolar lavage fluids, which indicates successful blockage of PAI-1 activity in the airways. The number of infiltrated inflammatory cells was reduced by tiplaxtinin treatment in the lungs of the OVA-challenged mice. Furthermore, oral administration of tiplaxtinin significantly attenuated the degree of goblet cell hyperplasia and collagen deposition in the airways of the OVA-challenged mice, and methacholine-induced airway hyperresponsiveness was effectively reduced by tiplaxtinin in these animals. This study supports our previous findings that PAI-1 promotes airway remodeling in a murine model of chronic asthma, and suggests that PAI-1 may be a novel target of treatment of airway remodeling in asthma. PMID:22323366

  17. Quantitative evaluation of inhaled radioactive aerosol deposition patterns in the lungs in obstructive airways disease

    International Nuclear Information System (INIS)

    Uneven distribution of inhaled aerosol in the lungs is the characteristics of obstructive airways disease such as chronic bronchitis and pulmonary emphysema, and has been classified typically into peripheral and central deposition patterns, respectively by visual inspection, whereas in the normal the distribution is homogeneous throughout the lungs. The purpose of the present study was to analyse the distribution of inhaled radioactivity in the lungs by way of matrixes by a computer. The seemingly homogeneous distribution pattern in normal subjects has been found to indicate a gradual change in count profile between the neighboring matrixes. The peripheral pattern indicates the patchy presence of small number of matrixes with excessive radioactivity throughout the lungs, and the central pattern, the presence of matrixes of excessive radioactivity along the major central airways forming a comma-like configuration superimposed on the peripheral pattern. Our computer analysis has a potentiality to characterize obstructive airways disease for a better understanding of their pathophysiology, which is not feasible by a simple visual inspection of images on a polaroid picture. (author)

  18. Airway Inflammation in Chronic Rhinosinusitis with Nasal Polyps and Asthma: The United Airways Concept Further Supported

    DEFF Research Database (Denmark)

    Håkansson, Kåre; Bachert, Claus; Konge, Lars; Thomsen, Simon Francis; Pedersen, Anders Elm; Poulsen, Steen Seier; Martin-Bertelsen, Tomas; Winther, Ole; Backer, Vibeke; von Buchwald, Christian

    2015-01-01

    Background It has been established that patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have co-existing asthma. Objective We aimed to test two hypotheses: (i) upper and lower airway inflammation in CRSwNP is uniform in agreement with the united airways concept; and (ii......) bronchial inflammation exists in all CRSwNP patients irrespective of clinical asthma status. Methods We collected biopsies from nasal polyps, inferior turbinates and bronchi of 27 CRSwNP patients and 6 controls. All participants were evaluated for lower airway disease according to international guidelines...... cytokines measured, IL-13 was significantly increased in bronchial biopsies from CRSwNP patients with, but not without asthma. Conclusion Our findings support the united airways concept; however, we did not find evidence for subclinical bronchial inflammation in CRSwNP patients without asthma. Finally, this...

  19. The microbiome in chronic inflammatory airway disease: A threatened species.

    Science.gov (United States)

    Green, Robin John; Van Niekerk, Andre; Jeevarathnum, Ashley C; Feldman, Charles; Richards On Behalf Of The South African Allergic Rhinitis Working Group, Guy A

    2016-08-01

    The human body is exposed to a multitude of microbes and infectious organisms throughout life. Many of these organisms colonise the skin, gastrointestinal tract (GIT) and airway. We now recognise that this colonisation includes the lower airway, previously thought to be sterile. These colonising organisms play an important role in disease prevention, including an array of chronic inflammatory conditions that are unrelated to infectious diseases. However, new evidence of immune dysregulation suggests that early colonisation, especially of the GITand airway, by pathogenic micro-organisms, has deleterious effects that may contribute to the potential to induce chronic inflammation in young children, which may only express itself in adult life. PMID:27499401

  20. Determinants of lung function and airway hyperresponsiveness in asthmatic children

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, S; Anhøj, J;

    2007-01-01

    effect of steroid treatment. METHODS: We analyzed determinants of lung function and airway hyperresponsiveness (AHR) in a Scandinavian study of 2390 subjects from 550 families. Families were selected for the presence of two or more asthmatic children as part of a genetic study, Scandinavian Asthma......BACKGROUND: Asthma patients exhibit an increased rate of loss of lung function. Determinants to such decline are largely unknown and the modifying effect of steroid therapy is disputed. This cross-sectional study aimed to elucidate factors contributing to such decline and the possible modifying...

  1. Neutralization of TSLP Inhibits Airway Remodeling in a Murine Model of Allergic Asthma Induced by Chronic Exposure to House Dust Mite

    OpenAIRE

    Chen, Zhuang-Gui; Zhang, Tian-Tuo; Li, Hong-Tao; Chen, Fen-Hua; Zou, Xiao-Ling; Ji, Jing-Zhi; Chen, Hong

    2013-01-01

    Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. However, the initiating factor that links airway inflammation to remodeling is unknown. Thymic stromal lymphopoietin (TSLP), an epithelium-derived cytokine, can strongly activate lung dendritic cells (DCs) through the TSLP-TSLPR and OX40L-OX40 signaling pathways to promote Th2 differentiation. To determine whether TSLP is the underlying trigger of ai...

  2. Magnetic resonance imaging in children: common problems and possible solutions for lung and airways imaging.

    Science.gov (United States)

    Ciet, Pierluigi; Tiddens, Harm A W M; Wielopolski, Piotr A; Wild, Jim M; Lee, Edward Y; Morana, Giovanni; Lequin, Maarten H

    2015-12-01

    Pediatric chest MRI is challenging. High-resolution scans of the lungs and airways are compromised by long imaging times, low lung proton density and motion. Low signal is a problem of normal lung. Lung abnormalities commonly cause increased signal intenstities. Among the most important factors for a successful MRI is patient cooperation, so the long acquisition times make patient preparation crucial. Children usually have problems with long breath-holds and with the concept of quiet breathing. Young children are even more challenging because of higher cardiac and respiratory rates giving motion blurring. For these reasons, CT has often been preferred over MRI for chest pediatric imaging. Despite its drawbacks, MRI also has advantages over CT, which justifies its further development and clinical use. The most important advantage is the absence of ionizing radiation, which allows frequent scanning for short- and long-term follow-up studies of chronic diseases. Moreover, MRI allows assessment of functional aspects of the chest, such as lung perfusion and ventilation, or airways and diaphragm mechanics. In this review, we describe the most common MRI acquisition techniques on the verge of clinical translation, their problems and the possible solutions to make chest MRI feasible in children. PMID:26342643

  3. Magnetic resonance imaging in children: common problems and possible solutions for lung and airways imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ciet, Pierluigi; Tiddens, Harm A.W.M. [Erasmus Medical Center, Department of Radiology, Sophia Children' s Hospital, Rotterdam (Netherlands); Erasmus Medical Center, Department of Pediatric Pulmonology and Allergology, Sophia Children' s Hospital, Rotterdam (Netherlands); Wielopolski, Piotr A. [Erasmus Medical Center, Department of Radiology, Sophia Children' s Hospital, Rotterdam (Netherlands); Wild, Jim M. [University of Sheffield, Academic Radiology, Sheffield (United Kingdom); Lee, Edward Y. [Boston Children' s Hospital and Harvard Medical School, Departments of Radiology and Medicine, Pulmonary Divisions, Boston, MA (United States); Morana, Giovanni [Ca' Foncello Regional Hospital, Department of Radiology, Treviso (Italy); Lequin, Maarten H. [University Medical Center, Department of Radiology, Wilhelmina Children' s Hospital, Utrecht (Netherlands)

    2015-12-15

    Pediatric chest MRI is challenging. High-resolution scans of the lungs and airways are compromised by long imaging times, low lung proton density and motion. Low signal is a problem of normal lung. Lung abnormalities commonly cause increased signal intensities. Among the most important factors for a successful MRI is patient cooperation, so the long acquisition times make patient preparation crucial. Children usually have problems with long breath-holds and with the concept of quiet breathing. Young children are even more challenging because of higher cardiac and respiratory rates giving motion blurring. For these reasons, CT has often been preferred over MRI for chest pediatric imaging. Despite its drawbacks, MRI also has advantages over CT, which justifies its further development and clinical use. The most important advantage is the absence of ionizing radiation, which allows frequent scanning for short- and long-term follow-up studies of chronic diseases. Moreover, MRI allows assessment of functional aspects of the chest, such as lung perfusion and ventilation, or airways and diaphragm mechanics. In this review, we describe the most common MRI acquisition techniques on the verge of clinical translation, their problems and the possible solutions to make chest MRI feasible in children. (orig.)

  4. Magnetic resonance imaging in children: common problems and possible solutions for lung and airways imaging

    International Nuclear Information System (INIS)

    Pediatric chest MRI is challenging. High-resolution scans of the lungs and airways are compromised by long imaging times, low lung proton density and motion. Low signal is a problem of normal lung. Lung abnormalities commonly cause increased signal intensities. Among the most important factors for a successful MRI is patient cooperation, so the long acquisition times make patient preparation crucial. Children usually have problems with long breath-holds and with the concept of quiet breathing. Young children are even more challenging because of higher cardiac and respiratory rates giving motion blurring. For these reasons, CT has often been preferred over MRI for chest pediatric imaging. Despite its drawbacks, MRI also has advantages over CT, which justifies its further development and clinical use. The most important advantage is the absence of ionizing radiation, which allows frequent scanning for short- and long-term follow-up studies of chronic diseases. Moreover, MRI allows assessment of functional aspects of the chest, such as lung perfusion and ventilation, or airways and diaphragm mechanics. In this review, we describe the most common MRI acquisition techniques on the verge of clinical translation, their problems and the possible solutions to make chest MRI feasible in children. (orig.)

  5. Lung Surfactant Protein D (SP-D) Response and Regulation During Acute and Chronic Lung Injury

    DEFF Research Database (Denmark)

    Gaunsbaek, Maria Quisgaard; Rasmussen, Karina Juhl; Beers, Michael F.;

    2013-01-01

    lung injury, with a sustained increment during chronic inflammation compared with acute inflammation. A quick upregulation of SP-D in serum in response to acute airway inflammation supports the notion that SP-D translocates from the airways into the vascular system, in favor of being synthesized......BACKGROUND: Surfactant protein D (SP-D) is a collection that plays important roles in modulating host defense functions and maintaining phospholipid homeostasis in the lung. The aim of current study was to characterize comparatively the SP-D response in bronchoalveolar lavage (BAL) and serum in...... three murine models of lung injury, using a validated ELISA technology for estimation of SP-D levels. METHODS: Mice were exposed to lipopolysaccharide, bleomycin, or Pneumocystis carinii (Pc) and sacrificed at different time points. RESULTS: In lipopolysaccharide-challenged mice, the level of SP-D in...

  6. Pericytes in chronic lung disease.

    Science.gov (United States)

    Rowley, Jessica E; Johnson, Jill R

    2014-01-01

    Pericytes are mesenchymal cells embedded within the abluminal surface of the endothelium of microvessels such as capillaries, pre-capillary arterioles, post-capillary and collecting venules, where they maintain microvascular homeostasis and participate in angiogenesis. In addition to their roles in supporting the vasculature and facilitating leukocyte extravasation, pericytes have been recently investigated as a subpopulation of mesenchymal stem cells (MSCs) due to their capacity to differentiate into numerous cell types including the classic MSC triad, i.e. osteocytes, chondrocytes and adipocytes. Other studies in models of fibrotic inflammatory disease of the lung have demonstrated a vital role of pericytes in myofibroblast activation, collagen deposition and microvascular remodelling, which are hallmark features of chronic lung diseases such as asthma, chronic obstructive pulmonary disorder, pulmonary fibrosis and pulmonary hypertension. Further studies into the mechanisms of the pericyte-to-myofibroblast transition and migration to fibrotic foci will hopefully clarify the role of these cells in chronic lung disease and confirm the importance of pericytes in human fibrotic pulmonary disease. PMID:25034005

  7. Airway resistance and deposition of particles in the lung.

    Science.gov (United States)

    Svartengren, M; Philipson, K; Linnman, L; Camner, P

    1984-01-01

    The percentage 24-h lung retention of 4-micrometers monodispersed Teflon particles, aerodynamic diameter about 6 micrometers, was studied twice in 8 healthy nonsmokers. The particles were inhaled at 0.5 liter/sec with maximally deep breaths. Bronchoconstriction was induced by inhalation of a methacholine-bromide aerosol for one exposure before and for the other 20-30 min after the inhalation of the Teflon particles. For both exposures, airway resistance (Raw) was measured with a whole body plethysmograph before and after the induction of the bronchoconstriction and was found on an average to increase with a factor of 2-3. For the exposure when bronchoconstriction was induced after the inhalation of the Teflon particles, Raw and 24-h lung retention correlated significantly. Retention at 24 h was markedly lower when bronchoconstriction was induced before inhalation of the Teflon particles than when bronchoconstriction was induced after, the ranges being 13-24% and 38-68%, respectively. The experimental data agreed well with theoretical data from a lung model wherein the diameters of the airways were varied. The results indicate that the magnitude of bronchoconstriction occurring in real life can protect the alveolar part of the lung by reducing the amount of inhaled particles that deposit there. PMID:6525990

  8. Effect of diosmetin on airway remodeling in a murine model of chronic asthma.

    Science.gov (United States)

    Ge, Ai; Liu, Yanan; Zeng, Xiaoning; Kong, Hui; Ma, Yuan; Zhang, Jiaxiang; Bai, Fangfang; Huang, Mao

    2015-08-01

    Bronchial asthma, one of the most common allergic diseases, is characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. The anti-oxidant flavone aglycone diosmetin ameliorates the inflammation in pancreatitis, but little is known about its impact on asthma. In this study, the effects of diosmetin on chronic asthma were investigated with an emphasis on the modulation of airway remodeling in BALB/c mice challenged with ovalbumin (OVA). It was found that diosmetin significantly relieved inflammatory cell infiltration, goblet cell hyperplasia, and collagen deposition in the lungs of asthmatic mice and notably reduced AHR in these animals. The OVA-induced increases in total cell and eosinophil counts in bronchoalveolar lavage fluid were reversed, and the level of OVA-specific immunoglobulin E in serum was attenuated by diosmetin administration, implying an anti-Th2 activity of diosmetin. Furthermore, diosmetin remarkably suppressed the expression of smooth muscle actin alpha chain, indicating a potent anti-proliferative effect of diosmetin on airway smooth muscle cells (ASMCs). Matrix metallopeptidase-9, transforming growth factor-β1, and vascular endothelial growth factor levels were also alleviated by diosmetin, suggesting that the remission of airway remodeling might be attributed to the decline of these proteins. Taken together, our findings provided a novel profile of diosmetin with anti-remodeling therapeutic benefits, highlighting a new potential of diosmetin in remitting the ASMC proliferation in chronic asthma. PMID:26033789

  9. Viral Bronchiolitis in Young Rats Causes Small Airway Lesions that Correlate with Reduced Lung Function

    OpenAIRE

    Sorkness, Ronald L.; Renee J Szakaly; Louis A Rosenthal; Sullivan, Ruth; James E Gern; Lemanske, Robert F.; Sun, Xin

    2013-01-01

    Viral illness with wheezing during infancy is associated with the inception of childhood asthma. Small airway dysfunction is a component of childhood asthma, but little is known about how viral illness at an early age may affect the structure and function of small airways. We used a well-characterized rat model of postbronchiolitis chronic airway dysfunction to address how postinfectious small airway lesions affect airway physiological function and if the structure/function correlates persist...

  10. Anaerobic bacteria colonizing the lower airways in lung cancer patients

    Directory of Open Access Journals (Sweden)

    Anna Malm

    2011-07-01

    Full Text Available Anaerobes comprise most of the endogenous oropharyngeal microflora, and can cause infections of airways in lung cancer patients who are at high risk for respiratory tract infections. The aim of this study was to determine the frequency and species diversity of anaerobes in specimens from the lower airways of lung cancer patients. Sensitivity of the isolates to conventional antimicrobial agents used in anaerobe therapy was assessed. Respiratory secretions obtained by bronchoscopy from 30 lung cancer patients were cultured onto Wilkins- -Chalgren agar in anaerobic conditions at 37°C for 72–96 hours. The isolates were identified using microtest Api 20A. The minimal inhibitory concentrations for penicillin G, amoxicillin/clavulanate, piperacillin/tazobactam, cefoxitin, imipenem, clindamycin, and metronidazole were determined by E-test. A total of 47 isolates of anaerobic bacteria were detected in 22 (73.3% specimens. More than one species of anaerobe was found in 16 (53.3% samples. The most frequently isolated were Actinomyces spp. and Peptostreptococcus spp., followed by Eubacterium lentum, Veillonella parvula, Prevotella spp., Bacteroides spp., Lactobacillus jensenii. Among antibiotics used in the study amoxicillin/clavulanate and imipenem were the most active in vitro (0% and 2% resistant strains, respectively. The highest resistance rate was found for penicillin G and metronidazole (36% and 38% resistant strains, respectively. The results obtained confirm the need to conduct analyses of anaerobic microflora colonizing the lower respiratory tract in patients with lung cancer to monitor potential etiologic factors of airways infections, as well as to propose efficient, empirical therapy. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 263–266

  11. Airway surface irregularities promote particle diffusion in the human lung

    International Nuclear Information System (INIS)

    Current NCRP and ICRP particle deposition models employed in risk assessment analyses treat the airways of the human lung as smooth-walled tubes. However, the upper airways of the tracheobronchial (TB) tree are line with cartilaginous rings. Recent supercomputer simulations of in vivo conditions (cited herein), where cartilaginous ring morphologies were based upon fibre-optic bronchoscope examinations, have clearly demonstrated their profound effects upon fluid dynamics. A physiologically based analytical model of fluid dynamics is presented, focusing upon applications to particle diffusion within the TB tree. The new model is the first to describe particle motion while simultaneously simulating effects of wall irregularities, entrance conditions and tube curvatures. This study may explain the enhanced deposition by particle diffusion detected in replica case experiments and have salient implications for the clinically observed preferential distributions of bronchogenic carcinomas associated with inhaled radionuclides. (author)

  12. Relationship between airway inflammation and remodeling in patients with asthma and chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Górska K

    2009-12-01

    Full Text Available Abstract Despite a number of important differences in the pathogenesis, course and prognosis of asthma and chronic obstructive pulmonary disease (COPD, these two entities also have common features with airway inflammation being one of them. Airway remodeling is a characteristic feature of asthma, but data on the bronchial wall thickening in COPD patients are still scarce. Aim To assess the relation between the inflammatory cell count in the bronchoalveolar lavage fluid (BALF and thickness of bronchial walls assessed by high resolution computed tomography (HRCT in asthma and COPD patients. Material and methods The study was conducted in 9 patients with mild-to-moderate asthma (M/F 4/5, mean age 35 ± 10 years and 11 patients with mild-to-moderate COPD (M/F 7/4, mean age 57 ± 9 years. In all subjects lung function tests and HRCT scanning of the chest were performed. External (D and internal (L diameters of the airways were assessed at five selected lung levels. The lumen area (AL, wall area (WA, wall thickness (WT and bronchial wall thickness (WT/D ratio were calculated. Eight patients with asthma and 8 patients with COPD underwent fiberoptic bronchoscopy and bronchoalveolar lavage (BAL. Total and differential cell counts were assessed in the BAL fluid. Results Mean FEV1% pred was 80 ± 19%, and 73 ± 20% in asthma and COPD patients, respectively (NS. No significant differences in the total and differential cell counts in BALF were found in patients with asthma and COPD. There were no significant differences in the airway diameter or airway wall thickness. The mean inner airway diameter was 1.4 ± 0.3 and 1.2 ± 0.3 mm and the mean lumen area was 1.8 ± 0.7 and 1.6 ± 0.7 mm2 in asthma and COPD, respectively (NS. Negative correlations between the eosinophil count in BALF and inner airway diameter (r = -0.7, P Conclusions In mild-to-moderate asthma and COPD the airway diameter and thickness are similar. In asthmatics, the airway diameter might be

  13. Right Ventricular Dysfunction in Chronic Lung Disease

    OpenAIRE

    Kolb, Todd M.; Hassoun, Paul M.

    2012-01-01

    Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, ex...

  14. Neutralisation of interleukin-13 in mice prevents airway pathology caused by chronic exposure to house dust mite.

    Directory of Open Access Journals (Sweden)

    Kate L Tomlinson

    Full Text Available BACKGROUND: Repeated exposure to inhaled allergen can cause airway inflammation, remodeling and dysfunction that manifests as the symptoms of allergic asthma. We have investigated the role of the cytokine interleukin-13 (IL-13 in the generation and persistence of airway cellular inflammation, bronchial remodeling and deterioration in airway function in a model of allergic asthma caused by chronic exposure to the aeroallergen House Dust Mite (HDM. METHODOLOGY/PRINCIPAL FINDINGS: Mice were exposed to HDM via the intranasal route for 4 consecutive days per week for up to 8 consecutive weeks. Mice were treated either prophylactically or therapeutically with a potent neutralising anti-IL-13 monoclonal antibody (mAb administered subcutaneously (s.c.. Airway cellular inflammation was assessed by flow cytometry, peribronchial collagen deposition by histocytochemistry and airway hyperreactivity (AHR by invasive measurement of lung resistance (R(L and dynamic compliance (C(dyn. Both prophylactic and therapeutic treatment with an anti-IL-13 mAb significantly inhibited (P<0.05 the generation and maintenance of chronic HDM-induced airway cellular inflammation, peribronchial collagen deposition, epithelial goblet cell upregulation. AHR to inhaled methacholine was reversed by prophylactic but not therapeutic treatment with anti-IL-13 mAb. Both prophylactic and therapeutic treatment with anti-IL-13 mAb significantly reversed (P<0.05 the increase in baseline R(L and the decrease in baseline C(dyn caused by chronic exposure to inhaled HDM. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that in a model of allergic lung disease driven by chronic exposure to a clinically relevant aeroallergen, IL-13 plays a significant role in the generation and persistence of airway inflammation, remodeling and dysfunction.

  15. The loss of Hoxa5 function promotes Notch-dependent goblet cell metaplasia in lung airways

    Directory of Open Access Journals (Sweden)

    Olivier Boucherat

    2012-05-01

    Hox genes encode transcription factors controlling complex developmental processes in various organs. Little is known, however, about how HOX proteins control cell fate. Herein, we demonstrate that the goblet cell metaplasia observed in lung airways from Hoxa5−/− mice originates from the transdifferentiation of Clara cells. Reduced CC10 expression in Hoxa5−/− embryos indicates that altered cell specification occurs prior to birth. The loss of Hoxa5 function does not preclude airway repair after naphthalene exposure, but the regenerated epithelium presents goblet cell metaplasia and less CC10-positive cells, demonstrating the essential role of Hoxa5 for correct differentiation. Goblet cell metaplasia in Hoxa5−/− mice is a FOXA2-independent process. However, it is associated with increased Notch signaling activity. Consistent with these findings, expression levels of activated NOTCH1 and the effector gene HEY2 are enhanced in patients with chronic obstructive pulmonary disease. In vivo administration of a γ-secretase inhibitor attenuates goblet cell metaplasia in Hoxa5−/− mice, highlighting the contribution of Notch signaling to the phenotype and suggesting a potential therapeutic strategy to inhibit goblet cell differentiation and mucus overproduction in airway diseases. In summary, the loss of Hoxa5 function in lung mesenchyme impacts on epithelial cell fate by modulating Notch signaling.

  16. Analysis of airways in computed tomography

    DEFF Research Database (Denmark)

    Petersen, Jens

    Chronic Obstructive Pulmonary Disease (COPD) is major cause of death and disability world-wide. It affects lung function through destruction of lung tissue known as emphysema and inflammation of airways, leading to thickened airway walls and narrowed airway lumen. Computed Tomography (CT) imaging...

  17. Lung-homing of endothelial progenitor cells and airway vascularization is only partially dependant on eosinophils in a house dust mite-exposed mouse model of allergic asthma.

    Directory of Open Access Journals (Sweden)

    Nirooya Sivapalan

    Full Text Available Asthmatic responses involve a systemic component where activation of the bone marrow leads to mobilization and lung-homing of progenitor cells. This traffic may be driven by stromal cell derived factor-1 (SDF-1, a potent progenitor chemoattractant. We have previously shown that airway angiogenesis, an early remodeling event, can be inhibited by preventing the migration of endothelial progenitor cells (EPC to the lungs. Given intranasally, AMD3100, a CXCR4 antagonist that inhibits SDF-1 mediated effects, attenuated allergen-induced lung-homing of EPC, vascularization of pulmonary tissue, airway eosinophilia and development of airway hyperresponsiveness. Since SDF-1 is also an eosinophil chemoattractant, we investigated, using a transgenic eosinophil deficient mouse strain (PHIL whether EPC lung accumulation and lung vascularization in allergic airway responses is dependent on eosinophilic inflammation.Wild-type (WT BALB/c and eosinophil deficient (PHIL mice were sensitized to house dust mite (HDM using a chronic exposure protocol and treated with AMD3100 to modulate SDF-1 stimulated progenitor traffic. Following HDM challenge, lung-extracted EPCs were enumerated along with airway inflammation, microvessel density (MVD and airway methacholine responsiveness (AHR.Following Ag sensitization, both WT and PHIL mice exhibited HDM-induced increase in airway inflammation, EPC lung-accumulation, lung angiogenesis and AHR. Treatment with AMD3100 significantly attenuated outcome measures in both groups of mice. Significantly lower levels of EPC and a trend for lower vascularization were detected in PHIL versus WT mice.This study shows that while allergen-induced lung-homing of endothelial progenitor cells, increased tissue vascularization and development lung dysfunction can occur in the absence of eosinophils, the presence of these cells worsens the pathology of the allergic response.

  18. Quantification of atopy, lung function and airway hypersensitivity in adults

    Directory of Open Access Journals (Sweden)

    Marinho Susana

    2011-12-01

    Full Text Available Abstract Background Studies in children have shown that concentration of specific serum IgE (sIgE and size of skin tests to inhalant allergens better predict wheezing and reduced lung function than the information on presence or absence of atopy. However, very few studies in adults have investigated the relationship of quantitative atopy with lung function and airway hyperresponsiveness (AHR. Objective To determine the association between lung function and AHR and quantitative atopy in a large sample of adults from the UK. Methods FEV1 and FVC (% predicted were measured using spirometry and airway responsiveness by methacholine challenge (5-breath dosimeter protocol in 983 subjects (random sample of 800 parents of children enrolled in a population-based birth cohort enriched with 183 patients with physician-diagnosed asthma. Atopic status was assessed by skin prick tests (SPT and measurement of sIgE (common inhalant allergens. We also measured indoor allergen exposure in subjects' homes. Results Spirometry was completed by 792 subjects and 626 underwent methacholine challenge, with 100 (16.0% having AHR (dose-response slope>25. Using sIgE as a continuous variable in a multiple linear regression analysis, we found that increasing levels of sIgE to mite, cat and dog were significantly associated with lower FEV1 (mite p = 0.001, cat p = 0.0001, dog p = 2.95 × 10-8. Similar findings were observed when using the size of wheal on skin testing as a continuous variable, with significantly poorer lung function with increasing skin test size (mite p = 8.23 × 10-8, cat p = 3.93 × 10-10, dog p = 3.03 × 10-15, grass p = 2.95 × 10-9. The association between quantitative atopy with lung function and AHR remained unchanged when we repeated the analyses amongst subjects defined as sensitised using standard definitions (sIgE>0.35 kUa/l, SPT-3 mm>negative control. Conclusions In the studied population, lung function decreased and AHR increased with increasing

  19. Grading obstructive lung disease using tomographic pulmonary scintigraphy in patients with chronic obstructive pulmonary disease (COPD) and long-term smokers

    OpenAIRE

    Bajc, Marika; Markstad, Hanna; Jarenbäck, Linnea; Tufvesson, Ellen; Bjermer, Leif; Jögi, Jonas

    2014-01-01

    Abstract The severity of chronic obstructive lung disease (COPD) is defined by the degree of flow limitation measured as forced expiratory volume in 1 s, which mainly reflects impairment of large and intermediate airways. However, COPD is primarily a small airways disease. Therefore, better diagnostic tools are needed. Ventilation-Perfusion (V/P) SPECT is a sensitive method to detect obstructive lung changes but criteria for staging airway obstruction are missing. Purpose To define and valida...

  20. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease.

    Science.gov (United States)

    George, Leena; Brightling, Christopher E

    2016-01-01

    The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 10-40% of patients with COPD. Consistently in both asthma and COPD a sputum eosinophilia is associated with a good response to corticosteroid therapy and tailored strategies aimed to normalize sputum eosinophils reduce exacerbation frequency and severity. Advances in our understanding of the multistep paradigm of eosinophil recruitment to the airway, and the consequence of eosinophilic inflammation, has led to the development of new therapies to target these molecular pathways. In this article we discuss the mechanisms of eosinophilic trafficking, the tools to assess eosinophilic airway inflammation in asthma and COPD during stable disease and exacerbations and review current and novel anti-eosinophilic treatments. PMID:26770668

  1. LF-15 & T7, synthetic peptides derived from tumstatin, attenuate aspects of airway remodelling in a murine model of chronic OVA-induced allergic airway disease.

    Directory of Open Access Journals (Sweden)

    Karryn T Grafton

    Full Text Available BACKGROUND: Tumstatin is a segment of the collagen-IV protein that is markedly reduced in the airways of asthmatics. Tumstatin can play an important role in the development of airway remodelling associated with asthma due to its anti-angiogenic properties. This study assessed the anti-angiogenic properties of smaller peptides derived from tumstatin, which contain the interface tumstatin uses to interact with the αVβ3 integrin. METHODS: Primary human lung endothelial cells were exposed to the LF-15, T3 and T7 tumstatin-derived peptides and assessed for cell viability and tube formation in vitro. The impact of the anti-angiogenic properties on airways hyperresponsiveness (AHR was then examined using a murine model of chronic OVA-induced allergic airways disease. RESULTS: The LF-15 and T7 peptides significantly reduced endothelial cell viability and attenuated tube formation in vitro. Mice exposed to OVA+ LF-15 or OVA+T7 also had reduced total lung vascularity and AHR was attenuated compared to mice exposed to OVA alone. T3 peptides reduced cell viability but had no effect on any other parameters. CONCLUSION: The LF-15 and T7 peptides may be appropriate candidates for use as novel pharmacotherapies due to their small size and anti-angiogenic properties observed in vitro and in vivo.

  2. Optimal surface segmentation using flow lines to quantify airway abnormalities in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Petersen, Jens; Nielsen, Mads; Lo, Pechin Chien Pau; Nordenmark, Lars Haug; Pedersen, Jesper Johannes Holst; Wille, Mathilde Marie Winkler; Dirksen, Asger; de Bruijne, Marleen

    2014-01-01

    .5%, the alternative approach in 11.2%, and in 20.3% no method was favoured. Airway abnormality measurements obtained with the method on 490 scan pairs from a lung cancer screening trial correlate significantly with lung function and are reproducible; repeat scan R(2) of measures of the airway lumen...

  3. Genetic Deletion and Pharmacological Inhibition of PI3Kγ Reduces Neutrophilic Airway Inflammation and Lung Damage in Mice with Cystic Fibrosis-Like Lung Disease

    Directory of Open Access Journals (Sweden)

    Maria Galluzzo

    2015-01-01

    Full Text Available Purpose. Neutrophil-dominated airway inflammation is a key feature of progressive lung damage in cystic fibrosis (CF. Thus, reducing airway inflammation is a major goal to prevent lung damage in CF. However, current anti-inflammatory drugs have shown several limits. PI3Kγ plays a pivotal role in leukocyte recruitment and activation; in the present study we determined the effects of genetic deletion and pharmacologic inhibition of PI3Kγ on airway inflammation and structural lung damage in a mouse model of CF lung disease. Methods. βENaC overexpressing mice (βENaC-Tg were backcrossed with PI3Kγ-deficient (PI3KγKO mice. Tissue damage was assessed by histology and morphometry and inflammatory cell number was evaluated in bronchoalveolar lavage fluid (BALF. Furthermore, we assessed the effect of a specific PI3Kγ inhibitor (AS-605240 on inflammatory cell number in BALF. Results. Genetic deletion of PI3Kγ decreased neutrophil numbers in BALF of PI3KγKO/βENaC-Tg mice, and this was associated with reduced emphysematous changes. Treatment with the PI3Kγ inhibitor AS-605240 decreased the number of neutrophils in BALF of βENaC-Tg mice, reproducing the effect observed with genetic deletion of the enzyme. Conclusions. These results demonstrate the biological efficacy of both genetic deletion and pharmacological inhibition of PI3Kγ in reducing chronic neutrophilic inflammation in CF-like lung disease in vivo.

  4. Induction of vascular remodeling in the lung by chronic house dust mite exposure.

    Science.gov (United States)

    Rydell-Törmänen, Kristina; Johnson, Jill R; Fattouh, Ramzi; Jordana, Manel; Erjefält, Jonas S

    2008-07-01

    Structural changes to the lung are associated with chronic asthma. In addition to alterations to the airway wall, asthma is associated with vascular modifications, although this aspect of remodeling is poorly understood. We sought to evaluate the character and kinetics of vascular remodeling in response to chronic aeroallergen exposure. Because many ovalbumin-driven models used to investigate allergic airway disease do so in the absence of persistent airway inflammation, we used a protocol of chronic respiratory exposure to house dust mite extract (HDME), which has been shown to induce persistent airway inflammation consistent with that seen in humans with asthma. Mice were exposed to HDME intranasally for 7 or 20 consecutive weeks, and resolution of the inflammatory and remodeling response to allergen was investigated 4 weeks after the end of a 7-week exposure protocol. Measures of vascular remodeling, including total collagen deposition, procollagen I production, endothelial and smooth muscle cell proliferation, smooth muscle area, and presence of myofibroblasts, were investigated histologically in lung vessels of different sizes and locations. We observed an increase in total collagen content, which did not resolve upon cessation of allergen exposure. Other parameters were significantly increased after 7 and/or 20 weeks of allergen exposure but returned to baseline after allergen withdrawal. We conclude that respiratory HDME exposure induces airway remodeling and pulmonary vascular remodeling, and, in accordance with airway remodeling, some components of these structural changes may be irreversible. PMID:18314535

  5. Haemodynamic effects of terbutaline in chronic obstructive airways disease.

    OpenAIRE

    Teule, G. J.; Majid, P A

    1980-01-01

    Terbutaline, a cardioselective beta-adrenoceptor agonist, administered intravenously (250 micrograms) to seven patients with chronic obstructive airways disease (mean FEV1 0.99 l) resulted in reduction of mean pulmonary artery pressure (resting 23 +/- 2 to 19 +/- 2 mmHg, p < 0.05; exercise 43 +/- 3 to 35 +/- 3 mmHg, p < 0.05) and calculated pulmonary vascular resistance (resting 168 +/- 27 to 109 +/- 17 dyne s cm-5, p < 0.01; exercise 170 +/- 30 to 119 +/- 18 dyne s cm-5, p < 0.01) accompanie...

  6. Eosinophils in the lung – modulating apoptosis and efferocytosis in airway inflammation

    Directory of Open Access Journals (Sweden)

    Jennifer M Felton

    2014-07-01

    Full Text Available Due to the key role of the lung in efficient transfer of oxygen in exchange for carbon dioxide, a controlled inflammatory response is essential for restoration of tissue homeostasis following airway exposure to bacterial pathogens or environmental toxins. Unregulated or prolonged inflammatory responses in the lungs can lead to tissue damage, disrupting normal tissue architecture and consequently compromising efficient gaseous exchange. Failure to resolve inflammation underlies the development and/or progression of a number of inflammatory lung diseases including asthma. Eosinophils, granulocytic cells of the innate immune system, are primarily involved in defence against parasitic infections. However, the propagation of the allergic inflammatory response in chronic asthma is thought to involve excessive recruitment and impaired apoptosis of eosinophils together with defective phagocytic clearance of apoptotic cells (efferocytosis. In terms of therapeutic approaches for treatment of asthma, the widespread use of glucocorticoids is associated with a number of adverse health consequences after long-term use, while some patients suffer from steroid-resistant disease. A new approach for therapeutic intervention would be to promote the resolution of inflammation via modulation of eosinophil apoptosis and the phagocytic clearance of apoptotic cells. This review focuses on the mechanisms underpinning eosinophil-mediated lung damage, currently available treatments and therapeutic targets that might in future be harnessed to facilitate inflammation resolution by the manipulation of cell survival and clearance pathways.

  7. Eosinophils in the lung - modulating apoptosis and efferocytosis in airway inflammation.

    Science.gov (United States)

    Felton, Jennifer M; Lucas, Christopher D; Rossi, Adriano G; Dransfield, Ian

    2014-01-01

    Due to the key role of the lung in efficient transfer of oxygen in exchange for carbon dioxide, a controlled inflammatory response is essential for restoration of tissue homeostasis following airway exposure to bacterial pathogens or environmental toxins. Unregulated or prolonged inflammatory responses in the lungs can lead to tissue damage, disrupting normal tissue architecture, and consequently compromising efficient gaseous exchange. Failure to resolve inflammation underlies the development and/or progression of a number of inflammatory lung diseases including asthma. Eosinophils, granulocytic cells of the innate immune system, are primarily involved in defense against parasitic infections. However, the propagation of the allergic inflammatory response in chronic asthma is thought to involve excessive recruitment and impaired apoptosis of eosinophils together with defective phagocytic clearance of apoptotic cells (efferocytosis). In terms of therapeutic approaches for the treatment of asthma, the widespread use of glucocorticoids is associated with a number of adverse health consequences after long-term use, while some patients suffer from steroid-resistant disease. A new approach for therapeutic intervention would be to promote the resolution of inflammation via modulation of eosinophil apoptosis and the phagocytic clearance of apoptotic cells. This review focuses on the mechanisms underpinning eosinophil-mediated lung damage, currently available treatments and therapeutic targets that might in future be harnessed to facilitate inflammation resolution by the manipulation of cell survival and clearance pathways. PMID:25071763

  8. Therapeutical Measures to Control Airway Tolerance in Asthma and Lung Cancer

    OpenAIRE

    Andreev, Katerina; Graser, Anna; Maier, Anja; Mousset, Stephanie; Finotto, Susetta

    2012-01-01

    Airway tolerance is a specialized immunological surveillance which is activated by the cells of the lung to deal with and distinguish between innocuous and pathogenic inhalants. However, this distinction does not always occur. Airway tolerance is necessary to avoid the development of allergic disorders, such as asthma, which is dominated by a pathological expansion of Th2 and Th17 cells in the airways. By contrast, tumor cells induce tolerogenic factors in their microenvironment to evade T-ce...

  9. Chronic cough in subjects with upper airway diseases - analysis of mechanisms and clinical applications

    OpenAIRE

    Plevkova, Jana; Song, Woo-Jung

    2013-01-01

    Cough is the commonest respiratory symptom leading to a medical consultation. Although acute cough which is usually associated with respiratory viral infection is not a problem to manage, chronic cough is frequently a diagnostic and therapeutic challenge as it does not respond to usual treatments. Specific group of chronic coughers are considered to have upper airway diseases, lately categorized as having upper airway cough syndrome. There is an increasing pool of evidence that upper airway d...

  10. Neutralization of TSLP inhibits airway remodeling in a murine model of allergic asthma induced by chronic exposure to house dust mite.

    Directory of Open Access Journals (Sweden)

    Zhuang-Gui Chen

    Full Text Available Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. However, the initiating factor that links airway inflammation to remodeling is unknown. Thymic stromal lymphopoietin (TSLP, an epithelium-derived cytokine, can strongly activate lung dendritic cells (DCs through the TSLP-TSLPR and OX40L-OX40 signaling pathways to promote Th2 differentiation. To determine whether TSLP is the underlying trigger of airway remodeling in chronic allergen-induced asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extracts for up to 5 consecutive weeks. We showed that repeated respiratory exposure to HDM caused significant airway eosinophilic inflammation, peribronchial collagen deposition, goblet cell hyperplasia, and airway hyperreactivity (AHR to methacholine. These effects were accompanied with a salient Th2 response that was characterized by the upregulation of Th2-typed cytokines, such as IL-4 and IL-13, as well as the transcription factor GATA-3. Moreover, the levels of TSLP and transforming growth factor beta 1 (TGF-β1 were also increased in the airway. We further demonstrated, using the chronic HDM-induced asthma model, that the inhibition of Th2 responses via neutralization of TSLP with an anti-TSLP mAb reversed airway inflammation, prevented structural alterations, and decreased AHR to methacholine and TGF-β1 level. These results suggest that TSLP plays a pivotal role in the initiation and persistence of airway inflammation and remodeling in the context of chronic allergic asthma.

  11. Chronic Bronchitis

    Science.gov (United States)

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Chronic bronchitis is one type ...

  12. Interleukin-1α drives the dysfunctional cross-talk of the airway epithelium and lung fibroblasts in COPD.

    Science.gov (United States)

    Osei, Emmanuel T; Noordhoek, Jacobien A; Hackett, Tillie L; Spanjer, Anita I R; Postma, Dirkje S; Timens, Wim; Brandsma, Corry-Anke; Heijink, Irene H

    2016-08-01

    Chronic obstructive pulmonary disease (COPD) has been associated with aberrant epithelial-mesenchymal interactions resulting in inflammatory and remodelling processes. We developed a co-culture model using COPD and control-derived airway epithelial cells (AECs) and lung fibroblasts to understand the mediators that are involved in remodelling and inflammation in COPD.AECs and fibroblasts obtained from COPD and control lung tissue were grown in co-culture with fetal lung fibroblast or human bronchial epithelial cell lines. mRNA and protein expression of inflammatory mediators, pro-fibrotic molecules and extracellular matrix (ECM) proteins were assessed.Co-culture resulted in the release of pro-inflammatory mediators interleukin (IL)-8/CXCL8 and heat shock protein (Hsp70) from lung fibroblasts, and decreased expression of ECM molecules (e.g. collagen, decorin) that was not different between control and COPD-derived primary cells. This pro-inflammatory effect was mediated by epithelial-derived IL-1α and increased upon epithelial exposure to cigarette smoke extract (CSE). When exposed to CSE, COPD-derived AECs elicited a stronger IL-1α response compared with control-derived airway epithelium and this corresponded with a significantly enhanced IL-8 release from lung fibroblasts.We demonstrate that, through IL-1α production, AECs induce a pro-inflammatory lung fibroblast phenotype that is further enhanced with CSE exposure in COPD, suggesting an aberrant epithelial-fibroblast interaction in COPD. PMID:27418555

  13. Adult stem cells for chronic lung diseases.

    Science.gov (United States)

    Mora, Ana L; Rojas, Mauricio

    2013-10-01

    Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are chronic, progressive and lethal lung diseases. The incidence of IPF and COPD increases with age, independent of exposure to common environmental risk factors. At present, there is limited understanding of the relationship between ageing and the development of chronic lung diseases. One hypothesis is that chronic injury drives to exhaustion the local and systemic repair responses in the lung. These changes are accentuated during ageing where there is a progressive accumulation of senescent cells. Recently, stem cells have emerged as a critical reparative mechanism for lung injury. In this review, we discuss the repair response of bone marrow-derived mesenchymal stem cells (B-MSC) after lung injury and how their function is affected by ageing. Our own work has demonstrated a protective role of B-MSC in several animal models of acute and chronic lung injury. We recently demonstrated the association, using animal models, between age and an increase in the susceptibility to develop severe injury and fibrosis. At the same time, we have identified functional differences between B-MSC isolated from young and old animals. Further studies are required to understand the functional impairment of ageing B-MSC, ultimately leading to a rapid stem cell depletion or fatigue, interfering with their ability to play a protective role in lung injury. The elucidation of these events will help in the development of rational and new therapeutic strategies for COPD and IPF. PMID:23648014

  14. Airway hyperresponsiveness and development of lung function in adolescence and adulthood

    DEFF Research Database (Denmark)

    Harmsen, Lotte; Ulrik, Charlotte S; Porsbjerg, Celeste;

    2014-01-01

    BACKGROUND: Long-term longitudinal studies of lung function from childhood to adulthood are important in linking our understanding of childhood risk factors to adult disease. Airway hyperresponsiveness has been shown to independently affect lung function growth in studies of adolescence. The...... objective of the study was to test the hypothesis that airway hyperresponsiveness has an independent deleterious effect on lung function in adolescence that extends into adulthood. METHODS: A random population sample (n = 983) aged 7-17 from Copenhagen was followed longitudinally for 20 years with four...... maximal attained level of lung function at age 18, which persisted throughout the follow-up until the last examination at age 27-37 years. CONCLUSION: Airway hyperresponsiveness has an independent deleterious effect on lung function development from 7 to 37 years resulting in a lower maximal attained lung...

  15. SIRT1 pathway dysregulation in the smoke-exposed airway epithelium and lung tumor tissue

    OpenAIRE

    Beane, Jennifer; Cheng, Luis; Soldi, Raffaella; Zhang, Xiaohui; Liu, Gang; Anderlind, Christina; Lenburg, Marc E.; Spira, Avrum; Bild, Andrea H

    2012-01-01

    Cigarette smoke produces a molecular “field of injury” in epithelial cells lining the respiratory tract. However, the specific signaling pathways that are altered in the airway of smokers and the signaling processes responsible for the transition from smoking-induced airway damage to lung cancer remain unknown. In this study, we use a genomic approach to study the signaling processes associated with tobacco smoke exposure and lung cancer. First, we developed and validated pathway-specific gen...

  16. Tracheobronchomalacia/excessive dynamic airway collapse in patients with chronic obstructive pulmonary disease with persistent expiratory wheeze: A pilot study

    Science.gov (United States)

    Sindhwani, Girish; Sodhi, Rakhee; Saini, Manju; Jethani, Varuna; Khanduri, Sushant; Singh, Baltej

    2016-01-01

    Background: Tracheobronchomalacia (TBM) refers to a condition in which structural integrity of cartilaginous wall of trachea is lost. Excessive dynamic airway collapse (EDAC) is characterized by excessive invagination of posterior wall of trachea. In both these conditions, airway lumen gets compromised, especially during expiration, which can lead to symptoms such as breathlessness, cough, and wheezing. Both these conditions can be present in obstructive lung diseases; TBM due to chronic airway inflammation and EDAC due to dynamic compressive forces during expiration. The present study was planned with the hypothesis that TBM/EDAC could also produce expiratory wheeze in patients with obstructive airway disorders. Hence, prevalence and factors affecting presence of this entity in patients with obstructive airway diseases were the aims and objectives of this study. Materials and Methods: Twenty-five patients with obstructive airway disorders (chronic obstructive pulmonary disease [COPD] or bronchial asthma), who were stable on medical management, but having persistent expiratory wheezing, were included in the study. They were evaluated for TBM/EDAC by bronchoscopy and computed tomographic scan of chest. The presence of TBM/EDAC was correlated with variables including age, sex, body mass index (BMI), smoking index, level of dyspnea, and severity of disease. Results: Mean age of the patients was 62.7 ± 7.81 years. Out of 25 patients, 14 were males. TBM/EDAC was found in 40% of study subjects. Age, sex, BMI, severity of disease, frequency of exacerbations and radiological findings etc., were not found to have any association with presence of TBM/EDAC. Conclusion: TBM/EDAC is common in patients with obstructive airway disorders and should be evaluated in these patients, especially with persistent expiratory wheezing as diagnosis of this entity could provide another treatment option in these patients with persistent symptoms despite medical management.

  17. Predominant constitutive CFTR conductance in small airways

    OpenAIRE

    Lytle Christian; Wang Xiaofei; Quinton Paul M

    2005-01-01

    Abstract Background The pathological hallmarks of chronic obstructive pulmonary disease (COPD) are inflammation of the small airways (bronchiolitis) and destruction of lung parenchyma (emphysema). These forms of disease arise from chronic prolonged infections, which are usually never present in the normal lung. Despite the fact that primary hygiene and defense of the airways presumably requires a well controlled fluid environment on the surface of the bronchiolar airway, very little is known ...

  18. Magnetic resonance imaging in children: common problems and possible solutions for lung and airways imaging

    OpenAIRE

    Ciet, Pierluigi; Tiddens, Harm A. W. M.; Wielopolski, Piotr A.; Wild, Jim M.; Lee, Edward Y.; Morana, Giovanni; Lequin, Maarten H.

    2015-01-01

    Pediatric chest MRI is challenging. High-resolution scans of the lungs and airways are compromised by long imaging times, low lung proton density and motion. Low signal is a problem of normal lung. Lung abnormalities commonly cause increased signal intenstities. Among the most important factors for a successful MRI is patient cooperation, so the long acquisition times make patient preparation crucial. Children usually have problems with long breath-holds and with the concept of quiet breathin...

  19. Small airway dysfunction and flow and volume bronchodilator responsiveness in patients with chronic obstructive pulmonary disease

    Science.gov (United States)

    Pisi, Roberta; Aiello, Marina; Zanini, Andrea; Tzani, Panagiota; Paleari, Davide; Marangio, Emilio; Spanevello, Antonio; Nicolini, Gabriele; Chetta, Alfredo

    2015-01-01

    Background We investigated whether a relationship between small airways dysfunction and bronchodilator responsiveness exists in patients with chronic obstructive pulmonary disease (COPD). Methods We studied 100 (20 female; mean age: 68±10 years) patients with COPD (forced expiratory volume in 1 second [FEV1]: 55% pred ±21%; FEV1/forced vital capacity [FVC]: 53%±10%) by impulse oscillometry system. Resistance at 5 Hz and 20 Hz (R5 and R20, in kPa·s·L−1) and the fall in resistance from 5 Hz to 20 Hz (R5 – R20) were used as indices of total, proximal, and peripheral airway resistance; reactance at 5 Hz (X5, in kPa·s·L−1) was also measured. Significant response to bronchodilator (salbutamol 400 μg) was expressed as absolute (≥0.2 L) and percentage (≥12%) change relative to the prebronchodilator value of FEV1 (flow responders, FRs) and FVC (volume responders, VRs). Results Eighty out of 100 participants had R5 – R20 >0.03 kPa·s·L−1 (> upper normal limit) and, compared to patients with R5 – R20 ≤0.030 kPa·s·L−1, showed a poorer health status, lower values of FEV1, FVC, FEV1/FVC, and X5, along with higher values of residual volume/total lung capacity and R5 (Preactance, worse spirometry results, more severe lung hyperinflation, and poorer health status. Small airway dysfunction was also associated with the bronchodilator responsiveness in terms of FVC, but not in terms of FEV1. PMID:26150710

  20. Generation of ESC-derived Mouse Airway Epithelial Cells Using Decellularized Lung Scaffolds.

    Science.gov (United States)

    Shojaie, Sharareh; Lee, Joyce; Wang, Jinxia; Ackerley, Cameron; Post, Martin

    2016-01-01

    Lung lineage differentiation requires integration of complex environmental cues that include growth factor signaling, cell-cell interactions and cell-matrix interactions. Due to this complexity, recapitulation of lung development in vitro to promote differentiation of stem cells to lung epithelial cells has been challenging. In this protocol, decellularized lung scaffolds are used to mimic the 3-dimensional environment of the lung and generate stem cell-derived airway epithelial cells. Mouse embryonic stem cell are first differentiated to the endoderm lineage using an embryoid body (EB) culture method with activin A. Endoderm cells are then seeded onto decellularized scaffolds and cultured at air-liquid interface for up to 21 days. This technique promotes differentiation of seeded cells to functional airway epithelial cells (ciliated cells, club cells, and basal cells) without additional growth factor supplementation. This culture setup is defined, serum-free, inexpensive, and reproducible. Although there is limited contamination from non-lung endoderm lineages in culture, this protocol only generates airway epithelial populations and does not give rise to alveolar epithelial cells. Airway epithelia generated with this protocol can be used to study cell-matrix interactions during lung organogenesis and for disease modeling or drug-discovery platforms of airway-related pathologies such as cystic fibrosis. PMID:27214388

  1. Cough sensitivity and extrathoracic airway responsiveness to inhaled capsaicin in chronic cough patients.

    OpenAIRE

    Cho, You Sook; Lee, Chang-Keun; Yoo, Bin; Moon, Hee-Bom

    2002-01-01

    Enhanced cough response has been frequently observed in chronic cough. Recently, extrathoracic airway constriction to inhaled histamine was demonstrated in some chronic cough patients. However, relation between extrathoracic airway hyperresponsiveness (EAHR) and cough sensitivity determined by capsaicin inhalation is unclear in each etiological entity of chronic cough. Seventy-seven patients, with dry cough persisting for 3 or more weeks, normal spirometry and chest radiography, and 15 contro...

  2. Association between chronic obstructive pulmonary disease and lung cancer: the missing link

    Institute of Scientific and Technical Information of China (English)

    WANG Zeng-li

    2013-01-01

    Objective This review focuses on current knowledge of specific processes that drive chronic airway inflammation which are important in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and lung cancer.Data sources The data used in this review were obtained mainly from studies reported in the PubMed database (1997-2012) using the terms of COPD and lung cancer.Study selection Data from published articles about prevalence of COPD-lung cancer overlap and mechanism involved in lung cancer development in COPD were identified,retrieved and reviewed.Results COPD prevalence,morbidity and mortality vary and are directly related to the prevalence of tobacco smoking except in developing countries where air pollution resulting from the burning of biomass fuels is also important.COPD is characterized by a chronic inflammation of lower airway and,importantly,the presence of COPD increases the risk of lung cancer up to 4.5 fold among long-term smokers.COPD is by far the greatest risk factor for lung cancer amongst smokers and is found in 50%-90% of patients with lung cancer.Conclusions Both COPD and lung cancer are tobacco smoking-associated chronic diseases that cluster in families and aggravate with age,and 50%-70% of patients diagnosed with lung cancer have declined spirometric evidence of COPD.Understanding and targeting common pathogenic mechanisms for lung cancer and COPD would have potential diagnostic and therapeutic implications for patients with these lung diseases and for people at risk.

  3. Hypoxia-induced pulmonary arterial hypertension augments lung injury and airway reactivity caused by ozone exposure.

    Science.gov (United States)

    Zychowski, Katherine E; Lucas, Selita N; Sanchez, Bethany; Herbert, Guy; Campen, Matthew J

    2016-08-15

    Ozone (O3)-related cardiorespiratory effects are a growing public health concern. Ground level O3 can exacerbate pre-existing respiratory conditions; however, research regarding therapeutic interventions to reduce O3-induced lung injury is limited. In patients with chronic obstructive pulmonary disease, hypoxia-associated pulmonary hypertension (HPH) is a frequent comorbidity that is difficult to treat clinically, yet associated with increased mortality and frequency of exacerbations. In this study, we hypothesized that established HPH would confer vulnerability to acute O3 pulmonary toxicity. Additionally, we tested whether improvement of pulmonary endothelial barrier integrity via rho-kinase inhibition could mitigate pulmonary inflammation and injury. To determine if O3 exacerbated HPH, male C57BL/6 mice were subject to either 3 weeks continuous normoxia (20.9% O2) or hypoxia (10.0% O2), followed by a 4-h exposure to either 1ppm O3 or filtered air (FA). As an additional experimental intervention fasudil (20mg/kg) was administered intraperitoneally prior to and after O3 exposures. As expected, hypoxia significantly increased right ventricular pressure and hypertrophy. O3 exposure in normoxic mice caused lung inflammation but not injury, as indicated by increased cellularity and edema in the lung. However, in hypoxic mice, O3 exposure led to increased inflammation and edema, along with a profound increase in airway hyperresponsiveness to methacholine. Fasudil administration resulted in reduced O3-induced lung injury via the enhancement of pulmonary endothelial barrier integrity. These results indicate that increased pulmonary vascular pressure may enhance lung injury, inflammation and edema when exposed to pollutants, and that enhancement of pulmonary endothelial barrier integrity may alleviate such vulnerability. PMID:27286659

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

    Directory of Open Access Journals (Sweden)

    R Patil

    2012-03-01

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

  5. S-nitrosoglutathione reductase inhibition regulates allergen-induced lung inflammation and airway hyperreactivity.

    Directory of Open Access Journals (Sweden)

    Maria E Ferrini

    Full Text Available Allergic asthma is characterized by Th2 type inflammation, leading to airway hyperresponsivenes, mucus hypersecretion and tissue remodeling. S-Nitrosoglutathione reductase (GSNOR is an alcohol dehydrogenase involved in the regulation of intracellular levels of S-nitrosothiols. GSNOR activity has been shown to be elevated in human asthmatic lungs, resulting in diminished S-nitrosothiols and thus contributing to increased airway hyperreactivity. Using a mouse model of allergic airway inflammation, we report that intranasal administration of a new selective inhibitor of GSNOR, SPL-334, caused a marked reduction in airway hyperreactivity, allergen-specific T cells and eosinophil accumulation, and mucus production in the lungs in response to allergen inhalation. Moreover, SPL-334 treatment resulted in a significant decrease in the production of the Th2 cytokines IL-5 and IL-13 and the level of the chemokine CCL11 (eotaxin-1 in the airways. Collectively, these observations reveal that GSNOR inhibitors are effective not only in reducing airway hyperresponsiveness but also in limiting lung inflammatory responses mediated by CD4(+ Th2 cells. These findings suggest that the inhibition of GSNOR may provide a novel therapeutic approach for the treatment of allergic airway inflammation.

  6. HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation.

    Directory of Open Access Journals (Sweden)

    Kieran A Brune

    Full Text Available Several clinical studies show that individuals with HIV are at an increased risk for worsened lung function and for the development of COPD, although the mechanism underlying this increased susceptibility is poorly understood. The airway epithelium, situated at the interface between the external environment and the lung parenchyma, acts as a physical and immunological barrier that secretes mucins and cytokines in response to noxious stimuli which can contribute to the pathobiology of chronic obstructive pulmonary disease (COPD. We sought to determine the effects of HIV on the lung epithelium. We grew primary normal human bronchial epithelial (NHBE cells and primary lung epithelial cells isolated from bronchial brushings of patients to confluence and allowed them to differentiate at an air- liquid interface (ALI to assess the effects of HIV on the lung epithelium. We assessed changes in monolayer permeability as well as the expression of E-cadherin and inflammatory modulators to determine the effect of HIV on the lung epithelium. We measured E-cadherin protein abundance in patients with HIV compared to normal controls. Cell associated HIV RNA and DNA were quantified and the p24 viral antigen was measured in culture supernatant. Surprisingly, X4, not R5, tropic virus decreased expression of E-cadherin and increased monolayer permeability. While there was some transcriptional regulation of E-cadherin, there was significant increase in lysosome-mediated protein degradation in cells exposed to X4 tropic HIV. Interaction with CXCR4 and viral fusion with the epithelial cell were required to induce the epithelial changes. X4 tropic virus was able to enter the airway epithelial cells but not replicate in these cells, while R5 tropic viruses did not enter the epithelial cells. Significantly, X4 tropic HIV induced the expression of intercellular adhesion molecule-1 (ICAM-1 and activated extracellular signal-regulated kinase (ERK. We demonstrate that HIV

  7. Regional lung aeration and ventilation during pressure support and biphasic positive airway pressure ventilation in experimental lung injury

    OpenAIRE

    Gama de Abreu, Marcelo; Cuevas, Maximiliano; Spieth, Peter M; Carvalho, Alysson R; Hietschold, Volker; Stroszczynski, Christian; Wiedemann, Bärbel; Koch, Thea; Pelosi, Paolo; Koch, Edmund

    2010-01-01

    Introduction There is an increasing interest in biphasic positive airway pressure with spontaneous breathing (BIPAP+SBmean), which is a combination of time-cycled controlled breaths at two levels of continuous positive airway pressure (BIPAP+SBcontrolled) and non-assisted spontaneous breathing (BIPAP+SBspont), in the early phase of acute lung injury (ALI). However, pressure support ventilation (PSV) remains the most commonly used mode of assisted ventilation. To date, the effects of BIPAP+SBm...

  8. Biphasic positive airway pressure minimizes biological impact on lung tissue in mild acute lung injury independent of etiology

    OpenAIRE

    Saddy, Felipe; Moraes, Lillian; Santos, Cintia Lourenço; Oliveira, Gisele Pena; Cruz, Fernanda Ferreira; Morales, Marcelo Marcos; Capelozzi, Vera Luiza; de Abreu, Marcelo Gama; Baez Garcia, Cristiane Souza Nascimento; Pelosi, Paolo; Rocco, Patricia Rieken Macêdo

    2013-01-01

    Introduction Biphasic positive airway pressure (BIVENT) is a partial support mode that employs pressure-controlled, time-cycled ventilation set at two levels of continuous positive airway pressure with unrestricted spontaneous breathing. BIVENT can modulate inspiratory effort by modifying the frequency of controlled breaths. Nevertheless, the optimal amount of inspiratory effort to improve respiratory function while minimizing ventilator-associated lung injury during partial ventilatory assis...

  9. Application of indigenous continuous positive airway pressure during one lung ventilation for thoracic surgery

    OpenAIRE

    Rahul Yadav; Arvind Chaturvedi; Girija Prasad Rath; Keshav Goyal

    2011-01-01

    During one lung ventilation (OLV) hypoxemia may occur due to ventilation-perfusion mismatch. It can be prevented with application of ventilation strategy that prevents atelectasis while minimally impairing perfusion of the dependant lung. Here, two cases are reported who required OLV and in whom hypoxemia could be prevented with the application of continuous positive airway pressure to the deflated or non-dependant lung, using an indigenous technique. We suggest use of this technique which is...

  10. ISO-1, a macrophage migration inhibitory factor antagonist, inhibits airway remodeling in a murine model of chronic asthma.

    Science.gov (United States)

    Chen, Pei-Fen; Luo, Ya-ling; Wang, Wei; Wang, Jiang-xin; Lai, Wen-yan; Hu, Si-ming; Cheng, Kai Fan; Al-Abed, Yousef

    2010-01-01

    Airway remodeling is the process of airway structural change that occurs in patients with asthma in response to persistent inflammation and leads to increasing disease severity. Drugs that decrease this persistent inflammation play a crucial role in managing asthma episodes. Mice sensitized (by intraperitoneal administration) and then challenged (by inhalation) with ovalbumin (OVA) develop an extensive eosinophilic inflammatory response, goblet cell hyperplasia, collagen deposition, airway smooth muscle thickening, and airway wall area increase, similar to pathologies observed in human asthma. We used OVA-sensitized/challenged mice as a murine model of chronic allergic airway inflammation with subepithelial fibrosis (i.e., asthma). In this OVA mouse model, mRNA and protein of macrophage migration inhibitory factor (MIF) are upregulated, a response similar to what has been observed in the pathogenesis of acute inflammation in human asthma. We hypothesized that MIF induces transforming growth factor-β1 (TGF-β1) synthesis, which has been shown to play an important role in asthma and airway remodeling. To explore the role of MIF in the development of airway remodeling, we evaluated the effects of an MIF small-molecule antagonist, (S,R)3-(4-hy-droxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), on pathologies associated with the airway-remodeling process in the OVA mouse model. We found that administration of ISO-1 significantly mitigated all symptoms caused by OVA treatment. In addition, the treatment of OVA-sensitized mice with the MIF antagonist ISO-1 significantly reduced TGF-β1 mRNA levels in pulmonary tissue and its protein level in bronchial alveolar lavage fluid supernatants. We believe the repression of MIF in the ISO-1 treatment group led to the significant suppression observed in the inflammatory responses associated with the allergen-induced lung inflammation and fibrosis in our murine asthma (OVA) model. Our results implicate a

  11. Update on the "Dutch hypothesis" for chronic respiratory disease

    DEFF Research Database (Denmark)

    Vestbo, J; Prescott, E

    1998-01-01

    BACKGROUND: Many patients with chronic obstructive lung disease show increased airways responsiveness to histamine. We investigated the hypothesis that increased airways responsiveness predicts the development and remission of chronic respiratory symptoms. METHODS: We used data from 24-year follow...

