Marked alveolar apoptosis/proliferation imbalance in end-stage emphysema.


BACKGROUND:Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema. METHODS:In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 alpha1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplantations. Six unused donor lungs served as controls. Apoptosis was evaluated by TUNEL analysis, single-stranded DNA laddering, electron microscopy and cell proliferation by an immunohistochemical method (MIB1). The role of the transforming growth factor (TGF)-beta1 pathway was also investigated and correlated with epithelial cell turnover and with the severity of inflammatory cell infiltrate. RESULTS:The apoptotic index (AI) was significantly higher in emphysematous lungs compared to the control group (p < or = 0.01), particularly if only lungs with AAT-deficiency emphysema were considered (p < or = 0.01 vs p = 0.09). The proliferation index was similar in patients and controls (1.9 +/- 2.2 vs 1.7 +/- 1.1). An increased number of T lymphocytes was observed in AAT-deficiency lungs than smoking-related cases (p < or = 0.05). TGF-beta1 expression in the alveolar wall was higher in patients with smoking-associated emphysema than in cases with AAT-deficiency emphysema (p < or = 0.05). A positive correlation between TGF-betaRII and AI was observed only in the control group (p < or = 0.005, r2 = 0.8). A negative correlation was found between the TGF-beta pathway (particularly TGF-betaRII) and T lymphocytes infiltrate in smoking-related cases (p < or = 0.05, r2 = 0.99) CONCLUSION:Our findings suggest that apoptosis of alveolar epithelial cells plays an important role even in end-stage emphysema particularly in AAT-deficiency disease. The TGFbeta-1 pathway does not seem to directly influence epithelial turnover in end-stage disease. Inflammatory cytokine different from TGF-beta1 may differently orchestrate cell fate in AAT and smoking-related emphysema types.


Respir Res


Respiratory research


Calabrese F,Giacometti C,Beghe B,Rea F,Loy M,Zuin R,Marulli G,Baraldo S,Saetta M,Valente M





Has Abstract


2005-02-10 00:00:00












  • IL-4 and IL-13 exposure during mucociliary differentiation of bronchial epithelial cells increases antimicrobial activity and expression of antimicrobial peptides.

    abstract::The airway epithelium forms a barrier against infection but also produces antimicrobial peptides (AMPs) and other inflammatory mediators to activate the immune system. It has been shown that in allergic disorders, Th2 cytokines may hamper the antimicrobial activity of the epithelium. However, the presence of Th2 cytok...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Zuyderduyn S,Ninaber DK,Schrumpf JA,van Sterkenburg MA,Verhoosel RM,Prins FA,van Wetering S,Rabe KF,Hiemstra PS

    更新日期:2011-05-02 00:00:00

  • Sirt1 expression is associated with CD31 expression in blood cells from patients with chronic obstructive pulmonary disease.

    abstract:BACKGROUND:Cigarette smoke induced oxidative stress has been shown to reduce silent information regulator 1 (Sirt1) levels in lung tissue from smokers and patients with COPD patients. Sirt1 is known to inhibit endothelial senescence and may play a protective role in vascular cells. Endothelial progenitor cells (EPCs) a...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Kato R,Mizuno S,Kadowaki M,Shiozaki K,Akai M,Nakagawa K,Oikawa T,Iguchi M,Osanai K,Ishizaki T,Voelkel NF,Toga H

    更新日期:2016-10-27 00:00:00

  • Epilysin (matrix metalloproteinase-28) contributes to airway epithelial cell survival.

    abstract::MMP28 is constitutively expressed by epithelial cells in many tissues, including the respiratory epithelium in the lung and keratinocytes in the skin. This constitutive expression suggests that MMP28 may serve a role in epithelial cell homeostasis. In an effort to determine its function in epithelial cell biology, we ...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Manicone AM,Harju-Baker S,Johnston LK,Chen AJ,Parks WC

    更新日期:2011-10-31 00:00:00

  • Pharmacology of airways and vessels in lung slices in situ: role of endogenous dilator hormones.