  12. Comparison of airway responses in sheep of different age in precision-cut lung slices (PCLS.

    Directory of Open Access Journals (Sweden)

    Verena A Lambermont

    Full Text Available Animal models should display important characteristics of the human disease. Sheep have been considered particularly useful to study allergic airway responses to common natural antigens causing human asthma. A rationale of this study was to establish a model of ovine precision-cut lung slices (PCLS for the in vitro measurement of airway responses in newborn and adult animals. We hypothesized that differences in airway reactivity in sheep are present at different ages.Lambs were delivered spontaneously at term (147d and adult sheep lived till 18 months. Viability of PCLS was confirmed by the MTT-test. To study airway provocations cumulative concentration-response curves were performed with different allergic response mediators and biogenic amines. In addition, electric field stimulation, passive sensitization with house dust mite (HDM and mast cells staining were evaluated.PCLS from sheep were viable for at least three days. PCLS of newborn and adult sheep responded equally strong to methacholine and endothelin-1. The responses to serotonin, leukotriene D4 and U46619 differed with age. No airway contraction was evoked by histamine, except after cimetidine pretreatment. In response to EFS, airways in PCLS from adult and newborn sheep strongly contracted and these contractions were atropine sensitive. Passive sensitization with HDM evoked a weak early allergic response in PCLS from adult and newborn sheep, which notably was prolonged in airways from adult sheep. Only few mast cells were found in the lungs of non-sensitized sheep at both ages.PCLS from sheep lungs represent a useful tool to study pharmacological airway responses for at least three days. Sheep seem well suited to study mechanisms of cholinergic airway contraction. The notable differences between newborn and adult sheep demonstrate the importance of age in such studies.

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

    OpenAIRE

    Patil, R.; KG Basavarajappa; K Nagendra; D. Sanjay; C Gouli; CS CS VinodKumar; NK Kalappanavar

    2012-01-01

    Background: It has been shown that inhalation of carbonaceous particulate matter may impair lung function in children. Objective: Using the carbon content of airway macrophages as a marker of individual exposure to particulate matter derived from fossil fuel, we sought direct evidence for this association.Methods: 300 children from puffed rice industrial areas and 300 children from population living in green zone were selected randomly. Airway macrophages were obtained from healthy children t...

  14. Lung function and airway inflammation monitoring after hematopoietic stem cell transplantation.

    OpenAIRE

    Moermans, Catherine; Poulet, Christophe; Henket, Monique; Bonnet, Christophe; WILLEMS, Evelyne; Baron, Frédéric; Beguin, Yves; Louis, Renaud

    2013-01-01

    Background Induced sputum is a non-invasive method to investigate airway inflammation, which has been used to assess pulmonary inflammatory diseases. However, this procedure has not been studied in the context of hematopoietic stem cell transplantation (HSCT). Methods We monitored lung function in 182 patients who underwent HSCT and measured airway inflammation by sputum induction in 80 of them. We prospectively measured FEV1, FVC, DLCO, KCO, TLC, RV, exhaled nitric oxide (FeNO) as ...

  15. Airway wall thickening and emphysema show independent familial aggregation in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Patel, Bipen D; Coxson, Harvey O; Pillai, Sreekumar G;

    2008-01-01

    RATIONALE: It is unclear whether airway wall thickening and emphysema make independent contributions to airflow limitation in chronic obstructive pulmonary disease (COPD) and whether these phenotypes cluster within families. OBJECTIVES: To determine whether airway wall thickening and emphysema (1...... severity of airway wall thickening and emphysema. MEASUREMENTS AND MAIN RESULTS: A total of 3,096 individuals were recruited to the study, of whom 1,159 (519 probands and 640 siblings) had technically adequate high-resolution computed tomography scans without significant non-COPD-related thoracic disease....... Airway wall thickness correlated with pack-years smoked (P < or = 0.001) and symptoms of chronic bronchitis (P < 0.001). FEV(1) (expressed as % predicted) was independently associated with airway wall thickness at a lumen perimeter of 10 mm (P = 0.0001) and 20 mm (P = 0.0013) and emphysema at -950...

  16. Ultrafine particles in the airway aggravated experimental lung injury through impairment in Treg function.

    Science.gov (United States)

    Li, Guanggang; Cao, Yinghua; Sun, Yue; Xu, Ruxiang; Zheng, Zhendong; Song, Haihan

    2016-09-01

    Acute lung injury (ALI) is a life-threatening condition characterized by rapid-onset alveolar-capillary damage mediated by pathogenic proinflammatory immune responses. Since exposure to airway particulate matter (PM) could significantly change the inflammatory status of the individual, we investigated whether PM instillation in the airway could alter the course of ALI, using a murine model with experimental lung injury induced by intratracheal LPS challenge. We found that PM-treated mice presented significantly aggravated lung injury, which was characterized by further reductions in body weight, increased protein concentration in the bronchoalveolar lavage (BAL), and higher mortality rate, compared to control saline-treated mice. The PM-treated mice also presented elevated lung and systemic type 1 T helper cell (Th1) frequency as well as reduced lung regulatory T cell (Treg) frequency, which was associated with severity of lung injury. Further examinations revealed that the Treg function was impaired in PM-treated mice, characterized by significantly repressed transforming growth factor beta production. Adoptive transfer of functional Tregs from control mice to PM-treated mice significantly improved their prognosis after intratracheal LPS challenge. Together, these results demonstrated that first, PM in the airway aggravated lung injury; second, severity of lung injury was associated with T cell subset imbalance in PM-treated mice; and third, PM treatment induced quantitative as well as qualitative changes in the Tregs. PMID:27179778

  17. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model.

    Science.gov (United States)

    Bonfield, Tracey L; Koloze, Mary; Lennon, Donald P; Zuchowski, Brandon; Yang, Sung Eun; Caplan, Arnold I

    2010-12-01

    Allogeneic human mesenchymal stem cells (hMSCs) introduced intravenously can have profound anti-inflammatory activity resulting in suppression of graft vs. host disease as well as regenerative events in the case of stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of these diseases. hMSCs produce bioactive factors that provide molecular cuing for: 1) immunosuppression of T cells; 2) antiscarring; 3) angiogenesis; 4) antiapoptosis; and 5) regeneration (i.e., mitotic for host-derived progenitor cells). Studies have shown that hMSCs have profound effects on the immune system and are well-tolerated and therapeutically active in immunocompetent rodent models of multiple sclerosis and stroke. Furthermore, intravenous administration of MSCs results in pulmonary localization. Asthma is a major debilitating pulmonary disease that impacts in excess of 150 million people in the world with uncontrolled asthma potentially leading to death. In addition, the socioeconomic impact of asthma-associated illnesses at the pediatric and adult level are in the millions of dollars in healthcare costs and lost days of work. hMSCs may provide a viable multiaction therapeutic for this inflammatory lung disease by secreting bioactive factors or directing cellular activity. Our studies show the effectiveness and specificity of the hMSCs on decreasing chronic airway inflammation associated with the murine ovalbumin model of asthma. In addition, the results from these studies verify the in vivo immunoeffectiveness of hMSCs in rodents and support the potential therapeutic use of hMSCs for the treatment of airway inflammation associated with chronic asthma. PMID:20817776

  18. Chronic inflammatory airway diseases: the central role of the epithelium revisited.

    Science.gov (United States)

    Gohy, S T; Hupin, C; Pilette, C; Ladjemi, M Z

    2016-04-01

    The respiratory epithelium plays a critical role for the maintenance of airway integrity and defense against inhaled particles. Physical barrier provided by apical junctions and mucociliary clearance clears inhaled pathogens, allergens or toxics, to prevent continuous stimulation of adaptive immune responses. The "chemical barrier", consisting of several anti-microbial factors such as lysozyme and lactoferrin, constitutes another protective mechanism of the mucosae against external aggressions before adaptive immune response starts. The reconstruction of damaged respiratory epithelium is crucial to restore this barrier. This review examines the role of the airway epithelium through recent advances in health and chronic inflammatory diseases in the lower conducting airways (in asthma and chronic obstructive pulmonary disease). Better understanding of normal and altered epithelial functions continuously provides new insights into the physiopathology of chronic airway diseases and should help to identify new epithelial-targeted therapies. PMID:27021118

  19. Small airway dysfunction and flow and volume bronchodilator responsiveness in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Pisi R

    2015-06-01

    Full Text Available Roberta Pisi,1 Marina Aiello,1 Andrea Zanini,2 Panagiota Tzani,1 Davide Paleari,3 Emilio Marangio,1 Antonio Spanevello,2,4 Gabriele Nicolini,5 Alfredo Chetta1 1Department of Clinical and Experimental Medicine, University of Parma, Parma, 2Division of Pneumology, IRCCS Rehabilitation Institute of Tradate, Salvatore Maugeri Foundation, Tradate, 3Medical Department, Chiesi Farmaceutici SpA, Parma, 4Department of Clinical and Experimental Medicine, University of Insubria, Varese, 5Corporate Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy Background: We investigated whether a relationship between small airways dysfunction and bronchodilator responsiveness exists in patients with chronic obstructive pulmonary disease (COPD.Methods: We studied 100 (20 female; mean age: 68±10 years patients with COPD (forced expiratory volume in 1 second [FEV1]: 55% pred ±21%; FEV1/forced vital capacity [FVC]: 53%±10% by impulse oscillometry system. Resistance at 5 Hz and 20 Hz (R5 and R20, in kPa·s·L-1 and the fall in resistance from 5 Hz to 20 Hz (R5 – R20 were used as indices of total, proximal, and peripheral airway resistance; reactance at 5 Hz (X5, in kPa·s·L-1 was also measured. Significant response to bronchodilator (salbutamol 400 µg was expressed as absolute (≥0.2 L and percentage (≥12% change relative to the prebronchodilator value of FEV1 (flow responders, FRs and FVC (volume responders, VRs.Results: Eighty out of 100 participants had R5 – R20 >0.03 kPa·s·L-1 (> upper normal limit and, compared to patients with R5 – R20 ≤0.030 kPa·s·L-1, showed a poorer health status, lower values of FEV1, FVC, FEV1/FVC, and X5, along with higher values of residual volume/total lung capacity and R5 (P<0.05 for all comparisons. Compared to the 69 nonresponders and the 8 FRs, the 16 VRs had significantly higher R5 and R5 – R20 values (P<0.05, lower X5 values (P<0.05, and greater airflow obstruction and lung

  20. The role of stem cells in airway repair: implications for the origins of lung cancer

    OpenAIRE

    Mulvihill, Michael S.; Kratz, Johannes R.; Patrick Pham; Jablons, David M.; Biao He

    2013-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. Recently, advancements in our ability to identify and study stem cell populations in the lung have helped researchers to elucidate the central role that cells with stem cell-like properties may have in lung tumorigenesis. Much of this research has focused on the use of the airway repair model to study response to injury. In this review, we discuss the primary evidence of the role that cancer stem cells play in lung cancer de...

  1. Bystander suppression of allergic airway inflammation by lung resident memory CD8+ T cells

    Science.gov (United States)

    Marsland, Benjamin J.; Harris, Nicola L.; Camberis, Mali; Kopf, Manfred; Hook, Sarah M.; Le Gros, Graham

    2004-04-01

    CD8+ memory T cells have recently been recognized as playing a key role in natural immunity against unrelated viral infections, a phenomenon referred to as "heterologous antiviral immunity." We now provide data that the cellular immunological interactions that underlie such heterologous immunity can play an equally important role in regulating T helper 2 immune responses and protecting mucosal surfaces from allergen-induced inflammation. Our data show that CD8+ T cells, either retained in the lung after infection with influenza virus, or adoptively transferred via the intranasal route can suppress allergic airway inflammation. The suppression is mediated by IFN-, which acts to reduce the activation level, T helper 2 cytokine production, airways hyperresponsiveness, and migration of allergen-specific CD4+ T cells into the lung, whereas the systemic and draining lymph node responses remain unchanged. Of note, adoptive transfer of previously activated transgenic CD8+ T cells conferred protection against allergic airway inflammation, even in the absence of specific-antigen. Airway resident CD8+ T cells produced IFN- when directly exposed to conditioned media from activated dendritic cells or the proinflammatory cytokines IL-12 and IL-18. Taken together these data indicate that effector/memory CD8+ T cells present in the airways produce IFN- after inflammatory stimuli, independent of specific-antigen, and as a consequence play a key role in modifying the degree and frequency of allergic responses in the lung.

  2. Sliding thin slab, minimum intensity projection of the lung in asymptomatic subjects: lower limits of lung attenuation, without airways

    International Nuclear Information System (INIS)

    A sliding thin slab, minimum intensity projection (STS-MinIP) is considered to be useful for detecting diseases that decrease lung attenuation. For evaluating these diseases, it would be useful to ascertain the lower limits of normal lung attenuation, allowing a division between normal and subnormal attenuation. However, normal lung attenuation may vary depending on respiratory status, anatomical position, and patient background factors. Our aim was to determine whether the lower limits of lung attenuation, without airways, in asymptomatic subjects using STS-MinIP varies under different conditions. The study subjects were 43 volunteers without pulmonary symptoms. STS-MinIP was performed at full inspiration and full expiration at three levels of the lung. The lower limits of lung attenuation were compared among the three lung levels and between full inspiration and full expiration, the sexes, age groups, smokers and nonsmokers, and the right and left lungs. The lower limits of lung attenuation had significantly different Hounsfield unit values among lung levels, between the sexes at full inspiration, and between age groups at full expiration. This study shows that the lower limits of lung attenuation are influenced by lung fields, sex, and, on expiration, age. (author)

  3. Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance

    OpenAIRE

    Soroosh, Pejman; Doherty, Taylor A.; Duan, Wei; Mehta, Amit Kumar; Choi, Heonsik; Adams, Yan Fei; Mikulski, Zbigniew; Khorram, Naseem; Rosenthal, Peter; Broide, David H.; Croft, Michael

    2013-01-01

    Airway tolerance is the usual outcome of inhalation of harmless antigens. Although T cell deletion and anergy are likely components of tolerogenic mechanisms in the lung, increasing evidence indicates that antigen-specific regulatory T cells (inducible Treg cells [iTreg cells]) that express Foxp3 are also critical. Several lung antigen-presenting cells have been suggested to contribute to tolerance, including alveolar macrophages (MØs), classical dendritic cells (DCs), and plasmacytoid DCs, b...

  4. Effects of pulmonary vascular pressures and flow on airway and parenchymal mechanics in isolated rat lungs

    OpenAIRE

    Petak, Ferenc; Habre, Walid; Hantos, Zoltán; Peter D Sly; Morel, Denis

    2002-01-01

    Changes in pulmonary hemodynamics have been shown to alter the mechanical properties of the lungs, but the exact mechanisms are not clear. We therefore investigated the effects of alterations in pulmonary vascular pressure and flow (Q(p)) on the mechanical properties of the airways and the parenchyma by varying these parameters independently in three groups of isolated perfused normal rat lungs. The pulmonary capillary pressure (Pc(est)), estimated from the pulmonary arterial (Ppa) and left a...

  5. Effect of Hedera helix on lung histopathology in chronic asthma.

    Directory of Open Access Journals (Sweden)

    Arzu Babayigit Hocaoglu

    2012-12-01

    Full Text Available Hedera helix  is widely used to treat bronchial asthma for many years. However, effects of this herb on lung histopathology is still far from clear. We aimed to determine the effect of oral administration of Hedera helix on lung histopathology in a murine model of chronic asthma.BALB/c  mice  were  divided  into  four  groups;   I  (Placebo,  II  (Hedera  helix, III (Dexamethasone and IV (Control. All mice except controls were sensitized and challenged with ovalbumin. Then, mice in group I received saline, group II 100 mg/kg Hedera helix and group III 1 mg/kg  dexamethasone via orogastic gavage once daily for one week. Airway histopathology was evaluated by using light and electron microscopy in all groups.Goblet  cell numbers and thicknesses of basement membrane were found  significantly lower in group II, but there was no statistically significant difference in terms of number of mast cells, thicknesses of epithelium and subepithelial smooth muscle layers between group I and II. When Hedera helix and dexamethasone groups were compared with each other, thickness of epithelium, subepithelial muscle layers, number of mast cells and goblet cells of group III were significantly ameliorated when compared with the group II.Although Hedera helix administration reduced only goblet cell counts and the thicknesses of basement membrane  in the  asthmatic airways, dexamethasone ameliorated all histopathologic parameters except thickness of  basement  membrane  better  than  Hedera helix.

  6. DEVELOPMENT OF THE HUMAN LUNG MEASURED BY AEROSOL-DERIVED AIRWAY MORPHEMETRY (ADAM).

    Science.gov (United States)

    We measured, in vivo, the airspace calibers of the small airways and alveoli by ADAM in the lungs of children of ages 6 to 18 years and adults aged 18 to 80 years. ADAM utilizes the gravitational settling time of inhaled monodisperse particles to infer the vertical distance to th...

  7. Environmental and genetic risk factors and gene-environment interactions in the pathogenesis of chronic obstructive lung disease.

    OpenAIRE

    Walter, R.; Gottlieb, D. J.; O'Connor, G T

    2000-01-01

    Current understanding of the pathogenesis of chronic obstructive pulmonary disease (COPD), a source of substantial morbidity and mortality in the United States, suggests that chronic inflammation leads to the airways obstruction and parenchymal destruction that characterize this condition. Environmental factors, especially tobacco smoke exposure, are known to accelerate longitudinal decline of lung function, and there is substantial evidence that upregulation of inflammatory pathways plays a ...

  8. Airway CD8(+) T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection.

    Science.gov (United States)

    Connors, Thomas J; Ravindranath, Thyyar M; Bickham, Kara L; Gordon, Claire L; Zhang, Feifan; Levin, Bruce; Baird, John S; Farber, Donna L

    2016-06-01

    Infants and young children are disproportionately susceptible to severe complications from respiratory viruses, although the underlying mechanisms remain unknown. Recent studies show that the T cell response in the lung is important for protective responses to respiratory infections, although details on the infant/pediatric respiratory immune response remain sparse. The objectives of the present study were to characterize the local versus systemic immune response in infants and young children with respiratory failure from viral respiratory tract infections and its association to disease severity. Daily airway secretions were sampled from infants and children 4 years of age and younger receiving mechanical ventilation owing to respiratory failure from viral infection or noninfectious causes. Samples were examined for immune cell composition and markers of T cell activation. These parameters were then correlated with clinical disease severity. Innate immune cells and total CD3(+) T cells were present in similar proportions in airway aspirates derived from infected and uninfected groups; however, the CD8:CD4 T cell ratio was markedly increased in the airways of patients with viral infection compared with uninfected patients, and specifically in infected infants with acute lung injury. T cells in the airways were phenotypically and functionally distinct from those in blood with activated/memory phenotypes and increased cytotoxic capacity. We identified a significant increase in airway cytotoxic CD8(+) T cells in infants with lung injury from viral respiratory tract infection that was distinct from the T cell profile in circulation and associated with increasing disease severity. Airway sampling could therefore be diagnostically informative for assessing immune responses and lung damage. PMID:26618559

  9. Relationship between airway inflammation and remodeling in patients with asthma and chronic obstructive pulmonary disease

    OpenAIRE

    Górska K; Krenke R; Kosciuch J; Korczynski P; Zukowska M; Domagala-Kulawik J; Maskey-Warzechowska M; Chazan R

    2009-01-01

    Abstract Despite a number of important differences in the pathogenesis, course and prognosis of asthma and chronic obstructive pulmonary disease (COPD), these two entities also have common features with airway inflammation being one of them. Airway remodeling is a characteristic feature of asthma, but data on the bronchial wall thickening in COPD patients are still scarce. Aim To assess the relation between the inflammatory cell count in the bronchoalveolar lavage fluid (BALF) and thickness o...

  10. Nontypeable Haemophilus influenzae in chronic obstructive pulmonary disease and lung cancer

    Directory of Open Access Journals (Sweden)

    Seyed Javad Moghaddam

    2011-01-01

    Full Text Available Seyed Javad Moghaddam1, Cesar E Ochoa1,2, Sanjay Sethi3, Burton F Dickey1,41Department of Pulmonary Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Tecnológico de Monterrey School of Medicine, Monterrey, Nuevo León, Mexico; 3Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY, USA; 4Center for Inflammation and Infection, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, USAAbstract: Chronic obstructive pulmonary disease (COPD is predicted to become the third leading cause of death in the world by 2020. It is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles and gases, most commonly cigarette smoke. Among smokers with COPD, even following withdrawal of cigarette smoke, inflammation persists and lung function continues to deteriorate. One possible explanation is that bacterial colonization of smoke-damaged airways, most commonly with nontypeable Haemophilus influenzae (NTHi, perpetuates airway injury and inflammation. Furthermore, COPD has also been identified as an independent risk factor for lung cancer irrespective of concomitant cigarette smoke exposure. In this article, we review the role of NTHi in airway inflammation that may lead to COPD progression and lung cancer promotion.Keywords: COPD, NTHi, inflammation

  11. Suppressive effect of compact bone-derived mesenchymal stem cells on chronic airway remodeling in murine model of asthma.

    Science.gov (United States)

    Ogulur, Ismail; Gurhan, Gulben; Aksoy, Ayca; Duruksu, Gokhan; Inci, Cigdem; Filinte, Deniz; Kombak, Faruk Erdem; Karaoz, Erdal; Akkoc, Tunc

    2014-05-01

    New therapeutic strategies are needed in the treatment of asthma besides vaccines and pharmacotherapies. For the development of novel therapies, the use of mesenchymal stem cells (MSCs) is a promising approach in regenerative medicine. Delivery of compact bone (CB) derived MSCs to the injured lungs is an alternative treatment strategy for chronic asthma. In this study, we aimed to isolate highly enriched population of MSCs from mouse CB with regenerative capacity, and to investigate the impact of these cells in airway remodeling and inflammation in experimental ovalbumin-induced mouse model of chronic asthma. mCB-MSCs were isolated, characterized, labeled with GFP and then transferred into mice with chronic asthma developed by ovalbumin (OVA) provocation. Histopathological changes including basement membrane, epithelium, subepithelial smooth thickness and goblet cell hyperplasia, and MSCs migration to lung tissues were evaluated. These histopathological alterations were increased in ovalbumin-treated mice compared to PBS group (Pasthma. The results reported here provided evidence that mCB-MSCs may be an alternative strategy for the treatment of remodeling and inflammation associated with chronic asthma. PMID:24613203

  12. Chronic exposure to perfluorinated compounds: Impact on airway hyperresponsiveness and inflammation

    OpenAIRE

    Ryu, Min H.; Jha, Aruni; Ojo, Oluwaseun O.; Mahood, Thomas H.; Basu, Sujata; Detillieux, Karen A.; Nikoobakht, Neda; Wong, Charles S.; Loewen, Mark; Allan B Becker; Halayko, Andrew J.

    2014-01-01

    Emerging epidemiological evidence reveals a link between lung disease and exposure to indoor pollutants such as perfluorinated compounds (PFCs). PFC exposure during critical developmental stages may increase asthma susceptibility. Thus, in a murine model, we tested the hypothesis that early life and continued exposure to two ubiquitous household PFCs, perfluorooctanoic acid (PFOA) and perflurooctanesulfonic acid (PFOS), can induce lung dysfunction that exacerbates allergen-induced airway hype...

  13. MR imaging of chronic infiltrative lung disease

    International Nuclear Information System (INIS)

    To assess the potential role of MR imaging in chronic infiltrative lung disease (CILD) by comparison with high-resolution CT (HRCT). Twenty patients with proved CILD (six with UIP, six with sarcoidosis, two with extrinsic allergic alveolities [EAA], and six miscellaneous) underwent 1.5-T MR imaging and HRCT of the chest. Cardiac-gated T1 (TR, 800 msec; TE, 20 msec) and proton density and T2 (TR, 2,000 msec; TE, 30/80 msec) sequences were performed. The MR images were reviewed by two chest radiologists, and the findings were compared with the HRCT scans. HRCT was superior to MR imaging in the anatomic assessment of the lung parenchyma and in the demonstration of mild fibrosis. However, MR images provided greater contrast between areas of airspace opacification and normal lung than did MRCT. In two patients with UIP, two with sarcoidosis, and two with EAA, MR images demonstrated airspace opacification not readily apparent on CT scans. In the two patients with EAA, the EAA had initially been missed with HRCT. HRCT is superior to MR imaging in anatomic assessment of the lung. However, the increased contrast on MR images allows better assessment of the presence and extent of airspace opacification, which has been shown to reflect disease activity. MR imaging may play an important role in the assessment of disease activity and response to treatment in patients with CILD

  14. Vitamin D and susceptibility of chronic lung diseases: Role of epigenetics

    Directory of Open Access Journals (Sweden)

    IrfanRahman

    2011-08-01

    Full Text Available Vitamin D deficiency is linked to accelerated decline in lung function, increased inflammation, and reduced immunity in chronic lung diseases. Epidemiological studies have suggested that vitamin D insufficiency is associated with low lung function in susceptible subjects who are exposed to higher levels of environmental agents (airborne particulates. Recent studies have highlighted the role of vitamin D and vitamin D receptor (VDR in regulation of several genes that are involved in inflammation, immunity, cellular proliferation, differentiation and apoptosis. Vitamin D has also been implicated in reversal of steroid resistance and airway remodeling, which are the hallmarks of chronic obstructive pulmonary disease (COPD and severe asthma. VDR protein level is decreased in lungs of patients with COPD and VDR deficient mice. These mice develop an abnormal lung phenotype with characteristics of COPD, such as airspace enlargement and decline in lung function associated with increased lung inflammatory cellular influx, and immune-lymphoid aggregates formation. Dietary vitamin D may regulate epigenetic events, in particular on genes which are responsible for COPD susceptibility. Active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 plays an essential role in cellular metabolism and differentiation via its nuclear receptor (VDR that cooperates with several other chromatin modification enzymes (HATs, and HDACs, thus result in mediating complex epigenetic events in vitamin D signaling and metabolism. This review provides an update on the current knowledge and understanding on vitamin D, and susceptibility of chronic lung diseases in relation to the possible role of epigenetics in its molecular action. Understanding the molecular epigenetic mechanisms of vitamin D/VDR would provide rationale for dietary vitamin D-mediated intervention in prevention and management of chronic lung diseases linked with vitamin D deficiency.

  15. Vitamin D deficiency causes airway hyperresponsiveness, increases airway smooth muscle mass, and reduces TGF‐β expression in the lungs of female BALB/c mice

    OpenAIRE

    Rachel E Foong; Shaw, Nicole C.; Berry, Luke J.; Hart, Prue H.; Gorman, Shelley; Zosky, Graeme R.

    2014-01-01

    Abstract Vitamin D deficiency is associated with disease severity in asthma. We tested whether there is a causal association between vitamin D deficiency, airway smooth muscle (ASM) mass, and the development of airway hyperresponsiveness (AHR). A physiologically relevant mouse model of vitamin D deficiency was developed by raising BALB/c mice on vitamin D‐deficient or ‐replete diets. AHR was assessed by measuring lung function responses to increasing doses of inhaled methacholine. Five‐micron...

  16. Nanoparticle mass transfer from lung airways to systemic regions--Part I: Whole-lung aerosol dynamics.

    Science.gov (United States)

    Kolanjiyil, Arun V; Kleinstreuer, Clement

    2013-12-01

    This is a two-part paper describing inhaled nanoparticle (NP) transport and deposition in a model of a human respiratory tract (Part I) as well as NP-mass transfer across barriers into systemic regions (Part II). Specifically, combining high-resolution computer simulation results of inhaled NP deposition in the human airways (Part I) with a multicompartmental model for NP-mass transfer (Part II) allows for the prediction of temporal NP accumulation in the blood and lymphatic systems as well as in organs. An understanding of nanoparticle transport and deposition in human respiratory airways is of great importance, as exposure to nanomaterial has been found to cause serious lung diseases, while the use of nanodrugs may have superior therapeutic effects. In Part I, the fluid-particle dynamics of a dilute NP suspension was simulated for the entire respiratory tract, assuming steady inhalation and planar airways. Thus, a realistic airway configuration was considered from nose/mouth to generation 3, and then an idealized triple-bifurcation unit was repeated in series and parallel to cover the remaining generations. Using the current model, the deposition of NPs in distinct regions of the lung, namely extrathoracic, bronchial, bronchiolar, and alveolar, was calculated. The region-specific NP-deposition results for the human lung model were used in Part II to determine the multicompartmental model parameters from experimental retention and clearance data in human lungs. The quantitative, experimentally validated results are useful in diverse fields, such as toxicology for exposure-risk analysis of ubiquitous nanomaterial as well as in pharmacology for nanodrug development and targeting. PMID:24008503

  17. The role of stem cells in airway repair: implications for the origins of lung cancer

    Institute of Scientific and Technical Information of China (English)

    Michael S.Mulvihill; Johannes R.Kratz; Patrick Pham; David M.Jablons; Biao He

    2013-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide.Recently,advancements in our ability to identify and study stem cell populations in the lung have helped researchers to elucidate the central role that cells with stem cell-like properties may have in lung tumorigenesis.Much of this research has focused on the use of the airway repair model to study response to injury.In this review,we discuss the primary evidence of the role that cancer stem cells play in lung cancer development.The implications of a stem cell origin of lung cancer are reviewed,and the importance of ongoing research to identify novel therapeutic and prognostic targets is reiterated.

  18. The role of stem cells in airway repair: implications for the origins of lung cancer

    Directory of Open Access Journals (Sweden)

    Michael S. Mulvihill

    2013-02-01

    Full Text Available Lung cancer is the leading cause of cancer-related deaths worldwide. Recently, advancements in our ability to identify and study stem cell populations in the lung have helped researchers to elucidate the central role that cells with stem cell-like properties may have in lung tumorigenesis. Much of this research has focused on the use of the airway repair model to study response to injury. In this review, we discuss the primary evidence of the role that cancer stem cells play in lung cancer development. The implications of a stem cell origin of lung cancer are reviewed, and the importance of ongoing research to identify novel therapeutic and prognostic targets is reiterated.

  19. Invasive Aspergillus infections in hospitalized patients with chronic lung disease

    Directory of Open Access Journals (Sweden)

    Wessolossky M

    2013-05-01

    Full Text Available Mireya Wessolossky,1 Verna L Welch,2 Ajanta Sen,1 Tara M Babu,1 David R Luke21Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, MA, USA; 2Medical Affairs, Pfizer Inc, Collegeville, PA, USABackground: Although invasive pulmonary aspergillosis (IPA is more prevalent in immunocompromised patients, critical care clinicians need to be aware of the occurrence of IPA in the nontraditional host, such as a patient with chronic lung disease. The purpose of this study was to describe the IPA patient with chronic lung disease and compare the data with that of immunocompromised patients.Methods: The records of 351 patients with Aspergillus were evaluated in this single-center, retrospective study for evidence and outcomes of IPA. The outcomes of 57 patients with chronic lung disease and 56 immunocompromised patients were compared. Patients with chronic lung disease were defined by one of the following descriptive terms: emphysema, asthma, idiopathic lung disease, bronchitis, bronchiectasis, sarcoid, or pulmonary leukostasis.Results: Baseline demographics were similar between the two groups. Patients with chronic lung disease were primarily defined by emphysema (61% and asthma (18%, and immunocompromised patients primarily had malignancies (27% and bone marrow transplants (14%. A higher proportion of patients with chronic lung disease had a diagnosis of IPA by bronchoalveolar lavage versus the immunocompromised group (P < 0.03. The major risk factors for IPA were found to be steroid use in the chronic lung disease group and neutropenia and prior surgical procedures in the immunocompromised group. Overall, 53% and 69% of chronic lung disease and immunocompromised patients were cured (P = 0.14; 55% of chronic lung patients and 47% of immunocompromised patients survived one month (P = 0.75.Conclusion: Nontraditional patients with IPA, such as those with chronic lung disease, have outcomes and mortality similar to that in the

  20. Therapeutical measures to control airway tolerance in asthma and lung cancer

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    Katerine eAndreev

    2012-07-01

    Full Text Available Airway tolerance is a specialized immunological surveillance which is activated by the cells of the lung to deal with and distinguish between innocuous and pathogenic inhalants. However, this distinction does not always occur. Airway tolerance is necessary to avoid the development of allergic disorders, such as asthma, which is dominated by a pathological expansion of Th2 and Th17 cells in the airways. By contrast, tumour cells induce tolerogenic factors in their microenvironment to evade T-cell mediated anti-tumour-immune responses. This review updates current understanding on the effect of the cytokines TGF-ƒÒ, IL-10 and IL-17A on the lung immune responses to antigen, and analyzes their involvement in allergic asthma and lung cancer. The aim of the review is to evaluate where therapeutic intervention may be feasible and where it might fail. The multifunctional role of these cytokines further complicates the decision on the timing and concentration for their use as therapeutical targets. In fact, TGF-ƒÒ has suppressive activity in early tumorigenesis, but may become tumourpromoting in the later stages of the disease. This dual behaviour is sometimes due to changes in the cellular target of TGF-£], and to the expansion of the induced (i-Tregs. Similarly, IL-17A has been found to elicit pro- as well as anti-tumour properties. Thus, this pro-inflammatory cytokine induces the production of IL-6 which interferes with Treg development. Yet IL-17A could promote tumour growth in conjunction with IL-6-dependent activation of Stat3. Thus, understanding the mechanisms of airway tolerance could help to improve the therapy to both, allergic asthma and lung cancer. Hereby asthma therapy aims to induce and maintain tolerance to inhaled allergens and therapy against lung cancer tries to inhibit the tolerogenic response surrounding the tumour.

  1. Therapeutical measures to control airway tolerance in asthma and lung cancer.

    Science.gov (United States)

    Andreev, Katerina; Graser, Anna; Maier, Anja; Mousset, Stephanie; Finotto, Susetta

    2012-01-01

    Airway tolerance is a specialized immunological surveillance which is activated by the cells of the lung to deal with and distinguish between innocuous and pathogenic inhalants. However, this distinction does not always occur. Airway tolerance is necessary to avoid the development of allergic disorders, such as asthma, which is dominated by a pathological expansion of Th2 and Th17 cells in the airways. By contrast, tumor cells induce tolerogenic factors in their microenvironment to evade T-cell mediated anti-tumor-immune responses. This review updates current understandings on the effect of the cytokines TGF-β, IL-10, and IL-17A on the lung immune responses to antigen, and analyzes their involvement in allergic asthma and lung cancer. The aim of the review is to evaluate where therapeutic intervention may be feasible and where it might fail. The multifunctional role of these cytokines further complicates the decision on the timing and concentration for their use as therapeutical targets. In fact, TGF-β has suppressive activity in early tumorigenesis, but may become tumor-promoting in the later stages of the disease. This dual behavior is sometimes due to changes in the cellular target of TGF-β, and to the expansion of the induced (i)-Tregs. Similarly, IL-17A has been found to elicit pro- as well as anti-tumor properties. Thus, this pro-inflammatory cytokine induces the production of IL-6 which interferes with Treg development. Yet IL-17A could promote tumor growth in conjunction with IL-6-dependent activation of Stat3. Thus, understanding the mechanisms of airway tolerance could help to improve the therapy to both, allergic asthma and lung cancer. Hereby, asthma therapy aims to induce and maintain tolerance to inhaled allergens and therapy against lung cancer tries to inhibit the tolerogenic response surrounding the tumor. PMID:22855687

  2. Within-breath respiratory impedance and airway obstruction in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Karla Kristine Dames da Silva

    2015-07-01

    Full Text Available OBJECTIVE: Recent work has suggested that within-breath respiratory impedance measurements performed using the forced oscillation technique may help to noninvasively evaluate respiratory mechanics. We investigated the influence of airway obstruction on the within-breath forced oscillation technique in smokers and chronic obstructive pulmonary disease patients and evaluated the contribution of this analysis to the diagnosis of chronic obstructive pulmonary disease. METHODS: Twenty healthy individuals and 20 smokers were assessed. The study also included 74 patients with stable chronic obstructive pulmonary disease. We evaluated the mean respiratory impedance (Zm as well as values for the inspiration (Zi and expiration cycles (Ze at the beginning of inspiration (Zbi and expiration (Zbe, respectively. The peak-to-peak impedance (Zpp=Zbe-Zbi and the respiratory cycle dependence (ΔZrs=Ze-Zi were also analyzed. The diagnostic utility was evaluated by investigating the sensitivity, the specificity and the area under the receiver operating characteristic curve. ClinicalTrials.gov: NCT01888705. RESULTS: Airway obstruction increased the within-breath respiratory impedance parameters that were significantly correlated with the spirometric indices of airway obstruction (R=−0.65, p90%. CONCLUSIONS: We conclude the following: (1 chronic obstructive pulmonary disease introduces higher respiratory cycle dependence, (2 this increase is proportional to airway obstruction, and (3 the within-breath forced oscillation technique may provide novel parameters that facilitate the diagnosis of respiratory abnormalities in chronic obstructive pulmonary disease.

  3. YAP is up-regulated in the bronchial airway smooth muscle of the chronic asthma mouse model.

    Science.gov (United States)

    Zhou, Jing; Xu, Fei; Yu, Jing Jing; Zhang, Wei

    2015-01-01

    Asthma is characterized by leukocytic infiltration and tissue remodeling with structural changes including subepithelial fibrosis and ASM cells proliferation. The Hippo pathway is a key regulatory point involved in cell proliferation, fibroblasts, and smooth muscle cell differentiation. In order to disclose the relation between asthma and the Hippo pathway, expression of the Yes-associated protein (YAP), a key gene in the Hippo pathway, in the bronchial smooth muscle of chronic asthma model (CAM) was studied. 40 mice were randomly divided into control (wide type) and experimental group to construct CAM using chicken ovalbumin (OVA). Pathological changes of the lung tissues were observed in the CAM mice compared with the control using HE staining method. Immunohistochemistry (IHC) was used to detect if YAP protein is expressed in the lung tissues. The pathological changes of the CAM group showed that a large number of inflammatory cells infiltration including mainly lymphocytes and a small amount of eosinophilic, with the presence of certain airway smooth muscle hyperplasia, was observed in comparison with the control. IHC results showed that the YAP protein was significantly increased compared with the control groups (P bronchial airway tissues of the CAM mice, and could be used as an indicator for asthma. PMID:26617833

  4. Chronic obstructive pulmonary disease: a complex comorbidity of lung cancer

    OpenAIRE

    Derek Grose; Robert Milroy

    2011-01-01

    Abstract: Chronic obstructive pulmonary disease (COPD) is a major burden throughout the world. It is associated with a signifi cantly increased incidence of lung cancer and may infl uence treatment options and outcome. Impaired lung function confi rming COPD is an independent risk factor for lung cancer. Oxidative stress and infl ammation may be a key link between COPD and lung cancer, with numerous molecular markers being analysed to attempt to understand the pathway of lung cancer developme...

  5. Cigarette smoke activates the proto-oncogene c-src to promote airway inflammation and lung tissue destruction.

    Science.gov (United States)

    Geraghty, Patrick; Hardigan, Andrew; Foronjy, Robert F

    2014-03-01

    The diagnosis of chronic obstructive pulmonary disease (COPD) confers a 2-fold increased lung cancer risk even after adjusting for cigarette smoking, suggesting that common pathways are operative in both diseases. Although the role of the tyrosine kinase c-Src is established in lung cancer, less is known about its impact in other lung diseases, such as COPD. This study examined whether c-Src activation by cigarette smoke contributes to the pathogenesis of COPD. Cigarette smoke increased c-Src activity in human small airway epithelial (SAE) cells from healthy donors and in the lungs of exposed mice. Similarly, higher c-Src activation was measured in SAE cells from patients with COPD compared with healthy control subjects. In SAE cells, c-Src silencing or chemical inhibition prevented epidermal growth factor (EGF) receptor signaling in response to cigarette smoke but not EGF stimulation. Further studies showed that cigarette smoke acted through protein kinase C α to trigger c-Src to phosphorylate EGF receptor and thereby to induce mitogen-activated protein kinase responses in these cells. To further investigate the role of c-Src, A/J mice were orally administered the specific Src inhibitor AZD-0530 while they were exposed to cigarette smoke for 2 months. AZD-0530 treatment blocked c-Src activation, decreased macrophage influx, and prevented airspace enlargement in the lungs of cigarette smoke-exposed mice. Moreover, inhibiting Src deterred the cigarette smoke-mediated induction of matrix metalloproteinase-9 and -12 in alveolar macrophages and lung expression of cathepsin K, IL-17, TNF-α, MCP-1, and KC, all key factors in the pathogenesis of COPD. These results indicate that activation of the proto-oncogene c-Src by cigarette smoke promotes processes linked to the development of COPD. PMID:24111605

  6. In Utero Cigarette Smoke Affects Allergic Airway Disease But Does Not Alter the Lung Methylome.

    Directory of Open Access Journals (Sweden)

    Kenneth R Eyring

    Full Text Available Prenatal and postnatal cigarette smoke exposure enhances the risk of developing asthma. Despite this as well as other smoking related risks, 11% of women still smoke during pregnancy. We hypothesized that cigarette smoke exposure during prenatal development generates long lasting differential methylation altering transcriptional activity that correlates with disease. In a house dust mite (HDM model of allergic airway disease, we measured airway hyperresponsiveness (AHR and airway inflammation between mice exposed prenatally to cigarette smoke (CS or filtered air (FA. DNA methylation and gene expression were then measured in lung tissue. We demonstrate that HDM-treated CS mice develop a more severe allergic airway disease compared to HDM-treated FA mice including increased AHR and airway inflammation. While DNA methylation changes between the two HDM-treated groups failed to reach genome-wide significance, 99 DMRs had an uncorrected p-value < 0.001. 6 of these 99 DMRs were selected for validation, based on the immune function of adjacent genes, and only 2 of the 6 DMRs confirmed the bisulfite sequencing data. Additionally, genes near these 6 DMRs (Lif, Il27ra, Tle4, Ptk7, Nfatc2, and Runx3 are differentially expressed between HDM-treated CS mice and HDM-treated FA mice. Our findings confirm that prenatal exposure to cigarette smoke is sufficient to modify allergic airway disease; however, it is unlikely that specific methylation changes account for the exposure-response relationship. These findings highlight the important role in utero cigarette smoke exposure plays in the development of allergic airway disease.

  7. Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance.

    Science.gov (United States)

    Soroosh, Pejman; Doherty, Taylor A; Duan, Wei; Mehta, Amit Kumar; Choi, Heonsik; Adams, Yan Fei; Mikulski, Zbigniew; Khorram, Naseem; Rosenthal, Peter; Broide, David H; Croft, Michael

    2013-04-01

    Airway tolerance is the usual outcome of inhalation of harmless antigens. Although T cell deletion and anergy are likely components of tolerogenic mechanisms in the lung, increasing evidence indicates that antigen-specific regulatory T cells (inducible Treg cells [iTreg cells]) that express Foxp3 are also critical. Several lung antigen-presenting cells have been suggested to contribute to tolerance, including alveolar macrophages (MØs), classical dendritic cells (DCs), and plasmacytoid DCs, but whether these possess the attributes required to directly promote the development of Foxp3(+) iTreg cells is unclear. Here, we show that lung-resident tissue MØs coexpress TGF-β and retinal dehydrogenases (RALDH1 and RALDH 2) under steady-state conditions and that their sampling of harmless airborne antigen and presentation to antigen-specific CD4 T cells resulted in the generation of Foxp3(+) Treg cells. Treg cell induction in this model depended on both TGF-β and retinoic acid. Transfer of the antigen-pulsed tissue MØs into the airways correspondingly prevented the development of asthmatic lung inflammation upon subsequent challenge with antigen. Moreover, exposure of lung tissue MØs to allergens suppressed their ability to generate iTreg cells coincident with blocking airway tolerance. Suppression of Treg cell generation required proteases and TLR-mediated signals. Therefore, lung-resident tissue MØs have regulatory functions, and strategies to target these cells might hold promise for prevention or treatment of allergic asthma. PMID:23547101

  8. Outgrowth of the Bacterial Airway Microbiome after Rhinovirus Exacerbation of Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Molyneaux, Philip L; Patrick Mallia; Cox, Michael J.; Joseph Footitt; Willis-Owen, Saffron A.G.; Daniel Homola; Maria-Belen Trujillo-Torralbo; Sarah Elkin; Onn Min Kon; Cookson, William O. C.; Moffatt, Miriam F.; Johnston, Sebastian L.

    2013-01-01

    Rationale: Rhinovirus infection is followed by significantly increased frequencies of positive, potentially pathogenic sputum cultures in chronic obstructive pulmonary disease (COPD). However, it remains unclear whether these represent de novo infections or an increased load of organisms from the complex microbial communities (microbiome) in the lower airways.

  9. Molecular epidemiology of chronic Pseudomonas aeruginosa airway infections in cystic fibrosis

    DEFF Research Database (Denmark)

    Cramer, Nina; Wiehlmann, Lutz; Ciofu, Oana;

    2012-01-01

    The molecular epidemiology of the chronic airway infections with Pseudomonas aeruginosa in individuals with cystic fibrosis (CF) was investigated by cross-sectional analysis of bacterial isolates from 51 CF centers and by longitudinal analysis of serial isolates which had been collected at the CF...

  10. Epithelium, Inflammation, and Immunity in the Upper Airways of Humans: Studies in Chronic Rhinosinusitis

    OpenAIRE

    Schleimer, Robert P.; Kato, Atsushi; Peters, Anju; Conley, David; Kim, Jean; Liu, Mark C.; Harris, Kathleen E.; Douglas A. Kuperman; Chandra, Rakesh; Favoreto, Silvio; Avila, Pedro C; Grammer, Leslie C.; Kern, Robert C.

    2009-01-01

    The purpose of this review is to discuss recent findings made during studies of the upper airways and sinuses of people with chronic rhinosinusitis (CRS) in the context of the literature. CRS is a chronic inflammatory disorder affecting nearly 30 million Americans and is generally resistant to therapy with antibiotics and glucocorticoids (Meltzer EO and coworkers, J Allergy Clin Immunol 2004;114:155–212). We have formed a collaboration that consists of otolaryngologists, allergists, and basic...

  11. Within-breath respiratory impedance and airway obstruction in patients with chronic obstructive pulmonary disease

    OpenAIRE

    Karla Kristine Dames da Silva; Alvaro Camilo Dias Faria; Agnaldo José Lopes; Pedro Lopes de Melo

    2015-01-01

    OBJECTIVE: Recent work has suggested that within-breath respiratory impedance measurements performed using the forced oscillation technique may help to noninvasively evaluate respiratory mechanics. We investigated the influence of airway obstruction on the within-breath forced oscillation technique in smokers and chronic obstructive pulmonary disease patients and evaluated the contribution of this analysis to the diagnosis of chronic obstructive pulmonary disease. METHODS: Twenty healthy indi...

  12. Oxidative stress–induced mitochondrial dysfunction drives inflammation and airway smooth muscle remodeling in patients with chronic obstructive pulmonary disease

    Science.gov (United States)

    Wiegman, Coen H.; Michaeloudes, Charalambos; Haji, Gulammehdi; Narang, Priyanka; Clarke, Colin J.; Russell, Kirsty E.; Bao, Wuping; Pavlidis, Stelios; Barnes, Peter J.; Kanerva, Justin; Bittner, Anton; Rao, Navin; Murphy, Michael P.; Kirkham, Paul A.; Chung, Kian Fan; Adcock, Ian M.; Brightling, Christopher E.; Davies, Donna E.; Finch, Donna K.; Fisher, Andrew J.; Gaw, Alasdair; Knox, Alan J.; Mayer, Ruth J.; Polkey, Michael; Salmon, Michael; Singh, David

    2015-01-01

    Background Inflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD). Mitochondrial oxidative stress might be involved in driving the oxidative stress–induced pathology. Objective We sought to determine the effects of oxidative stress on mitochondrial function in the pathophysiology of airway inflammation in ozone-exposed mice and human airway smooth muscle (ASM) cells. Methods Mice were exposed to ozone, and lung inflammation, airway hyperresponsiveness (AHR), and mitochondrial function were determined. Human ASM cells were isolated from bronchial biopsy specimens from healthy subjects, smokers, and patients with COPD. Inflammation and mitochondrial function in mice and human ASM cells were measured with and without the presence of the mitochondria-targeted antioxidant MitoQ. Results Mice exposed to ozone, a source of oxidative stress, had lung inflammation and AHR associated with mitochondrial dysfunction and reflected by decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial oxidative stress, and reduced mitochondrial complex I, III, and V expression. Reversal of mitochondrial dysfunction by the mitochondria-targeted antioxidant MitoQ reduced inflammation and AHR. ASM cells from patients with COPD have reduced ΔΨm, adenosine triphosphate content, complex expression, basal and maximum respiration levels, and respiratory reserve capacity compared with those from healthy control subjects, whereas mitochondrial reactive oxygen species (ROS) levels were increased. Healthy smokers were intermediate between healthy nonsmokers and patients with COPD. Hydrogen peroxide induced mitochondrial dysfunction in ASM cells from healthy subjects. MitoQ and Tiron inhibited TGF-β–induced ASM cell proliferation and CXCL8 release. Conclusions Mitochondrial dysfunction in patients with COPD is associated with excessive mitochondrial ROS levels, which contribute to enhanced inflammation and cell

  13. Marked stem cell factor expression in the airways of lung transplant recipients

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    Frossard Nelly

    2006-06-01

    Full Text Available Abstract Background Airways repair is critical to lung function following transplantation. We hypothesised that the stem cell factor (SCF could play a role in this setting. Methods We studied 9 lung transplant recipients (LTx recipients during their first year postgraft, and evaluated SCF mRNA expression in bronchial biopsy specimens using on-line fluorescent PCR and SCF protein levels in bronchoalveolar lavage (BAL and serum using ELISA. The expression of SCF receptor Kit was assessed using immunostaining of paraffin-embedded bronchial sections. Results SCF mRNA was highly expressed during the early postgraft period [Month (M1-M3] (300% increase vs controls: 356 vs 1.2 pg SCF/μg GAPDH cDNA, p p Conclusion SCF and Kit are expressed in bronchial biopsies from lung transplant recipients irrespective of the clinical status of the graft. A role for these factors in tissue repair following lung transplantation is hypothesised.

  14. Airway and tissue impedances of canine lungs after step volume changes.

    Science.gov (United States)

    Bates, J H; Donoso, F A; Peslin, R

    1993-10-01

    We investigated the changes in pulmonary mechanics in five anesthetized paralyzed tracheostomized open-chest dogs after step changes in lung volume. We applied small-amplitude (10-ml) volume oscillations at 6 Hz at the tracheal opening for 50-s periods, during which we applied a step volume change of 250, 500, or 750 ml to the lungs. Alveolar capsule measurements of alveolar pressure allowed us to calculate cycle-by-cycle values for airway resistance (Raw) and reactance (Xaw) and lung tissue resistance (Rti) and reactance (Xti). Before the step changes in lung volume, when transpulmonary pressure (Ptp) had a mean value of 0.65 kPa, Raw was markedly greater than Rti. The situation was reversed after the step changes, however, when Raw decreased and Rti increased. Both Raw and Xaw showed negative dependences on Ptp and hence on airway caliber, as expected, and also decreased transiently after the step volume changes, almost certainly due to a vagally mediated bronchodilation reflex. Both Rti and Xti showed clear linear dependences on Ptp and were themselves tightly coupled. Furthermore, our estimate of bulk modulus for lung tissue at 6 Hz is comparable to its previously reported values at much lower oscillation frequencies. PMID:8282590

  15. Bone Marrow Stromal Cells Attenuate Lung Injury in a Murine Model of Neonatal Chronic Lung Disease

    OpenAIRE

    Aslam, Muhammad; Baveja, Rajiv; Liang, Olin D.; Fernandez-Gonzalez, Angeles; Lee, Changjin; Mitsialis, S. Alex; Kourembanas, Stella

    2009-01-01

    Rationale: Neonatal chronic lung disease, known as bronchopulmonary dysplasia (BPD), remains a serious complication of prematurity despite advances in the treatment of extremely low birth weight infants.

  16. Morphological findings in lungs of the horses with chronic obstructive pulmonary disease (COPD

    Directory of Open Access Journals (Sweden)

    Marinković Darko

    2007-01-01

    Full Text Available The frequency and characteristics of chronic obstructive pulmonary disease (COPD based on morphological and cytological changes in equine lungs were studied in this paper. Lungs obtained from 51 horses of different age and sex were examined grossly and tissue samples were collected for pathohistological examination. Cytological examination was done on impression smears from the tracheal bifurcation. Pathohistological preparations were stained with hematoxylin eosin (HE, toluidine blue (TB, Giemsa staining, PAS staining and Pearls reaction for iron detection. The peroxidase anti-peroxidase technique was used to demonstrate CD3+ (T lymphocytes and CD79+ (B lymphocytes. Tracheal bifurcation cytology impression smears were stained with hematoxylin eosin (HE, Giemsa staining and PAS staining. Pulmonary emphysema and lack of pulmonary collapse were the most common gross lesions whereas alveolar emphysema was described in 70.59% of all examined horses, more frequently in the distensive form (54.90% and less frequently in the destructive form (15.69%. Pathohistological chronic bronchitis/bronchiolitis, with characteristic changes in the lumen, mucosa, submucosa and smooth muscle layer was described in all examined horses. Increased immunoreactivity was described in the lungs. The most common lesions seen on cytology impression smears from the tracheal bifurcation were thick, viscous, PAS positive mucus which forms Curschmann's spirals. The dominant cell population consisted of desquamated airway epithelial cells, as well as eosinophils, neutrophils, mast cells, erythrocytes and alveolar macrophages. Primary pulmonary pathogens as well as potential contaminants and secundary infection agens were isolated bacteriologically from lung samples. All the above-mentioned findings correlate pointing to the fact that chronic bronchitis/bronchiolitis represents the basic substrate of chronic obstructive pulmonary disease (COPD which has a combined inflammatory and

  17. Airway and Extracellular Matrix Mechanics in COPD

    OpenAIRE

    Bidan, Cécile M.; Veldsink, Annemiek C.; Meurs, Herman; Gosens, Reinoud

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is one of the most common lung diseases worldwide, and is characterized by airflow obstruction that is not fully reversible with treatment. Even though airflow obstruction is caused by airway smooth muscle contraction, the extent of airway narrowing depends on a range of other structural and functional determinants that impact on active and passive tissue mechanics. Cells and extracellular matrix in the airway and parenchymal compartments respond b...

  18. The association between combined non-cystic fibrosis bronchiectasis and lung cancer in patients with chronic obstructive lung disease

    Directory of Open Access Journals (Sweden)

    Kim YW

    2015-05-01

    Full Text Available Yeon Wook Kim,1 Kwang-Nam Jin,2 Eun Young Heo,3 Sung Soo Park,3 Hee Soon Chung,3 Deog Kyeom Kim31Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 2Department of Radiology, Seoul National University College of Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of KoreaBackground: Whereas the epidemiological association between lung cancer and chronic obstructive pulmonary disease (COPD, a chronic inflammatory respiratory disease, is well known, limited studies have examined the association between lung cancer and non-cystic fibrosis bronchiectasis, a representative chronic airway inflammatory disease. This study evaluated the association between bronchiectasis and lung cancer in patients with COPD.Methods: A matched case–control study was conducted in a referral hospital in South Korea. Among COPD patients with moderate to very severe airflow limitation (forced expiratory volume in one second/forced vital capacity <0.7 and forced expiratory volume in one second ≤70% [% predicted] who underwent chest computed tomography (CT between January 1, 2010 and May 30, 2013, patients with lung cancer and controls matched for age, sex, and smoking history were selected. The risk of lung cancer was assessed according to the presence of underlying bronchiectasis confirmed by chest CT.Results: The study enrolled 99 cases and 198 controls. Combined bronchiectasis on chest CT was inversely associated with the risk of lung cancer compared with controls (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.12–0.52, P<0.001. Significant associations were found in

  19. Accelerated decline in lung function in smoking women with airway obstruction: SAPALDIA 2 cohort study

    Directory of Open Access Journals (Sweden)

    Zemp Elisabeth

    2005-05-01

    Full Text Available Abstract Background The aim was to determine if effects from smoking on lung function measured over 11 years differ between men and women. Methods In a prospective population based cohort study (Swiss Study on Air Pollution and Lung Diseases in Adults current smokers in 1991 (18 – 60 yrs were reassessed in 2002 (n = 1792. Multiple linear regression was used to estimate effects from pack-years of cigarettes smoked to 1991 and mean packs of cigarettes smoked per day between 1991 and 2002 on change in lung volume and flows over the 11 years. Results In both sexes, packs smoked between assessments were related to lung function decline but pack-years smoked before 1991 were not. Mean annual decline in FEV1 was -10.4 mL(95%CI -15.3, -5.5 per pack per day between assessments in men and -13.8 mL(95%CI-19.5,-8.1 in women. Decline per pack per day between 1991 and 2002 was lower in women who smoked in 1991 but quit before 2002 compared to persistent smokers (-6.4 vs -11.6 mL, p = 0.05 but this was not seen in men (-14.3 vs -8.8 mL p = 0.49. Smoking related decline was accelerated in men and women with airway obstruction, particularly in women where decline in FEV1 was three fold higher in participants with FEV1/FVC Conclusion There are differences in effects from smoking on lung function between men and women. Lung function recovers faster in women quitters than in men. Women current smokers with airway obstruction experience a greater smoking related decline in lung function than men.

  20. Effect of smoking cessation on airway inflammation of rats with chronic bronchitis

    Institute of Scientific and Technical Information of China (English)

    LI Qing-yun; HUANG Shao-guang; WAN Huan-ying; WU Hua-cheng; ZHOU Tong; LI Min; DENG Wei-wu

    2007-01-01

    Background Smoking is the major cause of airway inflammation in chronic obstructive pulmonary disease (COPD),and smoking cessation is regarded as one of the important strategies for prevention and treatment of the inflammation.The inflammation of the chronic airway may be present and deteriorated even if the COPD patients stop smoking.Whether and how early smoking cessation affects the progress of inflammation is still obscure. This study was conducted to find the appropriate time for smoking cessation to terminate the airway inflammation in rats with smoke-induced chronic bronchitis.Methods A rat model of COPD was established by passively inhaling smoke mixture. Fifty-four young male Sprague-Dawley rats were randomly divided into 9 groups with different periods of smoke exposure and different time points of cessation. The inflammation markers to be detected included inflammatory cells in the bronchoalveolar lavage fluid (BALF), the myeloperoxidose (MPO) activity, the morphologic changes and the expression of ICAM-1 on the airway epithelium.Results When smoking was terminated at early stage, the inflammatory markers and related indexes were different from those of the typical chronic bronchitis group (group M7) (P<0.01). The pathologic score of group SC7 (2 weeks of smoking cessation after occurrence of typical chronic bronchitis ) was not different from that of group M7, and the level of ICAM-1 was still up-regulated (compared to group M7, P>0.05). Meanwhile, most of inflammatory cells in BALF were neutrophils compared to other groups (P<0.01).When smoking was terminated, the MPO activity was significantly lower than that of group M7 (P<0.01).Conclusions Smoking cessation at early stage can effectively inhibit the inflammatory reaction of COPD. Once chronic bronchitis occurs, little could be improved by smoking cessation.

  1. Mucoid Pseudomonas aeruginosa isolates maintain the biofilm formation capacity and the gene expression profiles during the chronic lung infection of CF patients

    DEFF Research Database (Denmark)

    Lee, Bao le ri; Schjerling, Charlotte K.; Kirkby, Nikolai;

    2011-01-01

    Phenotypic and genotypic diversifications of Pseudomonas aeruginosa in the airways of patients with cystic fibrosis (CF) promote long-term survival of bacteria during chronic lung infection. Twelve clonally related, sequential mucoid and non-mucoid paired P. aeruginosa isolates obtained from three...

  2. Vitronectin Expression in the Airways of Subjects with Asthma and Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Salazar-Peláez, Lina M.; Abraham, Thomas; Ana M Herrera; Mario A Correa; Ortega, Jorge E; Paré, Peter D.; Seow, Chun Y.

    2015-01-01

    Vitronectin, a multifunctional glycoprotein, is involved in coagulation, inhibition of the formation of the membrane attack complex (MAC), cell adhesion and migration, wound healing, and tissue remodeling. The primary cellular source of vitronectin is hepatocytes; it is not known whether resident cells of airways produce vitronectin, even though the glycoprotein has been found in exhaled breath condensate and bronchoalveolar lavage from healthy subjects and patients with interstitial lung dis...

  3. S-adenosylmethionine reduces airway inflammation and fibrosis in a murine model of chronic severe asthma via suppression of oxidative stress.

    Science.gov (United States)

    Yoon, Sun-Young; Hong, Gyong Hwa; Kwon, Hyouk-Soo; Park, Sunjoo; Park, So Young; Shin, Bomi; Kim, Tae-Bum; Moon, Hee-Bom; Cho, You Sook

    2016-01-01

    Increased oxidative stress has an important role in asthmatic airway inflammation and remodeling. A potent methyl donor, S-adenosylmethionine (SAMe), is known to protect against tissue injury and fibrosis through modulation of oxidative stress. The aim of this study was to evaluate the effect of SAMe on airway inflammation and remodeling in a murine model of chronic asthma. A mouse model was generated by repeated intranasal challenge with ovalbumin and Aspergillus fungal protease twice a week for 8 weeks. SAMe was orally administered every 24 h for 8 weeks. We performed bronchoalveolar lavage (BAL) fluid analysis and histopathological examination. The levels of various cytokines and 4-hydroxy-2-nonenal (HNE) were measured in the lung tissue. Cultured macrophages and fibroblasts were employed to evaluate the underlying anti-inflammatory and antifibrotic mechanisms of SAMe. The magnitude of airway inflammation and fibrosis, as well as the total BAL cell counts, were significantly suppressed in the SAMe-treated groups. A reduction in T helper type 2 pro-inflammatory cytokines and HNE levels was observed in mouse lung tissue after SAMe administration. Macrophages cultured with SAMe also showed reduced cellular oxidative stress and pro-inflammatory cytokine production. Moreover, SAMe treatment attenuated transforming growth factor-β (TGF-β)-induced fibronectin expression in cultured fibroblasts. SAMe had a suppressive effect on airway inflammation and fibrosis in a mouse model of chronic asthma, at least partially through the attenuation of oxidative stress and TGF-β-induced fibronectin expression. The results of this study suggest a potential role for SAMe as a novel therapeutic agent in chronic asthma. PMID:27256110

  4. Extracorporeal Lung Support as a Bridge to Airway Stenting and Radiotherapy for Airway-Obstructing Pancoast Tumor.

    Science.gov (United States)

    McLenon, Melissa; Bittle, Gregory J; Jones, Kevin; Menaker, Jay; Pham, Si M; Iacono, Aldo T; Sachdeva, Ashutosh; Rajagopal, Keshava

    2016-07-01

    Venovenous (V-V) extracorporeal membrane oxygenation (ECMO) is used for respiratory failure that is suspected to be reversible (bridge to recovery), or as a bridge to lung transplantation. Patients with proximal airway obstruction due to endobronchial malignancy can develop acute respiratory failure, and may benefit from V-V ECMO as a bridge to airway intervention, further treatment, and eventual recovery. We describe a case of a superior sulcus tumor with tracheobronchial and superior vena cava invasion causing both respiratory failure and superior vena cava syndrome. This was treated successfully with V-V ECMO, bronchial stenting, and radiotherapy. PMID:27343540

  5. Volumetric capnography for the evaluation of chronic airways diseases

    OpenAIRE

    Veronez L; Pereira MC; Doria da Silva SM; Barcaui LA; De Capitani EM; Moreira MM; Paschoal IA

    2014-01-01

    Liliani de Fátima Veronez,1 Monica Corso Pereira,2 Silvia Maria Doria da Silva,2 Luisa Affi Barcaui,2 Eduardo Mello De Capitani,2 Marcos Mello Moreira,2 Ilma Aparecida Paschoalz2 1Department of Physical Therapy, University of Votuporanga (Educational Foundation of Votuporanga), Votuporanga, 2Department of Internal Medicine, School of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Sao Paulo, BrazilBackground: Obstructive lung diseases of different etiologies pre...

  6. Airway hyperresponsiveness with chest strapping: A matter of heterogeneity or reduced lung volume?

    Science.gov (United States)

    Pellegrino, Riccardo; Pompilio, Pasquale P; Bruni, Giulia Innocenti; Scano, Giorgio; Crimi, Claudia; Biasco, Luigi; Coletta, Giuseppe; Cornara, Giuseppe; Torchio, Roberto; Brusasco, Vito; Dellacà, Raffaele L

    2009-03-31

    Chest wall strapping has been recently shown to be associated with an increase in airway responsiveness to methacholine. To investigate whether this is the result of the decreased lung volume or an increased heterogeneity due to chest wall distortion, ten healthy volunteers underwent a methacholine challenge at control conditions and after selective strapping of the rib cage, the abdomen or the whole chest wall resulting in similar decrements of functional residual capacity and total lung capacity but causing different distribution of the bronchoconstrictor. Methacholine during strapping reduced forced expiratory flow, dynamic compliance, and reactance at 5Hz and increased pulmonary resistance and respiratory resistance at 5Hz that were significantly greater than at control and associated with a blunted bronchodilator effect of the deep breath. However, no significant differences were observed between selective and total chest wall strapping, suggesting that the major mechanism for increasing airway responsiveness with chest wall strapping is the breathing at low lung volume rather than regional heterogeneities. PMID:19429518

  7. Parabronchial smooth muscle constitutes an airway epithelial stem cell niche in the mouse lung after injury.

    Science.gov (United States)

    Volckaert, Thomas; Dill, Erik; Campbell, Alice; Tiozzo, Caterina; Majka, Susan; Bellusci, Saverio; De Langhe, Stijn P

    2011-11-01

    During lung development, parabronchial SMC (PSMC) progenitors in the distal mesenchyme secrete fibroblast growth factor 10 (Fgf10), which acts on distal epithelial progenitors to promote their proliferation. β-catenin signaling within PSMC progenitors is essential for their maintenance, proliferation, and expression of Fgf10. Here, we report that this Wnt/Fgf10 embryonic signaling cascade is reactivated in mature PSMCs after naphthalene-induced injury to airway epithelium. Furthermore, we found that this paracrine Fgf10 action was essential for activating surviving variant Clara cells (the cells in the airway epithelium from which replacement epithelial cells originate) located at the bronchoalveolar duct junctions and adjacent to neuroendocrine bodies. After naphthalene injury, PSMCs secreted Fgf10 to activate Notch signaling and induce Snai1 expression in surviving variant Clara cells, which subsequently underwent a transient epithelial to mesenchymal transition to initiate the repair process. Epithelial Snai1 expression was important for regeneration after injury. We have therefore identified PSMCs as a stem cell niche for the variant Clara cells in the lung and established that paracrine Fgf10 signaling from the niche is critical for epithelial repair after naphthalene injury. These findings also have implications for understanding the misregulation of lung repair in asthma and cancer. PMID:21985786

  8. Structure and function of airway surface layer of the human lungs & mobility of probe particles in complex fluids

    Science.gov (United States)

    Cai, Liheng

    Numerous infectious particles such as bacteria and pathogens are deposited on the airway surface of the human lungs during our daily breathing. To avoid infection the lung has evolved to develop a smart and powerful defense system called mucociliary clearance. The airway surface layer is a critical component of this mucus clearance system, which consists of two parts: (1) a mucus layer, that traps inhaled particles and transports them out of the lung by cilia-generated flow; and (2) a periciliary layer, that provides a favorable environment for ciliary beating and cell surface lubrication. For 75 years, it has been dogma that a single gel-like mucus layer, which is composed of secreted mucin glycoproteins, is transported over a "watery" periciliary layer. This one-gel model, however, does not explain fundamental features of the normal system, e.g. formation of a distinct mucus layer, nor accurately predict how the mucus clearance system fails in disease. In the first part of this thesis we propose a novel "Gel-on-Brush" model with a mucus layer (the "gel") and a "brush-like" periciliary layer, composed of mucins tethered to the luminal of airway surface, and supporting data accurately describes both the biophysical and cell biological bases for normal mucus clearance and its failure in disease. Our "Gel-on-Brush" model describes for the first time how and why mucus is efficiently cleared in health and unifies the pathogenesis of major human diseases, including cystic fibrosis and chronic obstructive pulmonary disease. It is expected that this "Gel-on-Brush" model of airway surface layer opens new directions for treatments of airway diseases. A dilemma regarding the function of mucus is that, although mucus traps any inhaled harmful particulates, it also poses a long-time problem for drug delivery: mobility of cargos carrying pharmaceutical agents is slowed down in mucus. The second part of this thesis aims to answer the question: can we theoretically understand the

  9. Radioaerosol lung scanning in chronic obstructive pulmonary disease (COPD) and related disorders

    International Nuclear Information System (INIS)

    As a coordinated research project of the International Atomic Energy Agency (IAEA), a multicentre joint study on radioaerosol lung scan using the BARC nebulizer has prospectively been carried out during 1988-1992 with the participation of 10 member countries in Asia [Bangladesh, China, India, Indonesia, Japan, Korea, Pakistan, Philippines, Singapore and Thailand]. The study was designed so that it would primarily cover chronic obstructive pulmonary disease (COPD) and the other related and common pulmonary diseases. The study also included normal controls and asymptomatic smokers. The purposes of this presentation are three fold: firstly, to document the usefulness of the nebulizer and the validity of user's protocol in imaging COPD and other lung diseases; secondly, to discuss scan features of the individual COPD and other disorders studied and thirdly, to correlate scan alterations with radiographic findings. Before proceeding with a systematic analysis of aerosol scan patterns in the disease groups, we documented normal pattern. The next step was the assessment of scan features in those who had been smoking for more than several years but had no symptoms or signs referable to airways. The lung diseases we analyzed included COPD [emphysema, chronic bronchitis, asthma and bronchiectasis], bronchial obstruction, compensatory overinflation and other common lung diseases such as lobar pneumonia, tuberculosis, interstitial fibrosis, diffuse panbronchiolitis, lung edema and primary and metastatic lung cancers. Lung embolism, inhalation bums and glue-sniffer's lung are separately discussed by Dr. Sundram of Singapore elsewhere in this book. The larger portion of this chapter is allocated to the discussion of COPD with a special effort made in sorting out differential scan features. Diagnostic criteria in individual COPD were defined for each category of disease and basic clinical symptoms and signs and pertinent laboratory data as well as radiographic manifestations are

  10. Positive signature-tagged mutagenesis in Pseudomonas aeruginosa: Tracking patho-adaptive mutations promoting airways chronic infection

    OpenAIRE

    Bianconi, Irene; Milani, Andrea; Cigana, Cristina; Paroni, Moira; Levesque, Roger C.; Bertoni, Giovanni; Bragonzi, Alessandra

    2011-01-01

    The opportunistic pathogen Pseudomonas aeruginosa can establish life-long chronic infections in the airways of cystic fibrosis (CF) patients. Persistent lifestyle is established with P. aeruginosa patho-adaptive variants, which are clonal with the initially-acquired strains. Several reports indicated that P. aeruginosa adapts by loss-of-function mutations which enhance fitness in CF airways and sustain its clonal expansion during chronic infection. To validate this model of P. aeruginosa adap...

  11. Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers – Is There a Specific Role for Mast Cells?

    OpenAIRE

    Nussbaumer-Ochsner, Yvonne; Stolk, Jan; Ferraz da Silva, Luiz F.; van Schadewijk, Annemarie; de Jeu, Ronald C.; Prins, Frans A.; Mauad, Thais; Rabe, Klaus F; Hiemstra, Pieter S.

    2015-01-01

    Background Smoking is associated with a mixed inflammatory infiltrate in the airways. We evaluated whether airway inflammation in smokers is related to lung function parameters and inflammatory markers in exhaled breath. Methods Thirty-seven smokers undergoing lung resection for primary lung cancer were assessed pre-operatively by lung function testing including single-breath-nitrogen washout test (sb-N2-test), measurement of fractional exhaled nitric oxide (FeNO) and pH/8-isoprostane in exha...

  12. Pneumonectomy for chronic inflammatory lung disease: indications and complications

    Institute of Scientific and Technical Information of China (English)

    NIE Gang; LIU Guo-jun; Jean Deslauriers; FAN Zhi-min

    2010-01-01

    @@ Chronic inflammatory lung disease is a common health problem and often treated with potent antibiotics, anti-tuberculosis drugs, and antifungal agents. However, in case of medical therapy failure, surgical treatment has been often considered as an effective procedure.

  13. Nontypeable Haemophilus influenzae biofilms: role in chronic airway infections

    OpenAIRE

    Swords, W. Edward

    2012-01-01

    Like many pathogens inhabiting mucosal surfaces, nontypeable Haemophilus influenzae (NTHi) forms multicellular biofilm communities both in vitro and in various infection models. In the past 15 years much has been learned about determinants of biofilm formation by this organism and potential roles in bacterial virulence, especially in the context of chronic and recurrent infections. However, this concept has not been without some degree of controversy, and in the past some have expressed doubt...

  14. Phenotypes selected during chronic lung infection in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Ciofu, Oana; Mandsberg, Lotte F; Wang, Hengzhuang;

    2012-01-01

    During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated by...... importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis....

  15. Regulation of Th17/Treg function contributes to the attenuation of chronic airway inflammation by icariin in ovalbumin-induced murine asthma model.

    Science.gov (United States)

    Wei, Ying; Liu, Baojun; Sun, Jing; Lv, Yubao; Luo, Qingli; Liu, Feng; Dong, Jingcheng

    2015-06-01

    Icariin which is a flavonoid glucoside isolated from Epimedium brevicornu Maxim, has been reported to have anti-osteoporotic, anti-inflammatory and anti-depressant-like activities. In this study, we observed the effect of icariin on airway inflammation of ovalbumin (OVA)-induced murine asthma model and the associated regulatory mode on T-helper (Th)17 and regulatory T (Treg) cell function. Our data revealed that chronic OVA inhalation induced a dramatic increase in airway resistance (RL) and decrease in the lung dynamic compliance (Cdyn), and icariin and DEX treatment caused significant attenuation of such airway hyperresponsiveness (AHR). BALF cell counts demonstrated that icariin and DEX led to a prominent reduction in total leukocyte as well as lymphocyte, eosinophil, neutrophil, basophil and monocyte counts. Histological analysis results indicated that icariin and DEX alleviated the inflammatory cells infiltrating into the peribronchial tissues and goblet cells hyperplasia and mucus hyper-production. Flow cytometry test demonstrated that icariin or DEX administration resulted in a significant percentage reduction in CD4+RORγt+ T cells and elevation of CD4+Foxp3+ T cells in BALF. Furthermore, icariin or DEX caused a significant reduction in IL-6, IL-17 and TGF-β level in BALF. Unfortunately, icariin had no effect on IL-10 level in BALF. Western blot assay found that icariin or DEX suppressed RORγt and promoted Foxp3 expression in the lung tissue. qPCR analysis revealed that icariin and DEX resulted in a notable decrease in RORγt and increase in Foxp3 mRNA expression in isolated spleen CD4+ T cell. In conclusion, our results suggested that icariin was effective in the attenuation of AHR and chronic airway inflammatory changes in OVA-induced murine asthma model, and this effect was associated with regulation of Th17/Treg responses, which indicated that icariin may be used as a potential therapeutic method to treat asthma with Th17/Treg imbalance phenotype

  16. One lung ventilation in a patient with an upper and lower airway abnormality

    Directory of Open Access Journals (Sweden)

    Sangita R Kaza

    2012-01-01

    Full Text Available One-lung ventilation for a thoracotomy procedure was achieved with the help of a endobronchial blocker in a young girl with limited mouth opening, minimal neck extension, and a distorted tracheo-bronchial anatomy. As the patient would not cooperate for an awake nasotracheal intubation despite adequate preperation, an inhalational anesthetic was used to make the patient unconscious, taking care that spontaneous breathing was maintained. Nasotracheal intubation was done with the help of a fiberoptic bronchoscope. A wire-guided Arndt endobronchial blocker was placed coaxially through the endotracheal tube using a fiberoptic bronchoscope. This case report highlights that in a scenario of both upper and lower airway distortion, a bronchial blocker positioned through a nasotracheal tube under fiberoptic guidance might be the best option when one-lung ventilation is required.

  17. Allergic Airway Inflammation Decreases Lung Bacterial Burden following Acute Klebsiella pneumoniae Infection in a Neutrophil- and CCL8-Dependent Manner

    OpenAIRE

    Dulek, Daniel E.; Newcomb, Dawn C.; Goleniewska, Kasia; Cephus, Jaqueline; Zhou, Weisong; Reiss, Sara; Toki, Shinji; Ye, Fei; Zaynagetdinov, Rinat; Sherrill, Taylor P.; Timothy S. Blackwell; Moore, Martin L.; Boyd, Kelli L.; Kolls, Jay K.; Peebles, R. Stokes

    2014-01-01

    The Th17 cytokines interleukin-17A (IL-17A), IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens, including Klebsiella pneumoniae. Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminish ex vivo and in vivo IL-17A protein expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infect...

  18. Role of dystrophin in airway smooth muscle phenotype, contraction and lung function.

    Directory of Open Access Journals (Sweden)

    Pawan Sharma

    Full Text Available Dystrophin links the transmembrane dystrophin-glycoprotein complex to the actin cytoskeleton. We have shown that dystrophin-glycoprotein complex subunits are markers for airway smooth muscle phenotype maturation and together with caveolin-1, play an important role in calcium homeostasis. We tested if dystrophin affects phenotype maturation, tracheal contraction and lung physiology. We used dystrophin deficient Golden Retriever dogs (GRMD and mdx mice vs healthy control animals in our approach. We found significant reduction of contractile protein markers: smooth muscle myosin heavy chain (smMHC and calponin and reduced Ca2+ response to contractile agonist in dystrophin deficient cells. Immunocytochemistry revealed reduced stress fibers and number of smMHC positive cells in dystrophin-deficient cells, when compared to control. Immunoblot analysis of Akt1, GSK3β and mTOR phosphorylation further revealed that downstream PI3K signaling, which is essential for phenotype maturation, was suppressed in dystrophin deficient cell cultures. Tracheal rings from mdx mice showed significant reduction in the isometric contraction to methacholine (MCh when compared to genetic control BL10ScSnJ mice (wild-type. In vivo lung function studies using a small animal ventilator revealed a significant reduction in peak airway resistance induced by maximum concentrations of inhaled MCh in mdx mice, while there was no change in other lung function parameters. These data show that the lack of dystrophin is associated with a concomitant suppression of ASM cell phenotype maturation in vitro, ASM contraction ex vivo and lung function in vivo, indicating that a linkage between the DGC and the actin cytoskeleton via dystrophin is a determinant of the phenotype and functional properties of ASM.

  19. Effects of inhaled corticosteroids on airway inflammation in chronic obstructive pulmonary disease: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Jen R

    2012-09-01

    Full Text Available Rachel Jen,1 Stephen,1 Rennard,2 Don D Sin1,31Department of Medicine, Respiratory Division, University of British Columbia, Vancouver, BC, Canada; 2Internal Medicine Section of Pulmonary and Critical Care, Nebraska Medical Center, Omaha, NE, USA; 3Institute of Heart and Lung Health and the UBC James Hogg Research Center, St Paul's Hospital, Vancouver, BC, CanadaBackground: Chronic obstructive pulmonary disease (COPD is characterized by chronic inflammation in the small airways. The effect of inhaled corticosteroids (ICS on lung inflammation in COPD remains uncertain. We sought to determine the effects of ICS on inflammatory indices in bronchial biopsies and bronchoalveolar lavage fluid of patients with COPD.Methods: We searched Medline, Embase, Cinahl, and the Cochrane database for randomized, controlled clinical trials that used bronchial biopsies and bronchoalveolar lavage to evaluate the effects of ICS in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of inflammatory cells before and after treatment in both intervention and control groups. These values were then converted into standardized mean differences (SMD to accommodate the differences in patient selection, clinical treatment, and biochemical procedures that were employed across the original studies. If significant heterogeneity was present (P < 0.1, then a random effects model was used to pool the original data; otherwise, a fixed effects model was used.Results: We identified eight original studies that met the inclusion criteria. Four studies used bronchial biopsies (n = 102 participants and showed that ICS were effective in reducing CD4 and CD8 cell counts (SMD, −0.52 units and −0.66 units, 95% confidence interval. The five studies used bronchoalveolar lavage fluid (n = 309, which together showed that ICS reduced neutrophil and lymphocyte counts (SMD, −0.64 units and −0.64 units, 95% confidence interval. ICS on the other hand

  20. Bronchial airway gene expression in smokers with lung or head and neck cancer

    International Nuclear Information System (INIS)

    Cigarette smoking is the major cause of cancers of the respiratory tract, including non-small cell lung cancer (NSCLC) and head and neck cancer (HNC). In order to better understand carcinogenesis of the lung and upper airways, we have compared the gene expression profiles of tumor-distant, histologically normal bronchial biopsy specimens obtained from current smokers with NSCLC or HNC (SC, considered as a single group), as well as nonsmokers (NS) and smokers without cancer (SNC). RNA from a total of 97 biopsies was used for gene expression profiling (Affymetrix HG-U133 Plus 2.0 array). Differentially expressed genes were used to compare NS, SNC, and SC, and functional analysis was carried out using Ingenuity Pathway Analysis (IPA). Smoking-related cancer of the respiratory tract was found to affect the expression of genes encoding xenobiotic biotransformation proteins, as well as proteins associated with crucial inflammation/immunity pathways and other processes that protect the airway from the chemicals in cigarette smoke or contribute to carcinogenesis. Finally, we used the prediction analysis for microarray (PAM) method to identify gene signatures of cigarette smoking and cancer, and uncovered a 15-gene signature that distinguished between SNC and SC with an accuracy of 83%. Thus, gene profiling of histologically normal bronchial biopsy specimens provided insight into cigarette-induced carcinogenesis of the respiratory tract and gene signatures of cancer in smokers

  1. DEVELOPMENT OF THE SMALL AIRWAYS AND ALVEOLI FROM CHILDHOOD TO ADULT LUNG MEASURED BY AEROSOL-DERIVED AIRWAY MORPHOMETRY

    Science.gov (United States)

    Understanding the human development of pulmonary airspaces is important for calculating the dose from exposure to inhaled materials as a function of age. We have measured, in vivo, the airspace caliber of the small airways and alveoli by aerosol-derived airway morphometry (ADAM) ...

  2. Chronic exposure to a beta 2-adrenoceptor agonist increases the airway response to methacholine.

    Science.gov (United States)

    Witt-Enderby, P A; Yamamura, H I; Halonen, M; Palmer, J D; Bloom, J W

    1993-09-01

    Scheduled chronic administration of beta 2-adrenoceptor agonist bronchodilators in patients with asthma recently has been reported to be associated with a worsening of symptoms and an increase in bronchial responsiveness. We wanted to determine whether a 28-day in vivo exposure to albuterol (beta 2-adrenoceptor agonist) altered the response of rabbit airways to the cholinergic agonist methacholine. We found, using in vitro tissue bath techniques, that in mainstem bronchi from rabbits given a 28-day exposure to albuterol, maximum contraction to methacholine was increased in the albuterol-treated group (control group = 1.10 +/- 0.11 g vs. treated group = 1.50 +/- 0.13 g, P airway smooth muscle to methacholine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7901034

  3. IMD-4690, a novel specific inhibitor for plasminogen activator inhibitor-1, reduces allergic airway remodeling in a mouse model of chronic asthma via regulating angiogenesis and remodeling-related mediators.

    Science.gov (United States)

    Tezuka, Toshifumi; Ogawa, Hirohisa; Azuma, Masahiko; Goto, Hisatsugu; Uehara, Hisanori; Aono, Yoshinori; Hanibuchi, Masaki; Yamaguchi, Yoichi; Fujikawa, Tomoyuki; Itai, Akiko; Nishioka, Yasuhiko

    2015-01-01

    Plasminogen activator inhibitor (PAI)-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen, Dermatophagoides pteronyssinus (Dp). IMD-4690 was intraperitoneally administered during the challenge. Lung histopathology, hyperresponsiveness and the concentrations of mediators in lung homogenates were analyzed. The amount of active PAI-1 in the lungs was increased in mice treated with Dp. Administration with IMD-4690 reduced an active/total PAI-1 ratio. IMD-4690 also reduced the number of bronchial eosinophils in accordance with the decreased expressions of Th2 cytokines in the lung homogenates. Airway remodeling was inhibited by reducing subepithelial collagen deposition, smooth muscle hypertrophy, and angiogenesis. The effects of IMD-4690 were partly mediated by the regulation of TGF-β, HGF and matrix metalloproteinase. These results suggest that PAI-1 plays crucial roles in airway inflammation and remodeling, and IMD-4690, a specific PAI-1 inhibitor, may have therapeutic potential for patients with refractory asthma due to airway remodeling. PMID:25785861

  4. IMD-4690, a novel specific inhibitor for plasminogen activator inhibitor-1, reduces allergic airway remodeling in a mouse model of chronic asthma via regulating angiogenesis and remodeling-related mediators.

    Directory of Open Access Journals (Sweden)

    Toshifumi Tezuka

    Full Text Available Plasminogen activator inhibitor (PAI-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen, Dermatophagoides pteronyssinus (Dp. IMD-4690 was intraperitoneally administered during the challenge. Lung histopathology, hyperresponsiveness and the concentrations of mediators in lung homogenates were analyzed. The amount of active PAI-1 in the lungs was increased in mice treated with Dp. Administration with IMD-4690 reduced an active/total PAI-1 ratio. IMD-4690 also reduced the number of bronchial eosinophils in accordance with the decreased expressions of Th2 cytokines in the lung homogenates. Airway remodeling was inhibited by reducing subepithelial collagen deposition, smooth muscle hypertrophy, and angiogenesis. The effects of IMD-4690 were partly mediated by the regulation of TGF-β, HGF and matrix metalloproteinase. These results suggest that PAI-1 plays crucial roles in airway inflammation and remodeling, and IMD-4690, a specific PAI-1 inhibitor, may have therapeutic potential for patients with refractory asthma due to airway remodeling.

  5. The Lung Microbiome, Immunity, and the Pathogenesis of Chronic Lung Disease.

    Science.gov (United States)

    O'Dwyer, David N; Dickson, Robert P; Moore, Bethany B

    2016-06-15

    The development of culture-independent techniques for microbiological analysis has uncovered the previously unappreciated complexity of the bacterial microbiome at various anatomic sites. The microbiome of the lung has relatively less bacterial biomass when compared with the lower gastrointestinal tract yet displays considerable diversity. The composition of the lung microbiome is determined by elimination, immigration, and relative growth within its communities. Chronic lung disease alters these factors. Many forms of chronic lung disease demonstrate exacerbations that drive disease progression and are poorly understood. Mounting evidence supports ways in which microbiota dysbiosis can influence host defense and immunity, and in turn may contribute to disease exacerbations. Thus, the key to understanding the pathogenesis of chronic lung disease may reside in deciphering the complex interactions between the host, pathogen, and resident microbiota during stable disease and exacerbations. In this brief review we discuss new insights into these labyrinthine relationships. PMID:27260767

  6. Protective effects of phosphodiesterase inhibitors on lung function and remodeling in a murine model of chronic asthma

    Directory of Open Access Journals (Sweden)

    H.S. Campos

    2006-02-01

    Full Text Available The aim of the present study was to compare the efficacy of a novel phosphodiesterase 4 and 5 inhibitor, LASSBio596, with that of dexamethasone in a murine model of chronic asthma. Lung mechanics (airway resistance, viscoelastic pressure, and static elastance, histology, and airway and lung parenchyma remodeling (quantitative analysis of collagen and elastic fiber were analyzed. Thirty-three BALB/c mice were randomly assigned to four groups. In the asthma group (N = 9, mice were immunized with 10 µg ovalbumin (OVA, ip on 7 alternate days, and after day 40 they were challenged with three intratracheal instillations of 20 µg OVA at 3-day intervals. Control mice (N = 8 received saline under the same protocol. In the dexamethasone (N = 8 and LASSBio596 (N = 8 groups, the animals of the asthma group were treated with 1 mg/kg dexamethasone disodium phosphate (0.1 mL, ip or 10 mg/kg LASSBio596 dissolved in dimethyl sulfoxide (0.2 mL, ip 24 h before the first intratracheal instillation of OVA, for 8 days. Airway resistance, viscoelastic pressure and static elastance increased significantly in the asthma group (77, 56, and 76%, respectively compared to the control group. The asthma group presented more intense alveolar collapse, bronchoconstriction, and eosinophil and neutrophil infiltration than the control group. Both LASSBio596 and dexamethasone inhibited the changes in lung mechanics, tissue cellularity, bronchoconstriction, as well as airway and lung parenchyma remodeling. In conclusion, LASSBio596 at a dose of 10 mg/kg effectively prevented lung mechanical and morphometrical changes and had the potential to block fibroproliferation in a BALB/c mouse model of asthma.

  7. Protective effects of phosphodiesterase inhibitors on lung function and remodeling in a murine model of chronic asthma

    Directory of Open Access Journals (Sweden)

    Campos H.S.

    2006-01-01

    Full Text Available The aim of the present study was to compare the efficacy of a novel phosphodiesterase 4 and 5 inhibitor, LASSBio596, with that of dexamethasone in a murine model of chronic asthma. Lung mechanics (airway resistance, viscoelastic pressure, and static elastance, histology, and airway and lung parenchyma remodeling (quantitative analysis of collagen and elastic fiber were analyzed. Thirty-three BALB/c mice were randomly assigned to four groups. In the asthma group (N = 9, mice were immunized with 10 µg ovalbumin (OVA, ip on 7 alternate days, and after day 40 they were challenged with three intratracheal instillations of 20 µg OVA at 3-day intervals. Control mice (N = 8 received saline under the same protocol. In the dexamethasone (N = 8 and LASSBio596 (N = 8 groups, the animals of the asthma group were treated with 1 mg/kg dexamethasone disodium phosphate (0.1 mL, ip or 10 mg/kg LASSBio596 dissolved in dimethyl sulfoxide (0.2 mL, ip 24 h before the first intratracheal instillation of OVA, for 8 days. Airway resistance, viscoelastic pressure and static elastance increased significantly in the asthma group (77, 56, and 76%, respectively compared to the control group. The asthma group presented more intense alveolar collapse, bronchoconstriction, and eosinophil and neutrophil infiltration than the control group. Both LASSBio596 and dexamethasone inhibited the changes in lung mechanics, tissue cellularity, bronchoconstriction, as well as airway and lung parenchyma remodeling. In conclusion, LASSBio596 at a dose of 10 mg/kg effectively prevented lung mechanical and morphometrical changes and had the potential to block fibroproliferation in a BALB/c mouse model of asthma.

  8. Particles causing lung disease.

    OpenAIRE

    Kilburn, K H

    1984-01-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell ...

  9. Excessive dynamic airway collapse in a small cohort of chronic obstructive pulmonary disease patients

    Directory of Open Access Journals (Sweden)

    C Represas-Represas

    2015-01-01

    The percentage of collapse at each anatomic level was as follows: Aortic arch, 16.1% (SD, 13.6%; carina, 19.4% (SD, 15.9%; and bronchus intermedius, 21.7% (SD, 16.1%. At the point of maximal collapse, the percentage of collapse was 26.8% (SD, 16%. EDAC was demonstrated at any of the three anatomical points in five patients, corresponding to 9.4% (95% CI, 3.1% to 20.6% of the sample and affecting the three anatomical points in only two cases. A statistically significant correlation was only found with the total lung capacity (TLC. CONCLUSIONS: The prevalence of EDAC observed in a sample of patients with different levels of COPD severity is low. The degree of dynamic central airway collapse was not related to the patient′s epidemiological or clinical features, and did not affect lung function, symptoms, capacity for effort, or quality of life.

  10. Relationships between respiratory and airway resistances and activity-related dyspnea in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Plantier L

    2012-03-01

    Full Text Available Bruno Mahut1,2, Aurore Caumont-Prim3,4, Laurent Plantier1,5, Karine Gillet-Juvin1,6, Etienne Callens1, Olivier Sanchez5,6, Brigitte Chevalier-Bidaud3, Plamen Bokov1, Christophe Delclaux1,5,71Assistance Publique – Hôpitaux de Paris (AP-HP, Hôpital Européen Georges Pompidou, Service de Physiologie – Clinique de la Dyspnée, F-75015 Paris, France; 2Cabinet La Berma, 4 avenue de la Providence; F-92160 Antony, France; 3AP-HP, Hôpital Européen Georges Pompidou, Unité d'Épidémiologie et de Recherche Clinique, F-75015 Paris, France; 4INSERM, Centre d'Investigation Épidémiologique 4, F-75015 Paris, France; 5Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, F-75015 Paris, France; 6AP-HP, Hôpital Européen Georges Pompidou, Service de Pneumologie; F-75015 Paris, France; 7CIC 9201 Plurithématique, Hôpital Européen Georges Pompidou, F-75015 Paris, FranceBackground: The aims of the study were: (1 to compare numerical parameters of specific airway resistance (total, sRawtot, effective, sRaweff and at 0.5 L • s-1, sRaw0.5 and indices obtained from the forced oscillation technique (FOT: resistance extrapolated at 0 Hz [Rrs0 Hz], mean resistance [Rrsmean], and resistance/frequency slope [Rrsslope] and (2 to assess their relationships with dyspnea in chronic obstructive pulmonary disease (COPD.Methods: A specific statistical approach, principal component analysis that also allows graphic representation of all correlations between functional parameters was used. A total of 108 patients (mean ± SD age: 65 ± 9 years, 31 women; GOLD stages: I, 14; II, 47; III, 39 and IV, 8 underwent spirometry, body plethysmography, FOT, and Medical Research Council (MRC scale assessments.Results: Principal component analysis determined that the functional parameters were described by three independent dimensions (airway caliber, lung volumes and their combination, specific resistance and that resistance parameters of the two techniques

  11. Vitronectin expression in the airways of subjects with asthma and chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Lina M Salazar-Peláez

    Full Text Available Vitronectin, a multifunctional glycoprotein, is involved in coagulation, inhibition of the formation of the membrane attack complex (MAC, cell adhesion and migration, wound healing, and tissue remodeling. The primary cellular source of vitronectin is hepatocytes; it is not known whether resident cells of airways produce vitronectin, even though the glycoprotein has been found in exhaled breath condensate and bronchoalveolar lavage from healthy subjects and patients with interstitial lung disease. It is also not known whether vitronectin expression is altered in subjects with asthma and COPD. In this study, bronchial tissue from 7 asthmatic, 10 COPD and 14 control subjects was obtained at autopsy and analyzed by immunohistochemistry to determine the percent area of submucosal glands occupied by vitronectin. In a separate set of experiments, quantitative colocalization analysis was performed on tracheobronchial tissue sections obtained from donor lungs (6 asthmatics, 4 COPD and 7 controls. Vitronectin RNA and protein expressions in bronchial surface epithelium were examined in 12 subjects who undertook diagnostic bronchoscopy. Vitronectin was found in the tracheobronchial epithelium from asthmatic, COPD, and control subjects, although its expression was significantly lower in the asthmatic group. Colocalization analysis of 3D confocal images indicates that vitronectin is expressed in the glandular serous epithelial cells and in respiratory surface epithelial cells other than goblet cells. Expression of the 65-kDa vitronectin isoform was lower in bronchial surface epithelium from the diseased subjects. The cause for the decreased vitronectin expression in asthma is not clear, however, the reduced concentration of vitronectin in the epithelial/submucosal layer of airways may be linked to airway remodeling.

  12. Vitronectin expression in the airways of subjects with asthma and chronic obstructive pulmonary disease.

    Science.gov (United States)

    Salazar-Peláez, Lina M; Abraham, Thomas; Herrera, Ana M; Correa, Mario A; Ortega, Jorge E; Paré, Peter D; Seow, Chun Y

    2015-01-01

    Vitronectin, a multifunctional glycoprotein, is involved in coagulation, inhibition of the formation of the membrane attack complex (MAC), cell adhesion and migration, wound healing, and tissue remodeling. The primary cellular source of vitronectin is hepatocytes; it is not known whether resident cells of airways produce vitronectin, even though the glycoprotein has been found in exhaled breath condensate and bronchoalveolar lavage from healthy subjects and patients with interstitial lung disease. It is also not known whether vitronectin expression is altered in subjects with asthma and COPD. In this study, bronchial tissue from 7 asthmatic, 10 COPD and 14 control subjects was obtained at autopsy and analyzed by immunohistochemistry to determine the percent area of submucosal glands occupied by vitronectin. In a separate set of experiments, quantitative colocalization analysis was performed on tracheobronchial tissue sections obtained from donor lungs (6 asthmatics, 4 COPD and 7 controls). Vitronectin RNA and protein expressions in bronchial surface epithelium were examined in 12 subjects who undertook diagnostic bronchoscopy. Vitronectin was found in the tracheobronchial epithelium from asthmatic, COPD, and control subjects, although its expression was significantly lower in the asthmatic group. Colocalization analysis of 3D confocal images indicates that vitronectin is expressed in the glandular serous epithelial cells and in respiratory surface epithelial cells other than goblet cells. Expression of the 65-kDa vitronectin isoform was lower in bronchial surface epithelium from the diseased subjects. The cause for the decreased vitronectin expression in asthma is not clear, however, the reduced concentration of vitronectin in the epithelial/submucosal layer of airways may be linked to airway remodeling. PMID:25768308

  13. Chronic smoker lung dosimetry of radon progeny

    International Nuclear Information System (INIS)

    The purpose of this study is to determine how cigarette smoking affects the dose of radon progeny in the lungs. An extensive survey of the medical literature suggests that about six physiological parameters may influence deposition as well as clearance of radon progeny and thus, affecting the resulting doses received by sensitive bronchial target cells. The calculations reflect a difference between the dose of a nonsmoker lung and the lung of the heavy long-term smoker, of a multiplicative factor 1,8. (authors)

  14. Pulmonary and systemic blood flow contributions to upper airways in canine lung

    International Nuclear Information System (INIS)

    The blood flow contributions and drainage patterns of the pulmonary and systemic circulations in the upper airways (trachea and main bronchi) were assessed in anesthetized dogs by injecting 15-μm radiolabeled microspheres into the right and left heart, respectively. After the animals were killed, the tracheal cartilage, tracheal muscle-mucosa, and main bronchi were excised. The tracheal cartilage and tracheal muscle-mucosa were divided into lower, middle, and upper segments for blood flow determinations. The pulmonary contribution to tracheal blood flow was very small, being higher in the lower segments. The systemic contribution to these same tracheal regions was significantly higher, and higher in the upper segments. The pulmonary and systemic circulations each contributed ∼50% to the main bronchi blood flow. The pulmonary blood flow contribution alone to the trachea and main bronchi was also determined in subsequent experiments that utilized the isolated lung, and these blood flows were not significantly different from the pulmonary contribution measured in the intact lungs. The present results indicate that the systemic (bronchial) circulation is the primary source of tracheal blood flow and that both the pulmonary and systemic circulations may contribute ∼50% of the blood flow to the main bronchi in dog lungs

  15. A Lagrangian Approach for Calculating Microsphere Deposition in a One-Dimensional Lung-Airway Model.

    Science.gov (United States)

    Vaish, Mayank; Kleinstreuer, Clement

    2015-09-01

    Using the open-source software openfoam as the solver, a novel approach to calculate microsphere transport and deposition in a 1D human lung-equivalent trumpet model (TM) is presented. Specifically, for particle deposition in a nonlinear trumpetlike configuration a new radial force has been developed which, along with the regular drag force, generates particle trajectories toward the wall. The new semi-empirical force is a function of any given inlet volumetric flow rate, micron-particle diameter, and lung volume. Particle-deposition fractions (DFs) in the size range from 2 μm to 10 μm are in agreement with experimental datasets for different laminar and turbulent inhalation flow rates as well as total volumes. Typical run times on a single processor workstation to obtain actual total deposition results at comparable accuracy are 200 times less than that for an idealized whole-lung geometry (i.e., a 3D-1D model with airways up to 23rd generation in single-path only). PMID:26141916

  16. THE ROLE OF MICROBIAL COMMUNITIES OF AIRWAYS IN PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

    OpenAIRE

    S. V. Fedosenko; L. M. Ogorodova; M. A. Karnaushkina; Ye. S. Kulikov; I. A. Deyev; N. A. Kirillova

    2015-01-01

    This review summarizes the results of studies on the composition of microbial communities in the airways of healthy subjects and in patients with chronic obstructive pulmonary disease. Modern technologies of molecular-genetic identification methods of microorganisms allow to perform a deep analysis  of  the  respiratory  microbiom.  It  is  of  considerable  interest  to  determine  the  role  of  the microbiome in the development of human diseases of the bronchopulmonary system, and to under...

  17. Airway malacia in chronic obstructive pulmonary disease: prevalence, morphology and relationship with emphysema, bronchiectasis and bronchial wall thickening

    Energy Technology Data Exchange (ETDEWEB)

    Sverzellati, Nicola; Rastelli, Andrea; Schembri, Valentina; Filippo, Massimo de [University of Parma, Department of Clinical Sciences, Section of Radiology, Parma (Italy); Chetta, Alfredo [University of Parma, Department of Clinical Sciences, Section of Respiratory Diseases, Parma (Italy); Fasano, Luca; Pacilli, Angela Maria [Policlinico Sant' Orsola-Malpighi, Unita Operativa di Fisiopatologia Respiratoria, Bologna (Italy); Di Scioscio, Valerio; Bartalena, Tommaso; Zompatori, Maurizio [University of Bologna, Department of Radiology, Cardiothoracic Institute, Policlinico S.Orsola-Malpighi, Bologna (Italy)

    2009-07-15

    The aim of this study was to determine the prevalence of airway malacia and its relationship with ancillary morphologic features in patients with chronic obstructive pulmonary disease (COPD). A retrospective review was performed of a consecutive series of patients with COPD who were imaged with inspiratory and dynamic expiratory multidetector computed tomography (MDCT). Airway malacia was defined as {>=}50% expiratory reduction of the airway lumen. Both distribution and morphology of airway malacia were assessed. The extent of emphysema, extent of bronchiectasis and severity of bronchial wall thickness were quantified. The final study cohort was comprised of 71 patients. Airway malacia was seen in 38 of 71 patients (53%), and such proportion was roughly maintained in each stage of COPD severity. Almost all tracheomalacia cases (23/25, 92%) were characterised by an expiratory anterior bowing of the posterior membranous wall. Both emphysema and bronchiectasis extent did not differ between patients with and without airway malacia (p > 0.05). Bronchial wall thickness severity was significantly higher in patients with airway malacia and correlated with the degree of maximal bronchial collapse (p < 0.05). In conclusion, we demonstrated a strong association between airway malacia and COPD, disclosing a significant relationship with bronchial wall thickening. (orig.)

  18. Airway malacia in chronic obstructive pulmonary disease: prevalence, morphology and relationship with emphysema, bronchiectasis and bronchial wall thickening

    International Nuclear Information System (INIS)

    The aim of this study was to determine the prevalence of airway malacia and its relationship with ancillary morphologic features in patients with chronic obstructive pulmonary disease (COPD). A retrospective review was performed of a consecutive series of patients with COPD who were imaged with inspiratory and dynamic expiratory multidetector computed tomography (MDCT). Airway malacia was defined as ≥50% expiratory reduction of the airway lumen. Both distribution and morphology of airway malacia were assessed. The extent of emphysema, extent of bronchiectasis and severity of bronchial wall thickness were quantified. The final study cohort was comprised of 71 patients. Airway malacia was seen in 38 of 71 patients (53%), and such proportion was roughly maintained in each stage of COPD severity. Almost all tracheomalacia cases (23/25, 92%) were characterised by an expiratory anterior bowing of the posterior membranous wall. Both emphysema and bronchiectasis extent did not differ between patients with and without airway malacia (p > 0.05). Bronchial wall thickness severity was significantly higher in patients with airway malacia and correlated with the degree of maximal bronchial collapse (p < 0.05). In conclusion, we demonstrated a strong association between airway malacia and COPD, disclosing a significant relationship with bronchial wall thickening. (orig.)

  19. Studies of human airways in vitro: A review of the methodology

    OpenAIRE

    Hulsmann, Anthon; de Jongste, Johan

    1993-01-01

    textabstractThe pathophysiology of human airway narrowing is only partly understood. In order to gain more insight in the mechanisms of human lung diseases and potential beneficial therapeutic agents, adequate models are needed. Animal airway models are of limited value since lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are unique to humans and because the mechanisms of airway narrowing differ between species. Therefore, it is important to perform studies on h...

  20. Persistence of enhanced aerosol deposition in the lung after recovery from carbachol-induced airway obstruction.

    Science.gov (United States)

    Kim, C S; Garcia, L; Eldridge, M A; Wanner, A

    1990-12-01

    Time course recovery from induced airway obstruction by carbachol infusion (CI; 0.2 microgram.kg-1.min-1 for 40 min), carbachol aerosol (CA; 10 breaths of 2% solution), and histamine aerosol (HA; 25-50 breaths of 5% solution) challenge was investigated in conscious sheep (n = 6 each). Total lung aerosol deposition and airway caliber as assessed by pulmonary airflow resistance (RL) were measured every 20-30 min up to 4 h after the challenges. Aerosol deposition was measured by monitoring aerosol concentration continuously with a laser aerosol photometer while the sheep rebreathed 1.0-micron-diam inert oil droplets delivered by a 0.25-liter bag-in-box system driven by a respiratory pump at a breathing frequency of 30 breaths/min. Total accumulated deposition at the fifth breath (AD5) as percentage of the initial aerosol concentration was determined and used as an aerosol deposition index. Percent changes in AD5 from baseline were compared with corresponding changes in RL. Both RL and AD5 increased after Cl, CA, and HA: 192-477% for RL and 23-44% for AD5 (P less than 0.05). Mean RL return to baseline values 1 h after CI and HA and 2 h after CA. Mean AD5 returned to baseline at 1 h post-HA. In contrast, mean AD5 remained elevated for 2-4 h after CI and CA (P less than 0.05), and the increased AD5 could not be reversed by a bronchodilator aerosol. The persistence of enhanced aerosol deposition long after the return of RL to baseline suggests that complete recovery of airway conditions after CI and CA takes much longer than predicted by RL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2077007

  1. Pulmonary hypertension in chronic interstitial lung diseases

    OpenAIRE

    Antonella Caminati; Roberto Cassandro; Sergio Harari

    2013-01-01

    Pulmonary hypertension (PH) is a common complication of interstitial lung diseases (ILDs), particularly in idiopathic pulmonary fibrosis and ILD associated with connective tissue disease. However, other lung diseases, such as combined pulmonary fibrosis and emphysema syndrome, pulmonary Langerhans cell histiocytosis, and lymphangioleiomyomatosis, may also include PH in their clinical manifestations. In all of these diseases, PH is associated with reduced exercise capacity and poor prognosis. ...

  2. Aspergillus fumigatus chronic colonization and lung function decline in cystic fibrosis may have a two-way relationship.

    Science.gov (United States)

    Noni, M; Katelari, A; Dimopoulos, G; Doudounakis, S-E; Tzoumaka-Bakoula, C; Spoulou, V

    2015-11-01

    Aspergillus fumigatus is commonly found in cystic fibrosis (CF) airways. Our aim was to assess the relationship between A. fumigatus chronic colonization and lung function in CF patients. A case-control study of CF patients born from 1989 to 2002 was performed. Medical records were reviewed from the time of initial diagnosis until December 2013. Chronic colonization was defined as two or more positive sputum cultures in a given year. Each patient chronically colonized with A. fumigatus was matched with three control patients (never colonized by A. fumigatus) for age, sex, and year of birth (±3 years). A number of parameters were recorded and analyzed prospectively. The primary outcome measure was the difference in forced expiratory volume in 1 s (FEV1) in percent predicted between groups. Linear mixed models were used for longitudinal analyses to evaluate the relationship between A. fumigatus chronic colonization and lung function during a 7-year period and study the lung function 4 years before the time of enrollment (t0). Twenty patients had chronic colonization and were matched with 60 controls. A significant difference in lung function was detected throughout the 7-year period after adjustment for confounders (est = 8.66, p = 0.020). Four years before t0, FEV1 baseline was the only factor associated with the course of lung function (est = 0.64, p < 0.001) and was significantly different between groups (p = 0.001). In conclusion, a decreased FEV1 baseline appears to be a risk factor for chronic colonization by A. fumigatus, which, in turn, may cause a faster deterioration of lung function. PMID:26319147

  3. Lung cancer screening in patients with chronic obstructive pulmonary disease

    OpenAIRE

    Gonzalez, Jessica; Marín, Marta; Sánchez-Salcedo, Pablo; Zulueta, Javier J.

    2016-01-01

    Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emph...

  4. Mitochondrial N-formyl peptides cause airway contraction and lung neutrophil infiltration via formyl peptide receptor activation.

    Science.gov (United States)

    Wenceslau, Camilla Ferreira; Szasz, Theodora; McCarthy, Cameron G; Baban, Babak; NeSmith, Elizabeth; Webb, R Clinton

    2016-04-01

    Respiratory failure is a common characteristic of systemic inflammatory response syndrome (SIRS) and sepsis. Trauma and severe blood loss cause the release of endogenous molecules known as damage-associated molecular patterns (DAMPs). Mitochondrial N-formyl peptides (F-MITs) are DAMPs that share similarities with bacterial N-formylated peptides, and are potent immune system activators. Recently, we observed that hemorrhagic shock-induced increases in plasma levels of F-MITs associated with lung damage, and that antagonism of formyl peptide receptors (FPR) ameliorated hemorrhagic shock-induced lung injury in rats. Corroborating these data, in the present study, it was observed that F-MITs expression is higher in plasma samples from trauma patients with SIRS or sepsis when compared to control trauma group. Therefore, to better understand the role of F-MITs in the regulation of lung and airway function, we studied the hypothesis that F-MITs lead to airway contraction and lung inflammation. We observed that F-MITs induced concentration-dependent contraction in trachea, bronchi and bronchioles. However, pre-treatment with mast cells degranulator or FPR antagonist decreased this response. Finally, intratracheal challenge with F-MITs increased neutrophil elastase expression in lung and inducible nitric oxide synthase and cell division control protein 42 expression in all airway segments. These data suggest that F-MITs could be a putative target to treat respiratory failure in trauma patients. PMID:26923940

  5. [Therapeutic training and sports in chronic diseases of the lung].

    Science.gov (United States)

    Podolsky, A; Haber, P

    1993-01-01

    Training is defined as systematic physical activity in order to improve the physical working capacity, which causes measurable morphological and functional changes in organs. Effects and the rules of applying aerobic endurance training in patients with chronic diseases of the lungs are dealt with. Training does not replace the normal medication, but is an additional therapeutic mean in order to regain physical working capacity, lost by chronic immobilization in the natural course of disease. Contraindications are acute diseases and exacerbations, but not a certain degree of the disease. Training does not improve the lung function, but the function of the other organs, the physical working capacity ist based on (circulation, musculature). This helps to use optimally the remaining reserves of lung function. Methods of aerobic endurance training are described, the definition of aims, performance diagnostic and the finding of the exact doses of training according to intensity, duration, frequency and the weekly netto training time. The training in different diseases of the lungs is discussed: In asthma bronchiale the prophylaxis of the exercise induced asthma and permitted and forbidden drugs for asthmatics according to the rules of international olympic committee. In chronic bronchitis with arterial hypoxemia, in restrictive lung diseases and in pulmonary hypertension. At last the way to prescribing training for patients with chronic pulmonary diseases is described as well as the advising of patients wishing to do sport by their own motivation or planning projects, for instance touristic ones, which require physical stress. PMID:8465532

  6. The effect of airway deposition on the assessment of lung injury by 99mTc-DTPA clearance

    International Nuclear Information System (INIS)

    The 99mTc-DTPA aerosol inhalation method permits detection of pulmonary epithelial damage. We investigated one of several problems, airway deposition of inhaled aerosol, on the assessment of pulmonary epithelial permeability in healthy nonsmokers and patients with interstitial lung diseases. We used the rate constant of pulmonary 99mTc-DTPA clearance curve, k, as a parameter of the epithelial permeability. The alveolar-peripheral airway deposition of aerosol was estimated by the duplicated inhalation method, which we newly developed. The mean k in patients with interstitial lung disease (2.52±0.72%/min, n=8; pc) was higher in patients with interstitial lung disease (4.08±1.63%/min; pc in both groups (pc obtained among the subjects (r=0.951; p99mTc-DTPA aerosol inhalation method although the correction was significant in the individual subjects. (author)

  7. Pulmonary hypertension in chronic obstructive and interstitial lung diseases

    DEFF Research Database (Denmark)

    Andersen, Charlotte U; Mellemkjær, Søren; Nielsen-Kudsk, Jens Erik;

    2013-01-01

    systematically performed in clinical practice. Given the large number of patients with chronic lung disease, biomarkers to preclude or increase suspicion of PH are needed. NT-proBNP may be used as a rule-out test, but biomarkers with a high specificity for PH are still required. It is not known whether specific...... treatment with existent drugs effective in pulmonary arterial hypertension (PAH) is beneficial in lung disease related PH. Studies investigating existing PAH drugs in animal models of lung disease related PH have indicated a positive effect, and so have case reports and open label studies. However...

  8. In vivo imaging of the airway wall in asthma: fibered confocal fluorescence microscopy in relation to histology and lung function

    Directory of Open Access Journals (Sweden)

    Bel Elisabeth H

    2011-06-01

    Full Text Available Abstract Background Airway remodelling is a feature of asthma including fragmentation of elastic fibres observed in the superficial elastin network of the airway wall. Fibered confocal fluorescence microscopy (FCFM is a new and non-invasive imaging technique performed during bronchoscopy that may visualize elastic fibres, as shown by in vitro spectral analysis of elastin powder. We hypothesized that FCFM images capture in vivo elastic fibre patterns within the airway wall and that such patterns correspond with airway histology. We aimed to establish the concordance between the bronchial elastic fibre pattern in histology and FCFM. Second, we examined whether elastic fibre patterns in histology and FCFM were different between asthmatic subjects and healthy controls. Finally, the association between these patterns and lung function parameters was investigated. Methods In a cross-sectional study comprising 16 subjects (8 atopic asthmatic patients with controlled disease and 8 healthy controls spirometry and bronchoscopy were performed, with recording of FCFM images followed by endobronchial biopsy at the airway main carina. Elastic fibre patterns in histological sections and FCFM images were scored semi-quantitatively. Agreement between histology and FCFM was analysed using linearly weighted kappa κw. Results The patterns observed in histological sections and FCFM images could be divided into 3 distinct groups. There was good agreement between elastic fibre patterns in histology and FCFM patterns (κw 0.744. The semi-quantitative pattern scores were not different between asthmatic patients and controls. Notably, there was a significant difference in post-bronchodilator FEV1 %predicted between the different patterns by histology (p = 0.001 and FCFM (p = 0.048, regardless of asthma or atopy. Conclusion FCFM captures the elastic fibre pattern within the airway wall in humans in vivo. The association between post-bronchodilator FEV1 %predicted and

  9. Collagenolytic Matrix Metalloproteinases in Chronic Obstructive Lung Disease and Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Woode, Denzel; Shiomi, Takayuki; D’Armiento, Jeanine, E-mail: jmd12@cumc.columbia.edu [Department of Anesthesiology, Columbia University, College of Physicians and Surgeons, New York, NY 10033 (United States)

    2015-02-05

    Chronic obstructive pulmonary disease (COPD) and lung cancer result in significant morbidity and mortality worldwide. In addition to the role of environmental smoke exposure in the development of both diseases, recent epidemiological studies suggests a connection between the development of COPD and lung cancer. Furthermore, individuals with concomitant COPD and cancer have a poor prognosis when compared with individuals with lung cancer alone. The modulation of molecular pathways activated during emphysema likely lead to an increased susceptibility to lung tumor growth and metastasis. This review summarizes what is known in the literature examining the molecular pathways affecting matrix metalloproteinases (MMPs) in this process as well as external factors such as smoke exposure that have an impact on tumor growth and metastasis. Increased expression of MMPs provides a unifying link between lung cancer and COPD.

  10. Collagenolytic Matrix Metalloproteinases in Chronic Obstructive Lung Disease and Cancer

    International Nuclear Information System (INIS)

    Chronic obstructive pulmonary disease (COPD) and lung cancer result in significant morbidity and mortality worldwide. In addition to the role of environmental smoke exposure in the development of both diseases, recent epidemiological studies suggests a connection between the development of COPD and lung cancer. Furthermore, individuals with concomitant COPD and cancer have a poor prognosis when compared with individuals with lung cancer alone. The modulation of molecular pathways activated during emphysema likely lead to an increased susceptibility to lung tumor growth and metastasis. This review summarizes what is known in the literature examining the molecular pathways affecting matrix metalloproteinases (MMPs) in this process as well as external factors such as smoke exposure that have an impact on tumor growth and metastasis. Increased expression of MMPs provides a unifying link between lung cancer and COPD

  11. Collagenolytic Matrix Metalloproteinases in Chronic Obstructive Lung Disease and Cancer

    Directory of Open Access Journals (Sweden)

    Denzel Woode

    2015-02-01

    Full Text Available Chronic obstructive pulmonary disease (COPD and lung cancer result in significant morbidity and mortality worldwide. In addition to the role of environmental smoke exposure in the development of both diseases, recent epidemiological studies suggests a connection between the development of COPD and lung cancer. Furthermore, individuals with concomitant COPD and cancer have a poor prognosis when compared with individuals with lung cancer alone. The modulation of molecular pathways activated during emphysema likely lead to an increased susceptibility to lung tumor growth and metastasis. This review summarizes what is known in the literature examining the molecular pathways affecting matrix metalloproteinases (MMPs in this process as well as external factors such as smoke exposure that have an impact on tumor growth and metastasis. Increased expression of MMPs provides a unifying link between lung cancer and COPD.

  12. Endotoxin-induced nitric oxide production rescues airway growth and maturation in atrophic fetal rat lung explants

    International Nuclear Information System (INIS)

    Inflammation induces premature maturation of the fetal lung but the signals causing this effect remain unclear. We determined if nitric oxide (NO) synthesis, evoked by Escherichia coli lipopolysaccharide (LPS, 2 μg ml-1), participated in this process. Fetal rat lung airway surface complexity rose 2.5-fold over 96 h in response to LPS and was associated with increased iNOS protein expression and activity. iNOS inhibition by N6-(1-iminoethyl)-L-lysine-2HCl (L-NIL) abolished this and induced airway atrophy similar to untreated explants. Surfactant protein-C (SP-C) expression was also induced by LPS and abolished by L-NIL. As TGFβ suppresses iNOS activity, we determined if feedback regulation modulated NO-dependent maturation. LPS induced TGFβ1 release and SMAD4 nuclear translocation 96 h after treatment. Treatment of explants with a blocking antibody against TGFβ1 sustained NO production and airway morphogenesis whereas recombinant TGFβ1 antagonized these effects. Feedback regulation of NO synthesis by TGFβ may, thus, modulate airway branching and maturation of the fetal lung

  13. The effect of inspiration on airway dimensions measured in CT images from the Danish Lung Cancer Screening Trial

    DEFF Research Database (Denmark)

    Petersen, Jens; Wille, Mathilde; Thomsen, Laura; Feragen, Aasa; Dirksen, Asger; de Bruijne, Marleen

    2013-01-01

    scans of the same subject using image registration. Mixed effect models were used to predict the relative change in lumen diameter (LD) and wall thickness (WT) in airways of generation 0 (trachea) to 6 based on relative changes in the segmented total lung volume (TLV). Results: On average, 1.0, 2.0, 3...... and Materials: We selected from the Danish Lung Cancer Screening Trial 978 subjects without COPD who were scanned annually for 5 years with low-dose multi-slice CT. Using in-house developed software, the lungs and airways were automatically segmented and corresponding airway branches were found in all.......9, 7.6, 15.0, 25.0 and 27.3 airways per subject were included from generations 0, 1, 2, 3, 4, 5 and 6, respectively. Relative changes in LD were positively related to changes in TLV and coefficients increased with generation: 0.20 (+-0.02), 0.19 (+-0.02), 0.21 (+-0.01), 0.25 (+-0.01), 0.29 (+-0.01), 0...

  14. [Cardiovascular responses during laryngeal mask airway insertion in normotensive, hypertensive and chronic renal failure patients].

    Science.gov (United States)

    Yamauchi, M; Igarashi, M; Tsunoda, K; Edanaga, M; Suzuki, H; Tohdoh, Y; Namiki, A

    1999-08-01

    The hemodynamic response to the insertion of the laryngeal mask airway (LM) following induction with propofol 2 mg.kg-1 was assessed and compared in normotensive (Normal), hypertensive (HT) and chronic renal failure (CRF) patients (n = 23 in each group). Before induction, in HT and CRF groups blood pressure and rate pressure products (RPP) were higher than in Normal group (P < 0.05). Although blood pressure and RPP were decreased in every patient by induction with propofol, no patients needed vasopressor drugs. The decreases of blood pressure and RPP were larger in HT and CRF groups than in Normal group (P < 0.05). There were no differences between groups in heart rate and rate of successful LM insertion. We concluded that LM insertion with propofol 2 mg.kg-1 was an effective induction method preventing the adverse circulatory responses in normotensive, hypertensive and chronic renal failure patients. PMID:10481421

  15. The safety of dipyridamole myocardial perfusion scintigraphy (MPS) in patients with end-stage chronic airways limitations (CAL)

    International Nuclear Information System (INIS)

    Full text: Dipyridamole MPS is a well-established investigative technique in the diagnosis and pre-operative risk stratification of patients with possible coronary artery disease. However, there remains a concern of its use in patients with end-stage chronic airways limitations (CAL). Lung volume reduction surgery (LVRS) is a recent therapeutic option for such patients. The options for non-invasive pre-operative cardiac assessment in such patients are limited. This study reviewed the safety of dipyridamole use in such a clinical setting. 20 patients (10M, 10F, mean age 64.8 yrs) were evaluated. None had any history of ischaemic heart disease. Dipyridamole was administered intravenously at a dose of 0.05 mg/kg. Six patients remained asymptomatic throughout the procedure, while none experienced any chest pain. Two patients experienced moderate dyspnoea, which was rapidly relieved with aminophylline (100mg IV) during the recovery phase of the study. Two others developed mild dyspnoea; one settled spontaneously, while the other responded promptly to aminophylline. Aminophylline was administered to nine other patients to reverse minor symptoms (headache, flushing sensation). One other patient developed marked hypotension (SBP fell >20mmHg) and bradycardia, but no ECG changes for myocardial ischaemia. He responded well to aminophylline. His myocardial perfusion scan demonstrated extensive reversible myocardial ischaemia. Although the population size was small, dipyridamole appears safe to use in patients with end-stage CAL. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  16. Analysis of impulse oscillometric measures of lung function and respiratory system model parameters in small airway-impaired and healthy children over a 2-year period

    Directory of Open Access Journals (Sweden)

    Nava Pat

    2011-03-01

    Full Text Available Abstract Background Is Impulse Oscillometry System (IOS a valuable tool to measure respiratory system function in Children? Asthma (A is the most prevalent chronic respiratory disease in children. Therefore, early and accurate assessment of respiratory function is of tremendous clinical interest in diagnosis, monitoring and treatment of respiratory conditions in this subpopulation. IOS has been successfully used to measure lung function in children with a high degree of sensitivity and specificity to small airway impairments (SAI and asthma. IOS measures of airway function and equivalent electrical circuit models of the human respiratory system have been developed to quantify the severity of these conditions. Previously, we have evaluated several known respiratory models based on the Mead's model and more parsimonious versions based on fitting IOS data known as extended RIC (eRIC and augmented RIC (aRIC models have emerged, which offer advantages over earlier models. Methods IOS data from twenty-six children were collected and compared during pre-bronchodilation (pre-B and post- bronchodilation (post-B conditions over a period of 2 years. Results and Discussion Are the IOS and model parameters capable of differentiating between healthy children and children with respiratory system distress? Children were classified into two main categories: Healthy (H and Small Airway-Impaired (SAI. The IOS measures and respiratory model parameters analyzed differed consistently between H and SAI children. SAI children showed smaller trend of "growth" and larger trend of bronchodilator responses than H children. The two model parameters: peripheral compliance (Cp and peripheral resistance (Rp tracked IOS indices of small airway function well. Cp was a more sensitive index than Rp. Both eRIC and aRIC Cps and the IOS Reactance Area, AX, (also known as the "Goldman Triangle" showed good correlations. Conclusions What are the most useful IOS and model parameters? In

  17. High-resolution three-dimensional 19F-magnetic resonance imaging of rat lung in situ: evaluation of airway strain in the perfluorocarbon-filled lung

    International Nuclear Information System (INIS)

    Perfluorocarbons (PFC) are biologically and chemically inert fluids with high oxygen and CO2 carrying capacities. Their use as liquid intrapulmonary gas carriers during liquid ventilation has been investigated. We established a method of high resolution 3D-19F-MRI of the totally PFC-filled lung. The goal of this study was to investigate longitudinal and circumferential airway strain in the setting of increasing airway pressures on 3D-19F-MR images of the PFC-filled lung. Sixteen female Wistar rats were euthanized and the liquid perfluorocarbon FC-84 instilled into their lungs. 3D-19F-MRI was performed at various intrapulmonary pressures. Measurements of bronchial length and cross-sectional area were obtained from transversal 2D images for each pressure range. Changes in bronchial area were used to determine circumferential strain, while longitudinal strain was calculated from changes in bronchial length. Our method of 3D-19F-MRI allowed clear visualization of the great bronchi. Longitudinal strain increased significantly up to 31.1 cmH2O. The greatest strain could be found in the range of low airway pressures. Circumferential strain increased strongly with the initial pressure rise, but showed no significant changes above 10.4 cmH2O. Longitudinal strain was generally higher in distal airways, while circumferential strain showed no difference. Analysis of mechanical characteristics showed that longitudinal and circumferential airway expansion occurred in an anisotropic fashion. Whereas longitudinal strain still increased with higher pressures, circumferential strain quickly reached a 'strain limit'. Longitudinal strain was higher in distal bronchi, as dense PFCs gravitate to dependent, in this case to dorso-basal parts of the lung, acting as liquid positive end expiratory pressure

  18. Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats

    DEFF Research Database (Denmark)

    Johansen, H K; Espersen, F; Pedersen, S S;

    1993-01-01

    We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic changes...