    abstract::Small airway and vessels play a critical role in chronic airway and pulmonary vascular diseases, but their pharmacology has not been well characterised. We have studied airway and vascular responses in rat lung slices and separately in vitro using myography. In lung slices, under basal conditions, acetylcholine contra...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Moreno L,Perez-Vizcaino F,Harrington L,Faro R,Sturton G,Barnes PJ,Mitchell JA

    更新日期:2006-08-21 00:00:00

  • Recent advances in our understanding of human host responses to tuberculosis.

    abstract::Tuberculosis remains one of the world's greatest public health challenges: 2 billion persons have latent infection, 8 million people develop active tuberculosis annually, and 2-3 million die. Recently, significant advances in our understanding of the human immune response against tuberculosis have occurred. The presen...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审


    authors: Schluger NW

    更新日期:2001-01-01 00:00:00

  • Rituximab therapy in pulmonary alveolar proteinosis improves alveolar macrophage lipid homeostasis.

    abstract:RATIONALE:Pulmonary Alveolar Proteinosis (PAP) patients exhibit an acquired deficiency of biologically active granulocyte-macrophage colony stimulating factor (GM-CSF) attributable to GM-CSF specific autoantibodies. PAP alveolar macrophages are foamy, lipid-filled cells with impaired surfactant clearance and markedly r...

    journal_title:Respiratory research

    pub_type: 临床试验,杂志文章


    authors: Malur A,Kavuru MS,Marshall I,Barna BP,Huizar I,Karnekar R,Thomassen MJ

    更新日期:2012-06-14 00:00:00

  • Pleural inhibition of the caspase-1/IL-1β pathway diminishes profibrotic lung toxicity of bleomycin.

    abstract:BACKGROUND:Idiopathic and toxic pulmonary fibrosis are severe diseases starting classically in the subpleural area of the lung. It has recently been suggested that pleural mesothelial cells acquire a myofibroblast phenotype under fibrotic conditions induced by TGF-β1 or bleomycin. The importance and role of inflammatio...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Burgy O,Bellaye PS,Causse S,Beltramo G,Wettstein G,Boutanquoi PM,Goirand F,Garrido C,Bonniaud P

    更新日期:2016-11-29 00:00:00

  • Real world evaluation of a novel lateral flow assay (AlphaKit® QuickScreen) for the detection of alpha-1-antitrypsin deficiency.

    abstract:BACKGROUND:Alpha-1-Antitrypsin (AAT) deficiency (AATD) is a hereditary disorder that manifests primarily as pulmonary emphysema and liver cirrhosis. The clinically most relevant mutation causing AATD is a single nucleotide polymorphism Glu342Lys (Z-mutation). Despite the recommendation to test every COPD patient, the c...

    journal_title:Respiratory research

    pub_type: 杂志文章,多中心研究


    authors: Greulich T,Rodríguez-Frias F,Belmonte I,Klemmer A,Vogelmeier CF,Miravitlles M

    更新日期:2018-08-13 00:00:00

  • Apoptosis and the activity of ceramide, Bax and Bcl-2 in the lungs of neonatal rats exposed to limited and prolonged hyperoxia.

    abstract:BACKGROUND:The aim of the study is to examine the effect of limited and prolonged hyperoxia on neonatal rat lung. This is done by examining the morphologic changes of apoptosis, the expression of ceramide, an important mediator of apoptosis, the expression of inflammatory mediators represented by IL-1beta and the expre...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Husari AW,Dbaibo GS,Bitar H,Khayat A,Panjarian S,Nasser M,Bitar FF,El-Sabban M,Zaatari G,Mroueh SM

    更新日期:2006-07-26 00:00:00

  • The gene encoding interleukin-13: a susceptibility locus for asthma and related traits.

    abstract::Asthma is a complex inflammatory disorder controlled by both genetic and environmental influences. Multiple genetic analyses have identified the T helper type 2 (Th2) cytokine gene cluster on chromosome 5q as a susceptibility locus for asthma. Recently, the Th2 cytokine interleukin-13 has been shown to be a critical m...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审


    authors: Wills-Karp M

    更新日期:2000-01-01 00:00:00

  • Prevalence and incidence of sarcoidosis in Korea: a nationwide population-based study.