  19. No effect of elevated operating lung volumes on airway function during variable workrate exercise in asthmatic humans.

    Science.gov (United States)

    Klansky, Andrew; Irvin, Charlie; Morrison-Taylor, Adriane; Ahlstrand, Sarah; Labrie, Danielle; Haverkamp, Hans Christian

    2016-07-01

    In asthmatic adults, airway caliber fluctuates during variable intensity exercise such that bronchodilation (BD) occurs with increased workrate whereas bronchoconstriction (BC) occurs with decreased workrate. We hypothesized that increased lung mechanical stretch would prevent BC during such variable workrate exercise. Ten asthmatic and ten nonasthmatic subjects completed two exercise trials on a cycle ergometer. Both trials included a 28-min exercise bout consisting of alternating four min periods at workloads equal to 40 % (Low) and 70% (High) peak power output. During one trial, subjects breathed spontaneously throughout exercise (SVT), such that tidal volume (VT) and end-inspiratory lung volume (EILV) were increased by 0.5 and 0.6 liters during the high compared with the low workload in nonasthmatic and asthmatic subjects, respectively. During the second trial (MVT), VT and EILV were maintained constant when transitioning from the high to the low workload. Forced exhalations from total lung capacity were performed during each exercise workload. In asthmatic subjects, forced expiratory volume 1.0 s (FEV1.0) increased and decreased with the increases and decreases in workrate during both SVT (Low, 3.3 ± 0.3 liters; High, 3.6 ± 0.2 liters; P < 0.05) and MVT (Low, 3.3 ± 0.3 liters; High, 3.5 ± 0.2 liters; P < 0.05). Thus increased lung stretch during MVT did not prevent decreases in airway caliber when workload was reduced. We conclude that neural factors controlling airway smooth muscle (ASM) contractile activity during whole body exercise are more robust determinants of airway caliber than the ability of lung stretch to alter ASM actin-myosin binding and contraction. PMID:27150833

  20. The Airway Microbiome at Birth

    Science.gov (United States)

    Lal, Charitharth Vivek; Travers, Colm; Aghai, Zubair H.; Eipers, Peter; Jilling, Tamas; Halloran, Brian; Carlo, Waldemar A.; Keeley, Jordan; Rezonzew, Gabriel; Kumar, Ranjit; Morrow, Casey; Bhandari, Vineet; Ambalavanan, Namasivayam

    2016-01-01

    Alterations of pulmonary microbiome have been recognized in multiple respiratory disorders. It is critically important to ascertain if an airway microbiome exists at birth and if so, whether it is associated with subsequent lung disease. We found an established diverse and similar airway microbiome at birth in both preterm and term infants, which was more diverse and different from that of older preterm infants with established chronic lung disease (bronchopulmonary dysplasia). Consistent temporal dysbiotic changes in the airway microbiome were seen from birth to the development of bronchopulmonary dysplasia in extremely preterm infants. Genus Lactobacillus was decreased at birth in infants with chorioamnionitis and in preterm infants who subsequently went on to develop lung disease. Our results, taken together with previous literature indicating a placental and amniotic fluid microbiome, suggest fetal acquisition of an airway microbiome. We speculate that the early airway microbiome may prime the developing pulmonary immune system, and dysbiosis in its development may set the stage for subsequent lung disease. PMID:27488092

  1. The Airway Microbiome at Birth.

    Science.gov (United States)

    Lal, Charitharth Vivek; Travers, Colm; Aghai, Zubair H; Eipers, Peter; Jilling, Tamas; Halloran, Brian; Carlo, Waldemar A; Keeley, Jordan; Rezonzew, Gabriel; Kumar, Ranjit; Morrow, Casey; Bhandari, Vineet; Ambalavanan, Namasivayam

    2016-01-01

    Alterations of pulmonary microbiome have been recognized in multiple respiratory disorders. It is critically important to ascertain if an airway microbiome exists at birth and if so, whether it is associated with subsequent lung disease. We found an established diverse and similar airway microbiome at birth in both preterm and term infants, which was more diverse and different from that of older preterm infants with established chronic lung disease (bronchopulmonary dysplasia). Consistent temporal dysbiotic changes in the airway microbiome were seen from birth to the development of bronchopulmonary dysplasia in extremely preterm infants. Genus Lactobacillus was decreased at birth in infants with chorioamnionitis and in preterm infants who subsequently went on to develop lung disease. Our results, taken together with previous literature indicating a placental and amniotic fluid microbiome, suggest fetal acquisition of an airway microbiome. We speculate that the early airway microbiome may prime the developing pulmonary immune system, and dysbiosis in its development may set the stage for subsequent lung disease. PMID:27488092

  2. Pulmonary hypertension in chronic obstructive and interstitial lung diseases.

    Science.gov (United States)

    Andersen, Charlotte U; Mellemkjær, Søren; Nielsen-Kudsk, Jens Erik; Bendstrup, Elisabeth; Hilberg, Ole; Simonsen, Ulf

    2013-10-01

    The purpose of the present review is to summarize the current knowledge on PH in relation to COPD and ILD from a clinical perspective with emphasis on diagnosis, biomarkers, prevalence, impact, treatment, and practical implications. PH in COPD and ILD is associated with a poor prognosis, and is considered one of the most frequent types of PH. However, the prevalence of PH among patients with COPD and ILD is not clear. The diagnosis of PH in chronic lung disease is often established by echocardiographic screening, but definitive diagnosis requires right heart catheterization, which is not systematically performed in clinical practice. Given the large number of patients with chronic lung disease, biomarkers to preclude or increase suspicion of PH are needed. NT-proBNP may be used as a rule-out test, but biomarkers with a high specificity for PH are still required. It is not known whether specific treatment with existent drugs effective in pulmonary arterial hypertension (PAH) is beneficial in lung disease related PH. Studies investigating existing PAH drugs in animal models of lung disease related PH have indicated a positive effect, and so have case reports and open label studies. However, treatment with systemically administered pulmonary vasodilators implies the risk of worsening the ventilation-perfusion mismatch in patients with lung disease. Inhaled vasodilators may be better suited for PH in lung disease, but new treatment modalities are also required. PMID:23849967

  3. In vivo evaluation of adeno-associated virus gene transfer in airways of mice with acute or chronic respiratory infection.

    Science.gov (United States)

    Myint, Melissa; Limberis, Maria P; Bell, Peter; Somanathan, Suryanarayan; Haczku, Angela; Wilson, James M; Diamond, Scott L

    2014-11-01

    Patients with cystic fibrosis (CF) often suffer chronic lung infection with concomitant inflammation, a setting that may reduce the efficacy of gene transfer. While gene therapy development for CF often involves viral-based vectors, little is known about gene transfer in the context of an infected airway. In this study, three mouse models were established to evaluate adeno-associated virus (AAV) gene transfer in such an environment. Bordetella bronchiseptica RB50 was used in a chronic, nonlethal respiratory infection in C57BL/6 mice. An inoculum of ∼10(5) CFU allowed B. bronchiseptica RB50 to persist in the upper and lower respiratory tracts for at least 21 days. In this infection model, administration of an AAV vector on day 2 resulted in 2.8-fold reduction of reporter gene expression compared with that observed in uninfected controls. Postponement of AAV administration to day 14 resulted in an even greater (eightfold) reduction of reporter gene expression, when compared with uninfected controls. In another infection model, Pseudomonas aeruginosa PAO1 was used to infect surfactant protein D (SP-D) or surfactant protein A (SP-A) knockout (KO) mice. With an inoculum of ∼10(5) CFU, infection persisted for 2 days in the nasal cavity of either mouse model. Reporter gene expression was approximately ∼2.5-fold lower compared with uninfected mice. In the SP-D KO model, postponement of AAV administration to day 9 postinfection resulted in only a two fold reduction in reporter gene expression, when compared with expression seen in uninfected controls. These results confirm that respiratory infections, both ongoing and recently resolved, decrease the efficacy of AAV-mediated gene transfer. PMID:25144316

  4. Chronic aspergillosis of the lungs: Unravelling the terminology and radiology

    Energy Technology Data Exchange (ETDEWEB)

    Desai, S.R.; Hedayati, V.; Patel, K. [King' s College Hospital NHS Foundation Trust, The Department of Radiology, King' s Health Partners, King' s College London, London (United Kingdom); Hansell, D.M. [The Royal Brompton and Harefield NHS Foundation Trust, Department of Radiology, London (United Kingdom)

    2015-10-15

    The propensity for Aspergillus spp. to cause lung disease has long been recognised but the satisfactory classification of these disorders is challenging. The problems caused by invasive disease in severely neutropenic patients, saprophytic infection of pre-existing fibrotic cavities and allergic reactions to Aspergillus are well documented. In contrast, a more chronic form of Aspergillus-related lung disease that has the potential to cause significant morbidity and mortality is under-reported. The symptoms of this form of Aspergillus infection may be non-specific and the radiologist may be the first to suspect a diagnosis of chronic pulmonary aspergillosis. The current review considers the classification conundrums in diseases caused by Aspergillus spp. and discusses the typical clinical and radiological profile of patients with chronic pulmonary aspergillosis. (orig.)

  5. Neurally mediated airway constriction in human and other species: a comparative study using precision-cut lung slices (PCLS.

    Directory of Open Access Journals (Sweden)

    Marco Schlepütz

    Full Text Available The peripheral airway innervation of the lower respiratory tract of mammals is not completely functionally characterized. Recently, we have shown in rats that precision-cut lung slices (PCLS respond to electric field stimulation (EFS and provide a useful model to study neural airway responses in distal airways. Since airway responses are known to exhibit considerable species differences, here we examined the neural responses of PCLS prepared from mice, rats, guinea pigs, sheep, marmosets and humans. Peripheral neurons were activated either by EFS or by capsaicin. Bronchoconstriction in response to identical EFS conditions varied between species in magnitude. Frequency response curves did reveal further species-dependent differences of nerve activation in PCLS. Atropine antagonized the EFS-induced bronchoconstriction in human, guinea pig, sheep, rat and marmoset PCLS, showing cholinergic responses. Capsaicin (10 µM caused bronchoconstriction in human (4 from 7 and guinea pig lungs only, indicating excitatory non-adrenergic non-cholinergic responses (eNANC. However, this effect was notably smaller in human responder (30 ± 7.1% than in guinea pig (79 ± 5.1% PCLS. The transient receptor potential (TRP channel blockers SKF96365 and ruthenium red antagonized airway contractions after exposure to EFS or capsaicin in guinea pigs. In conclusion, the different species show distinct patterns of nerve-mediated bronchoconstriction. In the most common experimental animals, i.e. in mice and rats, these responses differ considerably from those in humans. On the other hand, guinea pig and marmoset monkey mimic human responses well and may thus serve as clinically relevant models to study neural airway responses.

  6. 133Xe three-phase ventilation scans characterize airways disease and aid diagnosis of pulmonary embolism on lung scintigraphy

    International Nuclear Information System (INIS)

    Full text: 133Xe has largely been replaced by 99Tcm aerosols for the ventilation component of lung scans performed for diagnosis of pulmonary embolism. However, aerosols such as Technegas are deposited in the small airways and alveoli and constitute only a snapshot of a single inhalation, which may also be compromised by deposition of activity in central airways. All three phases of ventilatory function - inhalation, equilibration and expiration - are characterized on 133Xe studies, which allows definition of focal ventilatory dysfunction, particularly in obstructive or bullous airways disease. A series of 15 patients with normal inspiratory studies but focal abnormalities in equilibrium and/or washout phases of the 133Xe ventilation scan were reviewed with the concomitant lung perfusion study. The normal inspiratory phase of the 133Xe ventilation scan in these patients reflects the expected deposition pattern of radiolabelled aerosols. However, focal retention of radioxenon activity in the washout phase matched perfusion deficits and allowed scintigraphic differentiation of airways disease from pulmonary embolism in these patients with a normal inspiratory study

  7. Pendelluft in Chronic Obstructive Lung Disease Measured with Lung Sounds

    Directory of Open Access Journals (Sweden)

    Andrey Vyshedskiy

    2012-01-01

    Full Text Available Objective. The phenomenon of pendelluft was described over five decades ago. In patients with regional variations in resistance and elastance, gas moves at the beginning of inspiration out of some alveoli into others. Gas moves in the opposite direction at the end of inspiration. The objective of this study was to apply the method of lung sounds mapping, which is known to provide regional information about gas flow, to study pendelluft in COPD patients. Methods. A 16-channel lung sound analyzer was used to collect sounds from patients with COPD (n=90 and age-matched normals (n=90. Pendelluft at the beginning of inspiration is expected to result in vesicular sounds leading the tracheal sound by a few milliseconds. Pendelluft at the end of inspiration is expected to result in vesicular sounds lagging the tracheal sound. These lead and lag times were calculated for the 14 chest wall sites. Results. The lead time was significantly longer in COPD patients: 123±107 ms versus 48±59 ms in controls (P<0.0001. The lag time was also significantly longer in COPD patients: 269±249 ms in COPD patients versus 147±124 ms in controls (P<0.0001. When normalized by the duration of the inspiration at the trachea, the lead was 14±13% for COPD versus 4±5% for controls (P<0.0001. The lag was 28±25% for COPD versus 13±12% for controls (P<0.0001. Both lead and lag correlated moderately with the GOLD stage (correlation coefficient 0.43. Conclusion. Increased lead and lag times in COPD patients are consistent with the phenomenon of pendelluft as has been observed by other methods.

  8. Chronic Rhino-Sinusitis and Asthma: Concept of Unified Airway Disease (UAD) and its Impact in Otolaryngology

    OpenAIRE

    Meena, Rakesh Singh; Meena, Deepali; Aseri, Yogesh; Singh, B.K.; Verma, P. C.

    2012-01-01

    The aim of our study is to understand the concept of unified airway disease, to know the advantage of this concept in the diagnosis and treatment of allergic rhinitis, chronic rhino-sinusitis and asthma, to know its impact on practice of otolaryngologists, to motivate the otorhinolaryngologist to apply this concept in diagnosis and treatment. This article is based on our experience on (20 cases) chronic rhino-sinusitis and asthma, and observations and results from various literatures. Impleme...

  9. Postnatal development of the bronchiolar club cells of distal airways in the mouse lung: stereological and molecular biological studies.

    Science.gov (United States)

    Karnati, Srikanth; Graulich, Tilman; Oruqaj, Gani; Pfreimer, Susanne; Seimetz, Michael; Stamme, Cordula; Mariani, Thomas J; Weissmann, Norbert; Mühlfeld, Christian; Baumgart-Vogt, Eveline

    2016-06-01

    Club (Clara) cells are nonciliated secretory epithelial cells present in bronchioles of distal pulmonary airways. So far, no information is available on the postnatal differentiation of club cells by a combination of molecular biological, biochemical, and stereological approaches in the murine lung. Therefore, the present study was designed to investigate the changes in the club cell secretory proteins (CC10, surfactant proteins A, B and D) and club cell abundance within the epithelium of bronchioles of distal airways during the postnatal development of the mouse lung. Perfusion-fixed murine lungs of three developmental stages (newborn, 15-day-old and adult) were used. Frozen, unfixed lungs were used for cryosectioning and subsequent laser-assisted microdissection of bronchiolar epithelial cells and RT-PCR analyses. High resolution analyses of the three-dimensional structures and composition of lung airways were obtained by scanning electron microscopy. Finally, using design-based stereology, the total and average club cell volume and the volume of secretory granules were quantified by light and transmission electron microscopy. Our results reveal that murine club cells are immature at birth and differentiate postnatally. Further, increase of the club cell volume and number of intracellular granules are closely correlated to the total lung volume enlargement. However, secretory granule density was only increased within the first 15 days of postnatal development. The differentiation is accompanied by a decrease in glycogen content, and a close positive relationship between CC10 expression and secretory granule abundance. Taken together, our data are consistent with the concept that the morphological and functional differentiation of club cells is a postnatal phenomenon. PMID:26796206

  10. Distal Airway Stem Cells Render Alveoli in Vitro and During Lung Regeneration Following H1N1 Influenza Infection

    OpenAIRE

    Kumar, Pooja A.; Hu, Yuanyu; Yamamoto, Yusuke; Hoe, Neo Boon; Wei, Tay Seok; Mu, Dakai; Sun, Yan; Joo, Lim Siew; Dagher, Rania; Zielonka, Elisabeth; Wang, Yun; Chow, Vincent T.; Crum, Christopher P.; Xian, Wa; McKeon, Frank

    2011-01-01

    The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these...

  11. Allergen-triggered airway hyperresponsiveness and lung pathology in mice sensitized with the biopesticide Metarhizium anisopliae.

    Science.gov (United States)

    Ward, M D; Madison, S L; Sailstad, D M; Gavett, S H; Selgrade, M K

    2000-02-21

    Metarhizium anisopliae is an entomopathogenic fungus recently licensed for indoor control of cockroaches, a major source of allergens. While M. anisopliae has been shown to be non-infectious and non-toxic to mammals there has been only limited research on potential allergenicity. Using a mouse model, we previously demonstrated allergic immune and inflammatory responses to this agent. The present study was designed to determine whether these responses were associated with changes in pulmonary responses, lung pathology, and the cytokine profile in bronchoalveolar lavage fluid (BALF). Soluble factors from fungal components were combined in equal protein amounts to form M. anisopliae crude antigen (MACA). BALB/C mice were intratracheally (i.t.) challenged with 10 microg MACA 14 days post intraperitoneal sensitization with 25 microg fungal antigen in aluminum hydroxide adjuvant. Physiological and cellular changes were examined. The mice were tested for airway hyperresponsiveness before (No Chal) and after (1, 3, and 8 days post challenge (DPIT)) MACA IT challenge. Subsequently, serum, BALF and the lungs were harvested. All treatment groups concurrently demonstrated significant non-specific pulmonary inflammation (neutrophil influx) and increased pulmonary sensitivity to methacholine (Mch) at 1 DPIT MACA challenge. Where as both adjuvant treated and naïve mice airway responses had returned to near normal levels by 3 DPIT, mice which were previously sensitized with MACA were still hyperresponsive to Mch challenge at 3 and 8 DPIT. This hyperresponsiveness correlates with eosinophil and lymphocyte influx, which is maximal at 3 DPIT and still elevated at 8 DPIT. Interleukin (IL) 5 was elevated for all treatment groups at 1 DPIT but only the MACA sensitized mice maintained elevated levels for both 3 and 8 DPIT. Furthermore, MACA sensitized mice had a more extensive inflammatory histopathology at all examined time points with peribronchial and perivascular infiltrates, like

  12. Study of the effect of Bronchipret on the lung function of five Austrian saddle horses suffering recurrent airway obstruction (heaves).

    Science.gov (United States)

    van den Hoven, R; Zappe, H; Zitterl-Eglseer, K; Jugl, M; Franz, C

    2003-05-01

    The effects of an oral preparation containing an extract of thyme and primula (Bronchipret; Bionorica) on the lung function of five horses suffering heaves were determined in a longitudinal study. The horses accepted the product well. The plasma concentrations of the marker substance, thymol, indicated that at least one of the substances in the extract had been absorbed from the gastrointestinal tract. The compliance, pulmonary pressure and airway resistance of the horses' lungs were all significantly improved after one month of treatment However, the severity of their clinical signs and their arterial oxygen partial pressure had not improved significantly. PMID:12751606

  13. Lung lobar volume in patients with chronic interstitial pneumonia

    International Nuclear Information System (INIS)

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

  14. Pulmonary hypertension in chronic interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Antonella Caminati

    2013-09-01

    Full Text Available Pulmonary hypertension (PH is a common complication of interstitial lung diseases (ILDs, particularly in idiopathic pulmonary fibrosis and ILD associated with connective tissue disease. However, other lung diseases, such as combined pulmonary fibrosis and emphysema syndrome, pulmonary Langerhans cell histiocytosis, and lymphangioleiomyomatosis, may also include PH in their clinical manifestations. In all of these diseases, PH is associated with reduced exercise capacity and poor prognosis. The degree of PH in ILDs is typically mild-to-moderate. However, some of these patients may develop a disproportionate increase in PH that cannot be justified solely by hypoxia and parenchymal injury: this condition has been termed “out-of-proportion” PH. The pathogenesis of PH in these diseases is various, incompletely understood and may be multifactorial. The clinical suspicion (i.e. increased dyspnoea, low diffusion capacity and echocardiographic assessment are the first steps towards proper diagnosis of PH; however, right heart catheterisation remains the current gold standard for diagnosis of PH. At present, no specific therapies have been approved for the treatment of PH in patients with ILDs.

  15. Spatial distribution of sequential ventilation during mechanical ventilation of the uninjured lung: an argument for cyclical airway collapse and expansion

    Directory of Open Access Journals (Sweden)

    Altemeier William A

    2010-05-01

    Full Text Available Abstract Background Ventilator-induced lung injury (VILI is a recognized complication of mechanical ventilation. Although the specific mechanism by which mechanical ventilation causes lung injury remains an active area of study, the application of positive end expiratory pressure (PEEP reduces its severity. We have previously reported that VILI is spatially heterogeneous with the most severe injury in the dorsal-caudal lung. This regional injury heterogeneity was abolished by the application of PEEP = 8 cm H2O. We hypothesized that the spatial distribution of lung injury correlates with areas in which cyclical airway collapse and recruitment occurs. Methods To test this hypothesis, rabbits were mechanically ventilated in the supine posture, and regional ventilation distribution was measured under four conditions: tidal volumes (VT of 6 and 12 ml/kg with PEEP levels of 0 and 8 cm H2O. Results We found that relative ventilation was sequentially redistributed towards dorsal-caudal lung with increasing tidal volume. This sequential ventilation redistribution was abolished with the addition of PEEP. Conclusions These results suggest that cyclical airway collapse and recruitment is regionally heterogeneous and spatially correlated with areas most susceptible to VILI.

  16. THE ROLE OF MICROBIAL COMMUNITIES OF AIRWAYS IN PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

    Directory of Open Access Journals (Sweden)

    S. V. Fedosenko

    2014-01-01

    Full Text Available This review summarizes the results of studies on the composition of microbial communities in the airways of healthy subjects and in patients with chronic obstructive pulmonary disease. Modern technologies of molecular-genetic identification methods of microorganisms allow to perform a deep analysis  of  the  respiratory  microbiom.  It  is  of  considerable  interest  to  determine  the  role  of  the microbiome in the development of human diseases of the bronchopulmonary system, and to understand the impact of the microbes communities as a course of disease and the important factor for the efficacy of current therapy.

  17. Surfactant proteins SP-B and SP-C and their precursors in bronchoalveolar lavages from children with acute and chronic inflammatory airway disease

    Directory of Open Access Journals (Sweden)

    Winter Tobias

    2008-04-01

    Full Text Available Abstract Background The surfactant proteins B (SP-B and C (SP-C are important for the stability and function of the alveolar surfactant film. Their involvement and down-regulation in inflammatory processes has recently been proposed, but their level during neutrophilic human airway diseases are not yet known. Methods We used 1D-electrophoresis and Western blotting to determine the concentrations and molecular forms of SP-B and SP-C in bronchoalveolar lavage (BAL fluid of children with different inflammatory airway diseases. 21 children with cystic fibrosis, 15 with chronic bronchitis and 14 with pneumonia were included and compared to 14 healthy control children. Results SP-B was detected in BAL of all 64 patients, whereas SP-C was found in BAL of all but 3 children; those three BAL fluids had more than 80% neutrophils, and in two patients, who were re-lavaged later, SP-C was then present and the neutrophil count was lower. SP-B was mainly present as a dimer, SP-C as a monomer. For both qualitative and quantitative measures of SP-C and SP-B, no significant differences were observed between the four evaluated patient groups. Conclusion Concentration or molecular form of SP-B and SP-C is not altered in BAL of children with different acute and chronic inflammatory lung diseases. We conclude that there is no down-regulation of SP-B and SP-C at the protein level in inflammatory processes of neutrophilic airway disease.

  18. Cigarette Smoke Activates the Proto-Oncogene c-Src to Promote Airway Inflammation and Lung Tissue Destruction

    OpenAIRE

    Geraghty, Patrick; Hardigan, Andrew; Foronjy, Robert F.

    2014-01-01

    The diagnosis of chronic obstructive pulmonary disease (COPD) confers a 2-fold increased lung cancer risk even after adjusting for cigarette smoking, suggesting that common pathways are operative in both diseases. Although the role of the tyrosine kinase c-Src is established in lung cancer, less is known about its impact in other lung diseases, such as COPD. This study examined whether c-Src activation by cigarette smoke contributes to the pathogenesis of COPD. Cigarette smoke increased c-Src...

  19. Efficacy of a Conservative Weight Loss Program in the Long-Term Management of Chronic Upper Airway Obstruction

    Directory of Open Access Journals (Sweden)

    Ryan C. Case

    2009-01-01

    Full Text Available Objective. Obesity is a significant contributor to oxygen demand and dynamic airway obstruction. The objective of the current study is to determine the long-term success of conservative measures directed toward weight reduction on airway management without respect to specific airway disease etiology. Methods. Patients with chronic airway obstruction secondary anatomic lesions or obstructive sleep apnea were recruited and followed prospectively. Demographics, initial and final weights, diagnosis, and followup information were recorded. Patients were referred to a registered dietician, provided counseling, and started on a weight-loss regimen. Outcome measures were change in body mass index (BMI and rate of decannulation from weight loss alone. Results. Of fourteen patients, ten remained tracheostomy-dependent and four had high-grade lesions with the potential for improvement in oxygen demand and dynamic airway collapse with weight loss. The mean follow up period was 25 months. The mean change in BMI was an increase of 1.4 kg/m2 per patient. Conclusions. Conservative measures alone were not effective in achieving weight reduction in the population studied. This may be due to comorbid disease and poor compliance. The promise of decannulation was an insufficient independent motivator for weight loss in this study. Although the theoretical benefits of weight loss support its continued recommendation, the long-term success rate of conservative measures is low. More aggressive facilitated interventions including pharmacotherapy or bariatric surgery should be considered early in the course of treating airway disease complicated by obesity.

  20. Effect of Hedera helix on lung histopathology in chronic asthma.

    OpenAIRE

    Arzu Babayigit Hocaoglu; Ozkan Karaman; Duygu Olmez Erge; Guven Erbil; Osman Yilmaz; Bijen Kivcak; H Alper Bagriyanik; Nevin Uzuner

    2012-01-01

    Hedera helix  is widely used to treat bronchial asthma for many years. However, effects of this herb on lung histopathology is still far from clear. We aimed to determine the effect of oral administration of Hedera helix on lung histopathology in a murine model of chronic asthma.BALB/c  mice  were  divided  into  four  groups;   I  (Placebo),  II  (Hedera  helix), III (Dexamethasone) and IV (Control). All mice except controls were sensitized and challenged with ovalbumin. Then, mice in group ...

  1. Lung angiotensin converting enzyme activity in chronically hypoxic rats.

    OpenAIRE

    Kay, J M; Keane, P. M.; Suyama, K L; Gauthier, D.

    1985-01-01

    A study was carried out to test the hypothesis that the reduced lung angiotensin converting enzyme (ACE) activity which occurs in chronic hypoxia is related to the development of pulmonary hypertension rather than to hypoxia per se. Right ventricular mean systolic pressure (Prvs, mm Hg) and ACE activity (nmol/mg protein/min) in lung tissue homogenates were measured in seven groups of four rats placed in a hypobaric chamber (380 mm Hg; 51 kPa) for two to 24 days. Identical measurements were ma...

  2. [Lung dysfunction in patients with severe chronic obstructive bronchitis].

    Science.gov (United States)

    Nefedov, V B; Popova, L A; Shergina, E A

    2005-01-01

    VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TCL, TGV, RV, Raw, Rin, Rex, DLCO-SS, PaO2, and PaCO2 were determined in 36 patients with severe chronic obstructive lung disease (FEV1 TGV, and TLC, and by decreased VC and FVC; pulmonary gas exchange dysfunction showed up as lowered PaO2 and DLCO-SS, as decreased or increased PaCO2. The observed bronchial patency disorders varied from significant to severe; functional changes in lung volumes and capacities were mild to severe. PMID:15938497

  3. Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease

    OpenAIRE

    Durham, Andrew L.; Caramori, Gaetano; Chung, Kian F; Adcock, Ian M.

    2016-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the airway, although the drivers and site of the inflammation differ between diseases. Asthmatics with a neutrophilic airway inflammation are associated with a poor response to corticosteroids, whereas asthmatics with eosinophilic inflammation respond better to corticosteroids. Biologicals targeting the Th2-eosinophil nexus such as anti–interleukin (IL)-4, anti–IL-5, and anti–IL-13 are ineffective in ...

  4. VEGF is deposited in the subepithelial matrix at the leading edge of branching airways and stimulates neovascularization in the murine embryonic lung.

    Science.gov (United States)

    Healy, A M; Morgenthau, L; Zhu, X; Farber, H W; Cardoso, W V

    2000-11-01

    We used whole lung cultures as a model to study blood vessel formation in vitro and to examine the role that epithelial-mesenchymal interactions play during embryonic pulmonary vascular development. Mouse lungs were isolated at embryonic day 11.5 (E11.5) and cultured for up to 4 days prior to blood vessel analysis. Platelet endothelial cell adhesion molecule-1 (PECAM/CD31) and thrombomodulin (TM/CD141) immunolocalization demonstrate that vascular development occurs in lung cultures. The vascular structures identified in lung cultures first appear as a loosely associated plexus of capillary-like structures that with time surround the airways. To investigate the potential role of vascular endothelial cell growth factor (VEGF) during pulmonary neovascularization, we immunolocalized VEGF in embryonic lungs. Our data demonstrate that VEGF is uniformly present in the airway epithelium and the subepithelial matrix of E11.5 lungs. At later time points, E13.5 and E15.5, VEGF is no longer detected in the proximal airways, but is restricted to the branching tips of airways in the distal lung. RT-PCR analysis reveals that VEGF(164) is the predominant isoform expressed in lung cultures. Grafting heparin-bound VEGF(164) beads onto lung explants locally stimulates a marked neovascular response within 48 hr in culture. Semi-quantitative RT-PCR reveals an 18% increase in PECAM mRNA in VEGF(164)-treated whole lung cultures as compared with untreated cultures. The restricted temporal and spatial expression of VEGF suggests that matrix-associated VEGF links airway branching with blood vessel formation by stimulating neovascularization at the leading edge of branching airways. PMID:11066091

  5. Interleukin-33 from Monocytes Recruited to the Lung Contributes to House Dust Mite-Induced Airway Inflammation in a Mouse Model.

    Directory of Open Access Journals (Sweden)

    Hiroki Tashiro

    Full Text Available Interleukin-33 (IL-33 activates group 2 innate lymphoid cells (ILC2, resulting in T-helper-2 inflammation in bronchial asthma. Airway epithelial cells were reported as sources of IL-33 during apoptosis and necrosis. However, IL-33 is known to be from sources other than airway epithelial cells such as leukocytes, and the mechanisms of IL-33 production and release are not fully understood. The aim of this study was to clarify the role of IL-33 production by monocytes in airway inflammation.BALB/c mice were sensitized and challenged with a house dust mite (HDM preparation. Airway inflammation was assessed by quantifying inflammatory cells in bronchoalveolar lavage (BAL fluid, and IL-25, IL-33, and thymic stromal lymphopoietin (TSLP levels in lung. Immunohistochemistry for IL-33 in lung sections was also performed. Ly6c, CD11b, and CD11c expression was examined by flow cytometry. Clodronate liposomes were used in the HDM-airway inflammation model to deplete circulating monocytes.The IL-33, but not IL-25 or TSLP, level in lung homogenates was markedly increased in HDM mice compared to control mice. IL-33-positive cells in the lungs were identified using immunohistochemistry and were increased in areas surrounding bronchi and vasculature. Furthermore, IL-33 levels were increased in mononuclear cells derived from lungs of HDM mice compared to controls. The expression of Ly6c in mononuclear cells was significantly higher in HDM mice than in controls. Treatment with clodronate liposomes led to inhibition of not only inflammatory cells in BAL fluid, airway hyper reactivity and Th2 cytokines in lung, but also IL-33 in lung.IL-33 from monocytes recruited to the lung may contribute to the pathogenesis of HDM-induced airway inflammation.

  6. Interleukin-33 from Monocytes Recruited to the Lung Contributes to House Dust Mite-Induced Airway Inflammation in a Mouse Model

    Science.gov (United States)

    Tashiro, Hiroki; Takahashi, Koichiro; Hayashi, Shinichiro; Kato, Go; Kurata, Keigo; Kimura, Shinya; Sueoka-Aragane, Naoko

    2016-01-01

    Background Interleukin-33 (IL-33) activates group 2 innate lymphoid cells (ILC2), resulting in T-helper-2 inflammation in bronchial asthma. Airway epithelial cells were reported as sources of IL-33 during apoptosis and necrosis. However, IL-33 is known to be from sources other than airway epithelial cells such as leukocytes, and the mechanisms of IL-33 production and release are not fully understood. The aim of this study was to clarify the role of IL-33 production by monocytes in airway inflammation. Methods BALB/c mice were sensitized and challenged with a house dust mite (HDM) preparation. Airway inflammation was assessed by quantifying inflammatory cells in bronchoalveolar lavage (BAL) fluid, and IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels in lung. Immunohistochemistry for IL-33 in lung sections was also performed. Ly6c, CD11b, and CD11c expression was examined by flow cytometry. Clodronate liposomes were used in the HDM-airway inflammation model to deplete circulating monocytes. Results The IL-33, but not IL-25 or TSLP, level in lung homogenates was markedly increased in HDM mice compared to control mice. IL-33-positive cells in the lungs were identified using immunohistochemistry and were increased in areas surrounding bronchi and vasculature. Furthermore, IL-33 levels were increased in mononuclear cells derived from lungs of HDM mice compared to controls. The expression of Ly6c in mononuclear cells was significantly higher in HDM mice than in controls. Treatment with clodronate liposomes led to inhibition of not only inflammatory cells in BAL fluid, airway hyper reactivity and Th2 cytokines in lung, but also IL-33 in lung. Conclusion IL-33 from monocytes recruited to the lung may contribute to the pathogenesis of HDM-induced airway inflammation. PMID:27310495

  7. Pulmonary rehabilitation improves sleep quality in chronic lung disease.

    Science.gov (United States)

    Soler, Xavier; Diaz-Piedra, Carolina; Ries, Andrew L

    2013-04-01

    Sleep-related disorders are common in patients with chronic obstructive pulmonary disease (COPD) and, possibily, other lung disorders. Exercise has been shown to improve sleep disturbances. In patients with COPD, pulmonary rehabilitation (PR) produces important health benefits with improvement in symptoms, exercise tolerance, and quality of life. However, the effect of PR on sleep quality remains unknown. The aim of this observational study was to evaluate sleep quality in patients with chronic lung disease and the role of PR as a non-pharmacologic treatment to improve sleep. Sixty-four patients with chronic lung disease enrolled in an 8-week comprehensive PR program, and completed the study (48% male; obstructive [72%], restrictive [20%], mixed [8%]; 44% on supplemental oxygen). Baseline spirometry [mean (SD)]: FEV1% pred = 48.9 (17.4), FVC% pred = 72.5 (18.1), and FEV1/FVC% = 53.1 (18.9). Exercise tolerance and questionnaires related to symptoms, health-related quality of life (HRQL), and sleep quality using the Pittsburgh Sleep Quality Index (PSQI) were obtained before and after PR. 58% reported poor sleep quality (PSQI > 5) at baseline. Sleep quality improved by 19% (p = 0.017) after PR, along with significant improvements in dyspnea, exercise tolerance, self-efficacy, and HRQL. Sleep quality in patients with chronic lung disease was poor. In addition to expected improvements in symptoms, exercise tolerance, and HRQL after PR, the subgroup of patients with COPD had a significant improvement in sleep quality. These findings suggest that PR may be an effective, non-pharmacologic treatment option for sleep problems in patients with COPD. PMID:23514215

  8. Single limb exercises in patients with chronic obstructive pulmonary disease : feasibility, methodology, effects and evidence

    OpenAIRE

    Nyberg, Andre

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. COPD is a slowly progressive, inflammatory disease in the airways and lungs, caused mainly by smoking. The inflammation leads to a narrowing of the small airways (airway obstruction) and a destruction of tissue in the lungs. This gives a decreased expiratory airflow which leads to dyspnea, the primary symptom of the disease. The chronic airflow limitation also is associated with the development...

  9. Towards the modeling of mucus draining from human lung: role of airways deformation on air-mucus interaction.

    Directory of Open Access Journals (Sweden)

    Benjamin eMauroy

    2015-08-01

    Full Text Available Chest physiotherapy is an empirical technique used to help secretions to get out of the lung whenever stagnation occurs. Although commonly used, little is known about the inner mechanisms of chest physiotherapy and controversies about its use are coming out regularly. Thus, a scientific validation of chest physiotherapy is needed to evaluate its effects on secretions.We setup a quasi-static numerical model of chest physiotherapy based on thorax and lung physiology and on their respective biophysics. We modeled the lung with an idealized deformable symmetric bifurcating tree. Bronchi and their inner fluids mechanics are assumed axisymmetric. Static data from the literature is used to build a model for the lung's mechanics. Secretions motion is the consequence of the shear constraints apply by the air flow. The input of the model is the pressure on the chest wall at each time, and the output is the bronchi geometry and air and secretions properties. In the limit of our model, we mimicked manual and mechanical chest physiotherapy techniques. We show that for secretions to move, air flow has to be high enough to overcome secretion resistance to motion. Moreover, the higher the pressure or the quicker it is applied, the higher is the air flow and thus the mobilization of secretions. However, pressures too high are efficient up to a point where airways compressions prevents air flow to increase any further. Generally, the first effects of manipulations is a decrease of the airway tree hydrodynamic resistance, thus improving ventilation even if secretions do not get out of the lungs. Also, some secretions might be pushed deeper into the lungs; this effect is stronger for high pressures and for mechanical chest physiotherapy. Finally, we propose and tested two adimensional numbers that depend on lung properties and that allow to measure the efficiency and comfort of a manipulation.

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-07-01

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

  12. Long-term effects of acupuncture treatment on airway smooth muscle in a rat model of smoke-induced chronic obstructive pulmonary disease

    Science.gov (United States)

    Li, Jia; Wu, Song; Tang, Hongtu; Huang, Wei; Wang, Lushan; Zhou, Huanjiao; Zhou, Miao; Wang, Hua; Li, Jing

    2016-01-01

    Background Chronic obstructive pulmonary disease (COPD) is one of the most common lung diseases. It is a chronic inflammatory process characterised by airway obstruction and progressive lung inflammation, associated with difficulty breathing and insensitivity to corticosteroid therapy. Although there is some preliminary evidence to suggest a beneficial effect of acupuncture on COPD, its mechanism of action has not been investigated. Our aim was to examine the anti-inflammatory effects of acupuncture in a rat model of COPD induced by exposure to cigarette smoke (CS). Methods Sixty Sprague–Dawley rats were exposed to the smoke of 15 cigarettes for 1 h/day, 6 days/week for 3 months to induce COPD and treated with acupuncture at BL13 (Feishu), BL23 (Shenshu) and Dingchuan (COPD+Acupuncture, n=15), sham acupuncture (COPD+Sham, n=15) or left untreated (n=15). Exposed rats were compared with controls not exposed to CS (control, n=15). Pulmonary function was measured, and tumour necrosis factor-α (TNF-α) and interleukin-8 (IL-8) levels were determined in bronchoalveolar lavage fluid by ELISA. Histone deacetylase 2 (HDAC2) protein and mRNA expression were examined in lung tissue and in bronchus. Results Acupuncture treatment appeared to protect pulmonary function and reduce the COPD-induced inflammatory response by decreasing cell inflammation and the production of TNF-α and IL-8. Acupuncture also enhanced HDAC2 mRNA and protein expression, suggesting a possible direct effect on protein structure through post-translational modifications. Conclusions Our results suggest that acupuncture regulates inflammatory cytokines and contributes to lung protection in a rat model of smoke-induced COPD by modulating HDAC2. PMID:26345700

  13. The relation of airway obstruction to asthma, chronic rhinosinusitis and age

    DEFF Research Database (Denmark)

    Obaseki, D; Potts, J; Joos, G;

    2014-01-01

    history, atopy, and treatment. Multiple regression was used to assess the interactive effects of age and diagnostic group on decline in postbronchodilator ventilatory function. RESULTS: A total of 3337 participants provided adequate data (778 with asthma, 399 with CRS, 244 with both asthma and CRS and......RATIONALE: There is conflicting evidence on whether patients with asthma experience an accelerated decline in lung function with age. We examined the association between postbronchodilator lung function, asthma, chronic rhinosinusitis (CRS), and atopy with age using a large European sample. METHODS......: In 17 centers in 11 European countries, case-control studies were nested within representative cross-sectional surveys of adults aged less than 75 years. Representative samples of participants with asthma, CRS or both and controls were assessed for postbronchodilator ventilatory function, smoking...

  14. Approaches to prevent the patients with chronic airway diseases from exacerbation in the haze weather

    Science.gov (United States)

    Ren, Jin; Li, Bo; Yu, Dan; Liu, Jing

    2016-01-01

    Haze weather is becoming one of the biggest problems in many big cities in China. It triggers both public anxiety and official concerns. Particulate matter (PM) plays the most important role in causing the adverse health effects. Chemical composition of PM2.5 includes primary particles and secondary particles. The toxicological mechanisms of PM2.5 to the human body include the oxidative stress, inflammation and carcinogenesis. Short or long-term exposure to PM (especially PM2.5) can cause a series of symptoms including respiratory symptoms such as cough, wheezing and dyspnea as well as other symptoms. There are positive associations between PM2.5 and mortality due to a number of causes. PM2.5 is considered to contribute to the onset of asthma, the exacerbation of chronic obstructive pulmonary disease (COPD) in haze weather. Some approaches including outdoor health care, indoor health care and preventive medications can prevent the patients with chronic airway diseases from exacerbations. PMID:26904232

  15. Quantification of neutrophil migration into the lungs of patients with chronic obstructive pulmonary disease

    Energy Technology Data Exchange (ETDEWEB)

    Ruparelia, Prina; Summers, Charlotte; Chilvers, Edwin R. [University of Cambridge School of Clinical Medicine, Department of Respiratory Medicine, Cambridge (United Kingdom); Szczepura, Katherine R. [University of Cambridge School of Clinical Medicine, Department of Radiology, Cambridge (United Kingdom); Solanki, Chandra K.; Balan, Kottekkattu [Cambridge University Hospitals NHS Foundation Trust, Nuclear Medicine, Addenbrooke' s Hospital, Cambridge (United Kingdom); Newbold, Paul [AstraZeneca R and D Charnwood, Loughborough (United Kingdom); Bilton, Diana [Papworth Hospital NHS Foundation Trust, Cystic Fibrosis and Lung Defence Unit, Papworth Everard (United Kingdom); Peters, A.M. [University of Cambridge School of Clinical Medicine, Department of Radiology, Cambridge (United Kingdom); Brighton Sussex Medical School, Brighton (United Kingdom)

    2011-05-15

    To quantify neutrophil migration into the lungs of patients with chronic pulmonary obstructive disease (COPD). Neutrophil loss via airways was assessed by dedicated whole-body counting 45 min, 24 h and 2, 4, 7 and 10 days after injection of very small activities of {sup 111}In-labelled neutrophils in 12 healthy nonsmokers, 5 healthy smokers, 16 patients with COPD (of whom 7 were ex-smokers) and 10 patients with bronchiectasis. Lung accumulation of {sup 99m}Tc-labelled neutrophils was assessed by sequential SPECT and Patlak analysis in six COPD patients and three healthy nonsmoking subjects. Whole body {sup 111}In counts, expressed as percentages of 24 h counts, decreased in all subjects. Losses at 7 days (mean {+-} SD) were similar in healthy nonsmoking subjects (5.5 {+-} 1.5%), smoking subjects (6.5 {+-} 4.4%) and ex-smoking COPD patients (5.8 {+-} 1.5%). In contrast, currently smoking COPD patients showed higher losses (8.0 {+-} 3.0%) than healthy nonsmokers (p = 0.03). Two bronchiectatic patients lost 25% and 26%, indicating active disease; mean loss in the remaining eight was 6.9 {+-} 2.5%. The rate of accumulation of {sup 99m}Tc-neutrophils in the lungs, determined by sequential SPECT, was increased in COPD patients (0.030-0.073 min{sup -1}) compared with healthy nonsmokers (0-0.002 min{sup -1}; p = 0.02). In patients with COPD, sequential SPECT showed increased lung accumulation of {sup 99m}Tc-labelled neutrophils, while whole-body counting demonstrated subsequent higher losses of {sup 111}In-labelled neutrophils in patients who continued to smoke. Sequential SPECT as a means of quantifying neutrophil migration deserves further evaluation. (orig.)

  16. Quantification of neutrophil migration into the lungs of patients with chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    To quantify neutrophil migration into the lungs of patients with chronic pulmonary obstructive disease (COPD). Neutrophil loss via airways was assessed by dedicated whole-body counting 45 min, 24 h and 2, 4, 7 and 10 days after injection of very small activities of 111In-labelled neutrophils in 12 healthy nonsmokers, 5 healthy smokers, 16 patients with COPD (of whom 7 were ex-smokers) and 10 patients with bronchiectasis. Lung accumulation of 99mTc-labelled neutrophils was assessed by sequential SPECT and Patlak analysis in six COPD patients and three healthy nonsmoking subjects. Whole body 111In counts, expressed as percentages of 24 h counts, decreased in all subjects. Losses at 7 days (mean ± SD) were similar in healthy nonsmoking subjects (5.5 ± 1.5%), smoking subjects (6.5 ± 4.4%) and ex-smoking COPD patients (5.8 ± 1.5%). In contrast, currently smoking COPD patients showed higher losses (8.0 ± 3.0%) than healthy nonsmokers (p = 0.03). Two bronchiectatic patients lost 25% and 26%, indicating active disease; mean loss in the remaining eight was 6.9 ± 2.5%. The rate of accumulation of 99mTc-neutrophils in the lungs, determined by sequential SPECT, was increased in COPD patients (0.030-0.073 min-1) compared with healthy nonsmokers (0-0.002 min-1; p = 0.02). In patients with COPD, sequential SPECT showed increased lung accumulation of 99mTc-labelled neutrophils, while whole-body counting demonstrated subsequent higher losses of 111In-labelled neutrophils in patients who continued to smoke. Sequential SPECT as a means of quantifying neutrophil migration deserves further evaluation. (orig.)

  17. Bronchial hyperresponsiveness, airway inflammation, and reversibility in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Zanini A

    2015-06-01

    Full Text Available Andrea Zanini,1 Francesca Cherubino,1 Elisabetta Zampogna,1 Stefania Croce,2 Patrizia Pignatti,2 Antonio Spanevello3 1Division of Pneumology, IRCCS Rehabilitation Institute of Tradate, Salvatore Maugeri Foundation (IRCCS, Tradate, Italy; 2Allergy and Immunology Unit, Salvatore Maugeri Foundation (IRCCS, Pavia, Italy; 3Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy Background: Bronchial hyperresponsiveness (BHR, sputum eosinophilia, and bronchial reversibility are often thought to be a hallmark of asthma, yet it has been shown to occur in COPD as well.Objectives: To evaluate the relationship between BHR, lung function, and airway inflammation in COPD patients.Methods: Thirty-one, steroid-free patients with stable, mild and moderate COPD were studied. The following tests were carried out: baseline lung function, reversibility, provocative dose of methacholine causing a 20% fall in forced expiratory volume in 1 second, a COPD symptom score, and sputum induction.Results: Twenty-nine patients completed the procedures. About 41.4% had BHR, 31.0% had increased sputum eosinophils, and 37.9% had bronchial reversibility. Some of the patients had only one of these characteristics while others had two or the three of them. Patients with BHR had higher sputum eosinophils than patients without BHR (P=0.046 and those with sputum eosinophils ≥3% had more exacerbations in the previous year and a higher COPD symptom score than patients with sputum eosinophils <3% (P=0.019 and P=0.031, respectively. In patients with BHR, the cumulative dose of methacholine was negatively related to the symptom score and the number of exacerbations in the previous year. When patients with bronchial reversibility were considered, bronchodilation was positively related to sputum eosinophils.Conclusion: Our study showed that BHR, sputum eosinophilia, and bronchial reversibility were not clustered in one single phenotype of COPD but could be

  18. Quantitative density-time measurements in the lungs of children with suspected airway obstruction using ultrafast CT

    International Nuclear Information System (INIS)

    Fourteen children under 3 years of age with possible airway obstruction were evaluated with an ultrafast CT scanner, Imatron C-100. Serial 0.05-second multilevel scans were obtained through the chest at rates of 17 images per second. No patitient sedation or contrast medium was used. Time-density curves generated over each lung and specific pulmonary zones were compared to characterize the normal variation of density during inspiration and expiration and to determine abnormal patterns associated with airway obstruction. There was a high, positive correlation value (r>0.79) between time density curoes overr those pulmonary regions in which there was no focal bronchial obstruction and a low, negative correlation value (r=<-0.58) with bronchial obstruction. Three studies with reconstruction artifacts were excluded. Furthermore, the results indicate that young children generally have denser lungs, particularly in expiration, than older children or adults. This preliminary study suggests that ultrafast CT offer a promising unique rapid and noninvasive approach for diagnosing airway obstruction in childhood. (orig.)

  19. Spirometric controlled quantitative CT for chronic obstructive lung disease

    International Nuclear Information System (INIS)

    Objective: To analyze the mean lung density (MLD) and pixel index (PI) of emphysema and chronic bronchitis using spirometric controlled quantitative CT. Methods: Forty healthy adults, 23 patients with emphysema, and 15 patients with chronic bronchitis performed lung spiral scans at 50% vital capacity (VC), and HRCT sections were acquired at carina and carina +- 5 cm at 10% VC and 90% VC. Results: At 10% VC, the MLD in patients with emphysema and chronic bronchitis decreased (the MLD were -831.8 HU and -796.8 HU, respectively) compared to healthy adults (-745.3 HU) (P < 0.01). At 90% VC, only the MLD in patients with emphysema significantly decreased (P < 0.05). PI had the same feature as MLD, but it increased. The lesions detected by quantitative CT were consistent with that demonstrated by morphology. Quantitative CT was more sensitive than PFTs. The quantitative parameters of 10% VC could detect chronic bronchitis even when CT indicated normal results. Conclusion: The combination of CT and quantitative CT can accomplish the unity of morphology and function, thus offer more diagnostic clues and make the diagnosis perfect

  20. [Chronic interstitial lung disease in children: Diagnostic approach and management].

    Science.gov (United States)

    Fuger, M; Clair, M-P; El Ayoun Ibrahim, N; L'Excellent, S; Nizery, L; O'Neill, C; Tabone, L; Truffinet, O; Yakovleff, C; de Blic, J

    2016-05-01

    Chronic interstitial lung disease (ILD) in children is a heterogeneous group of rare lung disorders characterized by an inflammatory process of the alveolar wall and the pulmonary interstitium that induces gas exchange disorders. The diagnostic approach to an ILD involves three essential steps: recognizing the ILD, appreciating the impact, and identifying the cause. The spectrum of clinical findings depends to a large extent on age. In the newborn, the beginning is often abrupt (neonatal respiratory distress), whereas there is a more gradual onset in infants (failure to thrive, tachypnea, indrawing of the respiratory muscles). In older children, the onset is insidious and the diagnosis can only be made at an advanced stage of the disease. The diagnosis is based on noninvasive methods (clinical history, respiratory function tests, chest X-ray, and high-resolution CT scan) and invasive techniques (bronchoalveolar lavage, transbronchial biopsy, video-assisted thoracoscopic biopsy, and open lung biopsy). The treatment of interstitial lung disease in children depends on the nature of the underlying pathology. The most common therapeutic approach involves the use of corticosteroids and immunosuppressive agents for their anti-inflammatory and antifibrotic effects. Children with ILD also need support therapy (oxygen therapy, nutritional support, treatment of pulmonary arterial hypertension, vaccination). Lung transplantation is discussed in patients with severe respiratory failure. PMID:27021883

  1. Inflammatory airway features and hypothalamic-pituitary adrenal axis function in asthmatic rats combined with chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    CAI Cui; CAO Yu-xue; ZHANG Hong-ying; LE Jing-jing; DONG Jing-cheng; CUI Yan; XU Chang-qing; LIU Bao-jun; WU Jin-feng; DUAN Xiao-hong

    2010-01-01

    Background Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are both inflammatory airway diseases with different characteristics. However, there are many patients who suffer from both BA and COPD. This study was to evaluate changes of inflammatory airway features and hypothalamic-pituitary-adrenal (HPA) axis function in asthmatic rats combined with COPD.Methods Brown Norway (BN) rats were used to model the inflammatory airway diseases of BA, COPD and COPD+BA.These three models were compared and evaluated with respect to clinical symptoms, pulmonary histopathology, airway hyperresponsiveness (AHR), inflammatory cytokines and HPA axis function.Results The inflammatory airway features and HPA axis function in rats in the COPD+BA model group were greatly influenced. Rats in this model group showed features of the inflammatory diseases BA and COPD. The expression of inflammatory cytokines in this model group might be up or downregulated when both disease processes are present. The levels of corticotrophin releasing hormone mRNA and corticosterone in this model group were both significantly decreased than those in the control group (P <0.05).Conclusions BN rat can be used as an animal model of COPD+BA. By evaluating this animal model we found that the features of inflammation in rats in this model group seem to be exaggerated. The HPA axis functions in rats in this model group have been disturbed or impaired, which is prominent at the hypothalamic level.

  2. Anesthetic techniques to facilitate lung lavage for pulmonary alveolar proteinosis in children-new airway techniques and a review of the literature.

    Science.gov (United States)

    Wilson, Caroline A; Wilmshurst, Sally L; Black, Ann E

    2015-06-01

    Pediatric patients with pulmonary alveolar proteinosis require whole lung lavage to clear the accumulation of lipoproteinaceous material within the alveoli, to maintain respiratory function. Anesthesia for this presents a challenge due to preexisting respiratory failure, and the small diameter and length of the pediatric airway, which is often unable to accommodate existing one-lung isolation and ventilation equipment. Novel techniques to facilitate lung lavage on seven occasions are described and placed in the context of the existing literature to date. PMID:25664978

  3. Increased hypoxia-inducible factor 1α expression in lung cells of horses with recurrent airway obstruction

    Directory of Open Access Journals (Sweden)

    Toussaint Marie

    2012-05-01

    Full Text Available Abstract Background Recurrent airway obstruction (RAO, also known as equine heaves is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological processes responsible for the development and the persistence of airway inflammation are still largely unknown. Hypoxia-inducible factor (Hif is mainly known as a major regulator of energy homeostasis and cellular adaptation to hypoxia. More recently however, Hif also emerged as an essential regulator of innate immune responses. Here, we aimed at investigating the potential involvement of Hif1-α in myeloid cells in horse with recurrent airway obstruction. Results In vitro, we observed that Hif is expressed in equine myeloid cells after hay dust stimulation and regulates genes such as tumor necrosis factor alpha (TNF-α, interleukin-8 (IL-8 and vascular endothelial growth factor A (VEGF-A. We further showed in vivo that airway challenge with hay dust upregulated Hif1-α mRNA expression in myeloid cells from the bronchoalveolar lavage fluid (BALF of healthy and RAO-affected horses, with a more pronounced effect in cells from RAO-affected horses. Finally, Hif1-α mRNA expression in BALF cells from challenged horses correlated positively with lung dysfunction. Conclusion Taken together, our results suggest an important role for Hif1-α in myeloid cells during hay dust-induced inflammation in horses with RAO. We therefore propose that future research aiming at functional inactivation of Hif1 in lung myeloid cells could open new therapeutic perspectives for RAO.

  4. CORRELATES BETWEEN HUMAN LUNG INJURY AFTER PARTICLE EXPOSURE AND RECURRENT AIRWAY OBSTRUCTION IN THE HORSE

    Science.gov (United States)

    Characteristics of the clinical presentation, physiologic changes, and pathology of the human response to particulate matter (PM) are comparable to inflammatory airway disease (lAD) and recurrent airway obstruction (RAO)lheaves in the horse. Both present with symptoms of cough,...

  5. New frontiers in CT imaging of airway disease

    Energy Technology Data Exchange (ETDEWEB)

    Grenier, Philippe A.; Beigelman-Aubry, Catherine [Department of Radiology, University Pierre et Marie Curie, Paris (France); Fetita, Catalin; Preteux, Francoise [Institut National des Telecommunications, Department ARTEMIS, Evry (France); Brauner, Michel W. [Avicenne Hospital, UFR SMBH Paris XIII, Bobigny (France); Lenoir, Stephane [Institut Mutualiste Montsouris, Paris (France)

    2002-05-01

    Combining helical volumetric CT acquisition and thin-slice thickness during breath hold provides an accurate assessment of both focal and diffuse airway diseases. With multiple detector rows, compared with single-slice helical CT, multislice CT can cover a greater volume, during a simple breath hold, and with better longitudinal and in-plane spatial resolution and improved temporal resolution. The result in data set allows the generation of superior multiplanar and 3D images of the airways, including those obtained from techniques developed specifically for airway imaging, such as virtual bronchography and virtual bronchoscopy. Complementary CT evaluation at suspended or continuous full expiration is mandatory to detect air trapping that is a key finding for depicting an obstruction on the small airways. Indications for CT evaluation of the airways include: (a) detection of endobronchial lesions in patients with an unexplained hemoptysis; (b) evaluation of extent of tracheobronchial stenosis for planning treatment and follow-up; (c) detection of congenital airway anomalies revealed by hemoptysis or recurrent infection; (d) detection of postinfectious or postoperative airway fistula or dehiscence; and (e) diagnosis and assessment of extent of bronchiectasis and small airway disease. Improvement in image analysis technique and the use of spirometrically control of lung volume acquisition have made possible accurate and reproducible quantitative assessment of airway wall and lumen areas and lung density. This contributes to better insights in physiopathology of obstructive lung disease, particularly in chronic obstructive pulmonary disease and asthma. (orig.)

  6. Inhaled Corticosteroids and Risk of Lung Cancer among Patients with Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Parimon, Tanyalak; Chien, Jason W.; Bryson, Chris L.; McDonell, Mary B; Udris, Edmunds M.; Au, David H

    2006-01-01

    Rationale and Objectives: Lung cancer is a frequent cause of death among patients with chronic obstructive pulmonary disease (COPD). We examined whether the use of inhaled corticosteroids among patients with COPD was associated with a decreased risk of lung cancer.

  7. Pulmonary Hypertension and Right Heart Dysfunction in Chronic Lung Disease

    Directory of Open Access Journals (Sweden)

    Amirmasoud Zangiabadi

    2014-01-01

    Full Text Available Group 3 pulmonary hypertension (PH is a common complication of chronic lung disease (CLD, including chronic obstructive pulmonary disease (COPD, interstitial lung disease, and sleep-disordered breathing. Development of PH is associated with poor prognosis and may progress to right heart failure, however, in the majority of the patients with CLD, PH is mild to moderate and only a small number of patients develop severe PH. The pathophysiology of PH in CLD is multifactorial and includes hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, small vessel destruction, and fibrosis. The effects of PH on the right ventricle (RV range between early RV remodeling, hypertrophy, dilatation, and eventual failure with associated increased mortality. The golden standard for diagnosis of PH is right heart catheterization, however, evidence of PH can be appreciated on clinical examination, serology, radiological imaging, and Doppler echocardiography. Treatment of PH in CLD focuses on management of the underlying lung disorder and hypoxia. There is, however, limited evidence to suggest that PH-specific vasodilators such as phosphodiesterase-type 5 inhibitors, endothelin receptor antagonists, and prostanoids may have a role in the treatment of patients with CLD and moderate-to-severe PH.

  8. Airway gene transfer in a non-human primate: lentiviral gene expression in marmoset lungs.

    Science.gov (United States)

    Farrow, N; Miller, D; Cmielewski, P; Donnelley, M; Bright, R; Parsons, D W

    2013-01-01

    Genetic therapies for cystic fibrosis (CF) must be assessed for safety and efficacy, so testing in a non-human primate (NHP) model is invaluable. In this pilot study we determined if the conducting airways of marmosets (n = 2) could be transduced using an airway pre-treatment followed by an intratracheal bolus dose of a VSV-G pseudotyped HIV-1 based lentiviral (LV) vector (LacZ reporter). LacZ gene expression (X-gal) was assessed after 7 days and found primarily in conducting airway epithelia as well as in alveolar regions. The LacZ gene was not detected in liver or spleen via qPCR. Vector p24 protein bio-distribution into blood was transient. Dosing was well tolerated. This preliminary study confirmed the transducibility of CF-relevant airway cell types. The marmoset is a promising NHP model for testing and translating genetic treatments for CF airway disease towards clinical trials. PMID:23412644

  9. Effects of Corni fructus on ovalbumin-induced airway inflammation and airway hyper-responsiveness in a mouse model of allergic asthma

    OpenAIRE

    Kim Seung-Hyung; Kim Bok-Kyu; Lee Young-Cheol

    2012-01-01

    Abstract Background Allergic asthma is a chronic inflammatory lung disease that is characterized by airway hyperresponsiveness (AHR) to allergens, airway oedema, increased mucus secretion, excess production of T helper-2 (Th2) cytokines, and eosinophil accumulation in the lungs. Corni fructus (CF) is a fruit of Cornus officinalis Sieb. Et. Zucc. (Cornaceae) and has been used in traditional Korean medicine as an anti-inflammatory, analgesic, and diuretic agent. To investigate the anti-asthmati...

  10. Inhibition of Toll-Like Receptor 2-Mediated Interleukin-8 Production in Cystic Fibrosis Airway Epithelial Cells via the α7-Nicotinic Acetylcholine Receptor

    OpenAIRE

    Shane J. O'Neill; McElvaney, Noel G; Wells, Robert J.; Hugh Ramsay; Greene, Catherine M

    2010-01-01

    Cystic Fibrosis (CF) is an inherited disorder characterised by chronic inflammation of the airways. The lung manifestations of CF include colonization with Pseudomonas aeruginosa and Staphylococcus aureus leading to neutrophil-dominated airway inflammation and tissue damage. Inflammation in the CF lung is initiated by microbial components which activate the innate immune response via Toll-like receptors (TLRs), increasing airway epithelial cell production of proinflammatory mediators such as ...

  11. Interleukin-19: a constituent of the regulome that controls antigen presenting cells in the lungs and airway responses to microbial products.

    Directory of Open Access Journals (Sweden)

    Carol Hoffman

    Full Text Available BACKGROUND: Interleukin (IL-19 has been reported to enhance chronic inflammatory diseases such as asthma but the in vivo mechanism is incompletely understood. Because IL-19 is produced by and regulates cells of the monocyte lineage, our studies focused on in vivo responses of CD11c positive (CD11c+ alveolar macrophages and lung dendritic cells. METHODOLOGY/PRINCIPAL FINDINGS: IL-19-deficient (IL-19-/- mice were studied at baseline (naïve and following intranasal challenge with microbial products, or recombinant cytokines. Naïve IL-19-/- mixed background mice had a decreased percentage of CD11c+ cells in the bronchoalveolar-lavage (BAL due to the deficiency in IL-19 and a trait inherited from the 129-mouse strain. BAL CD11c+ cells from fully backcrossed IL-19-/- BALB/c or C57BL/6 mice expressed significantly less Major Histocompatibility Complex class II (MHCII in response to intranasal administration of lipopolysaccharide, Aspergillus antigen, or IL-13, a pro-allergic cytokine. Neurogenic-locus-notch-homolog-protein-2 (Notch2 expression by lung monocytes, the precursors of BAL CD11c+ cells, was dysregulated: extracellular Notch2 was significantly decreased, transmembrane/intracellular Notch2 was significantly increased in IL-19-/- mice relative to wild type. Instillation of recombinant IL-19 increased extracellular Notch2 expression and dendritic cells cultured from bone marrow cells in the presence of IL-19 showed upregulated extracellular Notch2. The CD205 positive subset among the CD11c+ cells was 3-5-fold decreased in the airways and lungs of naïve IL-19-/- mice relative to wild type. Airway inflammation and histological changes in the lungs were ameliorated in IL-19-/- mice challenged with Aspergillus antigen that induces T lymphocyte-dependent allergic inflammation but not in IL-19-/- mice challenged with lipopolysaccharide or IL-13. CONCLUSIONS/SIGNIFICANCE: Because MHCII is the molecular platform that displays peptides to T

  12. Update on the roles of distal airways in COPD

    Directory of Open Access Journals (Sweden)

    N. Roche

    2011-03-01

    Full Text Available This review is the summary of a workshop on the role of distal airways in chronic obstructive pulmonary disease (COPD, which took place in 2009 in Vence, France. The evidence showing inflammation and remodelling in distal airways and the possible involvement of these in the pathobiology, physiology, clinical manifestations and natural history of COPD were examined. The usefulness and limitations of physiological tests and imaging techniques for assessing distal airways abnormalities were evaluated. Ex vivo studies in isolated lungs and invasive measurements of airway resistance in living individuals have revealed that distal airways represent the main site of airflow limitation in COPD. Structural changes in small conducting airways, including increased wall thickness and obstruction by muco-inflammatory exudates, and emphysema (resulting in premature airway closure, were important determinants of airflow limitation. Infiltration of small conducting airways by phagocytes (macrophages and neutrophils, dendritic cells and T and B lymphocytes increased with airflow limitation. Distal airways abnormalities were associated with patient-related outcomes (e.g. dyspnoea and reduced health-related quality of life and with the natural history of the disease, as reflected by lung function decline and mortality. These data provide a clear rationale for targeting distal airways in COPD.

  13. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    International Nuclear Information System (INIS)

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

  14. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico); Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gandolfi, A. Jay, E-mail: gandolfi@pharmacy.arizona.edu [Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ (United States); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Lantz, R. Clark, E-mail: lantz@email.arizona.edu [Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ (United States); González-Cortes, Tania, E-mail: taniagc2201@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gonzalez-De Alba, Cesar, E-mail: cesargonzalezalba@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Froines, John R., E-mail: jfroines@ucla.edu [Center for Environmental and Occupational Health, School of Public Health, University of California at Los Angeles, Los Angeles, CA (United States); Espinosa-Fematt, Jorge A., E-mail: dr.jorge.espinosa@gmail.com [School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico)

    2015-09-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

  15. Automated continuous quantitative measurement of proximal airways on dynamic ventilation CT: initial experience using an ex vivo porcine lung phantom

    Directory of Open Access Journals (Sweden)

    Yamashiro T

    2015-09-01

    Full Text Available Tsuneo Yamashiro,1 Maho Tsubakimoto,1 Yukihiro Nagatani,2 Hiroshi Moriya,3 Kotaro Sakuma,3 Shinsuke Tsukagoshi,4 Hiroyasu Inokawa,5 Tatsuya Kimoto,5 Ryuichi Teramoto,6 Sadayuki Murayama1 1Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara, Okinawa; 2Department of Radiology, Shiga University of Medical Science, Otsu; 3Department of Radiology, Ohara General Hospital, Fukushima; 4CT Systems Division, 5Center for Medical Research and Development, Toshiba Medical Systems Corporation, Otawara; 6Corporate Manufacturing Engineering Center, Toshiba Corporation, Yokohama, Japan Background: The purpose of this study was to evaluate the feasibility of continuous quantitative measurement of the proximal airways, using dynamic ventilation computed tomography (CT and our research software. Methods: A porcine lung that was removed during meat processing was ventilated inside a chest phantom by a negative pressure cylinder (eight times per minute. This chest phantom with imitated respiratory movement was scanned by a 320-row area-detector CT scanner for approximately 9 seconds as dynamic ventilatory scanning. Obtained volume data were reconstructed every 0.35 seconds (total 8.4 seconds with 24 frames as three-dimensional images and stored in our research software. The software automatically traced a designated airway point in all frames and measured the cross-sectional luminal area and wall area percent (WA%. The cross-sectional luminal area and WA% of the trachea and right main bronchus (RMB were measured for this study. Two radiologists evaluated the traceability of all measurable airway points of the trachea and RMB using a three-point scale. Results: It was judged that the software satisfactorily traced airway points throughout the dynamic ventilation CT (mean score, 2.64 at the trachea and 2.84 at the RMB. From the maximum inspiratory frame to the maximum expiratory frame, the cross-sectional luminal area of

  16. Chronic adaptations of lung function in breath-hold diving fishermen

    Directory of Open Access Journals (Sweden)

    Cristiane Diniz

    2014-04-01

    Full Text Available Objectives: The aim of this study was to verify and analyze the existence of chronic adaptations of lung function in freediving fishermen whose occupation is artisanal fishing. Material and Methods: This was a cross-sectional study involving 11 breath-hold diving fishermen and 10 non-breath-hold diving fishermen (control from the village of Bitupitá in the municipality of Barroquinha (Ceará - Brazil. Anthropometric measurements, chest and abdominal circumferences as well as spirometric and respiratory muscle strength tests were conducted according to the specifications of the American Thoracic Society/European Respiratory Society (ATS/ERS. In order to compare the measured values versus the predicted values, Student t test was used in the case of parametric test and Wilcoxon test in the case of nonparametric test. To compare the inter-group means Student t test was used for parametric test and Mann-Whitney test for the nonparametric one. The level of significance was set at α = 5%. Results: The forced vital capacity (FVC (4.9±0.6 l vs. 4.3±0.4 l and forced expiratory volume in 1 s (FEV1 (4.0±0.5 l vs. 3.6±0.3 l were, respectively, higher in the group of divers compared to the control group (p ≤ 0.05. Furthermore, in the group of free divers, the measured FVC, FEV1 and FEV1/FVC ratios were significantly greater than the predicted ones. No differences were found between the measured respiratory pressures. Conclusions: These results indicate that breath-hold diving seems to produce chronic adaptations of the respiratory system, resulting in elevated lung volumes with no airway obstruction.

  17. Response to Commentary on "The influence of lung airways branching structure and diffusion time on measurements and models of short-range 3He gas MR diffusion".

    Science.gov (United States)

    Parra-Robles, Juan; Wild, Jim M

    2014-02-01

    Our extensive investigation of the cylinder model theory through numerical modelling and purpose-designed experiments has demonstrated that it does produce inaccurate estimates of airway dimensions at all diffusion times currently used. This is due to a variety of effects: incomplete treatment of non-Gaussian effects, finite airway size, branching geometry, background susceptibility gradients and diffusion time dependence of the (3)He MR diffusion behaviour in acinar airways. The cylinder model is a good starting point for the development of a lung morphometry technique from (3)He diffusion MR but its limitations need to be understood and documented in the interest of reliable clinical interpretation. PMID:24342570

  18. CT findings of the upper airways in patients with chronic obstructive emphysema

    International Nuclear Information System (INIS)

    Objective: To analyze CT findings of the upper airways in patients with chronic obstructive emphysema (COE). Methods: Forty patients with COE proved by clinical and pulmonary function testing, and 39 control patients were examined by chest spiral CT scanning. Parameters were measured and statistically analyzed as follows: (1) the average tracheal cross sectional area (Ta); (2) the tracheal index (Ti), defined by the ratio between the coronal and sagittal diameters as measured 1 cm above the aorta arch; (3) the average right and left main stem bronchi diameters (Br, Bl); (4) the average bifurcate angle of the bronchi (Ba); (5) the thorax index (Thi); (6) the air trapping index (Ati). Results: In above-mentioned measurements, significant differences were revealed between COE group and control group except Ba. There were significant negative correlation between Ti and Ati (r=-0.593, P0.05), Ta and Ti (r=-0.125, P>0.05) in COE. Conclusion: The trachea change in patients with COE showed decreasing Ti, and Ti correlated significantly with Thi and Ati. (authors)

  19. Differential effects of allergen challenge on large and small airway reactivity in mice.

    Directory of Open Access Journals (Sweden)

    Chantal Donovan

    Full Text Available The relative contributions of large and small airways to hyperresponsiveness in asthma have yet to be fully assessed. This study used a mouse model of chronic allergic airways disease to induce inflammation and remodelling and determine whether in vivo hyperresponsiveness to methacholine is consistent with in vitro reactivity of trachea and small airways. Balb/C mice were sensitised (days 0, 14 and challenged (3 times/week, 6 weeks with ovalbumin. Airway reactivity was compared with saline-challenged controls in vivo assessing whole lung resistance, and in vitro measuring the force of tracheal contraction and the magnitude/rate of small airway narrowing within lung slices. Increased airway inflammation, epithelial remodelling and fibrosis were evident following allergen challenge. In vivo hyperresponsiveness to methacholine was maintained in isolated trachea. In contrast, methacholine induced slower narrowing, with reduced potency in small airways compared to controls. In vitro incubation with IL-1/TNFα did not alter reactivity. The hyporesponsiveness to methacholine in small airways within lung slices following chronic ovalbumin challenge was unexpected, given hyperresponsiveness to the same agonist both in vivo and in vitro in tracheal preparations. This finding may reflect the altered interactions of small airways with surrounding parenchymal tissue after allergen challenge to oppose airway narrowing and closure.

  20. Phenotyping airways disease: an A to E approach.

    Science.gov (United States)

    Gonem, S; Raj, V; Wardlaw, A J; Pavord, I D; Green, R; Siddiqui, S

    2012-12-01

    The airway diseases asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous conditions with overlapping pathophysiological and clinical features. It has previously been proposed that this heterogeneity may be characterized in terms of five relatively independent domains labelled from A to E, namely airway hyperresponsiveness (AHR), bronchitis, cough reflex hypersensitivity, damage to the airways and surrounding lung parenchyma, and extrapulmonary factors. Airway hyperresponsiveness occurs in both asthma and COPD, accounting for variable day to day symptoms, although the mechanisms most likely differ between the two conditions. Bronchitis, or airway inflammation, may be predominantly eosinophilic or neutrophilic, with different treatments required for each. Cough reflex hypersensitivity is thought to underlie the chronic dry cough out of proportion to other symptoms that can occur in association with airways disease. Structural changes associated with airway disease (damage) include bronchial wall thickening, airway smooth muscle hypertrophy, bronchiectasis and emphysema. Finally, a variety of extrapulmonary factors may impact upon airway disease, including rhinosinusitis, gastroesophageal reflux disease, obesity and dysfunctional breathing. This article discusses the A to E concept in detail and describes how this framework may be used to assess and treat patients with airway diseases in the clinic. PMID:23181785

  1. Interstitial Lung Disease in a Patient with Chronic Granulomatous Disease

    Directory of Open Access Journals (Sweden)

    Mozhgan Moghtaderi

    2012-03-01

    Full Text Available Background: Chronic granulomatous disease (CGD is an inherited phagocytes defect, characterized by defects of NADPH-oxidase and inability of bacterial killing, which leads to recurrent life-threatening infections. Respiratory problems, which are the major cause of morbidity in CGD, usually result from recurrent severe infections; however, vigorous inflammatory response could also cause respiratory diseases.Case Presentation: Herein, an 11 year-old patient with CGD is presented who suffered from chronic cough and dyspnea for 7 years. Considering the results of chest X-ray, high-resolution computed tomography, and pulmonary function test, the diagnosis of interstitial lung disease was made.Conclusion: Early recognition of manifestations associated with CGD and appropriate treatment could prevent further complications and reduce morbidity and mortality in this group of patients.

  2. Prediction of chronic lung disease from the chest radiograph appearance at seven days of age

    International Nuclear Information System (INIS)

    The aim of this study was to assess if the chest radiograph appearance at seven days of age could be used to predict chronic lung disease. 60 preterm infants who were ventilated and/or had supplementary oxygen at seven days of age and had a chest radiograph performed at that postnatal age, were prospectively recruited. These chest radiographs were scored according to lung volume, presence of opacification, haziness, interstitial changes and cystic elements. 28 infants subsequently developed chronic lung disease; their median chest radiograph score was 5.5 which was significantly higher than that of the non-chronic lung disease infants. A chest radiograph score of 4 had a 71% sensitivity and 88% specificity in predicting chronic lung disease. It is concluded that chest radiograph appearance at seven days of age is a sensitive and specific predictor of chronic lung disease and thus could be used to indicate the need for preventive therapy. 22 refs., 1 fig., 1 tab

  3. High resolution CT in obstructive and air-ways lung disease

    International Nuclear Information System (INIS)

    The topics briefly discussed i.e. emphysema, its diagnosis, bronchiectasis etc. HRTC (high resolution computerized tomography) in diagnosing both disease and small airways abnormalities also discussed. (33 refs.)

  4. The Lung Microbiome in Moderate and Severe Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Pragman, Alexa A.; Kim, Hyeun Bum; Reilly, Cavan S.; Wendt, Christine; Isaacson, Richard E.

    2012-01-01

    Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction. Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations. Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome. The role of the lung microbiome in the pathogenesis of COPD remains unknown. The COPD lung microbiome, like the healthy lung microbiome, appears ...

  5. Uncontrolled airway inflammation in lung disease represents a defect in counter-regulatory signaling

    OpenAIRE

    Planaguma, Anna; Levy, Bruce D.

    2008-01-01

    Counter-regulatory lipid mediators are generated during airway inflammation to promote resolution. Defects in the production of these lipid mediators have now been associated with several diseases of persistent airway inflammation. Lipoxins are the lead members of this class of anti-inflammatory and proresolving chemical mediators. Recently, several new families of fatty acid-derived counter-regulatory mediators have been discovered, including the resolvins and protectins. Diminished formatio...

  6. Interleukin 6 But Not T Helper 2 Cytokines Promotes Lung Carcinogenesis

    OpenAIRE

    Perez, Cesar Ochoa; Mirabolfathinejad, Seyedeh Golsar; Venado, Ana Ruiz; Evans, Scott E.; Gagea, Mihai; Evans, Christopher M.; Dickey, Burton F.; Moghaddam, Seyed Javad

    2010-01-01

    Several epidemiologic studies have found that smokers with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lung, have an increased risk of lung cancer compared to smokers without COPD. We have shown a causal role for COPD-like airway inflammation in lung cancer promotion in the CCSPCre/LSL–K-rasG12D mouse model (CC-LR). In contrast, existing epidemiologic data do not suggest any definite association between allergic airway inflammation and lung cancer. To test thi...

  7. Myofibroblast expression in airways and alveoli is affected by smoking and COPD

    OpenAIRE

    Karvonen, Henna M; Lehtonen, Siri T.; Harju, Terttu; Sormunen, Raija T.; Lappi-Blanco, Elisa; Mäkinen, Johanna M.; Laitakari, Kirsi; Johnson, Shirley; Kaarteenaho, Riitta L

    2013-01-01

    Background Chronic obstructive pulmonary disease (COPD) is characterized by structural changes in alveoli and airways. Our aim was to analyse the numbers of alpha-smooth muscle actin (α-SMA) positive cells, as a marker of myofibroblasts, in different lung compartments in non-smokers and smokers with normal lung function or COPD. Methods α-SMA, tenascin-C (Tn-C) and EDA-fibronectin in alveolar level and airways were assayed by immunohistochemistry and quantified by image analysis. Immunohistoc...

  8. CT based computerized identification and analysis of human airways: A review

    International Nuclear Information System (INIS)

    As one of the most prevalent chronic disorders, airway disease is a major cause of morbidity and mortality worldwide. In order to understand its underlying mechanisms and to enable assessment of therapeutic efficacy of a variety of possible interventions, noninvasive investigation of the airways in a large number of subjects is of great research interest. Due to its high resolution in temporal and spatial domains, computed tomography (CT) has been widely used in clinical practices for studying the normal and abnormal manifestations of lung diseases, albeit there is a need to clearly demonstrate the benefits in light of the cost and radiation dose associated with CT examinations performed for the purpose of airway analysis. Whereas a single CT examination consists of a large number of images, manually identifying airway morphological characteristics and computing features to enable thorough investigations of airway and other lung diseases is very time-consuming and susceptible to errors. Hence, automated and semiautomated computerized analysis of human airways is becoming an important research area in medical imaging. A number of computerized techniques have been developed to date for the analysis of lung airways. In this review, we present a summary of the primary methods developed for computerized analysis of human airways, including airway segmentation, airway labeling, and airway morphometry, as well as a number of computer-aided clinical applications, such as virtual bronchoscopy. Both successes and underlying limitations of these approaches are discussed, while highlighting areas that may require additional work.

  9. CT based computerized identification and analysis of human airways: A review

    Energy Technology Data Exchange (ETDEWEB)

    Pu Jiantao; Gu Suicheng; Liu Shusen; Zhu Shaocheng; Wilson, David; Siegfried, Jill M.; Gur, David [Imaging Research Center, Department of Radiology, University of Pittsburgh, 3362 Fifth Avenue, Pittsburgh, Pennsylvania 15213 (United States); School of Computing, University of Utah, Salt Lake City, Utah 84112 (United States); Department of Radiology, Henan Provincial People' s Hospital, Zhengzhou 450003 (China); Department of Medicine, University of Pittsburgh, 580 S. Aiken Avenue, Suite 400, Pittsburgh, Pennsylvania 15232 (United States); Department of Pharmacology and Chemical Biology, Hillman Cancer Center, Pittsburgh, Pennsylvania 15213 (United States); Imaging Research Center, Department of Radiology, University of Pittsburgh, 3362 Fifth Avenue, Pittsburgh, PA 15213 (United States)

    2012-05-15

    As one of the most prevalent chronic disorders, airway disease is a major cause of morbidity and mortality worldwide. In order to understand its underlying mechanisms and to enable assessment of therapeutic efficacy of a variety of possible interventions, noninvasive investigation of the airways in a large number of subjects is of great research interest. Due to its high resolution in temporal and spatial domains, computed tomography (CT) has been widely used in clinical practices for studying the normal and abnormal manifestations of lung diseases, albeit there is a need to clearly demonstrate the benefits in light of the cost and radiation dose associated with CT examinations performed for the purpose of airway analysis. Whereas a single CT examination consists of a large number of images, manually identifying airway morphological characteristics and computing features to enable thorough investigations of airway and other lung diseases is very time-consuming and susceptible to errors. Hence, automated and semiautomated computerized analysis of human airways is becoming an important research area in medical imaging. A number of computerized techniques have been developed to date for the analysis of lung airways. In this review, we present a summary of the primary methods developed for computerized analysis of human airways, including airway segmentation, airway labeling, and airway morphometry, as well as a number of computer-aided clinical applications, such as virtual bronchoscopy. Both successes and underlying limitations of these approaches are discussed, while highlighting areas that may require additional work.

  10. Bone marrow cell derived arginase I is the major source of allergen-induced lung arginase but is not required for airway hyperresponsiveness, remodeling and lung inflammatory responses in mice

    Directory of Open Access Journals (Sweden)

    Rothenberg Marc E

    2009-06-01

    Full Text Available Abstract Background Arginase is significantly upregulated in the lungs in murine models of asthma, as well as in human asthma, but its role in allergic airway inflammation has not been fully elucidated in mice. Results In order to test the hypothesis that arginase has a role in allergic airway inflammation we generated arginase I-deficient bone marrow (BM chimeric mice. Following transfer of arginase I-deficient BM into irradiated recipient mice, arginase I expression was not required for hematopoietic reconstitution and baseline immunity. Arginase I deficiency in bone marrow-derived cells decreased allergen-induced lung arginase by 85.8 ± 5.6%. In contrast, arginase II-deficient mice had increased lung arginase activity following allergen challenge to a similar level to wild type mice. BM-derived arginase I was not required for allergen-elicited sensitization, recruitment of inflammatory cells in the lung, and proliferation of cells. Furthermore, allergen-induced airway hyperresponsiveness and collagen deposition were similar in arginase-deficient and wild type mice. Additionally, arginase II-deficient mice respond similarly to their control wild type mice with allergen-induced inflammation, airway hyperresponsiveness, proliferation and collagen deposition. Conclusion Bone marrow cell derived arginase I is the predominant source of allergen-induced lung arginase but is not required for allergen-induced inflammation, airway hyperresponsiveness or collagen deposition.

  11. Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection.

    Directory of Open Access Journals (Sweden)

    Mette Kolpen

    Full Text Available Chronic lung infection by Pseudomonas aeruginosa is the major severe complication in cystic fibrosis (CF patients, where P. aeruginosa persists and grows in biofilms in the endobronchial mucus under hypoxic conditions. Numerous polymorphonuclear leukocytes (PMNs surround the biofilms and create local anoxia by consuming the majority of O2 for production of reactive oxygen species (ROS. We hypothesized that P. aeruginosa acquires energy for growth in anaerobic endobronchial mucus by denitrification, which can be demonstrated by production of nitrous oxide (N2O, an intermediate in the denitrification pathway. We measured N2O and O2 with electrochemical microsensors in 8 freshly expectorated sputum samples from 7 CF patients with chronic P. aeruginosa infection. The concentrations of NO3(- and NO2(- in sputum were estimated by the Griess reagent. We found a maximum median concentration of 41.8 µM N2O (range 1.4-157.9 µM N2O. The concentration of N2O in the sputum was higher below the oxygenated layers. In 4 samples the N2O concentration increased during the initial 6 h of measurements before decreasing for approximately 6 h. Concomitantly, the concentration of NO3(- decreased in sputum during 24 hours of incubation. We demonstrate for the first time production of N2O in clinical material from infected human airways indicating pathogenic metabolism based on denitrification. Therefore, P. aeruginosa may acquire energy for growth by denitrification in anoxic endobronchial mucus in CF patients. Such ability for anaerobic growth may be a hitherto ignored key aspect of chronic P. aeruginosa infections that can inform new strategies for treatment and prevention.

  12. [Lung dysfunction in patients with mild chronic obstructive bronchitis].

    Science.gov (United States)

    Nefedov, V B; Popova, L A; Shergina, E A

    2004-01-01

    VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TCL, TGV, RV, Ravt, Riin, Rex, DLCO-SS, PaO2, and PaO2 were determined in 33 patients with mild chronic obstructive lung disease (FEV1 > 70% of the normal value). All the patients were found to have impaired bronchial patency; most (63.6%) patients had lung volume and capacity changes, almost half (45.5%) the patients had pulmonary gas exchange dysfunction. Impaired bronchial patency mainly appeared as decreased MEF50, MEF15, and FEV1/VC%; altered lung volumes and capacities manifested chiefly by increased RV and decreased VC; pulmonary gas exchange dysfunction showed up primarily as lowered PaO2. The magnitude of the observed functional changes was generally slight. MEF50, MEF75, FEV1/VC%, and VC dropped to 59-20 and 79-70% of the normal value, respectively. RV increased up to 142-196% of the normal value; PaO2 reduced up to 79-60% mm Hg. PMID:15478560

  13. IL-33 mediates multi-walled carbon nanotube (MWCNT)-induced airway hyper-reactivity via the mobilization of innate helper cells in the lung

    OpenAIRE

    Beamer, Celine A.; Girtsman, Teri A.; Seaver, Benjamin P.; Finsaas, Krissy J.; Migliaccio, Christopher T.; Perry, Victoria K.; Rottman, James B.; Smith, Dirk E; Holian, Andrij

    2012-01-01

    Allergic asthma is a chronic inflammatory disorder of the airway associated with bronchial obstruction, airway hyper-reactivity (AHR), and mucus production. The epithelium may direct and propagate asthmatic-like responses. Central to this theory is the observation that viruses, air pollution, and allergens promote epithelial damage and trigger the generation of IL-25, IL-33, and TSLP via innate pathways such as TLRs and purinergic receptors. Similarly, engineered nanomaterials promote a Th2-a...

  14. The impact of oil spill to lung health--Insights from an RNA-seq study of human airway epithelial cells.

    Science.gov (United States)

    Liu, Yao-Zhong; Roy-Engel, Astrid M; Baddoo, Melody C; Flemington, Erik K; Wang, Guangdi; Wang, He

    2016-03-01

    The Deepwater Horizon oil spill (BP oil spill) in the Gulf of Mexico was a unique disaster event, where a huge amount of oil spilled from the sea bed and a large volume of dispersants were applied to clean the spill. The operation lasted for almost 3 months and involved >50,000 workers. The potential health hazards to these workers may be significant as previous research suggested an association of persistent respiratory symptoms with exposure to oil and oil dispersants. To reveal the potential effects of oil and oil dispersants on the respiratory system at the molecular level, we evaluated the transcriptomic profile of human airway epithelial cells grown under treatment of crude oil, the dispersants Corexit 9500 and Corexit 9527, and oil-dispersant mixtures. We identified a very strong effect of Corexit 9500 treatment, with 84 genes (response genes) differentially expressed in treatment vs. control samples. We discovered an interactive effect of oil-dispersant mixtures; while no response gene was found for Corexit 9527 treatment alone, cells treated with Corexit 9527+oil mixture showed an increased number of response genes (46 response genes), suggesting a synergic effect of 9527 with oil on airway epithelial cells. Through GO (gene ontology) functional term and pathway-based analysis, we identified upregulation of gene sets involved in angiogenesis and immune responses and downregulation of gene sets involved in cell junctions and steroid synthesis as the prevailing transcriptomic signatures in the cells treated with Corexit 9500, oil, or Corexit 9500+oil mixture. Interestingly, these key molecular signatures coincide with important pathological features observed in common lung diseases, such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Our study provides mechanistic insights into the detrimental effects of oil and oil dispersants to the respiratory system and suggests significant health impacts of the recent BP oil spill to those people

  15. Effect of chronic intermittent hypoxia on the reflex recruitment of the genioglossus during airway obstruction in the anesthetized rat.

    Science.gov (United States)

    Edge, Deirdre; McDonald, Fiona B; Jones, James F X; Bradford, Aidan; O'Halloran, Ken D

    2014-01-01

    We sought to test the hypothesis that chronic intermittent hypoxia (CIH)-a feature of sleep-disordered breathing in humans-impairs reflex recruitment of the genioglossus (GG, pharyngeal dilator) during obstructive airway events. Adult male Wistar rats were exposed to 20 cycles of normoxia and hypoxia (5% O2 at nadir) per hour, 8h a day for 7 days (CIH, N=7). The sham group (N=7) were exposed to normoxia in parallel. Following gas treatments, rats were anesthetized with an i.p. injection of urethane (1.5g/kg; 20%, w/v). Fine concentric needle electrodes were inserted into the GG and the costal diaphragm. Discriminated GG motor unit potentials and whole electromyograph (EMG), together with arterial blood pressure and arterial O2 saturation, were recorded during quiet basal breathing and during nasal airway occlusion. Airway occlusion significantly increased GG EMG activity in all animals; but there was no difference in the reflex response to airway occlusion between sham and CIH-treated animals (+105±22% vs. +105±17%, mean±SEM for area under the curve of integrated GG EMG, % increase from baseline, p=0.99). Occluded breaths were characterized by a significant increase in the firing frequency of phasically active units and the recruitment of large motor units that were quiescent under basal conditions. Though there are reports of impaired control of the upper airway following CIH in the rat, we conclude that reflexly evoked motor discharge to the GG is not affected by 7 days of CIH, a paradigm that we have shown increases apnea index in sleeping rats. PMID:24746047

  16. Effects of dexmedetomidine on oxygenation and lung mechanics in patients with moderate chronic obstructive pulmonary disease undergoing lung cancer surgery

    OpenAIRE

    Lee, Su Hyun; Kim, Namo; Lee, Chang Yeong; Ban, Min Gi; Oh, Young Jun

    2015-01-01

    BACKGROUND Chronic obstructive pulmonary disease (COPD) is a risk factor that increases the incidence of postoperative cardiopulmonary morbidity and mortality after lung resection. Dexmedetomidine, a selective α2-adrenoreceptor agonist, has been reported previously to attenuate intrapulmonary shunt during one-lung ventilation (OLV) and to alleviate bronchoconstriction. OBJECTIVE The objective is to determine whether dexmedetomidine improves oxygenation and lung mechanics in patients with mode...

  17. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation

    DEFF Research Database (Denmark)

    Nassini, Romina; Pedretti, Pamela; Moretto, Nadia;

    2012-01-01

    inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1.By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express...... functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells...... (BAL) fluid of wild-type mice. This effect of TRPA1 agonists was attenuated by TRPA1 antagonism or in TRPA1-deficient mice, but not by pharmacological ablation of sensory nerves.Our results demonstrate that, although either TRPV1 or TRPA1 activation causes airway neurogenic inflammation, solely TRPA1...

  18. Transient Receptor Potential Ankyrin 1 Channel Localized to Non-Neuronal Airway Cells Promotes Non-Neurogenic Inflammation

    DEFF Research Database (Denmark)

    Nassini, Romina; Pedretti, Pamela; Moretto, Nadia;

    2012-01-01

    inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1.By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express...... functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells...... (BAL) fluid of wild-type mice. This effect of TRPA1 agonists was attenuated by TRPA1 antagonism or in TRPA1-deficient mice, but not by pharmacological ablation of sensory nerves.Our results demonstrate that, although either TRPV1 or TRPA1 activation causes airway neurogenic inflammation, solely TRPA1...

  19. Impaired activation of adenylyl cyclase in lung of the Basenji-greyhound model of airway hyperresponsiveness: decreased numbers of high affinity beta-adrenoceptors.

    OpenAIRE

    Emala, C. W.; Aryana, A.; Hirshman, C. A.

    1996-01-01

    1. To evaluate mechanisms involved in the impaired beta-adrenoceptor stimulation of adenylyl cyclase in tissues from the Basenji-greyhound (BG) dog model of airway hyperresponsiveness, we compared agonist and antagonist binding affinity of beta-adrenoceptors, beta-adrenoceptor subtypes, percentage of beta-adrenoceptors sequestered, and coupling of the beta-adrenoceptor to Gs alpha in lung membranes from BG and control mongrel dogs. We found that lung membranes from the BG dog had higher total...

  20. Lung hyperinflation in chronic obstructive pulmonary disease: mechanisms, clinical implications and treatment

    OpenAIRE

    Langer, Daniel; Ciavaglia, Casey E; Neder, J. Alberto; Katherine A. Webb; O'Donnell, Denis E.

    2014-01-01

    Lung hyperinflation is highly prevalent in patients with chronic obstructive pulmonary disease and occurs across the continuum of the disease. A growing body of evidence suggests that lung hyperinflation contributes to dyspnea and activity limitation in chronic obstructive pulmonary disease and is an important independent risk factor for mortality. In this review, we will summarize the recent literature on pathogenesis and clinical implications of lung hyperinflation. We will outline the cont...

  1. Prevalence and risk factors for chronic bronchitis and farmer's lung in French dairy farmers.

    OpenAIRE

    Dalphin, J.C.; Debieuvre, D.; Pernet, D.; Maheu, M F; Polio, J. C.; Toson, B.; Dubiez, A.; Monnet, E; Laplante, J. J.; Depierre, A

    1993-01-01

    The prevalence of chronic bronchitis and of clinical farmer's lung was studied in 30 districts of the French Doubs province in relation to individual (age, sex, smoking) and geographical (altitude) factors. 5703 exclusively dairy farmers (response rate 83%) participated in the study by answering a medical questionnaire. Prevalences of chronic bronchitis and clinical farmer's lung were 9.3% and 1.4% respectively. A logistic regression model was used to evaluate risk factors for chronic bronchi...

  2. Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease

    DEFF Research Database (Denmark)

    Lange, Peter; Celli, Bartolome; Agustí, Alvar;

    2015-01-01

    value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseline FEV1 of at least 80% of the predicted value before 40 years of age, 158 (7%) had COPD after 22 years of observation (Ppersons with COPD......BACKGROUND: Chronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than...... population norms. METHODS: We stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV1 ≥80% or value) at cohort inception (mean age of patients, approximately...

  3. Investigation of mucus transport in an idealized lung airway model using multiphase CFD analysis

    Science.gov (United States)

    Rajendran, Rahul; Banerjee, Arindam

    2015-11-01

    Mucus, a Bingham fluid is transported in the pulmonary airways by consistent beating of the cilia and exhibits a wide range of physical properties in response to the core air flow and various pathological conditions. A better understanding of the interfacial instability is required as it plays a crucial role in gas transport, mixing, mucus clearance and drug delivery. In the current study, mucus is modelled as a Newtonian fluid and the two phase gas-liquid flow in the airways is investigated using an inhomogeneous Eulerian-Eulerian approach. The complex interface between the phases is tracked using the conventional VOF (Volume of Fluid) method. Results from our CFD simulations which are performed in idealized single and double bifurcation geometries will be presented and the influence of airflow rate, mucus layer thickness, mucus viscosity, airway geometry (branching & diameter) and surface tension on mucus flow behavior will be discussed. Mean mucus layer thickness, pressure drop due to momentum transfer & increased airway resistance, mucus transport speed and the flow morphology will be compared to existing experimental and theoretical data.

  4. The lungs need to be deflated: effects of glycopyrronium on lung hyperinflation in COPD patients

    OpenAIRE

    Sanguinetti, Claudio M.

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation caused by bronchial alterations, small airways disease and parenchymal destruction. In patients with COPD the structural and functional lung alterations can progress more or less rapidly from the initial small airways disease to an overt COPD where a severe expiratory flow limitation takes place. In these conditions, lung hyperinflation develops characterized by increase in functional residual capac...

  5. [Impaired lung function in patients with moderate chronic obstructive bronchitis].

    Science.gov (United States)

    Nefedov, V B; Popova, L A; Shergina, E A

    2004-01-01

    VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TLC, TGV, RV, Raw, Rin, Rex, DLCO-SS, paO2 and paCO2 were determined in 22 patients with moderate chronic obstructive bronchitis (FEV1, 79-50% of the normal value). All the patients were found to have impaired bronchial patency, 90.9% of the patients had lung volume and capacity changes; pulmonary gas exchange dysfunction was present in 72.7%. Bronchial patency impairments were manifested by a decrease in FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, and an increase in Raw, Rin, Rex. Changes in the lung volumes and capacities appeared as higher RV, TGV, TLC, lower VC and FVC. Pulmonary gas exchange dysfunction showed up as a reduction in pO2 and DLCO-SS a reduction and an increase in paCO2. The magnitude of the functional changes observed in most patients was low. Significant and pronounced disorders were seen in one third of the patients. PMID:15719666

  6. Continuous Positive Airway Pressure for Motion Management in Stereotactic Body Radiation Therapy to the Lung: A Controlled Pilot Study

    International Nuclear Information System (INIS)

    Objective: To determine the effect of continuous positive airway pressure (CPAP) on tumor motion, lung volume, and dose to critical organs in patients receiving stereotactic body radiation therapy (SBRT) for lung tumors. Methods and Materials: After institutional review board approval in December 2013, patients with primary or secondary lung tumors referred for SBRT underwent 4-dimensional computed tomographic simulation twice: with free breathing and with CPAP. Tumor excursion was calculated by subtracting the vector of the greatest dimension of the gross tumor volume (GTV) from the internal target volume (ITV). Volumetric and dosimetric determinations were compared with the Wilcoxon signed-rank test. CPAP was used during treatment if judged beneficial. Results: CPAP was tolerated well in 10 of the 11 patients enrolled. Ten patients with 18 lesions were evaluated. The use of CPAP decreased tumor excursion by 0.5 ± 0.8 cm, 0.4 ± 0.7 cm, and 0.6 ± 0.8 cm in the superior–inferior, right–left, and anterior–posterior planes, respectively (P≤.02). Relative to free breathing, the mean ITV reduction was 27% (95% confidence interval [CI] 16%-39%, P<.001). CPAP significantly augmented lung volume, with a mean absolute increase of 915 ± 432 cm3 and a relative increase of 32% (95% CI 21%-42%, P=.003), contributing to a 22% relative reduction (95% CI 13%-32%, P=.001) in mean lung dose. The use of CPAP was also associated with a relative reduction in mean heart dose by 29% (95% CI 23%-36%, P=.001). Conclusion: In this pilot study, CPAP significantly reduced lung tumor motion compared with free breathing. The smaller ITV, the planning target volume (PTV), and the increase in total lung volume associated with CPAP contributed to a reduction in lung and heart dose. CPAP was well tolerated, reproducible, and simple to implement in the treatment room and should be evaluated further as a novel strategy for motion management in radiation therapy

  7. Continuous Positive Airway Pressure for Motion Management in Stereotactic Body Radiation Therapy to the Lung: A Controlled Pilot Study

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, Jeffrey D. [Department of Radiation Oncology, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv (Israel); Lawrence, Yaacov R. [Department of Radiation Oncology, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv (Israel); Sackler School of Medicine, Tel Aviv University, Tel Aviv (Israel); Appel, Sarit; Landau, Efrat; Ben-David, Merav A.; Rabin, Tatiana; Benayun, Maoz; Dubinski, Sergey; Weizman, Noam; Alezra, Dror; Gnessin, Hila; Goldstein, Adam M.; Baidun, Khader [Department of Radiation Oncology, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv (Israel); Segel, Michael J.; Peled, Nir [Department of Pulmonary Medicine, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv (Israel); Sackler School of Medicine, Tel Aviv University, Tel Aviv (Israel); Symon, Zvi, E-mail: symonz@sheba.health.gov.il [Department of Radiation Oncology, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv (Israel); Sackler School of Medicine, Tel Aviv University, Tel Aviv (Israel)

    2015-10-01

    Objective: To determine the effect of continuous positive airway pressure (CPAP) on tumor motion, lung volume, and dose to critical organs in patients receiving stereotactic body radiation therapy (SBRT) for lung tumors. Methods and Materials: After institutional review board approval in December 2013, patients with primary or secondary lung tumors referred for SBRT underwent 4-dimensional computed tomographic simulation twice: with free breathing and with CPAP. Tumor excursion was calculated by subtracting the vector of the greatest dimension of the gross tumor volume (GTV) from the internal target volume (ITV). Volumetric and dosimetric determinations were compared with the Wilcoxon signed-rank test. CPAP was used during treatment if judged beneficial. Results: CPAP was tolerated well in 10 of the 11 patients enrolled. Ten patients with 18 lesions were evaluated. The use of CPAP decreased tumor excursion by 0.5 ± 0.8 cm, 0.4 ± 0.7 cm, and 0.6 ± 0.8 cm in the superior–inferior, right–left, and anterior–posterior planes, respectively (P≤.02). Relative to free breathing, the mean ITV reduction was 27% (95% confidence interval [CI] 16%-39%, P<.001). CPAP significantly augmented lung volume, with a mean absolute increase of 915 ± 432 cm{sup 3} and a relative increase of 32% (95% CI 21%-42%, P=.003), contributing to a 22% relative reduction (95% CI 13%-32%, P=.001) in mean lung dose. The use of CPAP was also associated with a relative reduction in mean heart dose by 29% (95% CI 23%-36%, P=.001). Conclusion: In this pilot study, CPAP significantly reduced lung tumor motion compared with free breathing. The smaller ITV, the planning target volume (PTV), and the increase in total lung volume associated with CPAP contributed to a reduction in lung and heart dose. CPAP was well tolerated, reproducible, and simple to implement in the treatment room and should be evaluated further as a novel strategy for motion management in radiation therapy.

  8. The Coordinated Action of CC Chemokines in the Lung Orchestrates Allergic Inflammation and Airway Hyperresponsiveness

    OpenAIRE

    Gonzalo, Jose-Angel; Lloyd, Clare M.; Wen, Danyi; Albar, Juan P.; Wells, Timothy N.C.; Proudfoot, Amanda; Martinez-A, C.; Dorf, Martin; Bjerke, Torbjörn; Coyle, Anthony J.; Gutierrez-Ramos, Jose-Carlos

    1998-01-01

    The complex pathophysiology of lung allergic inflammation and bronchial hyperresponsiveness (BHR) that characterize asthma is achieved by the regulated accumulation and activation of different leukocyte subsets in the lung. The development and maintenance of these processes correlate with the coordinated production of chemokines. Here, we have assessed the role that different chemokines play in lung allergic inflammation and BHR by blocking their activities in vivo. Our results show that bloc...

  9. Silibinin attenuates allergic airway inflammation in mice

    International Nuclear Information System (INIS)

    Highlights: ► Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. ► Silibinin reduces the levels of various cytokines into the lung of allergic mice. ► Silibinin prevents the development of airway hyperresponsiveness in allergic mice. ► Silibinin suppresses NF-κB transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-κB) pathway. Because NF-κB activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-κB activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-κB activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  10. Silibinin attenuates allergic airway inflammation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yun Ho [Department of Anatomy, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Jin, Guang Yu [Department of Radiology, Yanbian University Hospital, YanJi 133002 (China); Guo, Hui Shu [Centralab, The First Affiliated Hospital of Dalian Medical University, Dalian 116011 (China); Piao, Hong Mei [Department of Respiratory Medicine, Yanbian University Hospital, YanJi 133000 (China); Li, Liang chang; Li, Guang Zhao [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China); Lin, Zhen Hua [Department of Pathology, Yanbian University School of Basic Medical Sciences, YanJi 133000 (China); Yan, Guang Hai, E-mail: ghyan@ybu.edu.cn [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  11. Predictors of cardiovascular disease in asthma and chronic obstructive pulmonary disease

    OpenAIRE

    Bellocchia, Michela; Masoero, Monica; Ciuffreda, Antonio; Croce, Silvia; Vaudano, Arianna; Torchio, Roberto; Boita, Monica; Bucca, Caterina

    2013-01-01

    Background Cardiovascular disease (CVD) is a common comorbidity in patients with chronic airway obstruction, and is associated with systemic inflammation and airway obstruction. The aim of this study was to evaluate the predictors of CVD in two different conditions causing chronic airway obstruction, asthma and COPD. Methods Lung function tests, clinical and echocardiographic data were assessed in 229 consecutive patients, 100 with asthma and 129 with COPD. CVD was classified into: pressure o...

  12. Secondary flow measurements and passive tracer dispersion in multi-generational models of conducting airways of the lung

    Science.gov (United States)

    Fresconi, Frank; Prasad, Ajay

    2006-11-01

    A detailed knowledge of the flow and dispersion within the human respiratory tract is desirable for numerous reasons. Both risk assessments of exposure to toxic particles in the environment and the design of medical delivery systems targeting both lung-specific conditions (asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD)) and system-wide ailments (diabetes, cancer, hormone replacement) would profit from such an understanding. The present work features experimental efforts aimed at elucidating the fluid mechanics of the lung. Particle image velocimetry (PIV) and laser induced fluorescence (LIF) measurements of steady and oscillatory flows were undertaken in anatomically accurate models (single and multi-generational) of the conductive region of the lung. PIV results captured primary and secondary velocity fields. LIF allowed visualization of the time-dependent deformation of a passive tracer and also quantified convective dispersion through the usage of a transport profile.

  13. Airway Delivery of Mesenchymal Stem Cells Prevents Arrested Alveolar Growth in Neonatal Lung Injury in Rats

    OpenAIRE

    van Haaften, Timothy; Byrne, Roisin; Bonnet, Sebastien; Rochefort, Gael Y.; Akabutu, John; Bouchentouf, Manaf; Rey-Parra, Gloria J.; Galipeau, Jacques; Haromy, Alois; Eaton, Farah; Chen, Ming; Hashimoto, Kyoko; Abley, Doris; Korbutt, Greg; Archer, Stephen L.

    2009-01-01

    Rationale: Bronchopulmonary dysplasia (BPD) and emphysema are characterized by arrested alveolar development or loss of alveoli; both are significant global health problems and currently lack effective therapy. Bone marrow–derived mesenchymal stem cells (BMSCs) prevent adult lung injury, but their therapeutic potential in neonatal lung disease is unknown.

  14. Spontaneous breathing with airway pressure release ventilation favors ventilation in dependent lung regions and counters cyclic alveolar collapse in oleic-acid-induced lung injury: a randomized controlled computed tomography trial

    OpenAIRE

    Wrigge, Hermann; Zinserling, Jörg; Neumann, Peter; Muders, Thomas; Magnusson, Anders; Putensen, Christian; Hedenstierna, Göran

    2005-01-01

    Introduction Experimental and clinical studies have shown a reduction in intrapulmonary shunt with spontaneous breathing during airway pressure release ventilation (APRV) in acute lung injury. This reduction was related to reduced atelectasis and increased aeration. We hypothesized that spontaneous breathing will result in better ventilation and aeration of dependent lung areas and in less cyclic collapse during the tidal breath. Methods In this randomized controlled experimental trial, 22 pi...

  15. K(Ca3.1 channel-blockade attenuates airway pathophysiology in a sheep model of chronic asthma.

    Directory of Open Access Journals (Sweden)

    Joanne Van Der Velden

    Full Text Available BACKGROUND: The Ca(2+-activated K(+ channel K(Ca3.1 is expressed in several structural and inflammatory airway cell types and is proposed to play an important role in the pathophysiology of asthma. The aim of the current study was to determine whether inhibition of K(Ca3.1 modifies experimental asthma in sheep. METHODOLOGY AND PRINCIPAL FINDINGS: Atopic sheep were administered either 30 mg/kg Senicapoc (ICA-17073, a selective inhibitor of the K(Ca3.1-channel, or vehicle alone (0.5% methylcellulose twice daily (orally. Both groups received fortnightly aerosol challenges with house dust mite allergen for fourteen weeks. A separate sheep group received no allergen challenges or drug treatment. In the vehicle-control group, twelve weeks of allergen challenges resulted in a 60±19% increase in resting airway resistance, and this was completely attenuated by treatment with Senicapoc (0.25±12%; n = 10, P = 0.0147. The vehicle-control group had a peak-early phase increase in lung resistance of 82±21%, and this was reduced by 58% with Senicapoc treatment (24±14%; n = 10, P = 0.0288. Senicapoc-treated sheep also demonstrated reduced airway hyperresponsiveness, requiring a significantly higher dose of carbachol to increase resistance by 100% compared to allergen-challenged vehicle-control sheep (20±5 vs. 52±18 breath-units of carbachol; n = 10, P = 0.0340. Senicapoc also significantly reduced eosinophil numbers in bronchoalveolar lavage taken 48 hours post-allergen challenge, and reduced vascular remodelling. CONCLUSIONS: These findings suggest that K(Ca3.1-activity contributes to allergen-induced airway responses, inflammation and vascular remodelling in a sheep model of asthma, and that inhibition of K(Ca3.1 may be an effective strategy for blocking allergen-induced airway inflammation and hyperresponsiveness in humans.

  16. Inadequate Palliative Care in Chronic Lung Disease. An Issue of Health Care Inequality.

    Science.gov (United States)

    Brown, Crystal E; Jecker, Nancy S; Curtis, J Randall

    2016-03-01

    Patients with chronic lung diseases suffer higher symptom burden, lower quality of life, and greater social isolation compared with patients with other diagnoses, such as cancer. These conditions may be alleviated by palliative care, yet palliative care is used less by patients with chronic lung disease compared with patients with cancer. Underuse is due, in part, to poor implementation of primary palliative care and inadequate referral to specialty palliative care. Lack of primary and specialty palliative care in patients with chronic lung disease falls short of the minimum standard of competent health care, and represents a disparity in health care and a social injustice. We invoke the ethical principles of justice and sufficiency to highlight the importance of this issue. We identify five barriers to implementing palliative care in patients with chronic lung disease: uncertainty in prognosis; lack of provider skill to engage in discussions about palliative care; fear of using opioids among patients with chronic lung disease; fear of diminishing hope; and perceived and implicit bias against patients with smoking-related lung diseases. We propose mechanisms for improving implementation of palliative care for patients with chronic lung disease with the goal of enhancing justice in health care. PMID:26730490

  17. Lung Growth and Airway Function after Lobectomy in Infancy for Congenital Lobar Emphysema

    OpenAIRE

    McBride, John T.; Wohl, Mary Ellen B.; Strieder, Denise J.; Jackson, Andrew C.; Morton, John R.; Zwerdling, Robert G.; Griscom, N. Thorne; Treves, Salvador; Williams, Adrian J.; Schuster, Samuel

    1980-01-01

    To characterize the outcome of lobectomy in infancy and the low expiratory flows which persist after lobectomy for congenital lobar emphysema, 15 subjects with this history were studied at age 8-30 yr. Total lung capacity was normal in all, but higher values (P < 0.05) were observed in nine subjects with upper lobectomy than in five subjects with right middle lobectomy. Ratio of residual volume to total lung capacity was correlated (P < 0.05) with the amount of lung missing as estimated from ...

  18. Prolonged ozone exposure in an allergic airway disease model: Adaptation of airway responsiveness and airway remodeling

    Directory of Open Access Journals (Sweden)

    Park Chang-Soo

    2006-02-01

    Full Text Available Abstract Background Short-term exposure to high concentrations of ozone has been shown to increase airway hyper-responsiveness (AHR. Because the changes in AHR and airway inflammation and structure after chronic ozone exposure need to be determined, the goal of this study was to investigate these effects in a murine model of allergic airway disease. Methods We exposed BALB/c mice to 2 ppm ozone for 4, 8, and 12 weeks. We measured the enhanced pause (Penh to methacholine and performed cell differentials in bronchoalveolar lavage fluid. We quantified the levels of IL-4 and IFN-γ in the supernatants of the bronchoalveolar lavage fluids using enzyme immunoassays, and examined the airway architecture under light and electron microscopy. Results The groups exposed to ozone for 4, 8, and 12 weeks demonstrated decreased Penh at methacholine concentrations of 12.5, 25, and 50 mg/ml, with a dose-response curve to the right of that for the filtered-air group. Neutrophils and eosinophils increased in the group exposed to ozone for 4 weeks compared to those in the filtered-air group. The ratio of IL-4 to INF-γ increased significantly after exposure to ozone for 8 and 12 weeks compared to the ratio for the filtered-air group. The numbers of goblet cells, myofibroblasts, and smooth muscle cells showed time-dependent increases in lung tissue sections from the groups exposed to ozone for 4, 8, and 12 weeks. Conclusion These findings demonstrate that the increase in AHR associated with the allergic airway does not persist during chronic ozone exposure, indicating that airway remodeling and adaptation following repeated exposure to air pollutants can provide protection against AHR.

  19. Chronic obstructive lung disease and posttraumatic stress disorder: current perspectives

    Directory of Open Access Journals (Sweden)

    Abrams TE

    2015-10-01

    Full Text Available Thad E Abrams,1,2 Amy Blevins,1,3 Mark W Vander Weg1,2,4 1Department of Internal Medicine, University of Iowa, 2Center for Comprehensive Access and Delivery Research and Evaluation, Iowa City VA Health Care System, 3Hardin Health Sciences Library, 4Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, USA Background: Several studies have reported on the co-occurrence of chronic obstructive pulmonary disease (COPD and psychiatric conditions, with the most robust evidence base demonstrating an impact of comorbid anxiety and depression on COPD-related outcomes. In recent years, research has sought to determine if there is a co-occurrence between COPD and posttraumatic stress disorder (PTSD as well as for associations between PTSD and COPD-related outcomes. To date, there have been no published reviews summarizing this emerging literature.Objectives: The primary objective of this review was to determine if there is adequate evidence to support a co-occurrence between PTSD and COPD. Secondary objectives were to: 1 determine if there are important clinical considerations regarding the impact of PTSD on COPD management, and 2 identify targeted areas for further research.Methods: A structured review was performed using a systematic search strategy limited to studies in English, addressing adults, and to articles that examined: 1 the co-occurrence of COPD and PTSD and 2 the impact of PTSD on COPD-related outcomes. To be included, articles must have addressed some type of nonreversible obstructive lung pathology.Results: A total of 598 articles were identified for initial review. Upon applying the inclusion and exclusion criteria, n=19 articles or abstracts addressed our stated objectives. Overall, there is inconclusive evidence to support the co-occurrence between PTSD and COPD. Studies finding a significant co-occurrence generally had inferior methods of identifying COPD; in contrast, studies that utilized more robust COPD

  20. Influence of inspiratory flow rate, particle size, and airway caliber on aerosolized drug delivery to the lung.

    Science.gov (United States)

    Dolovich, M A

    2000-06-01

    A number of studies in the literature support the use of fine aerosols of drug, inhaled at low IFRs to target peripheral airways, with the objective of improving clinical responses to inhaled therapy (Fig. 8). Attempts have been made to separate response due to changes in total administered dose or the surface concentration of the dose from response due to changes in site of deposition--both are affected by the particle size of the aerosol, with IFR additionally influencing the latter. The tools for measuring dose and distribution have improved over the last 10-15 years, and thus we should expect greater accuracy in these measurements for assessing drug delivery to the lung. There are still issues, though, in producing radiolabeled (99m)technetium aerosols that are precise markers for the pharmaceutical product being tested and in quantitating absolute doses deposited in the lung. PET isotopes may provide the means for directly labelling a drug and perhaps can offer an alternative for making these measurements in the future, but deposition measurements should not be used in isolation; protocols should incorporate clinical tests to provide parallel therapeutic data in response to inhalation of the drug by the various patient populations being studied. PMID:10894453

  1. Mechanical properties and reactivity of vessels in isolated perfused lungs of chronically hypoxic rats.

    Science.gov (United States)

    Emery, C J; Bee, D; Barer, G R

    1981-11-01

    1. Chronically hypoxic rats kept in 10% (v/v) O2 for 3--6 weeks, were compared with littermate control rats. Pulmonary vascular resistance, measured from the slope of the pressure-flow relationship in isolated lungs perfused with blood of normal packed cell volume was higher in chronically hypoxic than control rats even during normoxia. 2. Chronically hypoxic rats weighed less than control rats but their pulmonary vascular volume, measured with labelled albumin was similar to control rats. This, together with evidence that the number of precapillary vessels is not reduced, does not suggest a large reduction in the vascular bed in chronic hypoxia. 3. A greater vasodilator action of isoprenaline and adenosine in chronically hypoxic than control lungs suggested a higher normoxic vascular tone. This higher tone was not the sole cause of increased resistance in chronically hypoxic lungs, since maximal vasodilatation did not reduce resistance to control levels. The chief cause was probably encroachment of new muscle on the vascular lumen of small vessels. 4. Pulmonary arterial compliance was reduced in chronically hypoxic lungs. 5. Reactivity of vessels to ventilation hypoxia, over a wide range of oxygen tension, to angiotensin II (ANG II) and to adenosine 5'-triphosphate (ATP) was significantly greater in chronically hypoxic than control lungs, but thresholds to these stimuli were not reduced. PMID:7285503

  2. Chronic allograft rejection in lung transplant recipients: assessment with paired inspiratory and expiratory CT

    OpenAIRE

    Bankier, Alexandre

    2011-01-01

    This work discusses the role of CT in the etection and quantification of chronic allograft rejection in patients after lung transplantation and provides solutions to the technical challenges involved with this approach.

  3. Elevated platelet-derived growth factor-BB concentrations in premature neonates who develop chronic lung disease

    Directory of Open Access Journals (Sweden)

    Adcock Kim G

    2004-06-01

    Full Text Available Abstract Background Chronic lung disease (CLD in the preterm newborn is associated with inflammation and fibrosis. Platelet-derived growth factor-BB (PDGF-BB, a potent chemotactic growth factor, may mediate the fibrotic component of CLD. The objectives of this study were to determine if tracheal aspirate (TA concentrations of PDGF-BB increase the first 2 weeks of life in premature neonates undergoing mechanical ventilation for respiratory distress syndrome (RDS, its relationship to the development of CLD, pulmonary hemorrhage (PH and its relationship to airway colonization with Ureaplasma urealyticum (Uu. Methods Infants with a birth weight less than 1500 grams who required mechanical ventilation for RDS were enrolled into this study with parental consent. Tracheal aspirates were collected daily during clinically indicated suctioning. Uu cultures were performed on TA collected in the first week of life. TA supernatants were assayed for PDGF-BB and secretory component of IgA concentrations using ELISA techniques. Results Fifty premature neonates were enrolled into the study. Twenty-eight infants were oxygen dependent at 28 days of life and 16 infants were oxygen dependent at 36 weeks postconceptual age. PDGF-BB concentrations peaked between 4 and 6 days of life. Maximum PDGF-BB concentrations were significantly higher in infants who developed CLD or died from respiratory failure. PH was associated with increased risk of CLD and was associated with higher PDGF-BB concentrations. There was no correlation between maximum PDGF-BB concentrations and Uu isolation from the airway. Conclusions PDGF-BB concentrations increase in TAs of infants who undergo mechanical ventilation for RDS during the first 2 weeks of life and maximal concentrations are greater in those infants who subsequently develop CLD. Elevation in lung PDGF-BB may play a role in the development of CLD.

  4. Cavitating Lung Lesions in Chronic Thromboembolic Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    edwin j r van beek

    2008-09-01

    Full Text Available Purpose: The aim of this study is to assess the incidence and natural history of cavitating lung lesions in chronic thromboembolic pulmonary hypertension (CTEPH, note thrombus position between patients with and without a cavity and determine whether their development is a predictor of mortality. Materials & Methods: All patients with confirmed CTEPH attending our Pulmonary Vascular Unit between February 1998 and January 2006 were identified, and a review of their notes and imaging was performed. Thrombus position, pre-disposing factors, cavity progression and mortality were noted, and comparisons made between those with and without a cavity. Results: 11 of 104 patients had a cavity (10.6%. Thrombus distribution was similar between those with and those without a cavity. Preceding infection was not proven in  most cases. 27.3% of patients with a cavity died compared to 26.8% of those without. Conclusion: Cavity formation in CTEPH is 3 times more common than in acute pulmonary embolism. Thrombus position does not predict cavity development, and the presence of a cavity may serve as an indicator of disease severity but does not appear to predict mortality.

  5. Determinants of chronic bronchitis and lung dysfunction in Western Australian gold miners

    OpenAIRE

    Humble, C; Wing, S.

    1989-01-01

    The relation of chronic bronchitis and respiratory dysfunction to age, tobacco smoking, and occupational exposure to surface and underground mining operations were examined in a cross sectional survey of 1363 men employed in the Kalgoorlie mining industry in 1985. Overall, the prevalence of chronic bronchitis was 14%. Eleven per cent of the workers had obstructive lung disorder (FEV1/FVC less than 0.70) and 9% had restrictive lung disorder (FVC less than 0.80 of predicted for height and age)....

  6. A large lung gene expression study identifying fibulin-5 as a novel player in tissue repair in COPD

    NARCIS (Netherlands)

    Brandsma, Corry-Anke; van den Berge, Maarten; Postma, Dirkje S.; Jonker, Marnix R.; Brouwer, Sharon; Pare, Peter D.; Sin, Don D.; Bosse, Yohan; Laviolette, Michel; Karjalainen, Juha; Fehrmann, Rudolf S. N.; Nickle, David C.; Hao, Ke; Spanjer, Anita I. R.; Timens, Wim; Franke, Lude

    2015-01-01

    Background Chronic obstructive pulmonary disease (COPD) is a progressive, incurable lung disease characterised by abnormal tissue repair causing emphysema and small airways fibrosis. Since current therapy cannot modify this abnormal repair, it is crucial to unravel its underlying molecular mechanism

  7. Work related distal airway obstruction in an agricultural population.

    OpenAIRE

    Vergnenegre, A.; D'arco, X; Melloni, B.; Antonini, M T; Courat, C; Dupont-Cuisinier, M; Bonnaud, F.

    1995-01-01

    OBJECTIVE--To assess the prevalence of distal airway obstruction and its risk factors in agricultural areas. METHODS--A cross sectional study of respiratory symptoms and lung function was performed among French farmers and their spouses (1122 subjects) who came for preventive medicine examinations. They answered a respiratory questionnaire and performed pulmonary function tests on a portable spirometer. Diagnoses of chronic bronchitis were made on the basis of reported chronic respiratory sym...

  8. Method of diagnosis of chronic non-specific diseases of lungs in children

    International Nuclear Information System (INIS)

    Method of diagnosis of chronic nonspecific diseases of lungs in children using bronchography and arteriography is suggested to improve diagnosis accuracy. The method lies in simultaneous contrasting of all bronchial arteries of both lungs. The suggested method of diagnosis enabled to obtain data on pathology of bronchial arteries and bronchial structurs, to reveal additional information about propogation and character of pathologic process

  9. 255 Chronic Obstructive Pulmonary Disease and Lung Cancer Share Inflammation Pathways

    OpenAIRE

    Kostas N. Syrigos; POLITI, EKATERINI; Makrilia, Nektaria; Tsimpoukis, Sotirios; Psarros, Fotis; Syrigou, Ekaterini; Dannos, Ioannis

    2012-01-01

    Background The relationship between inflammation, air obstruction and lung cancer is complex and there is still great uncertainty regarding their underlying pathophysiology. Our aim was to investigate the inflammation pathways that are implicated in both chronic obstructive pulmonary disease (COPD) and lung cancer. Methods A literature search was performed in PubMed to identify relative studies published until June 2011. Results The pathophysiology of both COPD and lung cancer includes dysreg...

  10. Lung cancer and its association with chronic obstructive pulmonary disease:update on nexus of epigenetics

    OpenAIRE

    Sundar, Isaac K.; Mullapudi, Nandita; Yao, Hongwei; Spivack, Simon D.; Rahman, Irfan

    2011-01-01

    PURPOSE OF REVIEW:Chronic obstructive pulmonary disease (COPD) and lung cancer are the leading causes of morbidity and mortality worldwide. The current research is focused on identifying the common and disparate events involved in epigenetic modifications that concurrently occur during the pathogenesis of COPD and lung cancer. The purpose of this review is to describe the current knowledge and understanding of epigenetic modifications in pathogenesis of COPD and lung cancer.RECENT FINDINGS:Th...

  11. Morphologic analysis of peripheral airway and lung by micro-CT

    International Nuclear Information System (INIS)

    The purpose of this study is to determine capability of the newly developed micro-computed tomography (micro-CT) system for imaging of the micro structures of normal preexisting lung, the fundamental elements of broncho-pulmonary physiology. The basic components of the micro-CT system consist of a microfocus X-ray source, a specimen manipulator, and an image intensifier detector coupled to charge-coupled device (CCD) camera. Three-dimensional (3D) image reconstruction was performed slice by slice. A standard fan-beam convolution and backprojection algorithm was used to reconstruct the center plane intersecting the X-ray source. The preprocessing of the 3-D image reconstruction included the correction of the geometrical distortions and the shading artifact introduced by the image intensifier. The main advances of the system is to obtain a high resolution minimal 5 μm. In this work we report on preliminary studies carried out with the micro CT for imaging surgically resected, inflated and fixed lung specimens of a normal lung. We compared the CT images with soft X-ray images and stereomicroscopic findings of the specimens. Experimental results reveal ultra fine structures of lung tissues, such as alveolar walls, interlobular septa, and bronchioles. From the results, the micro CT system is expected to have interesting potentials for experimental and clinical investigations. (author)

  12. Small airways dysfunction in long-term survivors of pediatric stem cell transplantation

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Mathiesen, Sidsel; Buchvald, Frederik;

    2015-01-01

    BACKGROUND: Chronic graft-versus-host disease (cGvHD) in the lungs is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). Pulmonary cGvHD is initiated in the peripheral airways, and diagnosis may be delayed by low sensitivity of standard pulmonary function...... performed spirometry, whole-body plethysmography and MBWN2 . From MBWN2 the lung clearance index (LCI) and indices reflecting ventilation inhomogeneity arising close to the acinar lung zone (Sacin ) and in the conductive airway zone (Scond ) were derived. Subjective respiratory morbidity was assessed using...

  13. Lung function and airway obstruction: associations with circulating markers of cardiac function and incident heart failure in older men-the British Regional Heart Study

    OpenAIRE

    Wannamethee, Goya; Shaper, Gerald; Papacosta, Olia; Lennon, Lucy; Welsh, Paul; Whincup, Peter,

    2016-01-01

    Aims The association between lung function and cardiac markers and heart failure (HF) has been little studied in the general older population. We have examined the association between lung function and airway obstruction with cardiac markers N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) and risk of incident HF in older men. Methods and results Prospective study of 3242 men aged 60–79 years without prevalent HF or myocardial infarction followed up for a...

  14. Lung function and airway obstruction: associations with circulating markers of cardiac function and incident heart failure in older men-the British Regional Heart Study

    OpenAIRE

    Wannamethee, S.G.; Shaper, A. G.; Papacosta, O.; LENNON, L; Welsh, P.; Whincup, P H

    2016-01-01

    AIMS: The association between lung function and cardiac markers and heart failure (HF) has been little studied in the general older population. We have examined the association between lung function and airway obstruction with cardiac markers N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) and risk of incident HF in older men. METHODS AND RESULTS: Prospective study of 3242 men aged 60-79 years without prevalent HF or myocardial infarction followed up for an ...

  15. Detection of DNA Aneuploidy in Exfoliated Airway Epithelia Cells of Sputum Specimens by the Automated Image Cytometry and Its Clinical Value in the Identification of Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    杨健; 周宜开

    2004-01-01

    To evaluate the value of detecton of DNA aneuploidy in exfoliated airway epithelia cells of sputum specimens by the automated image cytometry for the identification of lung cancer, 100patients were divided into patient group (50 patients with lung cancer)and control group (30 patients with tuberculosis and 20 healthy people). Sputum was obtained for the quantitative analysis of DNA content of exfoliated airway epithelial cells with the automated image cytometry, together with the examinations of brush cytology and conventional sputum cytology. Our results showed that DNA aneuploidy (DI>2.5 or 5c) was found in 20 out of 50 sputum samples of lung cancer, 1 out of 30 sputum samples from tuberculosis patients, and none of 20 sputum samples from healthy people. The positive rates of conventional sputum cytology and brush cytology were 16 % and 32 %,which was lower than that of DNA aneuploidy detection by the automated image cytometry (P<0.01 ,P>0.05). Our study showed that automated image cytometry, which uses DNA aneuploidy as a marker for tumor, can detect the malignant cells in sputum samples of lung cancer and it is a sensitive and specific method serving as a complement for the diagnosis of lung cancer.

  16. Indoor air pollution from solid fuel use, chronic lung diseases and lung cancer in Harbin, Northeast China

    Energy Technology Data Exchange (ETDEWEB)

    Galeone, C.; Pelucchi, C.; La Vecchia, C.; Negri, E.; Bosetti, C.; Hu, J.F. [Ist. ric. farmacologiche Mario Negri, Milan (Italy)

    2008-10-15

    In some areas of China, indoor air pollution (IAP) originating principally from the combustion of solid fuels has a relevant role in lung cancer. Most previous studies focused on the female population and only a few on both the sexes. We analyzed the relationship between IAP from solid fuel use and selected chronic lung diseases and lung cancer risk in Harbin, Northeast China, an area with a very high base line risk of lung cancer for both the sexes. We used data from a case-control study conducted between 1987 and 1990, including 218 patients with incident, histologically confirmed lung cancer and 436 controls admitted to the same hospitals as cases. We calculated an index of IAP from solid fuel use exposure using data on heating type, cooking fuel used, and house measurements. Cases reported more frequently than controls on exposure to coal fuel for house heating and/or cooking, and the odds ratio (OR) for ever versus never exposed was 2.19 (95% confidence interval (CI): 1.08-4.46). The ORs of lung cancer according to subsequent tertiles of IAP exposure index were 1.82 (95% CI: 1.14-2.89) and 1.99 (95% CI: 1.26-3.15) as compared with the lowest tertile. The ORs of lung cancer for participants with a history of chronic bronchitis and tuberculosis were 3.79 (95% CI: 2.38-6.02) and 3.82 (95% CI: 1.97-7.41), respectively. This study gives further support and quantification of the positive association between IAP, history of selected nonmalignant lung diseases, and lung cancer risk for both the sexes.

  17. Gene Expression Profiling in Lungs of Chronic Asthmatic Mice Treated with Galectin-3: Downregulation of Inflammatory and Regulatory Genes

    Directory of Open Access Journals (Sweden)

    Esther López

    2011-01-01

    Full Text Available Background. Asthma is a disorder characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS proteins act as negative regulators of cytokine signaling. In particular, SOCS1 and SOCS3 play an important role in immune response by controlling the balance between Th1 and Th2 cells. In a previous study, we demonstrated that treatment of chronic asthmatic mice with gene therapy using plasmid encoding galectin-3 (Gal-3 led to an improvement in Th2 allergic inflammation. Methods. Using a microarray approach, this study endeavored to evaluate the changes produced by therapeutic Gal-3 delivered by gene therapy in a well-characterized mouse model of chronic airway inflammation. Results were confirmed by real-time RT-PCR, Western blot and immunohistochemical analysis. Results. We identify a set of genes involved in different pathways whose expression is coordinately decreased/increased in mice treated with Gal-3 gene therapy. We report a correlation between Gal-3 treatment and inhibition of SOCS1 and SOCS3 expression in lungs. Conclusion. These results suggest that negative regulation of SOCS1 and 3 following Gal-3 treatment could be a valuable therapeutic approach in allergic disease.

  18. Update on Nonsurgical Lung Volume Reduction Procedures

    OpenAIRE

    Neder, J. Alberto; O’Donnell, Denis E

    2016-01-01

    There has been a surge of interest in endoscopic lung volume reduction (ELVR) strategies for advanced COPD. Valve implants, coil implants, biological LVR (BioLVR), bronchial thermal vapour ablation, and airway stents are used to induce lung deflation with the ultimate goal of improving respiratory mechanics and chronic dyspnea. Patients presenting with severe air trapping (e.g., inspiratory capacity/total lung capacity (TLC) 225% predicted) and thoracic hyperinflation...

  19. Local immunotherapy in experimental murine lung inflammation

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Caroline Uebel, Sonja Koch, Anja Maier, Nina Sopel, Anna Graser, Stephanie Mousset & Susetta Finotto ### Abstract Innovative local immunotherapy for severe lung diseases such as asthma, chronic obstructive pulmonary disease or lung cancer requires a successful delivery to access the desired cellular target in the lung. An important route is the direct instillation into the airways in contrast to delivery through the digestive tract. This protocol details a method to deliv...

  20. Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases.

    Science.gov (United States)

    Reuter, Sebastian; Beckert, Hendrik; Taube, Christian

    2016-02-01

    Bronchial asthma and chronic obstructive pulmonary disease (COPD) are chronic diseases that are associated with inflammation and structural changes in the airways and lungs. Recent findings have implicated Wnt pathways in critically regulating inflammatory responses, especially in asthma. Furthermore, canonical and noncanonical Wnt pathways are involved in structural changes such as airway remodeling, goblet cell metaplasia, and airway smooth muscle (ASM) proliferation. In COPD, Wnt pathways are not only associated with structural changes in the airways but also involved in the development of emphysema. The present review summarizes the role and function of the canonical and noncanonical Wnt pathway with regard to airway inflammation and structural changes in asthma and COPD. Further identification of the role and function of different Wnt molecules and pathways could help to develop novel therapeutic options for these diseases. PMID:26595171

  1. Distinct Tlr4-expressing cell compartments control neutrophilic and eosinophilic airway inflammation

    OpenAIRE

    McAlees, Jaclyn W.; Whitehead, Gregory S.; Harley, Isaac T. W.; Cappelletti, Monica; Rewerts, Cheryl L.; Holdcroft, A. Maria; Divanovic, Senad; Wills-Karp, Marsha; Finkelman, Fred D.; Karp, Christopher L.; Cook, Donald N.

    2014-01-01

    Allergic asthma is a chronic, inflammatory lung disease. Some forms of allergic asthma are characterized by Th2-driven eosinophilia while others are distinguished by Th17-driven neutrophilia. Stimulation of Toll-like receptor 4 (TLR4) on hematopoietic and airway epithelial cells (AECs) contributes to the inflammatory response to lipopolysaccharide (LPS) and allergens, but the specific contribution of TLR4 in these cell compartments to airway inflammatory responses remains poorly understood. W...

  2. Dietary intake, lung function and airway inflammation in Mexico City school children exposed to air pollutants

    Directory of Open Access Journals (Sweden)

    Díaz-Sánchez David

    2009-12-01

    Full Text Available Abstract Introduction Air pollutant exposure has been associated with an increase in inflammatory markers and a decline in lung function in asthmatic children. Several studies suggest that dietary intake of fruits and vegetables might modify the adverse effect of air pollutants. Methods A total of 158 asthmatic children recruited at the Children's Hospital of Mexico and 50 non-asthmatic children were followed for 22 weeks. Pulmonary function was measured and nasal lavage collected and analyzed every 2 weeks. Dietary intake was evaluated using a 108-item food frequency questionnaire and a fruit and vegetable index (FVI and a Mediterranean diet index (MDI were constructed. The impact of these indices on lung function and interleukin-8 (IL-8 and their interaction with air pollutants were determined using mixed regression models with random intercept and random slope. Results FVI was inversely related to IL-8 levels in nasal lavage (p 1 (test for trend p 1 and FVC as was with MDI and ozone for FVC. No effect of diet was observed among healthy children. Conclusion Our results suggest that fruit and vegetable intake and close adherence to the Mediterranean diet have a beneficial effect on inflammatory response and lung function in asthmatic children living in Mexico City.

  3. Alveolar flows of the developing lungs:from embryonic to early childhood airways

    Science.gov (United States)

    Tenenbaum-Katan, Janna; Hofemeier, Philipp; Fishler, Rami; Rothen-Rutishauser, Barbara; Sznitman, Josue

    2014-11-01

    At the onset of life in utero the respiratory system is simply a liquid-filled duct. With our first breath, alveoli are filled with air and become a significant port of entry for airborne particles. As such, alveolar lining is nearly fully functional at birth, though lung development continues during childhood as structural changes increase alveolar surface area to optimize ventilation. We hypothesize that such fluid dynamical changes potentially affect two phenomena occurring within alveoli: (i) flow patterns in airspaces at distinct stages of both in- and ex-utero life and (ii) fate of inhaled particles ex-utero. To investigate these phenomena, we combine experimental and numerical approaches where (i) microfluidic in vitro devices mimic liquid flows across the epithelium of fetal airspaces, and (ii) computational simulations are employed to examine particle transport and deposition in the deep alveolated regions of infants' lungs. Our approaches capture anatomically-inspired geometries based on morphometrical data, as well as physiological flows, including the convective-diffusive nature of submicron particle transport in alveolar regions.Overall, we investigate respiratory flows in alveolar regions of developing lungs, from early embryonic stages to late childhood

  4. Airway bacteria drive a progressive COPD-like phenotype in mice with polymeric immunoglobulin receptor deficiency.

    Science.gov (United States)

    Richmond, Bradley W; Brucker, Robert M; Han, Wei; Du, Rui-Hong; Zhang, Yongqin; Cheng, Dong-Sheng; Gleaves, Linda; Abdolrasulnia, Rasul; Polosukhina, Dina; Clark, Peter E; Bordenstein, Seth R; Blackwell, Timothy S; Polosukhin, Vasiliy V

    2016-01-01

    Mechanisms driving persistent airway inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood. As secretory immunoglobulin A (SIgA) deficiency in small airways has been reported in COPD patients, we hypothesized that immunobarrier dysfunction resulting from reduced SIgA contributes to chronic airway inflammation and disease progression. Here we show that polymeric immunoglobulin receptor-deficient (pIgR(-/-)) mice, which lack SIgA, spontaneously develop COPD-like pathology as they age. Progressive airway wall remodelling and emphysema in pIgR(-/-) mice are associated with an altered lung microbiome, bacterial invasion of the airway epithelium, NF-κB activation, leukocyte infiltration and increased expression of matrix metalloproteinase-12 and neutrophil elastase. Re-derivation of pIgR(-/-) mice in germ-free conditions or treatment with the anti-inflammatory phosphodiesterase-4 inhibitor roflumilast prevents COPD-like lung inflammation and remodelling. These findings show that pIgR/SIgA deficiency in the airways leads to persistent activation of innate immune responses to resident lung microbiota, driving progressive small airway remodelling and emphysema. PMID:27046438

  5. Bacterial sinusitis can be a focus for initial lung colonisation and chronic lung infection in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Aanæs, Kasper

    2013-01-01

    A major purpose of treating patients with cystic fibrosis (CF) is to prevent or delay chronic lung infections with CF-pathogenic Gram-negative bacteria. In the intermittent stage, bacteria can usually be eradicated from the lungs with antibiotics, but following eradication, the next lung...... CF patients. This is important since urgent treatment reduces morbidity when CF patients are early colonised with P. aeruginosa, however, there is a lack of diagnostic tools for detecting the early colonisation in the lungs and in the sinuses. We initiated a treatment strategy for CF patients to...... strategy, sinus bacteria could be eradicated in a large proportion of patients. Essentially, growth of CF-pathogenic bacteria from the lower respiratory tract was decreased following the treatment. Furthermore, a number of patients have been free from CF-pathogenic bacteria for more than one year after...

  6. Characterising novel anti-biofilm targets for the treatment of chronic Pseudomonas aeruginosa infection in the cystic fibrosis lung

    OpenAIRE

    McCarthy, Ronan

    2014-01-01

    The global rise in antibiotic resistance is a significant problem facing healthcare professionals. In particular within the cystic fibrosis (CF) lung, bacteria can establish chronic infection and resistance to a wide array of antibiotic therapies. One of the principle pathogens associated with chronic infection in the CF lung is Pseudomonas aeruginosa. P. aeruginosa can establish chronic infection in the CF lung partly through the use of the biofilm mode of growth. This biofilm mode of growth...

  7. Inspiratory inertial deposition of aerosols in human nasal airway replicate casts: implication for the proposed NCRP lung model

    International Nuclear Information System (INIS)

    Inertial deposition of aerosol particles of the size range 1-10 μm AED in the human upper airways (nasal, oral, pharyngeal, and laryngeal passages) is an important feature of the proposed NCRP lung model. The dependence of removal per cent upon particle size, flow rate, passage flow, and passage dimension is not well understood, but simple empirical models have been proposed for correlating human experimental data. A series of overall nasal passage deposition studies have been carried out in two accurate replicate models of an adult and an infant over a range of particle sizes and flow rates. When plotted against the intertial parameter dA2Q, deposition per cent at different flows fell on a single curve. Deposition differences due to area changes at the nasal valve could be scaled by Stokes' number. Deposition in the child nasal passage was greater than the adult at the same flow rate, but was similar in efficiency for equivalent states of rest or exercise breathing. These findings suggest that a single efficiency curve adopted for the NCRP models for inertial deposition is valid for physiologically realistic conditions of breathing, and that biological variability of deposition per cent is dependent upon the nasal passage geometry. For children, the same curve of nasal efficiency can be used for similar states of rest of exercise breathing. (author)

  8. Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography.

    Science.gov (United States)

    Subramanian, Deepak R; Gupta, Sumit; Burggraf, Dorothe; Vom Silberberg, Suzan J; Heimbeck, Irene; Heiss-Neumann, Marion S; Haeussinger, Karl; Newby, Chris; Hargadon, Beverley; Raj, Vimal; Singh, Dave; Kolsum, Umme; Hofer, Thomas P; Al-Shair, Khaled; Luetzen, Niklas; Prasse, Antje; Müller-Quernheim, Joachim; Benea, Giorgio; Leprotti, Stefano; Boschetto, Piera; Gorecka, Dorota; Nowinski, Adam; Oniszh, Karina; Castell, Wolfgang Zu; Hagen, Michael; Barta, Imre; Döme, Balázs; Strausz, Janos; Greulich, Timm; Vogelmeier, Claus; Koczulla, Andreas R; Gut, Ivo; Hohlfeld, Jens; Welte, Tobias; Lavae-Mokhtari, Mahyar; Ziegler-Heitbrock, Loems; Brightling, Christopher; Parr, David G

    2016-07-01

    EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.QCT indices were influenced by scanner non-conformity, but standardisation significantly reduced variability (pemphysema-dominant", "airway disease-dominant", "mixed" disease and "mild" disease. The emphysema-dominant group had significantly higher lung volumes, lower gas transfer coefficient, lower oxygen (PO2 ) and carbon dioxide (PCO2 ) tensions, higher haemoglobin and higher blood leukocyte numbers than the airway disease-dominant group.The utility of QCT for phenotyping in the setting of an international multicentre study is improved by standardisation. QCT indices of emphysema and airway disease can delineate within a population of patients with COPD, phenotypic groups that have typical clinical features known to be associated with emphysema-dominant and airway-dominant disease. PMID:27230444

  9. Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases

    Science.gov (United States)

    Arakelyan, Arsen; Nersisyan, Lilit; Petrek, Martin; Löffler-Wirth, Henry; Binder, Hans

    2016-01-01

    Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent. PMID:27200087

  10. Anticholinergic treatment in airways diseases.

    LENUS (Irish Health Repository)

    Flynn, Robert A

    2009-10-01

    The prevalence of chronic airways diseases such as chronic obstructive pulmonary disease and asthma is increasing. They lead to symptoms such as a cough and shortness of breath, partially through bronchoconstriction. Inhaled anticholinergics are one of a number of treatments designed to treat bronchoconstriction in airways disease. Both short-acting and long-acting agents are now available and this review highlights their efficacy and adverse event profile in chronic airways diseases.

  11. Increasing Prevalence of Chronic Lung Disease in Veterans of the Wars in Iraq and Afghanistan.

    Science.gov (United States)

    Pugh, Mary Jo; Jaramillo, Carlos A; Leung, Kar-Wei; Faverio, Paola; Fleming, Nicholas; Mortensen, Eric; Amuan, Megan E; Wang, Chen-Pin; Eapen, Blessen; Restrepo, Marcos; Morris, Michael J

    2016-05-01

    Research from the wars in Afghanistan and Iraq have focused on traumatic brain injury (TBI) and mental health conditions; however, it is becoming clear that other health concerns, such as respiratory illnesses, warrant further scientific inquiry. Early reports from theater and postdeployment health assessments suggested an association with deployment-related exposures (e.g., sand, burn pits, chemical, etc.) and new-onset respiratory symptoms. We used data from Veterans Affairs medical encounters between fiscal years 2003 and 2011 to identify trends in chronic obstructive pulmonary disease, asthma, and interstitial lung disease in veterans. We used data from Veterans Affairs and Department of Defense sources to identify sociodemographic (age, sex, race), military (e.g., service branch, multiple deployments) and clinical characteristics (TBI, smoking) of individuals with and without chronic lung diseases. Generalized estimating equations found significant increases over time for chronic obstructive pulmonary disease and asthma in both unadjusted and adjusted analyses. Trends for interstitial lung disease were significant only in adjusted analyses. Age, smoking, and TBI were also significantly associated with chronic lung diseases; however, multiple deployments were not associated. Research is needed to identify which characteristics of deployment-related exposures are linked with chronic lung disease. PMID:27136656

  12. Aspergillus tubingensis: a major filamentous fungus found in the airways of patients with lung disease.

    Science.gov (United States)

    Gautier, Magali; Normand, Anne-Cécile; L'Ollivier, Coralie; Cassagne, Carole; Reynaud-Gaubert, Martine; Dubus, Jean-Christophe; Brégeon, Fabienne; Hendrickx, Marijke; Gomez, Carine; Ranque, Stéphane; Piarroux, Renaud

    2016-07-01

    The black Aspergillus group comprises A. niger and 18 other species, which are morphologically indistinguishable. Among this species subset, A. tubingensis, described in less than 30 human cases before 2014, is primarily isolated from ear, nose, and throat samples. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has emerged as a powerful technique to identify microbes in diagnostic settings. We applied this method to identify 1,720 filamentous fungi routinely isolated from clinical samples our laboratory over a two-year study period. Accordingly, we found 85 isolates of A. niger, 58 of A. tubingensis, and six other black Aspergillus (4 A. carbonarius and 2 A. japonicus). A. tubingensis was the fifth most frequent mold isolated in our mycology laboratory, primarily isolated from respiratory samples (40/58 isolates). In this study, we mainly aimed to describe the clinical pattern of Aspergillus tubingensisWe analyzed the clinical features of the patients in whom A. tubingensis had been isolated from 40 respiratory samples. Thirty patients suffered from cystic fibrosis, chronic obstructive pulmonary disease or other types of chronic respiratory failure. Strikingly, 20 patients were experiencing respiratory acute exacerbation at the time the sample was collected. Antifungal susceptibility testing of 36 A. tubingensis isolates showed lower amphotericin B MICs (P cystic fibrosis and chronic pulmonary diseases. PMID:26773134

  13. Achieving therapeutic benefits of inhaled corticosteroids/beta2 agonist in chronic obstructive airway disease

    Institute of Scientific and Technical Information of China (English)

    WANG Zeng-li

    2007-01-01

    @@ Asthma and chronic obstructive pulmonary disease (COPD) are the two commonest causes of adult airflow obstruction. The fundamental differences and similarities between the pathological mechanisms of asthma and COPD are well recognized.1

  14. Using optical coherence tomography (OCT) imaging in the evaluation of airway dynamics (Conference Presentation)

    Science.gov (United States)

    Szabari, Margit V.; Kelly, Vanessa J.; Applegate, Matthew B.; Chee, Chunmin; Tan, Khay M.; Hariri, Lida P.; Harris, R. Scott; Winkler, Tilo; Suter, Melissa J.

    2016-03-01

    Asthma is a chronic disease resulting in periodic attacks of coughing and wheezing due to temporarily constricted and clogged airways. The pathophysiology of asthma and the process of airway narrowing are not completely understood. Appropriate in vivo imaging modality with sufficient spatial and temporal resolution to dynamically assess the behavior of airways is missing. Optical coherence tomography (OCT) enables real-time evaluation of the airways during dynamic and static breathing maneuvers. Our aim was to visualize the structure and function of airways in healthy and Methacholine (MCh) challenged lung. Sheep (n=3) were anesthetized, mechanically ventilated and imaged with OCT in 4 dependent and 4 independent airways both pre- and post-MCh administration. The OCT system employed a 2.4 Fr (0.8 mm diameter) catheter and acquired circumferential cross-sectional images in excess of 100 frames per second during dynamic tidal breathing, 20 second static breath-holds at end-inspiration and expiration pressure, and in a response to a single deep inhalation. Markedly different airway behavior was found in dependent versus non-dependent airway segments before and after MCh injection. OCT is a non-ionizing light-based imaging modality, which may provide valuable insight into the complex dynamic behavior of airway structure and function in the normal and asthmatic lung.

  15. Photodynamic Therapy (PDT with Chemotherapy for Advanced Lung Cancer with Airway Stenosis

    Directory of Open Access Journals (Sweden)

    Masakazu Kimura

    2015-10-01

    Full Text Available Intractable advanced lung cancer can be treated palliatively with photodynamic therapy (PDT combined with chemotherapy to remove central and peripheral (lobar or segmental bronchi bronchial stenosis and obstruction. We present data for 12 (eight men, four women consecutive patients with 13 advanced non-small cell lung carcinomas in whom curative operations were contraindicated, who underwent PDT combined with chemotherapy for local control of the intraluminal lesions. The mean age was 73.3 years (range, 58–80 years, and the stages of cancer were IIA–IV. The median stenosis rates before treatment, one week post-treatment, and one month post-treatment were 60% (range, 30%–100%, 15% (range, 15%–99%, and 15% (range 15%–60%, respectively. The mean and median survival times were 9.3 and 5.9 months, respectively. The overall 1-year survival rate was 30.0%. No PDT-related morbidity or mortality occurred. In this single-institution study, all patients experienced improved symptoms and quality of life at one week after treatment; furthermore, an objective response was evidenced by the substantial increase in the openings of the bronchial lumen and prevention of obstructive pneumonia. Therefore, PDT with chemotherapy was useful and safe for the treatment of bronchial obstruction.

  16. Epithelial mesenchymal transition in smokers: large versus small airways and relation to airflow obstruction

    Directory of Open Access Journals (Sweden)

    Mahmood MQ

    2015-08-01

    Full Text Available Malik Quasir Mahmood,1,* Sukhwinder Singh Sohal,1,2,* Shakti Dhar Shukla,1 Chris Ward,3 Ashutosh Hardikar,4 Wan Danial Noor,1 Hans Konrad Muller,1 Darryl A Knight,5 Eugene Haydn Walters1 1NHMRC Centre of Research Excellence for Chronic Respiratory Disease and Lung Ageing, School of Medicine, University of Tasmania, Hobart, TAS, Australia; 2School of Health Sciences, Faculty of Health, University of Tasmania, Launceston, TAS, Australia; 3Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK; 4Royal Hobart Hospital, Hobart, TAS, Australia; 5School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia *These authors contributed equally to this work Background: Small airway fibrosis is the main contributor in airflow obstruction in chronic obstructive pulmonary disease. Epithelial mesenchymal transition (EMT has been implicated in this process, and in large airways, is associated with angiogenesis, ie, Type-3, which is classically promalignant. Objective: In this study we have investigated whether EMT biomarkers are expressed in small airways compared to large airways in subjects with chronic airflow limitation (CAL and what type of EMT is present on the basis of vascularity. Methods: We evaluated epithelial activation, reticular basement membrane fragmentation (core structural EMT marker and EMT-related mesenchymal biomarkers in small and large airways from resected lung tissue from 18 lung cancer patients with CAL and 9 normal controls. Tissues were immunostained for epidermal growth factor receptor (EGFR; epithelial activation marker, vimentin (mesenchymal marker, and S100A4 (fibroblast epitope. Type-IV collagen was stained to demonstrate vessels. Results: There was increased expression of EMT-related markers in CAL small airways compared to controls: EGFR (P<0.001, vimentin (P<0.001, S100A4 (P<0.001, and fragmentation (P<0.001, but this was less than that in large airways

  17. Lung recruitment can improve oxygenation in patients ventilated in continuous positive airway pressure/pressure support mode

    Directory of Open Access Journals (Sweden)

    András eLovas

    2015-04-01

    Full Text Available Background: Recruitment maneuvers are often used in critical care patients with hypoxemic respiratory failure. Although continuous positive airway pressure/pressure support (CPAP/PS ventilation is a frequently used approach, but whether lung recruitment also improves oxygenation in spontaneously breathing patients has not been investigated yet. The primary objective was to analyse the effect of recruitment maneuver on oxygenation in patients ventilated in CPAP/PS mode. Methods: Following baseline measurements PEEP was increased by 5 cmH2O. Recruitment maneuver was applied for 40 seconds with 40 cmH2O of PS. Measurements of the difference in PaO2/FiO2 and airway parameters measured by the ventilator were recorded immediately after recruitment then 15 and 30 minutes later. Thirty patients ventilated in CPAP/PS mode with a PEEP ≥ 5 cmH2O were enrolled in this prospective, observational study if their PaO2/FiO2 ratio was 0.5. Results: Following recruitment maneuver patients were considered as non-responders (NR, n=15 if difference of PaO2/FiO2 < 20 % and responders (R, n=15 if difference of PaO2/FiO2 ≥ 20 %. In the NR-group PaO2/FiO2 decreased non-significantly from baseline: median [interquartile], PaO2/FiO2 = 176 [120-186] vs. after recruitment: 169 [121-182] mmHg, P = .307 while in the R-group there was significant improvement: 139 [117-164] vs. 230 [211-323] mmHg, P = .01. At the same time points dead space to tidal volume ratio (Vds/Vte significantly increased in the NR-group Vds/Vte = 32 [27-37] vs. 36 [25-42] %, P = .013 but no significant change was observed in the R-group: 26 [22-34] vs. 27 [24-33] %, p = .386.Conclusion: Recruitment maneuver improved PaO2/FiO2 ratio by ≥ 20 % in 50 % of patients ventilated in CPAP/PS mode.

  18. Evaluation of the regional lung function revealed in radioaerosol scintigram of chronic obstructive pulmonary disease, 1

    International Nuclear Information System (INIS)

    We classified the findings of radioaerosol inhalation scintigrams of patients with various stages of obstructive pulmonary disease (COPD) into 4 grades, according to the extent of peripheral irregularity and central hot spot formation; Stage I represents normal homogeneous distribution, stage II represents peripheral irregularity, stage III represents additional hot spot formation and stage IV represents further regional defect. This aerosol grading criteria was then compared with routine and specific lung function tests. The aerosol grading criterion correlated well with FEV sub(1.0)% which is a good indicator of the severity of COPD. The central hot spot formation correlated well with FEV sub(1.0)% and respiratory resistance (R.p.) determined by the oscillation method, both of which are good indicators of abnormality in central airway resistance. Peripheral irregularity correlated well with: 1) flows at 50%VC and 25%VC in a maximum forced expiratory flow volume curve; 2) closing volume (CV/VC%); 3) delta N2%/l in N2 single washout test; and 4) the regional delay of 133Xe washout process, all of which are sensitive indicators of small airway disease. It is therefore reasonable to conclude that the radioaerosol scintigram reveals the regional lung function both in terms of airway resistance (R) and compliance (C). This criterion was useful in quantitatively evaluating the regional ventilation distribution of COPD and the therapeutic effect on bronchial asthma. The mechanism of aerosol praticle deposition related to characteristic central hot spot formation accompanied with peripheral irregularity in a radioaerosol scintigram of COPD, needs further exploration concerning the aerodynamic behavior of aerosol particles in the airways both during inspiration and expiration. (author)

  19. Integrated care pathways for airway diseases (AIRWAYS-ICPs)

    DEFF Research Database (Denmark)

    Bousquet, J; Addis, A; Adcock, I;

    2014-01-01

    The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will...

  20. Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Wong Brian A

    2005-10-01

    associated with increased lung manganese concentrations and small airway inflammatory changes in the absence of observable clinical signs. Subchronic exposure to manganese sulfate at exposure concentrations (≤0.3 mg Mn/m3 similar to the current 8-hr occupational threshold limit value established for inhaled manganese was not associated with pulmonary pathology.

  1. Remodeling in asthma and chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Postma, Dirkje S; Timens, Wim

    2006-01-01

    Airway and lung tissue remodeling and fibrosis play an important role in the development of symptoms associated with lung function loss in asthma and chronic obstructive pulmonary disease (COPD). In the past decades, much attention has been paid to the inflammatory cellular process involved in airwa

  2. High-resolution computed tomography in chronic infiltrative lung disease

    International Nuclear Information System (INIS)

    HRCT is an exceedingly powerful tool when brought to bear on selected patients with diffuse lung disease. In many ways HRCT effectively bridges the gap between the gestalt impression of a chest radiograph and the detailed, but very local, information provided by lung biopsy specimens. In the diagnostic flow chart which takes a patient with dyspnoea and non-specific radiographic shadowing through many tests, and possibly on to lung biospy, there is now enough evidence to elevate HRCT to a prime position in the hierarchy of investigations. (orig./VHE)

  3. Morphological findings in lungs of the horses with chronic obstructive pulmonary disease (COPD)

    OpenAIRE

    Marinković Darko; Sanja Aleksić-Kovačević; Plamenac P.

    2007-01-01

    The frequency and characteristics of chronic obstructive pulmonary disease (COPD) based on morphological and cytological changes in equine lungs were studied in this paper. Lungs obtained from 51 horses of different age and sex were examined grossly and tissue samples were collected for pathohistological examination. Cytological examination was done on impression smears from the tracheal bifurcation. Pathohistological preparations were stained with hematoxylin eosin (HE), toluidine blue (TB),...

  4. Regional structure-function correlations in chronic obstructive lung disease measured with positron emission tomography.

    OpenAIRE

    Brudin, L H; Rhodes, C G; Valind, S O; Buckingham, P D; Jones, T; Hughes, J. M.

    1992-01-01

    BACKGROUND: Positron emission tomography, performed with isotopes of very short half life, can be used to relate local lung tissue density to local ventilation and to the ventilation:perfusion ratio. This method has been used in 10 patients with severe chronic airflow obstruction and differing values for carbon monoxide transfer factor (TLCO) and transfer coefficient (KCO). METHODS: Ventilation (VA) and the ventilation:perfusion ratio (V/Q), lung density, and blood volume were measured region...

  5. Sub-chronic exposure to second hand smoke induces airspace leukocyte infiltration and decreases lung elastance

    Directory of Open Access Journals (Sweden)

    John M. Hartney

    2012-07-01

    Full Text Available Exposure to second hand tobacco smoke is associated with the development and/or exacerbation of several different pulmonary diseases in humans. To better understand the possible effects of second hand smoke exposure in humans, we sub-chronically (4 weeks exposed mice to a mixture of mainstream and sidestream tobacco smoke at concentrations similar to second hand smoke exposure in humans. The inflammatory response to smoke exposures was assessed at the end of this time by enumeration of pulmonary leukocyte infiltration together with measurements of lung elastance and pathology. This response was measured in both healthy wild type (C57BL/6 mice as well as mouse mutants deficient in the expression of Arhgef1 (Arhgef1–/– that display constitutive pulmonary inflammation and decreased lung elastance reminiscent of emphysema. The results from this study show that sub-chronic second hand smoke exposure leads to significantly increased numbers of airspace leukocytes in both healthy and mutant animals. While sub-chronic cigarette smoke exposure is not sufficient to induce changes in lung architecture as measured by mean linear intercept, both groups exhibit a significant decrease in lung elastance. Together these data demonstrate that even sub-chronic exposure to second hand smoke is sufficient to induce pulmonary inflammation and decrease lung elastance in both healthy and diseased animals and in the absence of tissue destruction.

  6. 骨髓间充质干细胞移植对慢性哮喘小鼠气道炎症及气道重塑的影响%Effects of Bone Marrow-Derived Mesenchymal Stem Cells on Airway Inflammation and Airway Remodeling in Chronic Asthmatic Mice

    Institute of Scientific and Technical Information of China (English)

    戈霞晖; 白冲; 陈若华; 胡珍丽; 朱天怡; 李强

    2011-01-01

    目的 探讨同种异体骨髓间充质干细胞(BMSC)移植对慢性哮喘小鼠气道炎症和气道重塑的影响.方法 40只雌性BALB/c小鼠随机分为正常对照组、BMSC对照组、哮喘模型组和BMSC治疗组.从雄性BALB/c小鼠分离BMSC.用卵白蛋白(OVA)制备慢性哮喘模型.观察BMSC移植对慢性哮喘小鼠气道炎症和气道重塑的影响,并采用流式细胞术检测BMSC对脾组织CD4+CD25+调节性T细胞比例的影响.结果 哮喘模型组支气管上皮黏膜脱落,上皮黏膜有杯状细胞增生,部分管腔内有黏液栓塞,气道、血管旁有大量炎件浸润,以及气道平滑肌细胞增生和肥大.正常对照组及BMSC对照组无气道炎症及气道重塑的表现,而BMSC治疗组气道炎症及气道重塑明显减轻.与BMSC对照组及正常对照组比较,哮喘模型组CD4+CD25+调节性T细胞占淋巴细胞的比例显著降低(P<0.05);与哮喘模型组比较,BMSC治疗组CD4+CD25+调节性T细胞占淋巴细胞的比例明显提高(P<0.05);BMSC治疗组与正常对照组及BMSC对照组无显著差异.结论 BMSC移植能明显减轻慢性哮喘小鼠气道炎症及气道重塑程度,并能上调外周CD4+CD25+调节性T细胞的比例.%Objective To investigate the effect of allogeneic bone marrow-derived mesenchymal stem cells (BMSCs) transplantation on the airway inflammation and airway remodeling in chronic asthmatic mice. Methods Forty female BALB/c mice were equally randomized into four groups,ie. a normal control group,a BMSCs control group,an asthma model group, and a BMSCs transplantation group. BMSCs were generated from male donor mice, then the mice in the asthma model group and the BMSCs transplantation group were sensitized and challenged with OVA to establish chronic asthmatic mice model. Hematoxylin and eosin staining and Alcian blue-periodic acid-Schiff staining were used to analyze the effects on airway inflammation and airway remodeling after BMSC engraftment. The number of

  7. The Role of CLCA Proteins in Inflammatory Airway Disease

    Science.gov (United States)

    Patel, Anand C.; Brett, Tom J.; Holtzman, Michael J.

    2014-01-01

    Inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) exhibit stereotyped traits that are variably expressed in each person. In experimental mouse models of chronic lung disease, these individual disease traits can be genetically segregated and thereby linked to distinct determinants. Functional genomic analysis indicates that at least one of these traits, mucous cell metaplasia, depends on members of the calcium-activated chloride channel (CLCA) gene family. Here we review advances in the biochemistry of the CLCA family and the evidence of a role for CLCA family members in the development of mucous cell metaplasia and possibly airway hyperreactivity in experimental models and in humans. Based on this information, we develop the model that CLCA proteins are not integral membrane proteins with ion channel function, but instead are secreted signaling molecules that specifically regulate airway target cells in healthy and disease conditions. PMID:18954282

  8. Lung protease/anti-protease network and modulation of mucus production and surfactant activity.

    Science.gov (United States)

    Garcia-Verdugo, Ignacio; Descamps, Delphyne; Chignard, Michel; Touqui, Lhousseine; Sallenave, Jean-Michel

    2010-11-01

    Lung epithelium guarantees gas-exchange (performed in the alveoli) and protects from external insults (pathogens, pollutants…) present within inhaled air. Both functions are facilitated by secretions lining airway surface liquid, mucus (in the upper airways) and pulmonary surfactant (in the alveoli). Mucins, the main glycoproteins present within the mucus, are responsible for its rheologic properties and participate in lung defense mechanisms. In parallel, lung collectins are pattern recognition molecules present in pulmonary surfactant that also modulate lung defense. During chronic airways diseases, excessive protease activity can promote mucus hypersecretion and degradation of lung collectins and therefore contribute to the pathophysiology of these diseases. Importantly, secretion of local and systemic anti-proteases might be crucial to equilibrate the protease/anti-protease unbalance and therefore preserve the function of lung host defense compounds and airway surface liquid homeostasis. In this review we will present information relative to proteases able to modulate mucin production and lung collectin integrity, two important compounds of innate immune defense. One strategy to preserve physiological mucus production and collectin integrity during chronic airways diseases might be the over-expression of local 'alarm' anti-proteases such as SLPI and elafin. Interestingly, a cross-talk between lung collectins and anti-protease activity has recently been described, implicating the presence within the lung of a complex network between proteases, anti-proteases and pattern recognition molecules, which aims to keep or restore homeostasis in resting or inflamed lungs. PMID:20493919

  9. Regional perfusion of the lungs in patients with chronic nonspecific pulmonary diseases based on scintigraphy data

    International Nuclear Information System (INIS)

    Perfusion scintigraphy of lungs with 99mTc-albumin microspheres was used for a study of changes of regional perfusion of lesser circulation in patients with chronic bronchitis of a varying degree of disturbed pulmonary hemodynamics. Even before a stable rise of pulmonary vascular resistance and developmemt of pulmonary arterial hypertension, chronic bronchitis was characterized by redistribution of blood flow from the lower parts of lungs to the upper ones, which progressed with disturbance of pulmonary arterial circulation and the development of chronic cor pulmonale. The use of scintigraphic indices of the upper and lower parts (U/L) prefusion ratio led to adequate assessment of a degree of redistribution of the pulmonary blood flow in patients with chronic bronchitis

  10. Airway epithelial NF-κB activation promotes Mycoplasma pneumoniae clearance in mice.

    Directory of Open Access Journals (Sweden)

    Di Jiang

    Full Text Available Respiratory infections including atypical bacteria Mycoplasma pneumoniae (Mp contribute to the pathobiology of asthma and chronic obstructive pulmonary disease (COPD. Mp infection mainly targets airway epithelium and activates various signaling pathways such as nuclear factor κB (NF-κB. We have shown that short palate, lung, and nasal epithelium clone 1 (SPLUNC1 serves as a novel host defense protein and is up-regulated upon Mp infection through NF-κB activation in cultured human and mouse primary airway epithelial cells. However, the in vivo role of airway epithelial NF-κB activation in host defense against Mp infection has not been investigated. In the current study, we investigated the effects of in vivo airway epithelial NF-κB activation on lung Mp clearance and its association with airway epithelial SPLUNC1 expression.Non-antimicrobial tetracycline analog 9-t-butyl doxycycline (9-TB was initially optimized in mouse primary tracheal epithelial cell culture, and then utilized to induce in vivo airway epithelial specific NF-κB activation in conditional NF-κB transgenic mice (CC10-(CAIKKβ with or without Mp infection. Lung Mp load and inflammation were evaluated, and airway epithelial SPLUNC1 protein was examined by immunohistochemistry. We found that 9-TB treatment in NF-κB transgene positive (Tg+, but not transgene negative (Tg- mice significantly reduced lung Mp load. Moreover, 9-TB increased airway epithelial SPLUNC1 protein expression in NF-κB Tg+ mice.By using the non-antimicrobial 9-TB, our study demonstrates that in vivo airway epithelial NF-κB activation promotes lung bacterial clearance, which is accompanied by increased epithelial SPLUNC1 expression.

  11. Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs* **

    OpenAIRE

    Torres, Ronaldo Lopes; Torres, Iraci Lucena da Silva; Laste, Gabriela; Ferreira, Maria Beatriz Cardoso; Cardoso, Paulo Francisco Guerreiro; Belló-Klein, Adriane

    2014-01-01

    Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO) and total reactive antioxidant potential (TRAP), in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.); acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methy...

  12. Searching for synergistic bronchodilators and novel therapeutic regimens for chronic lung diseases from a traditional Chinese medicine, Qingfei Xiaoyan Wan.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Hou

    Full Text Available Classical Chinese pharmacopeias describe numerous excellent herbal formulations, and each prescription is an outstanding pool of effective compounds for drug discovery. Clarifying the bioactivity of the combined mechanisms of the ingredients in complex traditional Chinese medicine formulas is challenging. A classical formula known as Qingfei Xiaoyan Wan, used clinically as a treatment for prevalent chronic lung disease, was investigated in this work. A mutually enhanced bioactivity-guided ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS characterization system was proposed, coupled with a dual-luciferase reporter assay for β2AR-agonist cofactor screening. Arctiin, arctigenin, descurainoside and descurainolide B, four lignin compounds that showed synergistic bronchodilation effects with ephedrine, were revealed. The synergistic mechanism of arctigenin with the β2ARagonist involved with the reduction of free Ca2+ was clarified by a dual-luciferase reporter assay for intracellular calcium and the Ca2+ indicator fluo-4/AM to monitor changes in the fluorescence. The relaxant and contractile responses of airway smooth muscle are regulated by crosstalk between the intracellular cAMP and calcium signaling pathways. Our data indicated the non-selective βAR agonist ephedrine as the principal bronchodilator of the formula, whereas the lignin ingredients served as adjuvant ingredients. A greater understanding of the mechanisms governing the control of these pathways, based on conventional wisdom, could lead to the identification of novel therapeutic targets or new agents for the treatment of asthma and COPD.

  13. Searching for synergistic bronchodilators and novel therapeutic regimens for chronic lung diseases from a traditional Chinese medicine, Qingfei Xiaoyan Wan.

    Science.gov (United States)

    Hou, Yuanyuan; Cheng, Binfeng; Zhou, Mengge; Fang, Runping; Jiang, Min; Hou, Wenbin; Bai, Gang

    2014-01-01

    Classical Chinese pharmacopeias describe numerous excellent herbal formulations, and each prescription is an outstanding pool of effective compounds for drug discovery. Clarifying the bioactivity of the combined mechanisms of the ingredients in complex traditional Chinese medicine formulas is challenging. A classical formula known as Qingfei Xiaoyan Wan, used clinically as a treatment for prevalent chronic lung disease, was investigated in this work. A mutually enhanced bioactivity-guided ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) characterization system was proposed, coupled with a dual-luciferase reporter assay for β2AR-agonist cofactor screening. Arctiin, arctigenin, descurainoside and descurainolide B, four lignin compounds that showed synergistic bronchodilation effects with ephedrine, were revealed. The synergistic mechanism of arctigenin with the β2ARagonist involved with the reduction of free Ca2+ was clarified by a dual-luciferase reporter assay for intracellular calcium and the Ca2+ indicator fluo-4/AM to monitor changes in the fluorescence. The relaxant and contractile responses of airway smooth muscle are regulated by crosstalk between the intracellular cAMP and calcium signaling pathways. Our data indicated the non-selective βAR agonist ephedrine as the principal bronchodilator of the formula, whereas the lignin ingredients served as adjuvant ingredients. A greater understanding of the mechanisms governing the control of these pathways, based on conventional wisdom, could lead to the identification of novel therapeutic targets or new agents for the treatment of asthma and COPD. PMID:25397687

  14. Draft Genome Sequence of Burkholderia dolosa PC543 Isolated from Cystic Fibrosis Airways

    OpenAIRE

    Workentine, Matthew L; Michael G Surette; Bernier, Steve P

    2014-01-01

    Burkholderia dolosa is a member of the Burkholderia cepacia complex, a group of opportunistic bacterial pathogens often associated with fatal chronic infections in the lungs of patients suffering from cystic fibrosis (CF). Here, we announce the draft genome sequence of B. dolosa PC543 (LMG 19468), a CF airway isolate.

  15. Plethysmographic measurements of specific airway resistance in young children

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Nielsen, Kim G

    2005-01-01

    Validated methods for lung function measurements in young children are lacking. Plethysmographic measurement of specific airway resistance (sRaw) provides such a method applicable from 2 years of age. sRaw gauges airway resistance from the measurements of the pressure changes driving the airflow...... also been documented by this technique, and sRaw has recently been used in longitudinal studies of young children with chronic pulmonary diseases. Future developments should provide improved algorithms for thermal correction of the respired volumes and adapt the equipment to the special needs of young...

  16. Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells

    Energy Technology Data Exchange (ETDEWEB)

    Person, Rachel J.; Tokar, Erik J.; Xu, Yuanyuan; Orihuela, Ruben; Ngalame, Ntube N. Olive; Waalkes, Michael P., E-mail: waalkes@niehs.nih.gov

    2013-12-01

    Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LC cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell's ability to adapt to chronic cadmium exposure. - Highlights: • Chronic cadmium exposure induces cancer cell characteristics in human lung cells. • This provides an in vitro model of cadmium-induced human lung cell transformation. • This occurred with general and lung specific changes typical for cancer cells. • These findings add insight to the

  17. Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells

    International Nuclear Information System (INIS)

    Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LC cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell's ability to adapt to chronic cadmium exposure. - Highlights: • Chronic cadmium exposure induces cancer cell characteristics in human lung cells. • This provides an in vitro model of cadmium-induced human lung cell transformation. • This occurred with general and lung specific changes typical for cancer cells. • These findings add insight to the relationship

  18. Aspergillus-Related Lung Disease

    Directory of Open Access Journals (Sweden)

    Alia Al-Alawi

    2005-01-01

    Full Text Available Aspergillus is a ubiquitous dimorphic fungus that causes a variety of human diseases ranging in severity from trivial to life-threatening, depending on the host response. An intact host defence is important to prevent disease, but individuals with pre-existing structural lung disease, atopy, occupational exposure or impaired immunity are susceptible. Three distinctive patterns of aspergillus-related lung disease are recognized: saprophytic infestation of airways, cavities and necrotic tissue; allergic disease including extrinsic allergic alveolitis, asthma, allergic bronchopulmonary aspergillosis, bronchocentric granulomatosis and chronic eosinophilic pneumonia; and airway and tissue invasive disease -- pseudomembranous tracheobronchitis, acute bronchopneumonia, angioinvasive aspergillosis, chronic necrotizing aspergillosis and invasive pleural disease. A broad knowledge of these clinical presentations and a high index of suspicion are required to ensure timely diagnosis and treatment of the potentially lethal manifestations of aspergillus-related pulmonary disease. In the present report, the clinical, radiographic and pathological aspects of the various aspergillus-related lung diseases are briefly reviewed.

  19. Quantification of nonuniform distribution of hemi-lung perfusion in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Mitomo, Osamu

    2016-01-01

    Nonuniform distribution (NUD) of perfusion on single photon emission computed tomography (SPECT) is caused by impaired perfusion-related fluctuations of the functional volume (FFV). It was determined if digital analysis of NUD in each hemi-lung damaged by chronic obstructive pulmonary disease (COPD) could improve the whole lung impairment assessment. We examined 665 subjects and 8 controls by SPECT. The basic whole lung SPECT volume was defined at 10% of maximum whole lung count cutoff threshold (T h). For the whole lung and each hemi-lung, the 10% T h width volume, FFV rate, and misfit from the control were calculated at every T h width number (n) from 1 to 9 for every additional 10% T h from 10 to 100%. The misfit value integrated from 1 to 9 of n was defined by 3 NUD indices: D, whole lung NUD index; D rl , the index for the sum of each hemi-lung NUD; and D (I) , the NUD index with every interpolating pattern in which FFV rates of hemi-lungs comprised negative and positive value at the same n. D rl index was the sum of D and D (I) indices in all patients. D rl and D indices significantly increased in pulmonary disease subjects relative to those of the normal group and non-pulmonary disease subjects. D rl and D indices increased in COPD subjects. Progressive COPD subjects had larger D rl index values and "diffuse and even" hemi-lung impairment. The three indices quantizing FFV itself leading to NUD helped to digitally evaluate the degree of lung impairment of perfusion. Clinically, it is expected that the NUD indices and images obtained by SPECT, which visually and digitally show the pathological fluctuations in perfusion caused by lung impairment, will be able to provide specific and useful information for improving treatment and/or care of subjects with COPD. PMID:26644008

  20. ISO-1, a Macrophage Migration Inhibitory Factor Antagonist, Inhibits Airway Remodeling in a Murine Model of Chronic Asthma

    OpenAIRE

    Chen, Pei-Fen; Luo, Ya-ling; Wang, Wei; Wang, Jiang-xin; Lai, Wen-yan; Hu, Si-ming; Cheng, Kai Fan; Al-Abed, Yousef

    2010-01-01

    Airway remodeling is the process of airway structural change that occurs in patients with asthma in response to persistent inflammation and leads to increasing disease severity. Drugs that decrease this persistent inflammation play a crucial role in managing asthma episodes. Mice sensitized (by intraperitoneal administration) and then challenged (by inhalation) with ovalbumin (OVA) develop an extensive eosinophilic inflammatory response, goblet cell hyperplasia, collagen deposition, airway sm...

  1. Exposure conditions, lung function and airway symptoms in industrial production of wood pellets. A pilot project; Exponeringsfoerhaallanden, lungfunktion och luftvaegsbesaer vid industriell produktion av traepellets. Ett pilotprojekt

    Energy Technology Data Exchange (ETDEWEB)

    Edman, Katja; Loefstedt, Haakan; Berg, Peter; Bryngelsson, I.L.; Fedeli, Cecilia; Selden, Anders [Oerebro Univ. Hospital (Sweden). Yrkes- och miljoemedicinska kliniken; Eriksson, Kaare [Umeaa Univ. Hospital (Sweden); Holmstroem, Mats; Rask- Andersen, Anna [Uppsala Univ. Hospital (Sweden)

    2002-02-01

    The production of wood pellets is a relatively new branch of the Swedish wood industry and has increased during the last years. A pilot study was performed to investigate the prevalence of airway symptoms, lung function and exposure among all 39 men employed in industrial production of wood pellets at six companies. The study included a questionnaire, medical examination, registration of nasal-PEF (peak expiratory flow) during a week, allergy screening (Phadiatop) and lung function (spirometry) before and after work shift. The results were compared with different reference data from other Swedish studies. Exposure measurements of monoterpenes and wood dust on filter and with a data logger (DataRAM) were also performed. The study group reported a higher frequency of cough without phlegm, awakening due to breathlessness and current asthma medication compared with reference data. For five of the six participants with physician-diagnosed asthma the disease debuted before the current employment and the results did not indicate an unusual asthma morbidity. Spirometry showed lower lung function before work shift than expected. However no difference over work shift was observed. A negative and non-significant correlation was seen between time with current work task and lung function. The study group reported a higher frequency of nasal symptoms mostly blockage, sneezing and dryness compared with reference data. The registrations of nasal-PEF did not show any differences between work and spare time. The prevalence of positive Phadiatop (23 %) did not differ from reference data. No association between exposure (wood dust and monoterpenes) and acute effects on lung function was observed. The wood dust exposure (0.16-19 mg/m{sup 3}) was high and 11 of 24 measurements exceeded the present Swedish occupational exposure limit of 2 mg/m{sup 3}. Peak exposures could be identified, e.g. at cleaning of engines with compressed air, with the DataRAM. The exposure to monoterpenes (0

  2. Activation of pulmonary and lymph node dendritic cells during chronic Pseudomonas aeruginosa lung infection in mice.

    Science.gov (United States)

    Damlund, Dina Silke Malling; Christophersen, Lars; Jensen, Peter Østrup; Alhede, Morten; Høiby, Niels; Moser, Claus

    2016-06-01

    The majority of cystic fibrosis (CF) patients acquire chronic Pseudomonas aeruginosa lung infection, resulting in increased mortality and morbidity. The chronic P. aeruginosa lung infection is characterized by bacteria growing in biofilm surrounded by polymorphonuclear neutrophils (PMNs). However, the infection is not eradicated and the inflammatory response leads to gradual degradation of the lung tissue. In CF patients, a Th2-dominated adaptive immune response with a pronounced antibody response is correlated with poorer outcome. Dendritic cells (DCs) are crucial in bridging the innate immune system with the adaptive immune response. Once activated, the DCs deliver a set of signals to uncommitted T cells that induce development, such as expansion of regulatory T cells and polarization of Th1, Th2 or Th17 subsets. In this study, we characterized DCs in lungs and regional lymph nodes in BALB/c mice infected using intratracheal installation of P. aeruginosa embedded in seaweed alginate in the lungs. A significantly elevated concentration of DCs was detected earlier in the lungs than in the regional lymph nodes. To evaluate whether the chronic P. aeruginosa lung infection leads to activation of DCs, costimulatory molecules CD80 and CD86 were analyzed. During infection, the DCs showed significant elevation of CD80 and CD86 expression in both the lungs and the regional lymph nodes. Interestingly, the percentage of CD86-positive cells was significantly higher than the percentage of CD80-positive cells in the lymph nodes. In addition, cytokine production from Lipopolysaccharides (LPS)-stimulated DCs was analyzed demonstrating elevated production of IL-6, IL-10 and IL-12. However, production of IL-12 was suppressed earlier than IL-6 and IL-10. These results support that DCs are involved in skewing of the Th1/Th2 balance in CF and may be a possible treatment target. PMID:27009697

  3. A poroelastic model coupled to a fluid network with applications in lung modelling.

    Science.gov (United States)

    Berger, Lorenz; Bordas, Rafel; Burrowes, Kelly; Grau, Vicente; Tavener, Simon; Kay, David

    2016-01-01

    We develop a lung ventilation model based on a continuum poroelastic representation of lung parenchyma that is strongly coupled to a pipe network representation of the airway tree. The continuous system of equations is discretized using a low-order stabilised finite element method. The framework is applied to a realistic lung anatomical model derived from computed tomography data and an artificially generated airway tree to model the conducting airway region. Numerical simulations produce physiologically realistic solutions and demonstrate the effect of airway constriction and reduced tissue elasticity on ventilation, tissue stress and alveolar pressure distribution. The key advantage of the model is the ability to provide insight into the mutual dependence between ventilation and deformation. This is essential when studying lung diseases, such as chronic obstructive pulmonary disease and pulmonary fibrosis. Thus the model can be used to form a better understanding of integrated lung mechanics in both the healthy and diseased states. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26100614

  4. Social Stress Enhances Allergen-Induced Airway Inflammation in Mice and Inhibits Corticosteroid Responsiveness of Cytokine Production

    OpenAIRE

    Bailey, Michael; Kierstein, Sonja; Sharma, Satish; Spaits, Matthew; Kinsey, Steven G.; Tliba, Omar; Amrani, Yassine; John F Sheridan; Panettieri, Reynold A.; Haczku, Angela

    2009-01-01

    Chronic psychosocial stress exacerbates asthma but the underlying mechanisms remain poorly understood. We hypothesized that psychosocial stress aggravates allergic airway inflammation by altering innate immune cell function. The effects of stress on airway inflammation, lung function and glucocorticoid responsiveness were studied in a novel in vivo murine model of combined social disruption stress and allergic sensitization. The effects of corticosterone were assessed on cytokine profile and ...

  5. Pulmonary carcinogenesis and chronic beta irradiation of lung

    International Nuclear Information System (INIS)

    Light water nuclear power reactor fuel cycles at various stages contain substantial quantities of β-emitting radionuclides. Thus, in the event of an accident, there is potential for inhalation exposure of man to various types and forms of β-emitting radionuclides. In order to study the biological effects of such potential exposures, a series of life span studies have been initiated in which beagle dogs have been exposed to inhalation to achieve graded lung burdens of a relatively insoluble fused clay form of β-emitting radionuclides. The specific radionuclides, 90Y, 91Y, 144Ce, or 90Sr, were selected on the basis of physical half-life to produce a variety of radiation-dose patterns to the lung. Early effects have been the development of radiation pneumonitis and progressive pulmonary fibrosis. In general, dogs which receive high- and rapidly-declining dose-rate exposure from 90Y or 91Y die earlier and at lower cumulative doses than dogs exposed to 144Ce or 90Sr. By contrast, the incidence of later-occurring malignant lung tumors and the degree of inflammatory response is greater in dogs which received protracted low dose-rate exposure associated with 144Ce and 90Sr. Of particular note is the nature of the lung tumors thus far observed

  6. Interstitial pressure and lung oedema in chronic hypoxia

    Czech Academy of Sciences Publication Activity Database

    Rivolta, I.; Lucchini, G.; Rocchetti, M.; Kolář, František; Palazzo, F.; Zaza, A.; Miserocchi, G.

    2011-01-01

    Roč. 37, č. 4 (2011), s. 943-949. ISSN 0903-1936 Institutional research plan: CEZ:AV0Z50110509 Keywords : capillary patency * lung morphometry * microvascular permeability * pulmonary hypertension * pulmonary interstitial pressure Subject RIV: FC - Pulmology Impact factor: 5.895, year: 2011

  7. CT of chronic infiltrative lung disease: Prevalence of mediastinal lymphadenopathy

    Energy Technology Data Exchange (ETDEWEB)

    Niimi, Hiroshi; Kang, Eun-Young; Kwong, S. [Univ. of British Columbia and Vancouver Hospital and Health Sciences Centre (Canada)] [and others

    1996-03-01

    Our goal was to determine the prevalence of mediastinal lymph node enlargement at CT in patients with diffuse infiltrative lung disease. The study was retrospective and included 175 consecutive patients with diffuse infiltrative lung diseases. Diagnoses included idiopathic pulmonary fibrosis (IPF) (n = 61), usual interstitial pneumonia associated with collagen vascular disease (CVD) (n = 20), idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) (n = 22), extrinsic allergic alveolitis (EAA) (n = 17), and sarcoidosis (n = 55). Fifty-eight age-matched patients with CT of the chest performed for unrelated conditions served as controls. The presence, number, and sites of enlarged nodes (short axis {ge}10 mm in diameter) were recorded. Enlarged mediastinal nodes were present in 118 of 175 patients (67%) with infiltrative lung disease and 3 of 58 controls (5%) (p < 0.001). The prevalence of enlarged nodes was 84% (46 of 55) in sarcoidosis, 67% (41 of 61) in IPF, 70% (14 of 20) in CVD, 53% (9 of 17) in EAA, and 36% (8 of 22) in BOOP. The mean number of enlarged nodes was higher in sarcoidosis (mean 3.2) than in the other infiltrative diseases (mean 1.2) (p < 0.001). Enlarged nodes were most commonly present in station 10R, followed by 7, 4R, and 5. Patients with infiltrative lung disease frequently have enlarged mediastinal lymph nodes. However, in diseases other than sarcoid, usually only one or two nodes are enlarged and their maximal short axis diameter is <15 mm. 11 refs., 2 figs., 1 tab.

  8. Measures of reversibility in response to bronchodilators in chronic airflow obstruction: relation to airway calibre.

    OpenAIRE

    Weir, D C; Sherwood Burge, P

    1991-01-01

    A study was carried out to examine the independence from starting prebronchodilator FEV1 of four indices commonly used to express airflow (FEV1) reversibility in response to bronchodilators. In 121 patients with chronic airflow obstruction with a mean prebronchodilator FEV1 of 1.81 (43.9% of predicted values) the change in FEV1 expressed as a percentage of the patient's predicted FEV1 was the least dependent on starting FEV1. Reversibility, expressed as a percentage of the prebronchodilator v...

  9. Pseudomonas aeruginosa mutations in lasl and rhll quorum sensing systems result in milder chronic lung infection

    DEFF Research Database (Denmark)

    Wu, H.; Song, Z.J.; Givskov, Michael Christian;

    2001-01-01

    To understand the importance of quorum sensing in chronic Pseudomonas aeruginosa lung infection, the in vivo pathogenic effects of the wild-type P aeruginosa PAO1 and its double mutant, PAO1 lasI rhlI, in which the signal-generating parts of the quorum sensing systems are defective were compared...

  10. Anti-proline-glycine-proline or antielastin autoantibodies are not evident in chronic inflammatory lung disease.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2010-01-01

    In patients with chronic inflammatory lung disease, pulmonary proteases can generate neoantigens from elastin and collagen with the potential to fuel autoreactive immune responses. Antielastin peptide antibodies have been implicated in the pathogenesis of tobacco-smoke-induced emphysema. Collagen-derived peptides may also play a role.

  11. Lung functions at school age and chronic exposure to outdoor and indoor air pollution

    Energy Technology Data Exchange (ETDEWEB)

    Neuberger, M.; Kundi, M.; Wiesenberger, W. [Vienna Univ. (Austria). Dept. of Preventive Medicine

    1995-12-31

    Early signs of lung function impairment have been found correlated with annual concentrations of outdoor air pollutants and with passive smoking. To investigate the combined effects of both indicators of chronic exposure to air pollution pulmonary functions in all elementary and high school children of an Austrian town was examined for 5 years. (author)

  12. Lung mucociliary transport function in chronic bronchitis and radionuclide methods of its investigation (a review)

    International Nuclear Information System (INIS)

    Several methods for studying lung clearance of smokers and non-smoking patients with chronic bronchitis (CB) are described. Modified technique for investigating mucociliary transport (MCT) in CB patients, using 99mTc-macroaggregate of human serum albumin, is suggested. The method enables to examine more patients and obtain the most comprehensive data on MCT state on any level of tracheobronchial tree

  13. Epithelium-generated neuropeptide Y induces smooth muscle contraction to promote airway hyperresponsiveness.

    Science.gov (United States)

    Li, Shanru; Koziol-White, Cynthia; Jude, Joseph; Jiang, Meiqi; Zhao, Hengjiang; Cao, Gaoyuan; Yoo, Edwin; Jester, William; Morley, Michael P; Zhou, Su; Wang, Yi; Lu, Min Min; Panettieri, Reynold A; Morrisey, Edward E

    2016-05-01

    Asthma is one of the most common chronic diseases globally and can be divided into presenting with or without an immune response. Current therapies have little effect on nonimmune disease, and the mechanisms that drive this type of asthma are poorly understood. Here, we have shown that loss of the transcription factors forkhead box P1 (Foxp1) and Foxp4, which are critical for lung epithelial development, in the adult airway epithelium evokes a non-Th2 asthma phenotype that is characterized by airway hyperresponsiveness (AHR) without eosinophilic inflammation. Transcriptome analysis revealed that loss of Foxp1 and Foxp4 expression induces ectopic expression of neuropeptide Y (Npy), which has been reported to be present in the airways of asthma patients, but whose importance in disease pathogenesis remains unclear. Treatment of human lung airway explants with recombinant NPY increased airway contractility. Conversely, loss of Npy in Foxp1- and Foxp4-mutant airway epithelium rescued the AHR phenotype. We determined that NPY promotes AHR through the induction of Rho kinase activity and phosphorylation of myosin light chain, which induces airway smooth muscle contraction. Together, these studies highlight the importance of paracrine signals from the airway epithelium to the underlying smooth muscle to induce AHR and suggest that therapies targeting epithelial induction of this phenotype may prove useful in treatment of noneosinophilic asthma. PMID:27088802

  14. Detecting airway remodeling in COPD and emphysema using low-dose CT imaging

    Science.gov (United States)

    Rudyanto, R.; Ceresa, M.; Muñoz-Barrutia, A.; Ortiz-de-Solorzano, C.

    2012-03-01

    In this study, we quantitatively characterize lung airway remodeling caused by smoking-related emphysema and Chronic Obstructive Pulmonary Disease (COPD), in low-dose CT scans. To that end, we established three groups of individuals: subjects with COPD (n=35), subjects with emphysema (n=38) and healthy smokers (n=28). All individuals underwent a low-dose CT scan, and the images were analyzed as described next. First the lung airways were segmented using a fast marching method and labeled according to its generation. Along each airway segment, cross-section images were resampled orthogonal to the airway axis. Next 128 rays were cast from the center of the airway lumen in each crosssection slice. Finally, we used an integral-based method, to measure lumen radius, wall thickness, mean wall percentage and mean peak wall attenuation on every cast ray. Our analysis shows that both the mean global wall thickness and the lumen radius of the airways of both COPD and emphysema groups were significantly different from those of the healthy group. In addition, the wall thickness change starts at the 3rd airway generation in the COPD patients compared with emphysema patients, who display the first significant changes starting in the 2nd generation. In conclusion, it is shown that airway remodeling happens in individuals suffering from either COPD or emphysema, with some local difference between both groups, and that we are able to detect and accurately quantify this process using images of low-dose CT scans.

  15. SPECT perfusion lung scintigraphy in children with chronic pulmonary damage: Preliminary results of a prospective study

    International Nuclear Information System (INIS)

    The aim of this study was to describe SPECT perfusion lung scintigraphy findings in symptomatic children with chronic pulmonary damage. Material and Method: We studied 111 children (average age:3.9 yr, range:1 month- 15 yr, 61.3% boys) with chronic pulmonary pathology. The most common clinical diagnosis reported in this population were recurrent bronchopneumonia (45.9%), unknown origin chronic pulmonary damage (36.9%), chronic obstructed bronchitis (27.9%), adenovirus bronchopneumonia sequelae (27.9%) and bronchopulmonary dysplasia (14.4%). The SPECT lung perfusion scintigraphy (LS) was performed in a SMV DST XLi two headed gammacamera, 64x64 matrix, 32 steps of 15 sec each, using a HRLE collimator, after i.v. injection of a age-adjusted dose of Tc99m-MAA. The images were reconstructed using a iterative-post filter method and displayed in tomographic slices and 3D form. We took also planar images in frontal and posterior projections to assess the differential perfusion. The studies were separated according to scintigraphy findings and gender. Results: Ninety eight (88.3%) of realized LS were abnormal (59.2% boys). Fifty three (54.1%) of abnormal scans showed bilateral alterations, being this finding significantly (p:0.034) more frequent in boys (63.8% bilateral lesions) than in girls (40.0% bilateral lesions). When unilateral altered scans were analyzed, the right lung was more frequently affected than left lung (73.5% vs 26.5%) (p:0.002). Of whole abnormal group, 19.4% had diffuse perfusion alterations, 46.9% showed focal alterations and 33.7% had a mixed diffuse-focal pattern. In focal alterations group, the majority presented a segmental distribution (83.7%), being the more frequent localizations the right inferior lobe (39.8%), right upper lobe (34.7%) and left inferior lobe (34.7%). Sixteen patients (16,3%) had focal non-segmental alterations, being situated mainly in upper middle of right lung (47.6%). The range of differential perfusion quantification in

  16. Air pollution and chronic airway diseases: what should people know and do?

    Science.gov (United States)

    Jiang, Xu-Qin; Feng, Di

    2016-01-01

    The health effects of air pollution remain a public health concern worldwide. Exposure to air pollution has many substantial adverse effects on human health. Globally, seven million deaths were attributable to the joint effects of household and ambient air pollution. Subjects with chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma are especially vulnerable to the detrimental effects of air pollutants. Air pollution can induce the acute exacerbation of COPD and onset of asthma, increase the respiratory morbidity and mortality. The health effects of air pollution depend on the components and sources of pollutants, which varied with countries, seasons, and times. Combustion of solid fuels is a major source of air pollutants in developing countries. To reduce the detrimental effects of air pollution, people especially those with COPD or asthma should be aware of the air quality and take extra measures such as reducing the time outdoor and wearing masks when necessary. For reducing the air pollutants indoor, people should use clean fuels and improve the stoves so as to burn fuel more efficiently and vent emissions to the outside. Air cleaners that can improve the air quality efficiently are recommended. PMID:26904251

  17. Chronic diffuse infiltrative lung disease: Chest radiography diagnostic accuracy of CT versus

    International Nuclear Information System (INIS)

    The authors compared the accuracy of chest radiographic and CT findings in predicting diagnoses in 118 patients with chronic diffuse infiltrative lung disease, using three independent observers. First-choice diagnosis was correct with 57% of radiographs and 76% of CT scans (P<.001). CT was most accurate in silicosis (93%), UIP (89%), lymphangitic carcinomatosis (85%), and sarcoidosis (77%). The observers had a high degree of confidence in their first-choice diagnoses with 23% of radiographs and 49% of CT scans and were correct when confident in 77% and 93% of cases, respectively (P<.001). Observers correctly predicted whether a transbronchial or an open lung biopsy was indicated with 65% of radiographs and 87% of CT scans (P<.001). The authors conclude that CT is superior to the radiograph in evaluation of chronic infiltrative lung disease

  18. Pseudomonas aeruginosa Evolutionary Adaptation and Diversification in Cystic Fibrosis Chronic Lung Infections.

    Science.gov (United States)

    Winstanley, Craig; O'Brien, Siobhan; Brockhurst, Michael A

    2016-05-01

    Pseudomonas aeruginosa populations undergo a characteristic evolutionary adaptation during chronic infection of the cystic fibrosis (CF) lung, including reduced production of virulence factors, transition to a biofilm-associated lifestyle, and evolution of high-level antibiotic resistance. Populations of P. aeruginosa in chronic CF lung infections typically exhibit high phenotypic diversity, including for clinically important traits such as antibiotic resistance and toxin production, and this diversity is dynamic over time, making accurate diagnosis and treatment challenging. Population genomics studies reveal extensive genetic diversity within patients, including for transmissible strains the coexistence of highly divergent lineages acquired by patient-to-patient transmission. The inherent spatial structure and spatial heterogeneity of selection in the CF lung appears to play a key role in driving P. aeruginosa diversification. PMID:26946977

  19. Proteases and antiproteases in chronic neutrophilic lung disease - relevance to drug discovery.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2009-10-01

    Chronic inflammatory lung diseases such as cystic fibrosis and emphysema are characterized by higher-than-normal levels of pulmonary proteases. While these enzymes play important roles such as bacterial killing, their dysregulated expression or activity can adversely impact on the inflammatory process. The existence of efficient endogenous control mechanisms that can dampen or halt this overexuberant protease activity in vivo is essential for the effective resolution of inflammatory lung disease. The function of pulmonary antiproteases is to fulfil this role. Interestingly, in addition to their antiprotease activity, protease inhibitors in the lung also often possess other intrinsic properties that contribute to microbial killing or termination of the inflammatory process. This review will outline important features of chronic inflammation that are regulated by pulmonary proteases and will describe the various mechanisms by which antiproteases attempt to counterbalance exaggerated protease-mediated inflammatory events. These proteases, antiproteases and their modifiers represent interesting targets for therapeutic intervention.

  20. Ultrasonography for clinical decision-making and intervention in airway management: From the mouth to the lungs and pleurae

    DEFF Research Database (Denmark)

    Kristensen, M. S.; Teoh, W. H.; Graumann, O.;

    2014-01-01

    prior to difficult airway management, perform nerve blocks for awake intubation, confirm tracheal or oesophageal intubation and facilitate localisation of tracheal rings for tracheostomy. Ultrasonography is an excellent diagnostic tool in intraoperative and emergency diagnosis of pneumothorax. It also...

  1. Lung function score including a parameter of small airway disease as a highly predictive indicator of survival after allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Nakamae, Mika; Yamashita, Mariko; Koh, Hideo; Nishimoto, Mitsutaka; Hayashi, Yoshiki; Nakane, Takahiko; Nakashima, Yasuhiro; Hirose, Asao; Hino, Masayuki; Nakamae, Hirohisa

    2016-06-01

    Some studies on the predictive value of determining pulmonary function prior to allogeneic hematopoietic cell transplantation (allo-HCT) have shown a significant association between pulmonary function test (PFT) parameters and pulmonary complications, and mortality. However, the percentage of patients showing abnormalities in pretransplant PFT parameters is low. We comprehensively evaluated the effect of pretransplant PFT parameters, including a marker of small airway disease (ratio of the airflow rate of 50% vital capacity to the airflow rate of 25% vital capacity (V˙50/V˙25), on outcomes in 206 evaluable patients who underwent allo-HCT at our institute. Notable among the significant parameters in a univariable analysis, V˙50/V˙25 was the most powerful indicator of survival following allo-HCT (delta-Akaike information criterion [∆AIC] = 12.47, ∆χ(2)  = 14.47; P = 0.0001). Additionally, a pretransplant lung function score (pLFS) established by applying three parameters with superior predictive values including V˙50/V˙25 represented a better discriminating variable for the prediction of survival. Our data demonstrate that a pLFS incorporating a parameter of small airway disease, rather than the parameters of central airway obstruction, may be useful for predicting patient survival following allo-HCT. PMID:27018997

  2. The Role of the Epithelium in Airway Remodeling in Asthma

    OpenAIRE

    Davies, Donna E.

    2009-01-01

    The bronchial epithelium is the barrier to the external environment and plays a vital role in protection of the internal milieu of the lung. It functions within the epithelial-mesenchymal trophic unit to control the local microenvironment and help maintain tissue homeostasis. However, in asthma, chronic perturbation of these homeostatic mechanisms leads to alterations in the structure of the airways, termed remodeling. Damage to the epithelium is now recognized to play a key role in driving a...

  3. Ginseng treatment reduces bacterial load and lung pathology in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Song, Z; Johansen, H K; Faber, V;

    1997-01-01

    The predominant pathogen in patients with cystic fibrosis (CF) is Pseudomonas aeruginosa, which results in a chronic lung infection associated with progressive pulmonary insufficiency. In a rat model of chronic P. aeruginosa pneumonia mimicking that in patients with CF, we studied whether the...... inflammation and antibody responses could be changed by treatment with the Chinese herbal medicine ginseng. An aqueous extract of ginseng was injected subcutaneously, and cortisone and saline were used as controls. Two weeks after challenge with P. aeruginosa, the ginseng-treated group showed a significantly...... against P. aeruginosa sonicate and a shift from an acute type to a chronic type of lung inflammation compared to those in the control and cortisone-treated groups were observed. These findings indicate that ginseng treatment of an experimental P. aeruginosa pneumonia in rats promotes a cellular response...

  4. Airway Remodeling in Chronic Obstructive Pulmonary Disease and Asthma: the Role of Matrix Metalloproteinase-9.

    Science.gov (United States)

    Grzela, Katarzyna; Litwiniuk, Malgorzata; Zagorska, Wioletta; Grzela, Tomasz

    2016-02-01

    Chronic obstructive pulmonary disease (COPD) and asthma are both associated with airflow restriction and progressive remodeling, which affect the respiratory tract. Among various biological factors involved in the pathomechanisms of both diseases, proteolytic enzymes--matrix metalloproteinases (MMPs)--play an important role, especially MMP-9. In this review, the authors discuss the current topics of research concerning the possible role of MMP-9 in both mentioned diseases. They include the analysis of protein levels, nucleotide polymorphisms of MMP-9 gene and their possible correlation with asthma and COPD. Finally, the authors refer to the studies on MMP-9 inhibition as a new perspective for increasing the effectiveness of treatment in asthma and COPD. PMID:26123447

  5. Chronic hepatitis E infection in lung transplant recipients

    NARCIS (Netherlands)

    Riezebos-Brilman, Annelies; Puchhammer-Stockl, Elisabeth; van der Weide, Hinke Y.; Haagsma, Elizabeth B.; Jaksch, Peter; Bejvl, Isabella; Niesters, Hubert G.; Verschuuren, Erik A. M.

    2013-01-01

    BACKGROUND: Hepatitis E virus (HEV) genotype 3 has been identified in patients with autochthonous HEV infections in developed countries and is currently being recognized as an emerging zoonotic pathogen. HEV infection may lead to a chronic hepatitis in immune-compromised patients. METHODS: We studie

  6. Non-invasive ventilation used as an adjunct to airway clearance treatments improves lung function during an acute exacerbation of cystic fibrosis: a randomised trial

    Directory of Open Access Journals (Sweden)

    Tiffany J Dwyer

    2015-07-01

    Full Text Available Question: During an acute exacerbation of cystic fibrosis, is non-invasive ventilation beneficial as an adjunct to the airway clearance regimen? Design: Randomised controlled trial with concealed allocation and intention-to-treat analysis. Participants: Forty adults with moderate to severe cystic fibrosis lung disease and who were admitted to hospital for an acute exacerbation. Intervention: Comprehensive inpatient care (control group compared to the same care with the addition of non-invasive ventilation during airway clearance treatments from Day 2 of admission until discharge (experimental group. Outcome measures: Lung function and subjective symptom severity were measured daily. Fatigue was measured at admission and discharge on the Schwartz Fatigue Scale from 7 (no fatigue to 63 (worst fatigue points. Quality of life and exercise capacity were also measured at admission and discharge. Length of admission and time to next hospital admission were recorded. Results: Analysed as the primary outcome, the experimental group had a greater rate of improvement in forced expiratory volume in 1 second (FEV1 than the control group, but this was not statistically significant (MD 0.13% predicted per day, 95% CI –0.03 to 0.28. However, the experimental group had a significantly higher FEV1 at discharge than the control group (MD 4.2% predicted, 95% CI 0.1 to 8.3. The experimental group reported significantly lower levels of fatigue on the Schwartz fatigue scale at discharge than the control group (MD 6 points, 95% CI 1 to 11. There was no significant difference between the experimental and control groups in subjective symptom severity, quality of life, exercise capacity, length of hospital admission or time to next hospital admission. Conclusion: Among people hospitalised for an acute exacerbation of cystic fibrosis, the use of non-invasive ventilation as an adjunct to the airway clearance regimen significantly improves FEV1 and fatigue. Trial

  7. Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses of cystic fibrosis children have implications for chronic lung infection

    DEFF Research Database (Denmark)

    Hansen, Susse Kirkelund; Rau, Martin Holm; Johansen, Helle Krogh;

    2012-01-01

    The opportunistic pathogen Pseudomonas aeruginosa is a frequent colonizer of the airways of patients suffering from cystic fibrosis (CF). Depending on early treatment regimens, the colonization will, with high probability, develop into chronic infections sooner or later, and it is important to es...

  8. Chronic obstructive pulmonary disease and altered risk of lung cancer in a population-based case-control study.

    Directory of Open Access Journals (Sweden)

    Jill Koshiol

    Full Text Available BACKGROUND: Chronic obstructive pulmonary disease (COPD has been consistently associated with increased risk of lung cancer. However, previous studies have had limited ability to determine whether the association is due to smoking. METHODOLOGY/PRINCIPAL FINDINGS: The Environment And Genetics in Lung cancer Etiology (EAGLE population-based case-control study recruited 2100 cases and 2120 controls, of whom 1934 cases and 2108 controls reported about diagnosis of chronic bronchitis, emphysema, COPD (chronic bronchitis and/or emphysema, or asthma more than 1 year before enrollment. We estimated odds ratios (OR and 95% confidence intervals (CI using logistic regression. After adjustment for smoking, other previous lung diseases, and study design variables, lung cancer risk was elevated among individuals with a history of chronic bronchitis (OR = 2.0, 95% CI = 1.5-2.5, emphysema (OR = 1.9, 95% CI = 1.4-2.8, or COPD (OR = 2.5, 95% CI = 2.0-3.1. Among current smokers, association between chronic bronchitis and lung cancer was strongest among lighter smokers. Asthma was associated with a decreased risk of lung cancer in males (OR = 0.48, 95% CI = 0.30-0.78. CONCLUSIONS/SIGNIFICANCE: These results suggest that the associations of personal history of chronic bronchitis, emphysema, and COPD with increased risk of lung cancer are not entirely due to smoking. Inflammatory processes may both contribute to COPD and be important for lung carcinogenesis.

  9. Clinical approach to chronic beryllium disease and other nonpneumoconiotic interstitial lung diseases.

    Science.gov (United States)

    Maier, Lisa A

    2002-10-01

    Exposures in the workplace result in a diverse set of diseases ranging from the pneumoconiosis to other interstitial lung diseases to acute lung injury. Physician awareness of the potential disease manifestations associated with specific exposures is important in defining these diseases and in preventing additional disease. Most occupational diseases mimic other forms of lung disease, including pulmonary fibrosis, sarcoidosis, adult respiratory distress syndrome (ARDS), and bronchiolitis. A "sarcoidosis"-like syndrome, usually limited to the lungs, may result from exposure to bioaerosols and a number of metals. Exposure to beryllium in the workplace produces a granulomatous lung disease clinically indistinguishable from sarcoidosis, chronic beryllium disease (CBD). Beryllium's ability to produce a beryllium-specific immune response is used in the beryllium lymphocyte proliferation tests to confirm a diagnosis of CBD and exclude sarcoidosis. Exposure to other metals must also be considered in the differential diagnosis of sarcoidosis. When an individual presents acutely with ARDS or acute lung injury, an acute inhalational exposure must be considered. Exposure to a number of irritant substances at high levels may cause a "chemical pneumonitis" or acute lung injury, depending on the solubility and physicochemical properties of the substance. Some of the most notable agents include nitrogen and sulfur oxides, phosgene, and smoke breakdown products. Ingestion of paraquat may also result in an ARDS syndrome, with pulmonary fibrosis eventually resulting. Bronchiolitis is a rare manifestation of inhalational exposures but must also be considered in the clinical evaluation of inhalational exposure. PMID:12362066

  10. Lung transplantation in chronic obstructive pulmonary disease: patient selection and special considerations.

    Science.gov (United States)

    Lane, C Randall; Tonelli, Adriano R

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity. Lung transplantation is one of the few treatments available for end-stage COPD with the potential to improve survival and quality of life. The selection of candidates and timing of listing present challenges, as COPD tends to progress fairly slowly, and survival after lung transplantation remains limited. Though the natural course of COPD is difficult to predict, the use of assessments of functional status and multivariable indices such as the BODE index can help identify which patients with COPD are at increased risk for mortality, and hence which are more likely to benefit from lung transplantation. Patients with COPD can undergo either single or bilateral lung transplantation. Although many studies suggest better long-term survival with bilateral lung transplant, especially in younger patients, this continues to be debated, and definitive recommendations about this cannot be made. Patients may be more susceptible to particular complications of transplant for COPD, including native lung hyperinflation, and development of lung cancer. PMID:26491282

  11. Lung transplantation in chronic obstructive pulmonary disease: patient selection and special considerations

    Directory of Open Access Journals (Sweden)

    Lane CR

    2015-10-01

    Full Text Available C Randall Lane, Adriano R Tonelli Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA Abstract: Chronic obstructive pulmonary disease (COPD is a leading cause of mortality and morbidity. Lung transplantation is one of the few treatments available for end-stage COPD with the potential to improve survival and quality of life. The selection of candidates and timing of listing present challenges, as COPD tends to progress fairly slowly, and survival after lung transplantation remains limited. Though the natural course of COPD is difficult to predict, the use of assessments of functional status and multivariable indices such as the BODE index can help identify which patients with COPD are at increased risk for mortality, and hence which are more likely to benefit from lung transplantation. Patients with COPD can undergo either single or bilateral lung transplantation. Although many studies suggest better long-term survival with bilateral lung transplant, especially in younger patients, this continues to be debated, and definitive recommendations about this cannot be made. Patients may be more susceptible to particular complications of transplant for COPD, including native lung hyperinflation, and development of lung cancer. Keywords: emphysema, pulmonary hypertension, mortality, prognosis, outcomes, alpha-1 antitrypsin deficiency

  12. Detection and Severity Scoring of Chronic Obstructive Pulmonary Disease Using Volumetric Analysis of Lung CT Images

    International Nuclear Information System (INIS)

    Chronic obstructive pulmonary disease (COPD) is a devastating disease.While there is no cure for COPD and the lung damage associated with this disease cannot be reversed, it is still very important to diagnose it as early as possible. In this paper, we propose a novel method based on the measurement of air trapping in the lungs from CT images to detect COPD and to evaluate its severity. Twenty-five patients and twelve normal adults were included in this study. The proposed method found volumetric changes of the lungs from inspiration to expiration. To this end, trachea CT images at full inspiration and expiration were compared and changes in the areas and volumes of the lungs between inspiration and expiration were used to define quantitative measures (features). Using these features,the subjects were classified into two groups of normal and COPD patients using a Bayesian classifier. In addition, t-tests were applied to evaluate discrimination powers of the features for this classification. For the cases studied, the proposed method estimated air trapping in the lungs from CT images without human intervention. Based on the results, a mathematical model was developed to relate variations of lung volumes to the severity of the disease. As a computer aided diagnosis (CAD) system, the proposed method may assist radiologists in the detection of COPD. It quantifies air trapping in the lungs and thus may assist them with the scoring of the disease by quantifying the severity of the disease

  13. The lung microbiome in moderate and severe chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Alexa A Pragman

    Full Text Available Chronic obstructive pulmonary disease (COPD is an inflammatory disorder characterized by incompletely reversible airflow obstruction. Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations. Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome. The role of the lung microbiome in the pathogenesis of COPD remains unknown. The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora. Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients. The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid. Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats. Our results showed a significant increase in microbial diversity with the development of COPD. The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria. Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity. However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators. Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples.

  14. Asthma and public awareness in Italy: results from CHAOS (Chronic Airway Obstruction Survey

    Directory of Open Access Journals (Sweden)

    Stefano Uleri

    2007-06-01

    Full Text Available Despite last years advances in asthma knowledge and treatment, its management and control remains a critical issue. Many surveys on general practitioners (GPs and patients were conducted but no data, in Italy, are collected about the public awareness.
The population cognition appears critic on decision maker health programs.
This survey, with a face to face questionnaire, explored the perception of social relevance of asthma through the main chronic diseases and tests the disease knowledge in 1161 Italian citizens.
Even if the sensibility of asthmatic (82 and their relatives (243 is superior to general population, some critical issues outcrop regarding beliefs, habits and therapy. 
People not related to asthma have not cognition of social and economic burden.
Asthmatic group is not confident with therapy value and possibility to measure organic damage.
Educational intervention would be addressed first of all to GPs and then to patients and their relatives, while on the other hand it is important to enhance the public and decision maker sensibility to reduce the disease welfare and social cost. 


  15. Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease.

    Science.gov (United States)

    Durham, Andrew L; Caramori, Gaetano; Chung, Kian F; Adcock, Ian M

    2016-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the airway, although the drivers and site of the inflammation differ between diseases. Asthmatics with a neutrophilic airway inflammation are associated with a poor response to corticosteroids, whereas asthmatics with eosinophilic inflammation respond better to corticosteroids. Biologicals targeting the Th2-eosinophil nexus such as anti-interleukin (IL)-4, anti-IL-5, and anti-IL-13 are ineffective in asthma as a whole but are more effective if patients are selected using cellular (eg, eosinophils) or molecular (eg, periostin) biomarkers. This highlights the key role of individual inflammatory mediators in driving the inflammatory response and for accurate disease phenotyping to allow greater understanding of disease and development of patient-oriented antiasthma therapies. In contrast to asthmatic patients, corticosteroids are relatively ineffective in COPD patients. Despite stratification of COPD patients, the results of targeted therapy have proved disappointing with the exception of recent studies using CXC chemokine receptor (CXCR)2 antagonists. Currently, several other novel mediator-targeted drugs are undergoing clinical trials. As with asthma specifically targeted treatments may be of most benefit in specific COPD patient endotypes. The use of novel inflammatory mediator-targeted therapeutic agents in selected patients with asthma or COPD and the detection of markers of responsiveness or nonresponsiveness will allow a link between clinical phenotypes and pathophysiological mechanisms to be delineated reaching the goal of endotyping patients. PMID:26334389

  16. Chronic effort dyspnea explained by lung function tests and by HRCT and CRX radiographic patterns in COPD: a post-hoc analysis in 51 patients.

    Science.gov (United States)

    Giuntini, Carlo; Camiciottoli, Gianna; Maluccio, Nazzarena Maria; Mariani, Laura; Lavorini, Federico; Pistolesi, Massimo

    2007-09-01

    This paper is a post-hoc analysis of a previous study performed to investigate the relationship between computerized tomography (CT) and lung function in 51 outpatients with mild-to-moderate COPD. We studied whether changes in lung function and radiographic patterns may help to explain dyspnea, the most disturbing symptom in patients with COPD. The Medical Research Council (MRC) dyspnea scale shows, by univariate analysis, a similar strength of association to CT expiratory lung density and to DL(CO), a functional index of lung parenchymal loss. The MRC dyspnea scale shows a somewhat less strength of association with a small vertical heart on plain chest films. In multivariate analysis, the model with the strongest association to the MRC dyspnea scale (r = 0.76, p hyperinflation, associated by definition with destruction of terminal airspace walls, as distinct from the air trapping component, which is ascribed to airway obstruction and associated with FRC. PaCO(2) mainly reflects the ventilatory components, i.e., ventilatory drive and ventilatory constraints, of pulmonary gas exchange in COPD, while radiographic pattern of pulmonary hypertension likely reflects hypoxic vascular changes, which depend mainly on ventilation/perfusion mismatch and give rise to pulmonary arterial hypertension that may contribute per se to dyspnea. In conclusion, our analysis points out that chronic effort dyspnea variance may account for up to 58% (r(2) = 0.58) by lung function tests and radiographic patterns. Thus, about 42% of the MRC dyspnea variance remains unexplained by this model. On the other hand, dyspnea ascertainment is dependent on subjective behavior and evaluation and in tests is influenced by individual performance and perception. For example in the 6-minute walk test, a similar or higher proportion (60%) of the overall variance is unexplained. PMID:17729059

  17. Study of regional ventilation of the lungs in patients with chronic bronchitis, making use of scanning densitometry of tomograms

    International Nuclear Information System (INIS)

    Method for investigation of regional ventilation of the lungs with the use of tomography and scanning densitometry was suggested. The method makes it possible to assess the expressiveness of changes in the lungs in patients with chronic bronchitis before and in the process of treatment. The new method permitted to reveal the disturbances of regional ventilation of the lungs in patients with chronic obstructive and non-obstructive bronchitis and to establish a latent respiratory insufficiency. The data of suggested method of scanning densitometry of tomograms of the lungs are in agreement with results of examinations of external respiration function

  18. Occurrence of hypermutable Pseudomonas aeruginosa in cystic fibrosis patients is associated with the oxidative stress caused by chronic lung inflammation

    DEFF Research Database (Denmark)

    Ciofu, Oana; Riis, Bente; Pressler, Tacjana; Poulsen, Henrik Enghusen; Høiby, Niels

    2005-01-01

    Oxidative stress caused by chronic lung inflammation in patients with cystic fibrosis (CF) and chronic lung infection with Pseudomonas aeruginosa is characterized by the reactive oxygen species (ROS) liberated by polymorphonuclear leukocytes (PMNs). We formulated the hypothesis that oxidation of....../patient) collected from the 1st and up to the 25th year of their chronic lung infection. The level of oxidized guanine moiety 8-oxo-2'-deoxyguanosine (8-oxodG), which is a frequently investigated DNA oxidative lesion, was measured. Hypermutable P. aeruginosa isolates were found in the sputum bacterial population of...

  19. Downregulation of aquaporin-1 in alveolar microvessels in lungs adapted to chronic heart failure

    DEFF Research Database (Denmark)

    Müllertz, Katrine M; Strøm, Claes; Trautner, Simon;

    2011-01-01

    The threshold pressure for lung edema formation is increased in severe chronic heart failure (CHF) due to reduced microvascular permeability. The water channel aquaporin-1 (AQP1) is present in the pulmonary microvascular endothelium, and a number of studies suggest the importance of AQP1...... as a molecular determinant of pulmonary microvascular water transport. The present study examined the abundance and localization of AQP1 in lungs from rats with CHF. We used two different models of CHF: ligation of the left anterior descending coronary artery (LAD ligation) and aorta-banding (AB). Sham...

  20. Mucosal exposure to cockroach extract induces allergic sensitization and allergic airway inflammation

    Directory of Open Access Journals (Sweden)

    Arizmendi Narcy G

    2011-12-01

    Full Text Available Abstract Background Allergic sensitization to aeroallergens develops in response to mucosal exposure to these allergens. Allergic sensitization may lead to the development of asthma, which is characterized by chronic airway inflammation. The objective of this study is to describe in detail a model of mucosal exposure to cockroach allergens in the absence of an exogenous adjuvant. Methods Cockroach extract (CE was administered to mice intranasally (i.n. daily for 5 days, and 5 days later mice were challenged with CE for 4 consecutive days. A second group received CE i.n. for 3 weeks. Airway hyperresponsiveness (AHR was assessed 24 h after the last allergen exposure. Allergic airway inflammation was assessed by BAL and lung histology 48 h after the last allergen exposure. Antigen-specific antibodies were assessed in serum. Lungs were excised from mice from measurement of cytokines and chemokines in whole lung lysate. Results Mucosal exposure of Balb/c mice to cockroach extract induced airway eosinophilic inflammation, AHR and cockroach-specific IgG1; however, AHR to methacholine was absent in the long term group. Lung histology showed patchy, multicentric damage with inflammatory infiltrates at the airways in both groups. Lungs from mice from the short term group showed increased IL-4, CCL11, CXCL1 and CCL2 protein levels. IL4 and CXCL1 were also increased in the BAL of cockroach-sensitized mice in the short-term protocol. Conclusions Mucosal exposure to cockroach extract in the absence of adjuvant induces allergic airway sensitization characterized by AHR, the presence of Th2 cytokines in the lung and eosinophils in the airways.

  1. Patterns of airway involvement in inflammatory bowel diseases

    Institute of Scientific and Technical Information of China (English)

    Ilias; Papanikolaou; Konstantinos; Kagouridis; Spyros; A; Papiris

    2014-01-01

    Extraintestinal manifestations occur commonly in inflammatory bowel diseases(IBD). Pulmonary manifestations(PM) of IBD may be divided in airway disorders, interstitial lung disorders, serositis, pulmonary vasculitis, necrobiotic nodules, drug-induced lung disease, thromboembolic lung disease and enteropulmonary fistulas. Pulmonary involvement may often be asymptomatic and detected solely on the basis of abnormal screening tests. The common embryonic origin of the intestine and the lungs from the primitive foregut, the co-existence of mucosa associated lymphoid tissue in both organs, autoimmunity, smoking and bacterial translocation from the colon to the lungs may all be involved in the pathogenesis of PM in IBD. PM are mainly detected by pulmonary function tests and highresolution computed tomography. This review will focus on the involvement of the airways in the context of IBD, especially stenoses of the large airways, tracheo-bronchitis, bronchiectasis, bronchitis, mucoid impaction, bronchial granulomas, bronchiolitis, bronchiolitis obliterans syndrome and the co-existence of IBD with asthma, chronic obstructive pulmonary disease, sarcoidosis and a1-antitrypsin deficiency.

  2. Chronic obstructive lung disease and posttraumatic stress disorder: current perspectives

    OpenAIRE

    Abrams TE; Blevins A; Vander Weg MW

    2015-01-01

    Thad E Abrams,1,2 Amy Blevins,1,3 Mark W Vander Weg1,2,4 1Department of Internal Medicine, University of Iowa, 2Center for Comprehensive Access and Delivery Research and Evaluation, Iowa City VA Health Care System, 3Hardin Health Sciences Library, 4Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, USA Background: Several studies have reported on the co-occurrence of chronic obstructive pulmonary disease (COPD) and psychiatric conditions, with the most robust...

  3. Antibodies against beta-lactamase can improve ceftazidime treatment of lung infection with beta-lactam-resistant Pseudomonas aeruginosa in a rat model of chronic lung infection

    DEFF Research Database (Denmark)

    Ciofu, Oana; Bagge, Niels; Høiby, Niels

    2002-01-01

    To test the hypothesis that antibodies against the chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) might act as beta-lactamase inhibitors in patients with cystic fibrosis and chronic lung infection with P. aeruginosa, we compared in a rat model of chronic lung infection the...... efficacy of treatment with ceftazidime in beta-lactamase-immunized (group I) and non-immunized (group II) rats. Chronic lung infection was established with alginate-embedded P. aeruginosa producing high amounts of beta-lactamase in 133 Lewis rats. Prior to infection, group I (66 rats) was immunized three...... times at 2-week intervals with purified beta-lactamase in incomplete Freund's adjuvant (IFA) and group II (67 rats) received IFA. Ceftazidime treatment was initiated after challenge and continued for 10 days, after which the rats were sacrificed and the lung bacteriology and pathology were analysed. Rat...

  4. Delivery of Alpha-1 Antitrypsin to Airways.

    Science.gov (United States)

    Griese, Matthias; Scheuch, Gerhard

    2016-08-01

    Treatment with exogenous alpha-1 antitrypsin (AAT), a potent serine protease inhibitor, was developed originally for chronic obstructive pulmonary disease associated with AAT deficiency; however, other lung conditions involving neutrophilic inflammation and proteolytic tissue injury related to neutrophil elastase and other serine proteases may also be considered for AAT therapy. These conditions include bronchiectasis caused by primary ciliary dyskinesia, cystic fibrosis, and other diseases associated with an increased free elastase activity in the airways. Inhaled AAT may be a viable option to counteract proteolytic tissue damage. This form of treatment requires efficient drug delivery to the targeted pulmonary compartment. Aerosol technology meeting this requirement is currently available and offers an alternative therapeutic approach to systemic AAT administration. To date, early studies in humans have shown biochemical efficacy and have established the safety of inhaled AAT. However, to bring aerosol AAT therapy to patients, large phase 3 protocols in carefully selected patient populations (i.e., subgroups of patients with AAT deficiency, cystic fibrosis, or other lung diseases with bronchiectasis) will be needed with clinical end points in addition to the measurement of proteolytic activity in the airway. The outcomes likely will have to include lung function, lung structure assessed by computed tomography imaging, disease exacerbations, health status, and mortality. PMID:27564672

  5. Classification of pulmonary airway disease based on mucosal color analysis

    Science.gov (United States)

    Suter, Melissa; Reinhardt, Joseph M.; Riker, David; Ferguson, John Scott; McLennan, Geoffrey

    2005-04-01

    Airway mucosal color changes occur in response to the development of bronchial diseases including lung cancer, cystic fibrosis, chronic bronchitis, emphysema and asthma. These associated changes are often visualized using standard macro-optical bronchoscopy techniques. A limitation to this form of assessment is that the subtle changes that indicate early stages in disease development may often be missed as a result of this highly subjective assessment, especially in inexperienced bronchoscopists. Tri-chromatic CCD chip bronchoscopes allow for digital color analysis of the pulmonary airway mucosa. This form of analysis may facilitate a greater understanding of airway disease response. A 2-step image classification approach is employed: the first step is to distinguish between healthy and diseased bronchoscope images and the second is to classify the detected abnormal images into 1 of 4 possible disease categories. A database of airway mucosal color constructed from healthy human volunteers is used as a standard against which statistical comparisons are made from mucosa with known apparent airway abnormalities. This approach demonstrates great promise as an effective detection and diagnosis tool to highlight potentially abnormal airway mucosa identifying a region possibly suited to further analysis via airway forceps biopsy, or newly developed micro-optical biopsy strategies. Following the identification of abnormal airway images a neural network is used to distinguish between the different disease classes. We have shown that classification of potentially diseased airway mucosa is possible through comparative color analysis of digital bronchoscope images. The combination of the two strategies appears to increase the classification accuracy in addition to greatly decreasing the computational time.

  6. High-resolution CT in the differential diagnosis of consolidative lung processes. Pt. 2. Chronic processes

    International Nuclear Information System (INIS)

    Consolidations are characterized on CT by the presence of one or more air-space opacities with little or no volume loss. Because HRCT findings overlap among various entities, it may be sometimes to be impossible to make a definite diagnosis with imaging criteria alone. If the symptoms are chronic (weeks to months) the differential diagnosis may include alveolar proteinosis, bronchioloalveolar carcinoma, lymphoma as well as inflammatory diseases. This review describes the most common types of lung diseases associated with chronic appearance of consolidation and discuss the differential diagnosis. (orig.)

  7. Morphological changes in the lungs with chronic inhalation of thorium dioxide

    International Nuclear Information System (INIS)

    Pathological changes of critical organs are described following long-term chronic inhalation of thorium dioxide found in micropathogenic dust of loparite concentrate in different percentages. A relation was established between the specific activity of dust in the air, the dose absorbed by the lungs, and the development of pneumoconiosis. Dust of thorium dioxide with chronic inhalation in the course of nine months caused the development of vigorously progressing diffuse-focal pneumosclerosis in an absorbed dose of more than 1000 rad. In the lymph nodes progressing atrophy of lymphoid cells developed

  8. Intelectin is required for IL-13-induced monocyte chemotactic protein-1 and -3 expression in lung epithelial cells and promotes allergic airway inflammation

    OpenAIRE

    Gu, Naibing; Kang, Guannan; Jin, Chang'E; Xu, Yongjian; ZHANG, ZHENXIANG; Erle, David J.; Zhen, Guohua

    2009-01-01

    Asthma is characterized by airway inflammation, mucus overproduction, airway hyperreactivity, and peribronchial fibrosis. Intelectin has been shown to be increased in airway epithelium of asthmatics. However, the role of intelectin in the pathogenesis of asthma is unknown. Airway epithelial cells can secrete chemokines such as monocyte chemotactic protein (MCP)-1 and -3 that play crucial roles in asthmatic airway inflammation. We hypothesized that intelectin plays a role in allergic airway in...

  9. Children developing asthma by school-age display aberrant immune responses to pathogenic airway bacteria as infants

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura; Pedersen, Susanne Brix; Thysen, Anna Hammerich;

    2014-01-01

    Asthma is a highly prevalent chronic lung disease that commonly originates in early childhood. Colonisation of neonatal airways with the pathogenic bacterial strains H. influenzae, M. catarrhalis and S. pneumoniae is associated with increased risk of later childhood asthma. We hypothesized that c...

  10. Curcumin regulates airway epithelial cell cytokine responses to the pollutant cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Rennolds, Jessica; Malireddy, Smitha; Hassan, Fatemat; Tridandapani, Susheela; Parinandi, Narasimham [Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH 43210 (United States); Boyaka, Prosper N. [Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210 (United States); Cormet-Boyaka, Estelle, E-mail: Estelle.boyaka@osumc.edu [Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH 43210 (United States)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Cadmium induces secretion of IL-6 and IL-8 by two distinct pathways. Black-Right-Pointing-Pointer Cadmium increases NAPDH oxidase activity leading to Erk activation and IL-8 secretion. Black-Right-Pointing-Pointer Curcumin prevents cadmium-induced secretion of both IL-6 and IL-8 by airway cells. Black-Right-Pointing-Pointer Curcumin could be use to suppress lung inflammation due to cadmium inhalation. -- Abstract: Cadmium is a toxic metal present in the environment and its inhalation can lead to pulmonary disease such as lung cancer and chronic obstructive pulmonary disease. These lung diseases are characterized by chronic inflammation. Here we show that exposure of human airway epithelial cells to cadmium promotes a polarized apical secretion of IL-6 and IL-8, two pivotal pro-inflammatory cytokines known to play an important role in pulmonary inflammation. We also determined that two distinct pathways controlled secretion of these proinflammatory cytokines by human airway epithelial cells as cadmium-induced IL-6 secretion occurs via an NF-{kappa}B dependent pathway, whereas IL-8 secretion involves the Erk1/2 signaling pathway. Interestingly, the natural antioxidant curcumin could prevent both cadmium-induced IL-6 and IL-8 secretion by human airway epithelial cells. In conclusion, curcumin could be used to prevent airway inflammation due to cadmium inhalation.

  11. Curcumin regulates airway epithelial cell cytokine responses to the pollutant cadmium

    International Nuclear Information System (INIS)

    Highlights: ► Cadmium induces secretion of IL-6 and IL-8 by two distinct pathways. ► Cadmium increases NAPDH oxidase activity leading to Erk activation and IL-8 secretion. ► Curcumin prevents cadmium-induced secretion of both IL-6 and IL-8 by airway cells. ► Curcumin could be use to suppress lung inflammation due to cadmium inhalation. -- Abstract: Cadmium is a toxic metal present in the environment and its inhalation can lead to pulmonary disease such as lung cancer and chronic obstructive pulmonary disease. These lung diseases are characterized by chronic inflammation. Here we show that exposure of human airway epithelial cells to cadmium promotes a polarized apical secretion of IL-6 and IL-8, two pivotal pro-inflammatory cytokines known to play an important role in pulmonary inflammation. We also determined that two distinct pathways controlled secretion of these proinflammatory cytokines by human airway epithelial cells as cadmium-induced IL-6 secretion occurs via an NF-κB dependent pathway, whereas IL-8 secretion involves the Erk1/2 signaling pathway. Interestingly, the natural antioxidant curcumin could prevent both cadmium-induced IL-6 and IL-8 secretion by human airway epithelial cells. In conclusion, curcumin could be used to prevent airway inflammation due to cadmium inhalation.

  12. Soluble CD59 is a Novel Biomarker for the Prediction of Obstructive Chronic Lung Allograft Dysfunction After Lung Transplantation.

    Science.gov (United States)

    Budding, Kevin; van de Graaf, Eduard A; Kardol-Hoefnagel, Tineke; Kwakkel-van Erp, Johanna M; Luijk, Bart D; Oudijk, Erik-Jan D; van Kessel, Diana A; Grutters, Jan C; Hack, C Erik; Otten, Henderikus G

    2016-01-01

    CD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung diseases, however overall survival is hampered by chronic lung allograft dysfunction development, which presents itself obstructively as the bronchiolitis obliterans syndrome (BOS). We hypothesized that, due to cellular damage and activation during chronic inflammation, sCD59 serum levels can be used as biomarker preceding BOS development. We analyzed sCD59 serum concentrations in 90 LTx patients, of whom 20 developed BOS. We observed that BOS patients exhibited higher sCD59 serum concentrations at the time of diagnosis compared to clinically matched non-BOS patients (p = 0.018). Furthermore, sCD59 titers were elevated at 6 months post-LTx (p = 0.0020), when patients had no BOS-related symptoms. Survival-analysis showed that LTx patients with sCD59 titers ≥400 pg/ml 6 months post-LTx have a significant (p < 0.0001) lower chance of BOS-free survival than patients with titers ≤400 pg/ml, 32% vs. 80% respectively, which was confirmed by multivariate analysis (hazard ratio 6.2, p < 0.0001). We propose that circulating sCD59 levels constitute a novel biomarker to identify patients at risk for BOS following LTx. PMID:27215188

  13. Differences in tidal breathing between infants with chronic lung diseases and healthy controls

    OpenAIRE

    Wilitzki S; Schmalisch G; Wauer RR

    2005-01-01

    Abstract Background The diagnostic value of tidal breathing (TB) measurements in infants is controversially discussed. The aim of this study was to investigate to what extent the breathing pattern of sleeping infants with chronic lung diseases (CLD) differ from healthy controls with the same postconceptional age and to assess the predictive value of TB parameters. Methods In the age of 36–42 postconceptional weeks TB measurements were performed in 48 healthy newborns (median age and weight 7d...

  14. Toxicogenomic analysis of susceptibility to inhaled urban particulate matter in mice with chronic lung inflammation

    OpenAIRE

    Yauk Carole L; Williams Andrew; Thomson Errol M; Vincent Renaud

    2009-01-01

    Abstract Background Individuals with chronic lung disease are at increased risk of adverse health effects from airborne particulate matter. Characterization of underlying pollutant-phenotype interactions may require comprehensive strategies. Here, a toxicogenomic approach was used to investigate how inflammation modifies the pulmonary response to urban particulate matter. Results Transgenic mice with constitutive pulmonary overexpression of tumour necrosis factor (TNF)-α under the control of ...

  15. Supplemental oxygen and quality of sleep in patients with chronic obstructive lung disease.

    OpenAIRE

    McKeon, J L; Murree-Allen, K; Saunders, N. A.

    1989-01-01

    The hypothesis that supplemental oxygen could improve the quality of sleep was tested in 23 consecutive patients (14 male, nine female; age 42-74 years) with chronic obstructive lung disease (mean (SD) FEV1 0.81 (0.32) litre, FEV1/FVC 37% (12%). Patients breathed compressed air or supplemental oxygen via nasal cannulas on consecutive nights in a randomised, double blind, crossover trial. Quality of sleep was assessed by questionnaire and by electroencephalographic sleep staging. The study had...

  16. Impact of chronic kidney disease on quality of life, lung function, and functional capacity

    OpenAIRE

    2014-01-01

    OBJECTIVES: To evaluate the impact of the chronic kidney disease (CKD) on quality of life, from the children's and their parents' perspective, respiratory muscle strength, lung function, and functional capacity in children and adolescents. METHOD: Cross-sectional study of children with CKD aged 8 to 17 years. Those incapable of taking the tests were excluded. After an interview, quality of life by Pediatric Quality of Life Inventory) (PedsQLTM), muscular strength, pulmonary function test...

  17. Chronic adaptations of lung function in breath-hold diving fishermen

    OpenAIRE

    Cristiane Diniz; Tiago Farias; Mayane Pereira; Caio Pires; Luciana Gonçalves; Patrícia Coertjens; Marcelo Coertjens

    2014-01-01

    Objectives: The aim of this study was to verify and analyze the existence of chronic adaptations of lung function in freediving fishermen whose occupation is artisanal fishing. Material and Methods: This was a cross-sectional study involving 11 breath-hold diving fishermen and 10 non-breath-hold diving fishermen (control) from the village of Bitupitá in the municipality of Barroquinha (Ceará - Brazil). Anthropometric measurements, chest and abdominal circumferences as well as spirometric and ...

  18. Antibody response to accelerated Hib immunisation in preterm infants receiving dexamethasone for chronic lung disease

    OpenAIRE

    Robinson, M.; Campbell, F.; Powell, P; Sims, D; Thornton, C

    1999-01-01

    AIM—To study the effect of dexamethasone on the routine immunisation of preterm infants with chronic lung disease.
METHODS—Serum samples were obtained before and after immunisation from an unselected cohort of 59 preterm infants. Haemophilus influenzae antibodies were measured using an ELISA method and differences in the geometric mean values between the two groups of babies analysed.
RESULTS—Sixteen infants received no dexamethasone. Before and after immunisation antibody t...

  19. Reducing the incidence of chronic lung disease in very premature infants with aminophylline

    OpenAIRE

    Amir-Mohammad Armanian; Zohreh Badiee; Raha Afghari; Nima Salehimehr; Akbar Hassanzade; Soghra Sheikhzadeh; Maryam Shariftehrani; Gohar Rezvan

    2014-01-01

    Background: The objective of this study is to assess the safety and preventative effects of aminophylline on the incidence of chronic lung disease (CLD) in very premature infants. Methods: This was a long follow-up randomized clinical trial. The prophylactic effect of aminophylline on the incidence of CLD was investigated in very premature infants. The study group received aminophylline for the 1 st 10 days of life and control infants received no aminophylline during the 1 st 10 days of l...

  20. [Chronic disseminated intravascular coagulopathy in a dog with lung worm infection].

    Science.gov (United States)

    Schmitz, S; Moritz, A

    2009-06-01

    The clinical and laboratory findings in a 1-year-old male Jack Russel Terrier dog with lung worm induced coagulopathy are described. The diagnosis was based upon history, clinical findings, radiography, endoscopy, cytology and laboratory results. The presenting complaint was chronic cough. Radiographically, a diffuse interstitial to bronchial lung pattern was observed. Blood analysis revealed thrombocytopaenia and prolonged coagulation times. Disseminated intravascular coagulopathy (DIC) was diagnosed based on D-dimer and fibrinogen measurements, and by thrombelastogram results. After stabilisation of the patient, bronchoscopy with a bronchoalveolar lavage was performed, where large amounts of lung worm larvae were found cytologically. After treatment with fresh frozen plasma and fenbendazole, coagulation parameters improved and the cough resolved. PMID:19496048

  1. In situ growth rates and biofilm development of Pseudomonas aeruginosa populations in chronic lung infections

    DEFF Research Database (Denmark)

    Yang, L.; Haagensen, J.A.; Jelsbak, L.; Sternberg, C.; Høiby, Niels; Molin, S.; Johansen, Helle Krogh

    2008-01-01

    The growth dynamics of bacterial pathogens within infected hosts are a fundamental but poorly understood feature of most infections. We have focused on the in situ distribution and growth characteristics of two prevailing and transmissible Pseudomonas aeruginosa clones that have caused chronic lung...... matrix, whereas nonmucoid variants were present mainly as dispersed cells. To obtain estimates of the growth rates of P. aeruginosa in CF lungs, we used quantitative FISH to indirectly measure growth rates of bacteria in sputum samples (reflecting the in vivo lung conditions). The concentration of r......-phase subpopulation seemed to be present in sputa. This was found for both mucoid and nonmucoid variants despite their different organizations in sputum. The results suggest that the bacterial population may be confronted with selection forces that favor optimized growth activities. This scenario constitutes a new...

  2. Temporal and Spatial Expression of Transforming Growth Factor-β after Airway Remodeling to Tobacco Smoke in Rats.

    Science.gov (United States)

    Hoang, Laura L; Nguyen, Yen P; Aspeé, Rayza; Bolton, Sarah J; Shen, Yi-Hsin; Wang, Lei; Kenyon, Nicholas J; Smiley-Jewell, Suzette; Pinkerton, Kent E

    2016-06-01

    Airway remodeling is strongly correlated with the progression of chronic obstructive pulmonary disease (COPD). In this study, our goal was to characterize progressive structural changes in site-specific airways, along with the temporal and spatial expression of transforming growth factor (TGF)-β in the lungs of male spontaneously hypertensive rats exposed to tobacco smoke (TS). Our studies demonstrated that TS-induced changes of the airways is dependent on airway generation and exposure duration for proximal, midlevel, and distal airways. Stratified squamous epithelial cell metaplasia was evident in the most proximal airways after 4 and 12 weeks but with minimal levels of TGF-β-positive epithelial cells after only 4 weeks of exposure. In contrast, epithelial cells in midlevel and distal airways were strongly TGF-β positive at both 4 and 12 weeks of TS exposure. Airway smooth muscle volume increased significantly at 4 and 12 weeks in midlevel airways. Immunohistochemistry of TGF-β was also found to be significantly increased at 4 and 12 weeks in lymphoid tissues and alveolar macrophages. ELISA of whole-lung homogenate demonstrated that TGF-β2 was increased after 4 and 12 weeks of TS exposure, whereas TGF-β1 was decreased at 12 weeks of TS exposure. Airway levels of messenger RNA for TGF-β2, as well as platelet-derived growth factor-A, granulocyte-macrophage colony-stimulating factor, and vascular endothelial growth factor-α, growth factors regulated by TGF-β, were significantly decreased in animals after 12 weeks of TS exposure. Our data indicate that TS increases TGF-β in epithelial and inflammatory cells in connection with airway remodeling, although the specific role of each TGF-β isoform remains to be defined in TS-induced airway injury and disease. PMID:26637070

  3. Cytosolic phospholipase A2α mediates Pseudomonas aeruginosa LPS-induced airway constriction of CFTR -/- mice

    Directory of Open Access Journals (Sweden)

    Lagranderie Micheline

    2010-04-01

    Full Text Available Abstract Background Lungs of cystic fibrosis (CF patients are chronically infected with Pseudomonas aeruginosa. Increased airway constriction has been reported in CF patients but underplaying mechanisms have not been elucidated. Aim: to examine the effect of P. aeruginosa LPS on airway constriction in CF mice and the implication in this process of cytosolic phospholipase A2α (cPLA2α, an enzyme involved in arachidonic acid (AA release. Methods Mice were instilled intra-nasally with LPS. Airway constriction was assessed using barometric plethysmograph. MIP-2, prostaglandin E2 (PGE2, leukotrienes and AA concentrations were measured in BALF using standard kits and gas chromatography. Results LPS induced enhanced airway constriction and AA release in BALF of CF compared to littermate mice. This was accompanied by increased levels of PGE2, but not those of leukotrienes. However, airway neutrophil influx and MIP-2 production remained similar in both mouse strains. The cPLA2α inhibitor arachidonyl trifluoro-methyl-ketone (ATK, but not aspirin which inhibit PGE2 synthesis, reduced LPS-induced airway constriction. LPS induced lower airway constriction and PGE2 production in cPLA2α -/- mice compared to corresponding littermates. Neither aspirin nor ATK interfered with LPS-induced airway neutrophil influx or MIP-2 production. Conclusions CF mice develop enhanced airway constriction through a cPLA2α-dependent mechanism. Airway inflammation is dissociated from airway constriction in this model. cPLA2α may represent a suitable target for therapeutic intervention in CF. Attenuation of airway constriction by cPLA2α inhibitors may help to ameliorate the clinical status of CF patients.

  4. Randomised crossover trial of salbutamol aerosol delivered by metered dose inhaler, jet nebuliser, and ultrasonic nebuliser in chronic lung disease

    OpenAIRE

    Fok, T; Lam, K.; Ng, P; So, H.; Cheung, K; Wong, Van W.; So, K

    1998-01-01

    AIMS—To compare the efficacy of salbutamol delivered by metered dose inhaler (MDI), jet nebuliser, and ultrasonic nebuliser in ventilated infants with chronic lung disease.
METHODS—Twenty preterm ventilated infants with chronic lung disease were enrolled in two studies. In study 1 (n=10), each infant was given 200 µg of salbutamol at 4 hour intervals and in random sequence from a metered dose inhaler-spacer device, a jet nebuliser, and an ultrasonic nebuliser with a small me...

  5. NGS meta data analysis for identification of SNP and INDEL patterns in human airway transcriptome: A preliminary indicator for lung cancer

    Directory of Open Access Journals (Sweden)

    Sathya B.

    2015-03-01

    Full Text Available High-throughput sequencing of RNA (RNA-Seq was developed primarily to analyze global gene expression in different tissues. It is also an efficient way to discover coding SNPs and when multiple individuals with different genetic backgrounds were used, RNA-Seq is very effective for the identification of SNPs. The objective of this study was to perform SNP and INDEL discoveries in human airway transcriptome of healthy never smokers, healthy current smokers, smokers without lung cancer and smokers with lung cancer. By preliminary comparative analysis of these four data sets, it is expected to get SNP and INDEL patterns responsible for lung cancer. A total of 85,028 SNPs and 5738 INDELs in healthy never smokers, 32,671 SNPs and 1561 INDELs in healthy current smokers, 50,205 SNPs and 3008 INDELs in smokers without lung cancer and 51,299 SNPs and 3138 INDELs in smokers with lung cancer were identified. The analysis of the SNPs and INDELs in genes that were reported earlier as differentially expressed was also performed. It has been found that a smoking person has SNPs at position 62,186,542 and 62,190,293 in SCGB1A1 gene and 180,017,251, 180,017,252, and 180,017,597 in SCGB3A1 gene and INDELs at position 35,871,168 in NFKBIA gene and 180,017,797 in SCGB3A1 gene. The SNPs identified in this study provides a resource for genetic studies in smokers and shall contribute to the development of a personalized medicine. This study is only a preliminary kind and more vigorous data analysis and wet lab validation are required.

  6. Chronic Exposure to Particulate Nickel Induces Neoplastic Transformation in Human Lung Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Amie L. Holmes

    2013-11-01

    Full Text Available Nickel is a well-known human lung carcinogen with the particulate form being the most potent; however, the carcinogenic mechanism remains largely unknown. Few studies have investigated the genotoxicity and carcinogenicity of nickel in its target cell, human bronchial epithelial cells. Thus, the goal of this study was to investigate the effects of particulate nickel in human lung epithelial cells. We found that nickel subsulfide induced concentration- and time-dependent increases in both cytotoxicity and genotoxicity in human lung epithelial cells (BEP2D. Chronic exposure to nickel subsulfide readily induced cellular transformation, inducing 2.55, 2.9 and 2.35 foci per dish after exposure to 1, 2.5 and 5 μg/cm2 nickel subsulfide, respectively. Sixty-one, 100 and 70 percent of the foci isolated from 1, 2.5, and 5 μg/cm2 nickel subsulfide treatments formed colonies in soft agar and the degree of soft agar colony growth increased in a concentration-dependent manner. Thus, chronic exposure to particulate nickel induces genotoxicity and cellular transformation in human lung epithelial cells.

  7. A cubic B-spline-based hybrid registration of lung CT images for a dynamic airway geometric model with large deformation

    International Nuclear Information System (INIS)

    The goal of this study is to develop a matching algorithm that can handle large geometric changes in x-ray computed tomography (CT)-derived lung geometry occurring during deep breath maneuvers. These geometric relationships are further utilized to build a dynamic lung airway model for computational fluid dynamics (CFD) studies of pulmonary air flow. The proposed algorithm is based on a cubic B-spline-based hybrid registration framework that incorporates anatomic landmark information with intensity patterns. A sequence of invertible B-splines is composed in a multiresolution framework to ensure local invertibility of the large deformation transformation and a physiologically meaningful similarity measure is adopted to compensate for changes in voxel intensity due to inflation. Registrations are performed using the proposed approach to match six pairs of 3D CT human lung datasets. Results show that the proposed approach has the ability to match the intensity pattern and the anatomical landmarks, and ensure local invertibility for large deformation transformations. Statistical results also show that the proposed hybrid approach yields significantly improved results as compared with approaches using either landmarks or intensity alone.

  8. A cubic B-spline-based hybrid registration of lung CT images for a dynamic airway geometric model with large deformation

    Energy Technology Data Exchange (ETDEWEB)

    Yin Youbing; Lin, Ching-Long [Department of Mechanical and Industrial Engineering, University of Iowa, Iowa City, IA 52242 (United States); Hoffman, Eric A [Department of Radiology, University of Iowa, Iowa City, IA 52242 (United States); Ding Kai; Reinhardt, Joseph M, E-mail: ching-long-lin@uiowa.edu [Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242 (United States)

    2011-01-07

    The goal of this study is to develop a matching algorithm that can handle large geometric changes in x-ray computed tomography (CT)-derived lung geometry occurring during deep breath maneuvers. These geometric relationships are further utilized to build a dynamic lung airway model for computational fluid dynamics (CFD) studies of pulmonary air flow. The proposed algorithm is based on a cubic B-spline-based hybrid registration framework that incorporates anatomic landmark information with intensity patterns. A sequence of invertible B-splines is composed in a multiresolution framework to ensure local invertibility of the large deformation transformation and a physiologically meaningful similarity measure is adopted to compensate for changes in voxel intensity due to inflation. Registrations are performed using the proposed approach to match six pairs of 3D CT human lung datasets. Results show that the proposed approach has the ability to match the intensity pattern and the anatomical landmarks, and ensure local invertibility for large deformation transformations. Statistical results also show that the proposed hybrid approach yields significantly improved results as compared with approaches using either landmarks or intensity alone.

  9. 养阴清肺法治疗感染后气道高反应性咳嗽%Discussion of Tonifying Yin and Clearing Lung Method in Treating Airway Hyperreactivity Cough Post Infectionem

    Institute of Scientific and Technical Information of China (English)

    陈新; 车德亚

    2013-01-01

    Objective;To study the application of tonifying yin and clearing lung method in treating airway hyperreactivity cough post in-fectionem. Methods:To discuss the pathogenesis characteristic of airway hyperreactivity cough post infectionem from lung impairment caused by pathogen dryness and qi-yin asthenia. Results: Lung impairment caused by pathogen dryness and qi-yin asthenia are the internal condition of airway hyperreactivity cough post infectionem and asthenia in origin and asthenia in superficiality is the precipitating factors. Conclusion: Lung impairment caused by pathogen dryness and qi-yin asthenia are the basic pathogenesis characteristics of airway hyperreactivity cough post infectionem. Tonifying yin and clearing lung provides new thread and method in treating airway hyperreactivity cough post infectionem in clinic.%目的:探讨养阴清肺法在感染后气道高反应性咳嗽中的运用.方法:从燥邪伤肺、气阴两虚等方面阐述感染后气道高反应性咳嗽的中医病机特征.结果:燥邪伤肺、气阴两虚是感染后气道高反应性咳嗽发生的内在条件,本虚标实是其发病的必然因素.结论:燥邪伤肺、气阴两虚是感染后气道高反应性咳嗽的基本病机特征,临床选用养阴清肺法治疗,为感染后气道高反应性咳嗽的治疗提供了新的思路和方法.

  10. Clinical heterogeneity of dominant chronic mucocutaneous candidiasis disease: presenting as treatment-resistant candidiasis and chronic lung disease.

    Science.gov (United States)

    Dotta, Laura; Scomodon, Omar; Padoan, Rita; Timpano, Silviana; Plebani, Alessandro; Soresina, Annarosa; Lougaris, Vassilios; Concolino, Daniela; Nicoletti, Angela; Giardino, Giuliana; Licari, Amelia; Marseglia, Gianluigi; Pignata, Claudio; Tamassia, Nicola; Facchetti, Fabio; Vairo, Donatella; Badolato, Raffaele

    2016-03-01

    In gain-of-function STAT1 mutations, chronic mucocutaneous candidiasis disease (CMCD) represents the phenotypic manifestation of a complex immunodeficiency characterized by clinical and immunological heterogeneity. We aimed to study clinical manifestations, long-term complications, molecular basis, and immune profile of patients with dominant CMCD. We identified nine patients with heterozygous mutations in STAT1, including novel amino acid substitutions (L283M, L351F, L400V). High risk of azole-resistance was observed, particularly when intermittent regimens of antifungal treatment or use of suboptimal dosage occurs. We report a case of Cryptococcosis and various bacterial and viral infections. Risk of developing bronchiectasis in early childhood or gradually evolving to chronic lung disease in adolescent or adult ages emerges. Lymphopenia is variable, likely progressing by adulthood. We conclude that continuous antifungal prophylaxis associated to drug monitoring might prevent resistance to treatment; prompt diagnosis and therapy of lung disease might control long-term progression; careful monitoring of lymphopenia-related infections might improve prognosis. PMID:26732859

  11. Expression and Methylation of Mitochondrial Transcription Factor A in Chronic Obstructive Pulmonary Disease Patients with Lung Cancer

    OpenAIRE

    Hong Peng; Min Yang; Zhi-yong Chen; Ping Chen; Cha-xiang Guan; Xu-dong Xiang; Shan Cai; Yan Chen; Xiang Fang

    2013-01-01

    BACKGROUND: Apoptosis plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD), and this process can be regulated by mitochondrial transcription factor A (mtTFA). Epigenetics is involved in the regulation and modification of the genes involved in lung cancer and COPD. In this study, we determined the expression of mtTFA and its methylation levels in the COPD patients with lung cancer. METHODS: Twenty-one squamous cell lung cancer patients, 11 with COPD and 10 w...

  12. Airways Disease: Phenotyping Heterogeneity Using Measures of Airway Inflammation

    OpenAIRE

    Siddiqui Salman; Brightling Christopher E

    2007-01-01

    Despite asthma and chronic obstructive pulmonary disease being widely regarded as heterogeneous diseases, a consensus for an accurate system of classification has not been agreed. Recent studies have suggested that the recognition of subphenotypes of airway disease based on the pattern of airway inflammation may be particularly useful in increasing our understanding of the disease. The use of non-invasive markers of airway inflammation has suggested the presence of four distinct phenotypes: ...

  13. Continuous aerosol inhalation scintigraphy in the evaluation of early and advanced airways obstruction

    International Nuclear Information System (INIS)

    By means of continuous lung imaging, regional mucociliary removal rates of inhaled sup(99m)Tc-labeled human serum albumin minimicrospheres were determined over upper, middle, lower, central, and peripheral anterior lung areas. Additionally, an index was employed for analysis of initial pulmonary radioaerosol distribution in order to quantify the site of particle deposition in various degrees of airways obstruction. The study involved 15 volunter healthy subjects, 20 asymptomatic smokers with early small airways obstruction, and 30 patients with advanced chronic obstruction of large airways. The healthy group showed evenly distributed lung activity and (normal) clearance rates consistent with data from earlier work. While most uneven lung aerosol distribution was seen in the patients with large airways obstruction, slowest mucociliary clearance velocity was encountered in the smokers with small airways dysfunction. The aerosol technique, if carefully controlled, can be a useful supplement to pulmonary ventilatory function testing, showing reduction of bronchial mucous velocity to be one of the earliest sign of functional impairment in asymptomatic cigarette smokers. (orig.)

  14. Sarcoidosis of the upper and lower airways.

    Science.gov (United States)

    Morgenthau, Adam S; Teirstein, Alvin S

    2011-12-01

    Sarcoidosis is a systemic granulomatous disease of undetermined etiology characterized by a variable clinical presentation and disease course. Although clinical granulomatous inflammation may occur within any organ system, more than 90% of sarcoidosis patients have lung disease. Sarcoidosis is considered an interstitial lung disease that is frequently characterized by restrictive physiologic dysfunction on pulmonary function tests. However, sarcoidosis also involves the airways (large and small), causing obstructive airways disease. It is one of a few interstitial lung diseases that affects the entire length of the respiratory tract - from the nose to the terminal bronchioles - and causes a broad spectrum of airways dysfunction. This article examines airway dysfunction in sarcoidosis. The anatomical structure of the airways is the organizational framework for our discussion. We discuss sarcoidosis involving the nose, sinuses, nasal passages, larynx, trachea, bronchi and small airways. Common complications of airways disease, such as, atelectasis, fibrosis, bullous leions, bronchiectasis, cavitary lesions and mycetomas, are also reviewed. PMID:22082167

  15. Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling.

    Science.gov (United States)

    Rock, Jason R; Randell, Scott H; Hogan, Brigid L M

    2010-01-01

    The small airways of the human lung undergo pathological changes in pulmonary disorders, such as chronic obstructive pulmonary disease (COPD), asthma, bronchiolitis obliterans and cystic fibrosis. These clinical problems impose huge personal and societal healthcare burdens. The changes, termed 'pathological airway remodeling', affect the epithelium, the underlying mesenchyme and the reciprocal trophic interactions that occur between these tissues. Most of the normal human airway is lined by a pseudostratified epithelium of ciliated cells, secretory cells and 6-30% basal cells, the proportion of which varies along the proximal-distal axis. Epithelial abnormalities range from hypoplasia (failure to differentiate) to basal- and goblet-cell hyperplasia, squamous- and goblet-cell metaplasia, dysplasia and malignant transformation. Mesenchymal alterations include thickening of the basal lamina, smooth muscle hyperplasia, fibrosis and inflammatory cell accumulation. Paradoxically, given the prevalence and importance of airway remodeling in lung disease, its etiology is poorly understood. This is due, in part, to a lack of basic knowledge of the mechanisms that regulate the differentiation, maintenance and repair of the airway epithelium. Specifically, little is known about the proliferation and differentiation of basal cells, a multipotent stem cell population of the pseudostratified airway epithelium. This Perspective summarizes what we know, and what we need to know, about airway basal cells to evaluate their contributions to normal and abnormal airway remodeling. We contend that exploiting well-described model systems using both human airway epithelial cells and the pseudostratified epithelium of the genetically tractable mouse trachea will enable crucial discoveries regarding the pathogenesis of airway disease. PMID:20699479

  16. Lack of efficacy of pre bronchoscopy inhaled salbutamol on symptoms and lung functions in patients with pre-existing airway obstruction

    Science.gov (United States)

    Mohan, Anant; Momin, Indrajit; Poulose, Rosemary; Mohan, Charu; Madan, Karan; Hadda, Vijay; Guleria, Randeep; Pandey, RM

    2016-01-01

    Background: Fiberoptic bronchoscopy (FOB) may exaggerate symptoms and lung functions in patients with pre-existing airway obstruction. Interventions which can alleviate or minimize this procedure-related bronchospasm, especially in this high-risk group are, therefore, required. Methods: A double-blinded randomized controlled trial was conducted to evaluate the efficacy of 400 μg of inhaled salbutamol on patients with spirometric evidence of airflow obstruction planned for FOB. Patient's dyspnea, procedure tolerability, and change in spirometry were assessed before and after the procedure. Results: A total of 50 patients were enrolled (78% males), with a mean (standard deviation) age of 49.8 (6.2) years. There was a significant fall in % predicted FEV1 within each group compared to their respective pre-bronchoscopy values. However, no significant difference in the % predicted or absolute FEV1 level was observed between the two groups. Similarly, although both groups experienced increased dyspnea immediately following FOB, this difference was not significant between the two groups either on the Borg or visual analog scale scales. Pre-FOB anxiety levels and the tolerability of the procedure as assessed by the bronchoscopist were similar in both groups. Conclusion: FOB in patients with pre-existing airway obstruction aggravates cough and dyspnea, with a concomitant decline in FEV1 and FVC. The administration of pre-FOB inhaled salbutamol does not have any significant beneficial effect on procedure-related outcomes.

  17. Retention of various types and sizes of particle in the large airways of the rat: implications for assessing the risk of lung cancer

    International Nuclear Information System (INIS)

    Clearance kinetics and retention in rat trachea have been compared for fused aluminosilicate particles (FAP) of count media diameters 1.1 and 5.7 μm, and for 1.0 μm BaSO4 particles. A 2.5 μ1 suspension was deposited in the distal trachea of conscious rats. In each case there was an initial fast phase of clearance from the deposition zone, removing 88 percent of 1.1 μm FAP, 73 percent of 5.7 μm FAP, and 82 percent of BaSO4. The remainder was cleared more slowly with half-times of 24 hours, 17 hours, and 15 hours, respectively. Retention in the tracheal wall after 7 days was 0.45 percent, 0.75 percent and 0.83 percent, respectively. The 5.7 μm FAP particles retained after 7 days were shown by autoradiography to be located either in the epithelium of the trachea or beneath the epithelium in the lamina propria. Electron microscopic evidence suggested that the particles were within macrophages. These and previous results demonstrate similar retention in the airways for different kinds and sizes of particle. The particles are retained in or beneath the airway epithelium, mostly within 440 μm of the basal cells. Thus, or inhaled insoluble α-emitters, a small proportion of particles can be retained at sites where they may constitute the greatest risk of inducing bronchogenic lung cancer

  18. How Lungs Work

    Science.gov (United States)

    ... Health and Diseases > How Lungs Work How Lungs Work The Respiratory System Your lungs are part of ... Parts of the Respiratory System and How They Work Airways SINUSES are hollow spaces in the bones ...

  19. Eosinophilic airway inflammation in COPD

    OpenAIRE

    Saha, Shironjit; Brightling, Christopher E.

    2006-01-01

    Chronic obstructive pulmonary disease is a common condition and a major cause of mortality. COPD is characterized by irreversible airflow obstruction. The physiological abnormalities observed in COPD are due to a combination of emphysema and obliteration of the small airways in association with airway inflammation. The predominant cells involved in this inflammatory response are CD8+ lymphocytes, neutrophils, and macrophages. Although eosinophilic airway inflammation is usually considered a f...

  20. Chronic obstructive pulmonary disease with lung cancer: Prevalence, severity, and common pathogenesis

    Directory of Open Access Journals (Sweden)

    Griffin JP

    2016-01-01

    Full Text Available Objectives: To develop a clinical prediction model of contribution of chronic obstructive pulmonary disease (COPD to the pathogenesis of lung cancer, by reporting the estimated prevalence and severity by GOLD criteria in a single-institution cohort of patients with newly diagnosed lung cancer. Primary objective was investigating the effects of impaired lung function with various histological cell types on crude survival, while considering the initial staging of disease extent. Materials & methods: A total of 441 patients, in this historical cohort from electronic medical records, completed spirometry prior to invasive diagnostic procedures and initial treatment of their lung cancer. All statistical analyses, including ANOVA and survival analysis, were performed using SAS version 9.1 software. Results: Estimated prevalence of COPD was 79.1% (95% confidence interval: 71.3%-82.9%. Lung function as measured by spirometry was a significant predictor of survival time in months (p<0.0001 both with and without adjusting for tumor-cell-type, age, and stage of disease. Median survival was similar (p=0.32 and longer among those patients with normal pulmonary function, those with restrictive disease patterns, and those with COPD–GOLD-1 defects. Median survival was shortest among patients with COPD–GOLD-4 impairment (p=0.001. Those patients with COPD–GOLD-2 and COPD-GOLD-3 impairment levels had intermediate survival times (p=0.003. Conclusions: This investigation suggests that strategies for early detection and slowing the progression of COPD before the development of lung cancer might increase patient survival. As demonstrated in this study, the presence and severity of COPD in lung cancer patients is an independent predictor of survival time, different from the established staging of initial extent of disease.

  1. Methods of airway resistance assessment.

    Science.gov (United States)

    Urbankowski, Tomasz; Przybyłowski, Tadeusz

    2016-01-01

    Airway resistance is the ratio of driving pressure to the rate of the airflow in the airways. The most frequent methods used to measure airway resistance are whole-body plethysmography, the interrupter technique and the forced oscillation technique. All these methods allow to measure resistance during respiration at the level close to tidal volume, they do not require forced breathing manoeuvres or deep breathing during measurement. The most popular method for measuring airway resistance is whole-body plethysmography. The results of plethysmography include among others the following parameters: airway resistance (Raw), airway conductance (Gaw), specific airway resistance (sRaw) and specific airway conductance (sGaw). The interrupter technique is based on the assumption that at the moment of airway occlusion, air pressure in the mouth is equal to the alveolar pressure . In the forced oscillation technique (FOT), airway resistance is calculated basing on the changes in pressure and flow caused by air vibration. The methods for measurement of airway resistance that are described in the present paper seem to be a useful alternative to the most common lung function test - spirometry. The target group in which these methods may be widely used are particularly the patients who are unable to perform spirometry. PMID:27238174

  2. Chronic kidney disease after liver, cardiac, lung, heart–lung, and hematopoietic stem cell transplant

    OpenAIRE

    Hingorani, Sangeeta

    2008-01-01

    Patient survival after cardiac, liver, and hematopoietic stem cell transplant (HSCT) is improving; however, this survival is limited by substantial pretransplant and treatment-related toxicities. A major cause of morbidity and mortality after transplant is chronic kidney disease (CKD). Although the majority of CKD after transplant is attributed to the use of calcineurin inhibitors, various other conditions such as thrombotic microangiopathy, nephrotic syndrome, and focal segmental glomerulosc...

  3. Differential Gene Expression Profiles and Selected Cytokine Protein Analysis of Mediastinal Lymph Nodes of Horses with Chronic Recurrent Airway Obstruction (RAO Support an Interleukin-17 Immune Response.

    Directory of Open Access Journals (Sweden)

    Alexandra Korn

    Full Text Available Recurrent airway obstruction (RAO is a pulmonary inflammatory condition that afflicts certain mature horses exposed to organic dust particulates in hay. Its clinical and pathological features, manifested by reversible bronchoconstriction, excessive mucus production and airway neutrophilia, resemble the pulmonary alterations that occur in agricultural workers with occupational asthma. The immunological basis of RAO remains uncertain although its chronicity, its localization to a mucosal surface and its domination by a neutrophilic, non-septic inflammatory response, suggest involvement of Interleukin-17 (IL-17. We examined global gene expression profiles in mediastinal (pulmonary-draining lymph nodes isolated from RAO-affected and control horses. Differential expression of > 200 genes, coupled with network analysis, supports an IL-17 response centered about NF-κB. Immunohistochemical analysis of mediastinal lymph node sections demonstrated increased IL-17 staining intensity in diseased horses. This result, along with the finding of increased IL-17 concentrations in lymph node homogenates from RAO-affected horses (P = 0.1 and a down-regulation of IL-4 gene and protein expression, provides additional evidence of the involvement of IL-17 in the chronic stages of RAO. Additional investigations are needed to ascertain the cellular source of IL-17 in this equine model of occupational asthma. Understanding the immunopathogenesis of this disorder likely will enhance the development of therapeutic interventions beneficial to human and animal pulmonary health.

  4. SU-C-BRA-07: Virtual Bronchoscopy-Guided IMRT Planning for Mapping and Avoiding Radiation Injury to the Airway Tree in Lung SAbR

    Energy Technology Data Exchange (ETDEWEB)

    Sawant, A; Modiri, A; Bland, R; Yan, Y; Ahn, C; Timmerman, R [University of Texas SouthWestern Medical Center, Dallas, TX (United States)

    2015-06-15

    Purpose: Post-treatment radiation injury to central and peripheral airways is a potentially important, yet under-investigated determinant of toxicity in lung stereotactic ablative radiotherapy (SAbR). We integrate virtual bronchoscopy technology into the radiotherapy planning process to spatially map and quantify the radiosensitivity of bronchial segments, and propose novel IMRT planning that limits airway dose through non-isotropic intermediate- and low-dose spillage. Methods: Pre- and ∼8.5 months post-SAbR diagnostic-quality CT scans were retrospectively collected from six NSCLC patients (50–60Gy in 3–5 fractions). From each scan, ∼5 branching levels of the bronchial tree were segmented using LungPoint, a virtual bronchoscopic navigation system. The pre-SAbR CT and the segmented bronchial tree were imported into the Eclipse treatment planning system and deformably registered to the planning CT. The five-fraction equivalent dose from the clinically-delivered plan was calculated for each segment using the Universal Survival Curve model. The pre- and post-SAbR CTs were used to evaluate radiation-induced segmental collapse. Two of six patients exhibited significant segmental collapse with associated atelectasis and fibrosis, and were re-planned using IMRT. Results: Multivariate stepwise logistic regression over six patients (81 segments) showed that D0.01cc (minimum point dose within the 0.01cc receiving highest dose) was a significant independent factor associated with collapse (odds-ratio=1.17, p=0.010). The D0.01cc threshold for collapse was 57Gy, above which, collapse rate was 45%. In the two patients exhibiting segmental collapse, 22 out of 32 segments showed D0.01cc >57Gy. IMRT re-planning reduced D0.01cc below 57Gy in 15 of the 22 segments (68%) while simultaneously achieving the original clinical plan objectives for PTV coverage and OAR-sparing. Conclusion: Our results indicate that the administration of lung SAbR can Result in significant injury to

  5. SU-C-BRA-07: Virtual Bronchoscopy-Guided IMRT Planning for Mapping and Avoiding Radiation Injury to the Airway Tree in Lung SAbR

    International Nuclear Information System (INIS)

    Purpose: Post-treatment radiation injury to central and peripheral airways is a potentially important, yet under-investigated determinant of toxicity in lung stereotactic ablative radiotherapy (SAbR). We integrate virtual bronchoscopy technology into the radiotherapy planning process to spatially map and quantify the radiosensitivity of bronchial segments, and propose novel IMRT planning that limits airway dose through non-isotropic intermediate- and low-dose spillage. Methods: Pre- and ∼8.5 months post-SAbR diagnostic-quality CT scans were retrospectively collected from six NSCLC patients (50–60Gy in 3–5 fractions). From each scan, ∼5 branching levels of the bronchial tree were segmented using LungPoint, a virtual bronchoscopic navigation system. The pre-SAbR CT and the segmented bronchial tree were imported into the Eclipse treatment planning system and deformably registered to the planning CT. The five-fraction equivalent dose from the clinically-delivered plan was calculated for each segment using the Universal Survival Curve model. The pre- and post-SAbR CTs were used to evaluate radiation-induced segmental collapse. Two of six patients exhibited significant segmental collapse with associated atelectasis and fibrosis, and were re-planned using IMRT. Results: Multivariate stepwise logistic regression over six patients (81 segments) showed that D0.01cc (minimum point dose within the 0.01cc receiving highest dose) was a significant independent factor associated with collapse (odds-ratio=1.17, p=0.010). The D0.01cc threshold for collapse was 57Gy, above which, collapse rate was 45%. In the two patients exhibiting segmental collapse, 22 out of 32 segments showed D0.01cc >57Gy. IMRT re-planning reduced D0.01cc below 57Gy in 15 of the 22 segments (68%) while simultaneously achieving the original clinical plan objectives for PTV coverage and OAR-sparing. Conclusion: Our results indicate that the administration of lung SAbR can Result in significant injury to

  6. Chronic Exposure to Ambient Levels of Urban Particles Affects Mouse Lung Development

    Science.gov (United States)

    Mauad, Thais; Rivero, Dolores Helena Rodriguez Ferreira; de Oliveira, Regiani Carvalho; de Faria Coimbra Lichtenfels, Ana Julia; Guimarães, Eliane Tigre; de Andre, Paulo Afonso; Kasahara, David Itiro; de Siqueira Bueno, Heloisa Maria; Saldiva, Paulo Hilário Nascimento

    2008-01-01

    Rationale: Chronic exposure to air pollution has been associated with adverse effects on children's lung growth. Objectives: We analyzed the effects of chronic exposure to urban levels of particulate matter (PM) on selected phases of mouse lung development. Methods: The exposure occurred in two open-top chambers (filtered and nonfiltered) placed 20 m from a street with heavy traffic in São Paulo, 24 hours/day for 8 months. There was a significant reduction of the levels of PM2.5 inside the filtered chamber (filtered = 2.9 ± 3.0 μg/m3, nonfiltered = 16.8 ± 8.3 μg/m3; P = 0.001). At this exposure site, vehicular sources are the major components of PM2.5 (PM ≤ 2.5μm). Exposure of the parental generation in the two chambers occurred from the 10th to the 120th days of life. After mating and birth of offspring, a crossover of mothers and pups occurred within the chambers, resulting in four groups of pups: nonexposed, prenatal, postnatal, and pre+postnatal. Offspring were killed at the age of 15 (n = 42) and 90 (n = 35) days; lungs were analyzed by morphometry for surface to volume ratio (as an estimator of alveolization). Pressure–volume curves were performed in the older groups, using a 20-ml plethysmograph. Measurements and Main Results: Mice exposed to PM2.5 pre+postnatally presented a smaller surface to volume ratio when compared with nonexposed animals (P = 0.036). The pre+postnatal group presented reduced inspiratory and expiratory volumes at higher levels of transpulmonary pressure (P = 0.001). There were no differences among prenatal and postnatal exposure and nonexposed animals. Conclusions: Our data provide anatomical and functional support to the concept that chronic exposure to urban PM affects lung growth. PMID:18596224

  7. SGLT1 activity in lung alveolar cells of diabetic rats modulates airway surface liquid glucose concentration and bacterial proliferation

    OpenAIRE

    Tales Lyra Oliveira; Návylla Candeia-Medeiros; Polliane M. Cavalcante-Araújo; Igor Santana Melo; Elaine Fávaro-Pípi; Luciana Alves Fátima; Antônio Augusto Rocha; Luiz Ricardo Goulart; Ubiratan Fabres Machado; Ruy R. Campos; Robinson Sabino-Silva

    2016-01-01

    High glucose concentration in the airway surface liquid (ASL) is an important feature of diabetes that predisposes to respiratory infections. We investigated the role of alveolar epithelial SGLT1 activity on ASL glucose concentration and bacterial proliferation. Non-diabetic and diabetic rats were intranasally treated with saline, isoproterenol (to increase SGLT1 activity) or phlorizin (to decrease SGLT1 activity); 2 hours later, glucose concentration and bacterial proliferation (methicillin-...

  8. Predominant constitutive CFTR conductance in small airways

    Directory of Open Access Journals (Sweden)

    Lytle Christian

    2005-01-01

    Full Text Available Abstract Background The pathological hallmarks of chronic obstructive pulmonary disease (COPD are inflammation of the small airways (bronchiolitis and destruction of lung parenchyma (emphysema. These forms of disease arise from chronic prolonged infections, which are usually never present in the normal lung. Despite the fact that primary hygiene and defense of the airways presumably requires a well controlled fluid environment on the surface of the bronchiolar airway, very little is known of the fluid and electrolyte transport properties of airways of less than a few mm diameter. Methods We introduce a novel approach to examine some of these properties in a preparation of minimally traumatized porcine bronchioles of about 1 mm diameter by microperfusing the intact bronchiole. Results In bilateral isotonic NaCl Ringer solutions, the spontaneous transepithelial potential (TEP; lumen to bath of the bronchiole was small (mean ± sem: -3 ± 1 mV; n = 25, but when gluconate replaced luminal Cl-, the bionic Cl- diffusion potentials (-58 ± 3 mV; n = 25 were as large as -90 mV. TEP diffusion potentials from 2:1 NaCl dilution showed that epithelial Cl- permeability was at least 5 times greater than Na+ permeability. The anion selectivity sequence was similar to that of CFTR. The bionic TEP became more electronegative with stimulation by luminal forskolin (5 μM+IBMX (100 μM, ATP (100 μM, or adenosine (100 μM, but not by ionomycin. The TEP was partially inhibited by NPPB (100 μM, GlyH-101* (5–50 μM, and CFTRInh-172* (5 μM. RT-PCR gave identifying products for CFTR, α-, β-, and γ-ENaC and NKCC1. Antibodies to CFTR localized specifically to the epithelial cells lining the lumen of the small airways. Conclusion These results indicate that the small airway of the pig is characterized by a constitutively active Cl- conductance that is most likely due to CFTR.

  9. Acute or chronic transplant rejection - high resolution CT of the chest in lung transplant recipients

    International Nuclear Information System (INIS)

    Purpose: Aim of the study was to evaluate the postoperative changes in patients with single (SLTX) or double lung transplantation (DLTX) with HRCT and to correlate those findings with the clinical diagnosis. Material and methods: 29 patients with SLTX (n = 14) or DLTX (n = 15) were observed for more than 6 years after transplantation by HRCT (n = 82). CT examinations were performed in inspiration and expiration (n = 70) with a slice thickness of 1 mm and a feed of 10 mm. The image material was evaluated by 2 experienced radiologists in consensus. Criteria for acute rejection at HRCT were: ground glass opacities and focal air trapping in expiration. Criteria for chronic transplant rejection were: bronchial dilatation, bronchial wall thickening and thickening of interlobar septae. The clinical evaluation consisted of laboratory tests, lung function tests, and bronchoscopy including bronchial lavage in special cases. Results: 20/29 patients are still alive (mean 21 months). 5/9 patients died because of chronic transplantant rejection, 1 patient suffered from a non-Hodgkin's lymphoma localised at the right hilus. Severe threatening pneumonia occurred in 13 cases. 10/29 patients showed symptoms of acute rejection. Expiratory HRCT found a focal air trapping in all cases and extended ground glass opacities in 11/14 cases. Also a bronchial dilatation was observed in more than 50% (9/14). 12/29 patients suffered from chronic transplant rejection. HRCT showed bronchial dilatation in 26/27 investigations and severe ground glass opacities in 21/27 investigations. Thickening of the interlobal septa as well as centrilobular opacities were found in more than 50% of the examinations. Conclusion: High resolution CT of the chest in patients after lung transplantation is able to show numerous pathological alterations. Without clinical information a confident differentiation in acute or chronic transplant rejection or pneumonia can be difficult or impossible. (orig.)

  10. Noninvasive clearance of airway secretions.

    Science.gov (United States)

    Hardy, K A; Anderson, B D

    1996-06-01

    Airway clearance techniques are indicated for specific diseases that have known clearance abnormalities (Table 2). Murray and others have commented that such techniques are required only for patients with a daily sputum production of greater than 30 mL. The authors have observed that patients with diseases known to cause clearance abnormalities can have sputum clearance with some techniques, such as positive expiratory pressure, autogenic drainage, and active cycle of breathing techniques, when PDPV has not been effective. Hasani et al has shown that use of the forced exhalatory technique in patients with nonproductive cough still resulted in movement of secretions proximally from all regions of the lung in patients with airway obstruction. It is therefore reasonable to consider airway clearance techniques for any patient who has a disease known to alter mucous clearance, including CF, dyskinetic cilia syndromes, and bronchiectasis from any cause. Patients with atelectasis from mucous plugs and hypersecretory states, such as asthma and chronic bronchitis, patients with pain secondary to surgical procedures, and patients with neuromuscular disease, weak cough, and abnormal patency of the airway may also benefit from the application of airway clearance techniques. Infants and children up to 3 years of age with airway clearance problems need to be treated with PDPV. Manual percussion with hands alone or a flexible face mask or cup and small mechanical vibrator/percussors, such as the ultrasonic devices, can be used. The intrapulmonary percussive ventilator shows growing promise in this area. The high-frequency oscillator is not supplied with vests of appropriate sizes for tiny babies and has not been studied in this group. Young patients with neuromuscular disease may require assisted ventilation and airway oscillations can be applied. CPAP alone has been shown to improve achievable flow rates that will increase air-liquid interactions for patients with these diseases

  11. Intratracheal Administration of Mesenchymal Stem Cells Modulates Tachykinin System, Suppresses Airway Remodeling and Reduces Airway Hyperresponsiveness in an Animal Model.

    Directory of Open Access Journals (Sweden)

    Konrad Urbanek

    Full Text Available The need for new options for chronic lung diseases promotes the research on stem cells for lung repair. Bone marrow-derived mesenchymal stem cells (MSCs can modulate lung inflammation, but the data on cellular processes involved in early airway remodeling and the potential involvement of neuropeptides are scarce.To elucidate the mechanisms by which local administration of MSCs interferes with pathophysiological features of airway hyperresponsiveness in an animal model.GFP-tagged mouse MSCs were intratracheally delivered in the ovalbumin mouse model with subsequent functional tests, the analysis of cytokine levels, neuropeptide expression and histological evaluation of MSCs fate and airway pathology. Additionally, MSCs were exposed to pro-inflammatory factors in vitro.Functional improvement was observed after MSC administration. Although MSCs did not adopt lung cell phenotypes, cell therapy positively affected airway remodeling reducing the hyperplastic phase of the gain in bronchial smooth muscle mass, decreasing the proliferation of epithelium in which mucus metaplasia was also lowered. Decrease of interleukin-4, interleukin-5, interleukin-13 and increase of interleukin-10 in bronchoalveolar lavage was also observed. Exposed to pro-inflammatory cytokines, MSCs upregulated indoleamine 2,3-dioxygenase. Moreover, asthma-related in vivo upregulation of pro-inflammatory neurokinin 1 and neurokinin 2 receptors was counteracted by MSCs that also determined a partial restoration of VIP, a neuropeptide with anti-inflammatory properties.Intratracheally administered MSCs positively modulate airway remodeling, reduce inflammation and improve function, demonstrating their ability to promote tissue homeostasis in the course of experimental allergic asthma. Because of a limited tissue retention, the functional impact of MSCs may be attributed to their immunomodulatory response combined with the interference of neuropeptide system activation and tissue

  12. Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines

    Directory of Open Access Journals (Sweden)

    Thurmond Robin L

    2010-06-01

    Full Text Available Abstract Background Airway remodeling and dysfunction are characteristic features of asthma thought to be caused by aberrant production of Th2 cytokines. Histamine H4 receptor (H4R perturbation has previously been shown to modify acute inflammation and Th2 cytokine production in a murine model of asthma. We examined the ability of H4R antagonists to therapeutically modify the effects of Th2 cytokine production such as goblet cell hyperplasia (GCH, and collagen deposition in a sub-chronic model of asthma. In addition, effects on Th2 mediated lung dysfunction were also determined. Methods Mice were sensitized to ovalbumin (OVA followed by repeated airway challenge with OVA. After inflammation was established mice were dosed with the H4R antagonist, JNJ 7777120, or anti-IL-13 antibody for comparison. Airway hyperreactivity (AHR was measured, lungs lavaged and tissues collected for analysis. Results Therapeutic H4R antagonism inhibited T cell infiltration in to the lung and decreased Th2 cytokines IL-13 and IL-5. IL-13 dependent remodeling parameters such as GCH and lung collagen were reduced. Intervention with H4R antagonist also improved measures of central and peripheral airway dysfunction. Conclusions These data demonstrate that therapeutic H4R antagonism can significantly ameliorate allergen induced, Th2 cytokine driven pathologies such as lung remodeling and airway dysfunction. The ability of H4R antagonists to affect these key manifestations of asthma suggests their potential as novel human therapeutics.

  13. HLA-E(⁎)01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence.

    Science.gov (United States)

    Di Cristofaro, Julie; Pelardy, Mathieu; Loundou, Anderson; Basire, Agnès; Gomez, Carine; Chiaroni, Jacques; Thomas, Pascal; Reynaud-Gaubert, Martine; Picard, Christophe

    2016-01-01

    Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E(⁎)01:01 and HLA-E(⁎)01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p = 0.01). In multivariate analysis, HLA-E(⁎)01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E(⁎)01:01 status (HR: 3.563 (CI 95%, 1.016-12), p = 0.047). HLA-E allele did not affect pathogen infection or the production of de novo DSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort. PMID:27493971

  14. HLA-E⁎01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence

    Directory of Open Access Journals (Sweden)

    Julie Di Cristofaro

    2016-01-01

    Full Text Available Lung transplantation (LTx is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E⁎01:01 and HLA-E⁎01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD. HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p=0.01. In multivariate analysis, HLA-E⁎01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E⁎01:01 status (HR: 3.563 (CI 95%, 1.016–12, p=0.047. HLA-E allele did not affect pathogen infection or the production of de novo DSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort.

  15. Arsenic alters ATP-dependent Ca²+ signaling in human airway epithelial cell wound response.

    Science.gov (United States)

    Sherwood, Cara L; Lantz, R Clark; Burgess, Jefferey L; Boitano, Scott

    2011-05-01

    Arsenic is a natural metalloid toxicant that is associated with occupational inhalation injury and contaminates drinking water worldwide. Both inhalation of arsenic and consumption of arsenic-tainted water are correlated with malignant and nonmalignant lung diseases. Despite strong links between arsenic and respiratory illness, underlying cell responses to arsenic remain unclear. We hypothesized that arsenic may elicit some of its detrimental effects on the airway through limitation of innate immune function and, specifically, through alteration of paracrine ATP (purinergic) Ca²+ signaling in the airway epithelium. We examined the effects of acute (24 h) exposure with environmentally relevant levels of arsenic (i.e., immune functions (e.g., ciliary beat, salt and water transport, bactericide production, and wound repair). Arsenic-induced compromise of such airway defense mechanisms may be an underlying contributor to chronic lung disease. PMID:21357385

  16. How should we measure function in patients with chronic heart and lung disease?

    Science.gov (United States)

    Guyatt, G H; Thompson, P J; Berman, L B; Sullivan, M J; Townsend, M; Jones, N L; Pugsley, S O

    1985-01-01

    To elucidate the characteristics of measures of function in patients with chronic heart failure and chronic lung disease we administered four functional status questionnaires, a 6-min walk test and a cycle ergometer exercise test, to 43 patients limited in their day to day activities as a result of their underlying heart or lung disease. Correlations between these measures were calculated using Spearman's rank order correlation coefficient. The walk test correlated well with the cycle ergometer (r = 0.579), and almost as well with the four functional status questionnaires (r = 0.473-0.590) as the questionnaires did with one another (0.423-0.729). On the other hand, correlations between cycle ergometer results and the questionnaires was in each case 0.295 or lower, and none of these correlations reached statistical significance. These results suggest that exercise capacity in the laboratory can be differentiated from functional exercise capacity (the ability to undertake physically demanding activities of daily living) and that the walk test provides a good measure of function in patients with heart and lung disease. PMID:4008592

  17. Vessel-guided Airway Tree Segmentation

    DEFF Research Database (Denmark)

    Lo, P.; Sporring, J.; Ashraf, H.;

    2010-01-01

    This paper presents a method for airway tree segmentation that uses a combination of a trained airway appearance model, vessel and airway orientation information, and region growing. We propose a voxel classification approach for the appearance model, which uses a classifier that is trained to...... differentiate between airway and non-airway voxels. This is in contrast to previous works that use either intensity alone or hand crafted models of airway appearance. We show that the appearance model can be trained with a set of easily acquired, incomplete, airway tree segmentations. A vessel orientation...... method is evaluated on 250 low dose computed tomography images from a lung cancer screening trial. Our experiments showed that applying the region growing algorithm on the airway appearance model produces more complete airway segmentations, leading to on average 20% longer trees, and 50% less leakage...

  18. Impact of Aspergillus fumigatus in allergic airway diseases

    Directory of Open Access Journals (Sweden)

    Chaudhary Neelkamal

    2011-06-01

    Full Text Available Abstract For decades, fungi have been recognized as associated with asthma and other reactive airway diseases. In contrast to type I-mediated allergies caused by pollen, fungi cause a large number of allergic diseases such as allergic bronchopulmonary mycoses, rhinitis, allergic sinusitis and hypersensitivity pneumonitis. Amongst the fungi, Aspergillus fumigatus is the most prevalent cause of severe pulmonary allergic disease, including allergic bronchopulmonary aspergillosis (ABPA, known to be associated with chronic lung injury and deterioration in pulmonary function in people with chronic asthma and cystic fibrosis (CF. The goal of this review is to discuss new understandings of host-pathogen interactions in the genesis of allergic airway diseases caused by A. fumigatus. Host and pathogen related factors that participate in triggering the inflammatory cycle leading to pulmonary exacerbations in ABPA are discussed.

  19. Attenuation of cigarette smoke-induced airway mucus production by hydrogen-rich saline in rats.

    Directory of Open Access Journals (Sweden)

    Yunye Ning

    Full Text Available BACKGROUND: Over-production of mucus is an important pathophysiological feature in chronic airway disease such as chronic obstructive pulmonary disease (COPD and asthma. Cigarette smoking (CS is the leading cause of COPD. Oxidative stress plays a key role in CS-induced airway abnormal mucus production. Hydrogen protected cells and tissues against oxidative damage by scavenging hydroxyl radicals. In the present study we investigated the effect of hydrogen on CS-induced mucus production in rats. METHODS: Male Sprague-Dawley rats were divided into four groups: sham control, CS group, hydrogen-rich saline pretreatment group and hydrogen-rich saline control group. Lung morphology and tissue biochemical changes were determined by immunohistochemistry, Alcian Blue/periodic acid-Schiff staining, TUNEL, western blot and realtime RT-PCR. RESULTS: Hydrogen-rich saline pretreatment attenuated CS-induced mucus accumulation in the bronchiolar lumen, goblet cell hyperplasia, muc5ac over-expression and abnormal cell apoptosis in the airway epithelium as well as malondialdehyde increase in the BALF. The phosphorylation of EGFR at Tyr1068 and Nrf2 up-regulation expression in the rat lungs challenged by CS exposure were also abrogated by hydrogen-rich saline. CONCLUSION: Hydrogen-rich saline pretreatment ameliorated CS-induced airway mucus production and airway epithelium damage in rats. The protective role of hydrogen on CS-exposed rat lungs was achieved at least partly by its free radical scavenging ability. This is the first report to demonstrate that intraperitoneal administration of hydrogen-rich saline protected rat airways against CS damage and it could be promising in treating abnormal airway mucus production in COPD.

  20. Alterations in particle accumulation and clearance in lungs of rats chronically exposed to diesel exhaust

    International Nuclear Information System (INIS)

    F344 rats were chronically exposed to diesel exhaust at target soot concentrations of 0 (control, C), 0.35 (low, L), 3.5 (medium, M), and 7.0 (high, H) mg/m3. Accumulated lung burdens of diesel soot were measured after 6, 12, 18, and 24 months of exposure. Parallel measurements of particle deposition and clearance were made to provide insight into the mechanisms of particle accumulation in lungs. The fractional deposition of inhaled 67Ga2O3 particles after 6, 12, 18, and 24 months of exposure and of inhaled 134Cs-fused aluminosilicate particles after 24 months were similar for all groups. Progressive increases in lung burdens of soot particles were observed in M and H exposed rats, reaching levels of 11.5 +/- 0.5 and 20.5 +/- 0.8 mg/lung (mean +/- SE), respectively, after 24 months. Rats in the L group had smaller relative increases in lung burden, reaching levels of 0.60 +/- 0.02 mg/lung after 24 months. Tracheal mucociliary clearance measurements, using 99mTc-macroaggregated albumin deposited in the trachea, showed no changes at anytime. There were statistically significant increases in clearance half-times of inhaled radiolabeled particles of 67Ga2O3 as early as 6 months at the H level and 18 months at the M level; no significant changes were seen at the L level. Rats inhaled fused aluminosilicate particles labeled with 134Cs after 24 months of diesel exhaust exposure to measure long-term components of pulmonary clearance. The long-term clearance half-times were 79 +/- 5, 81 +/- 5, 264 +/- 50, and 240 +/- 50 days (mean +/- SE) for the C, L, M, and H groups, respectively. Differences were significant between the C and both the M and H exposure groups (p less than 0.01)

  1. Severe acute respiratory failure managed with continuous positive airway pressure and partial extracorporeal carbon dioxide removal by an artificial membrane lung. A controlled, randomized animal study.

    Science.gov (United States)

    Borelli, M; Kolobow, T; Spatola, R; Prato, P; Tsuno, K

    1988-12-01

    Using an animal model of acute respiratory failure (ARF), we evaluated two treatments: conventional mechanical pulmonary ventilation (MV) and continuous positive airway pressure (CPAP) with extracorporeal removal of CO2 by an artificial membrane lung. We developed a model of "mild" ARF and a model of "severe" ARF after ventilating healthy sheep at a peak inspiratory pressure of 50 cm H2O for various lengths of time. Sheep from either injury models were randomly assigned to one of the above treatment groups. All 16 sheep from the model with "severe" ARF died, with progressive deterioration in pulmonary function and multiorgan failure irrespective of the treatment. Of 11 sheep from the model with "mild" ARF treated by MV, only three survived, whereas all 11 sheep from the model with "mild" ARF treated with CPAP and extracorporeal removal of CO2 responded well, and nine sheep ultimately recovered. We conclude that CPAP with extracorporeal removal of CO2 provided a better environment for the recovery in our model with "mild" ARF than the conventional arrangement centered on MV alone. Our studies also suggest that lung injury can progress (i.e., model with "severe" ARF) to where neither of the two treatments can succeed. PMID:3144216

  2. Epithelial injury and repair in airways diseases.

    Science.gov (United States)

    Grainge, Christopher L; Davies, Donna E

    2013-12-01

    Asthma is a common chronic disease characterized by variable respiratory distress with underlying airway inflammation and airflow obstruction. The incidence of asthma has risen inexorably over the past 50 years, suggesting that environmental factors are important in its etiology. All inhaled environmental stimuli interact with the lung at the respiratory epithelium, and it is a testament to the effectiveness of the airway innate defenses that the majority of inhaled substances are cleared without the need to elicit an inflammatory response. However, once this barrier is breached, effective communication with immune and inflammatory cells is required to protect the internal milieu of the lung. In asthma, the respiratory epithelium is known to be structurally and functionally abnormal. Structurally, the epithelium shows evidence of damage and has more mucus-producing cells than normal airways. Functionally, the airway epithelial barrier can be more permeable and more sensitive to oxidants and show a deficient innate immune response to respiratory virus infection compared with that in normal individuals. The potential of a susceptible epithelium and the underlying mesenchyme to create a microenvironment that enables deviation of immune and inflammatory responses to external stimuli may be crucial in the development and progression of asthma. In this review, we consider three important groups of environmental stimuli on the epithelium in asthma: oxidants, such as environmental pollution and acetaminophen; viruses, including rhinovirus; and agents that cause barrier disruption, such as house dust mite allergens. The pathology associated with each stimulus is considered, and potential future treatments arising from research on their effects are presented. PMID:24297122

  3. Computational modeling of the obstructive lung diseases asthma and COPD.

    OpenAIRE

    Burrowes, K. S.; Doel, T.; Brightling, C

    2014-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway obstruction and airflow limitation and pose a huge burden to society. These obstructive lung diseases impact the lung physiology across multiple biological scales. Environmental stimuli are introduced via inhalation at the organ scale, and consequently impact upon the tissue, cellular and sub-cellular scale by triggering signaling pathways. These changes are propagated upwards to the organ level again and vice...

  4. Assessment of the right ventricle by magnetic resonance imaging in chronic obstructive lung disease.

    OpenAIRE

    Turnbull, L W; Ridgway, J P; Biernacki, W; McRitchie, H; Muir, A L; Best, J J; MacNee, W

    1990-01-01

    Right ventricular wall and chamber volume were measured by magnetic resonance imaging in 16 patients with stable chronic obstructive lung disease who subsequently underwent measurement of pulmonary haemodynamics by right heart catheterisation. The patients had a forced expiratory volume in one second of 0.7 (SD 0.3) litres, a forced vital capacity of 2.4 (1.0) l, an arterial oxygen tension (PaO2) of 6.5 (1.3) kPa, an arterial carbon dioxide tension (PaCO2) of 6.5 (1.0) kPa, and a mean pulmona...

  5. Multifocal periostitis as a complication of chronic use of voriconazole in a lung transplant recipient.

    Science.gov (United States)

    Tedja, R; El-Sherief, A; Olbrych, T; Gordon, S

    2013-08-01

    Fungal infections are common in solid organ transplantation. An increasing number of transplant recipients receive antifungal therapy for prolonged duration owing to invasive fungal infections. Herein, we describe a diagnosis of periostitis as a complication of chronic use of voriconazole in a lung transplant recipient. The patient was diagnosed with probable pulmonary aspergillosis and was treated with oral voriconazole for a total of 9 months. Evidence of multifocal periostitis was observed in the axial and appendicular skeleton. Early recognition of this phenomenon is important to prevent unnecessary tests and procedures. Prompt discontinuation of voriconazole should result in improvement of symptoms. PMID:23663268

  6. Total respiratory resistance and reactance in patients with upper airway obstruction.

    Science.gov (United States)

    van Noord, J A; Wellens, W; Clarysse, I; Cauberghs, M; Van de Woestijne, K P; Demedts, M

    1987-09-01

    In 18 patients with upper airway obstruction, we measured dynamic lung volumes, maximal flows, airway resistance (Raw), and total respiratory resistance (Rrs) and reactance (Xrs) at various frequencies by means of a forced oscillation method. Patients were classified according to the site and the type of the obstruction. The values of Raw, Rrs and Xrs were tightly correlated and reflected the overall importance of the obstruction. In comparison with patients with chronic obstructive pulmonary disease the values of Rrs tend to be higher and to be influenced more by support of the cheeks during the measurement. These differences are not diagnostic, however. PMID:3622024

  7. Multiple Hypothesis Tracking Based Extraction Of Airway Trees From CT Data

    DEFF Research Database (Denmark)

    Selvan, Raghavendra; Petersen, Jens; de Bruijne, Marleen

    Segmentation of airway trees from CT scans of lungs has important clinical applications, in relation to the diagnosis of chronic obstructive pulmonary disease (COPD). Here we present a method based on multiple hypothesis tracking (MHT) and template matching, originally de- vised for vessel...... segmentation, to extract airway trees. Idealized tubular templates are constructed and ranked using scores assigned based on the image data. Several such regularly spaced hy- potheses are used in constructing a hypothesis tree, which is then traversed to obtain improved segmentation results....

  8. Aquaporin 5 polymorphisms and rate of lung function decline in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Nadia N Hansel

    Full Text Available RATIONALE: Aquaporin-5 (AQP5 can cause mucus overproduction and lower lung function. Genetic variants in the AQP5 gene might be associated with rate of lung function decline in chronic obstructive pulmonary disease (COPD. METHODS: Five single nucleotide polymorphisms (SNPs in AQP5 were genotyped in 429 European American individuals with COPD randomly selected from the NHLBI Lung Health Study. Mean annual decline in FEV(1 % predicted, assessed over five years, was calculated as a linear regression slope, adjusting for potential covariates and stratified by smoking status. Constructs containing the wildtype allele and risk allele of the coding SNP N228K were generated using site-directed mutagenesis, and transfected into HBE-16 (human bronchial epithelial cell line. AQP5 abundance and localization were assessed by immunoblots and confocal immunofluorescence under control, shear stress and cigarette smoke extract (CSE 10% exposed conditions to test for differential expression or localization. RESULTS: Among continuous smokers, three of the five SNPs tested showed significant associations (0.02>P>0.004 with rate of lung function decline; no associations were observed among the group of intermittent or former smokers. Haplotype tests revealed multiple association signals (0.012>P>0.0008 consistent with the single-SNP results. In HBE16 cells, shear stress and CSE led to a decrease in AQP5 abundance in the wild-type, but not in the N228K AQP5 plasmid. CONCLUSIONS: Polymorphisms in AQP5 were associated with rate of lung function decline in continuous smokers with COPD. A missense mutation modulates AQP-5 expression in response to cigarette smoke extract and shear stress. These results suggest that AQP5 may be an important candidate gene for COPD.

  9. Clinical applications of gene-based risk prediction for Lung Cancer and the central role of Chronic Obstructive Pulmonary Disease.

    Directory of Open Access Journals (Sweden)

    Robert P Young

    2012-10-01

    Full Text Available Lung cancer is the leading cause of cancer death worldwide and nearly 90% of cases are attributable to smoking. Quitting smoking and early diagnosis of lung cancer, through computed tomographic screening, are the only ways to reduce mortality from lung cancer. Recent epidemiological studies show that risk prediction for lung cancer is optimized by using multivariate risk models that include age, smoking exposure, history of chronic obstructive pulmonary disease (COPD, family history of lung cancer and body mass index. Several recent epidemiological studies have shown that COPD predates lung cancer in 65-70% of cases and confers a 4-6 fold greater risk of lung cancer compared to smokers with normal lung function. In separate studies, genome-wide association studies have identified a number of genetic variants associated with COPD or lung cancer, several of which overlap. In a case control study, where smokers with normal lungs were compared to those who had spirometry-defined COPD and histology confirmed lung cancer, several of these overlapping variants were shown to confer the same susceptibility or protective effects on both COPD and lung cancer (independent of COPD status. In this perspective article, we demonstrate how combining clinical data with genetic variants can help identify heavy smokers at the greatest risk of lung cancer. Using this approach, we found that gene-based risk testing helped engage smokers in risk mitigating activities like quitting smoking and undertaking lung cancer screening. We suggest that such an approach could facilitate the targeted selection of smokers for cost-effective, life-saving interventions.

  10. IL-1β, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs.

    Science.gov (United States)

    Bal, Suzanne M; Bernink, Jochem H; Nagasawa, Maho; Groot, Jelle; Shikhagaie, Medya M; Golebski, Kornel; van Drunen, Cornelis M; Lutter, Rene; Jonkers, Rene E; Hombrink, Pleun; Bruchard, Melanie; Villaudy, Julien; Munneke, J Marius; Fokkens, Wytske; Erjefält, Jonas S; Spits, Hergen; Ros, Xavier Romero

    2016-06-01

    Group 2 innate lymphoid cells (ILC2s) secrete type 2 cytokines, which protect against parasites but can also contribute to a variety of inflammatory airway diseases. We report here that interleukin 1β (IL-1β) directly activated human ILC2s and that IL-12 induced the conversion of these activated ILC2s into interferon-γ (IFN-γ)-producing ILC1s, which was reversed by IL-4. The plasticity of ILCs was manifested in diseased tissues of patients with severe chronic obstructive pulmonary disease (COPD) or chronic rhinosinusitis with nasal polyps (CRSwNP), which displayed IL-12 or IL-4 signatures and the accumulation of ILC1s or ILC2s, respectively. Eosinophils were a major cellular source of IL-4, which revealed cross-talk between IL-5-producing ILC2s and IL-4-producing eosinophils. We propose that IL-12 and IL-4 govern ILC2 functional identity and that their imbalance results in the perpetuation of type 1 or type 2 inflammation. PMID:27111145

  11. Effects of second hand smoke on airway secretion and mucociliary clearance

    Directory of Open Access Journals (Sweden)

    Yanyan eLiu

    2012-08-01

    Full Text Available The airway acts as the first defense against inhaled pathogens and particulate matter from the environment. One major way for the airway to clear inhaled foreign objects is through mucociliary clearance (MCC, an important component of the respiratory innate immune defense against lung disease. MCC is characterized by the upward movement of mucus by ciliary motion that requires a balance between the volume and composition of the mucus, adequate periciliary liquid (PCL volume, and normal ciliary beat frequency. Airway surface fluid (ASL is a thin layer liquid that consists of the highly viscous mucus upper gel layer, and the watery lubricating lower sol layer. Mucus production, secretion and clearance are considered to play a critical role in maintenance of airway health because it maintains hydration in the airway and traps particulates, bacteria, and viruses. Different types of epithelial cells, including secretory cells and ciliated cells, contribute to the MCC function. Cigarette smoke (CS contains chemicals and particulates that significantly affect airway secretion. Active- and passive cigarette smoke-induced chronic obstructive pulmonary disease (COPD is frequently associated with hyperplasia of goblet cells and submucosal glands, thus increasing the secretory capacity of the airways that impairs MCC.

  12. Towards the modeling of mucus draining from human lung: role of airways deformation on air-mucus interaction

    CERN Document Server

    Mauroy, Benjamin; Pelca, Dominique; Fausser, Christian; Merckx, Jacques; Mitchell, Barrett R

    2015-01-01

    Chest physiotherapy is an empirical technique used to help secretions to get out of the lung whenever stagnation occurs. Although commonly used, little is known about the inner mechanisms of chest physiotherapy and controversies about its use are coming out regularly. Thus, a scientific validation of chest physiotherapy is needed to evaluate its effects on secretions. We setup a quasi-static numerical model of chest physiotherapy based on thorax and lung physiology and on their respective biophysics. We modeled the lung with an idealized deformable symmetric bifurcating tree. Bronchi and their inner fluids mechanics are assumed axisymmetric. Static data from the literature is used to build a model for the lung's mechanics. Secretions motion is the consequence of the shear constraints apply by the air flow. The input of the model is the pressure on the chest wall at each time, and the output is the bronchi geometry and air and secretions properties. In the limit of our model, we mimicked manual and mechanical ...

  13. Investigating the geometry of pig airways using computed tomography

    Science.gov (United States)

    Mansy, Hansen A.; Azad, Md Khurshidul; McMurray, Brandon; Henry, Brian; Royston, Thomas J.; Sandler, Richard H.

    2015-03-01

    Numerical modeling of sound propagation in the airways requires accurate knowledge of the airway geometry. These models are often validated using human and animal experiments. While many studies documented the geometric details of the human airways, information about the geometry of pig airways is scarcer. In addition, the morphology of animal airways can be significantly different from that of humans. The objective of this study is to measure the airway diameter, length and bifurcation angles in domestic pigs using computed tomography. After imaging the lungs of 3 pigs, segmentation software tools were used to extract the geometry of the airway lumen. The airway dimensions were then measured from the resulting 3 D models for the first 10 airway generations. Results showed that the size and morphology of the airways of different animals were similar. The measured airway dimensions were compared with those of the human airways. While the trachea diameter was found to be comparable to the adult human, the diameter, length and branching angles of other airways were noticeably different from that of humans. For example, pigs consistently had an early airway branching from the trachea that feeds the superior (top) right lung lobe proximal to the carina. This branch is absent in the human airways. These results suggested that the human geometry may not be a good approximation of the pig airways and may contribute to increasing the errors when the human airway geometric values are used in computational models of the pig chest.

  14. Toxicogenomic analysis of susceptibility to inhaled urban particulate matter in mice with chronic lung inflammation

    Directory of Open Access Journals (Sweden)

    Yauk Carole L

    2009-03-01

    Full Text Available Abstract Background Individuals with chronic lung disease are at increased risk of adverse health effects from airborne particulate matter. Characterization of underlying pollutant-phenotype interactions may require comprehensive strategies. Here, a toxicogenomic approach was used to investigate how inflammation modifies the pulmonary response to urban particulate matter. Results Transgenic mice with constitutive pulmonary overexpression of tumour necrosis factor (TNF-α under the control of the surfactant protein C promoter and wildtype littermates (C57BL/6 background were exposed by inhalation for 4 h to particulate matter (0 or 42 mg/m3 EHC-6802 and euthanized 0 or 24 h post-exposure. The low alveolar dose of particles (16 μg did not provoke an inflammatory response in the lungs of wildtype mice, nor exacerbate the chronic inflammation in TNF animals. Real-time PCR confirmed particle-dependent increases of CYP1A1 (30–100%, endothelin-1 (20–40%, and metallothionein-II (20–40% mRNA in wildtype and TNF mice (p Conclusion Our data support the hypothesis that health effects of acute exposure to urban particles are dominated by activation of specific physiological response cascades rather than widespread changes in gene expression.

  15. Regional ventilation-perfusion ratio in chronic lung diseases measured with krypton-81m

    International Nuclear Information System (INIS)

    We measured regional ventilation-perfusion ratio (V radical/Q radical) by continuous inhalation of Kr-81 m and also continuous injection of Kr-81 m. The V radical/Q radical distribution can be divided four types. Type I is the normal pattern and V radical/Q radical value is the highest at apex. Type II has the highest V radical/Q radical value not at the apex but one third lower from the apex and the V radical/Q radical value gradually decreases towards the base. In type III V radical/Q radical has no gradient from the apex to the base. In type IV V radical/Q radical of the base higher than that of the apex. Most pulmonary emphysema show type I, most chronic bronchitis show type II and many interstitial pneumonia denote type IV. The ratio between the area in which the V radical/Q radical value was lower than 0.75, and the area of total lung (% 0.75) correlated with PaO2 (r = 0.59 p < 0.01). Coefficiency of variation (COV) of V radical/Q radical was larger in pulmonary emphysema and in interstitial pneumonia than in normal lung and COV of V radical/Q radical was the largest in chronic bronchitis. (author)

  16. Non-invasive evaluation for pulmonary circulatory impairment during exercise in patients with chronic lung disease

    International Nuclear Information System (INIS)

    Thallium-201 myocardial scintigraphy was performed at rest and during exercise on sixteen patients with chronic lung disease to evaluate the secondary pulmonary hypertension during exercise with non-invasive technique. An inverse significant correlation was found between thallium activity ratio (TAR) of left ventricle plus ventricular septum to right ventricle and both of pulmonary vascular resistance and right to left ventricular work index ratio during exercise. The patients were divided into three groups according to mean pulmonary arterial pressure (P-barPA) at rest and during exercise: the first group consisted of six patients with pulmonary hypertension during exercise (P-barPA: below 25 mmHg at rest and above 30 mmHg during exercise), the second group consisted of four patients with pulmonary hypertension at rest (P-barPA above 25 mmHg at rest), and the third group consisted of six patients without pulmonary hypertension (P-barPA below 25 mmHg at rest, below 30 mmHg during exercise). In the first group, TAR during exercise was lowered than at rest in four patients, and in the second group TAR during exercise was lowered than at rest in all, while in the third group TAR during exercise was increased than at rest in five patients. These results suggest that thallium-201 myocardial scintigraphy can reflect pulmonary hemodynamics during exercise in patients with chronic lung disease and it is of great use to predict the patients with pulmonary hypertension during exercise. (author)

  17. Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J., E-mail: tokare@niehs.nih.gov

    2015-07-01

    Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

  18. The Prognostic Value of Residual Volume/Total Lung Capacity in Patients with Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Shin, Tae Rim; Oh, Yeon-Mok; Park, Joo Hun; Lee, Keu Sung; Oh, Sunghee; Kang, Dae Ryoung; Sheen, Seungsoo; Seo, Joon Beom; Yoo, Kwang Ha; Lee, Ji-Hyun; Kim, Tae-Hyung; Lim, Seong Yong; Yoon, Ho Il; Rhee, Chin Kook; Choe, Kang-Hyeon

    2015-01-01

    The prognostic role of resting pulmonary hyperinflation as measured by residual volume (RV)/total lung capacity (TLC) in chronic obstructive pulmonary disease (COPD) remains poorly understood. Therefore, this study aimed to identify the factors related to resting pulmonary hyperinflation in COPD and to determine whether resting pulmonary hyperinflation is a prognostic factor in COPD. In total, 353 patients with COPD in the Korean Obstructive Lung Disease cohort recruited from 16 hospitals wer...

  19. Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

    International Nuclear Information System (INIS)

    Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

  20. Analysis of the molecular expression profile of non small cell lung carcinoma associated to chronic obstructive pulmonary disease

    OpenAIRE

    Garcia-Lujan, Ricardo; Conde-Gallego, Esther; Lopez-Ríos, Fernando; Martin de Nicolas, Jose Luis; Sanchez-Céspedes, Montserrat; García-Quero, Cristina; Echave-Sustaeta, José María; Lopez-Encuentra, Angel

    2009-01-01

    Chronic obstructive pulmonary disease (COPD) is an independent risk factor to develop lung cancer but there are no different functional clusters of biomarkers between patients with non-small cell lung cancer (NSCLC) with or without COPD. To analyse protein expression, in order to find out whether samples of resected NSCLC from patients with COPD present a different molecular expression. Observational, cohort, concurrent study with sampling since treatment of disease...