    abstract:BACKGROUND:The prevalence and incidence of sarcoidosis varies worldwide. We estimated the prevalence and incidence of sarcoidosis in Korea using nationwide claims data from the Korean Health Insurance Review and Assessment Service. METHODS:Cases of sarcoidosis were identified for any visit between 2007 to 2016 that li...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Yoon HY,Kim HM,Kim YJ,Song JW

    更新日期:2018-08-28 00:00:00

  • Inhaled furosemide for relief of air hunger versus sense of breathing effort: a randomized controlled trial.

    abstract:BACKGROUND:Inhaled furosemide offers a potentially novel treatment for dyspnoea, which may reflect modulation of pulmonary stretch receptor feedback to the brain. Specificity of relief is unclear because different neural pathways may account for different components of clinical dyspnoea. Our objective was to evaluate i...

    journal_title:Respiratory research

    pub_type: 杂志文章,随机对照试验


    authors: Grogono JC,Butler C,Izadi H,Moosavi SH

    更新日期:2018-09-20 00:00:00

  • Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung Cancer.

    abstract:BACKGROUND:Radiation pneumonitis (RP) is a frequent complication of concurrent chemoradiotherapy (CCRT) and is associated with severe symptoms that decrease quality of life and might result in pulmonary fibrosis or death. The aim of this study is to identify whether pulmonary function test (PFT) abnormalities may predi...

    journal_title:Respiratory research

    pub_type: 杂志文章,多中心研究


    authors: Torre-Bouscoulet L,Muñoz-Montaño WR,Martínez-Briseño D,Lozano-Ruiz FJ,Fernández-Plata R,Beck-Magaña JA,García-Sancho C,Guzmán-Barragán A,Vergara E,Blake-Cerda M,Gochicoa-Rangel L,Maldonado F,Arroyo-Hernández M,Arrieta O

    更新日期:2018-04-24 00:00:00

  • Weighing the evidence for pharmacological treatment interventions in mild COPD; a narrative perspective.

    abstract::There is increasing focus on understanding the nature of chronic obstructive pulmonary disease (COPD) during the earlier stages. Mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 or the now-withdrawn GOLD stage 0) represents an early stage of COPD that may progress to more severe disease...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审


    authors: Singh D,D'Urzo AD,Donohue JF,Kerwin EM

    更新日期:2019-07-08 00:00:00

  • Cigarette smoke-induced accumulation of lung dendritic cells is interleukin-1α-dependent in mice.

    abstract:BACKGROUND:Evidence suggests that dendritic cells accumulate in the lungs of COPD patients and correlate with disease severity. We investigated the importance of IL-1R1 and its ligands IL-1α and β to dendritic cell accumulation and maturation in response to cigarette smoke exposure. METHODS:Mice were exposed to cigare...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Botelho FM,Nikota JK,Bauer CM,Morissette MC,Iwakura Y,Kolbeck R,Finch D,Humbles AA,Stämpfli MR

    更新日期:2012-09-19 00:00:00

  • CCR2 and CXCR3 agonistic chemokines are differently expressed and regulated in human alveolar epithelial cells type II.

    abstract::The attraction of leukocytes from circulation to inflamed lungs depends on the activation of both the leukocytes and the resident cells within the lung. In this study we determined gene expression and secretion patterns for monocyte chemoattractant protein-1 (MCP-1/CCL2) and T-cell specific CXCR3 agonistic chemokines ...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Pechkovsky DV,Goldmann T,Ludwig C,Prasse A,Vollmer E,Müller-Quernheim J,Zissel G

    更新日期:2005-07-20 00:00:00

  • Therapeutic effect of budesonide/formoterol, montelukast and N-acetylcysteine for bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation.

    abstract:BACKGROUND:Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) is currently treated with systemic corticosteroids despite poor efficacy and side effects. This study investigated the therapeutic effect of budesonide/formoterol, montelukast and n-acetylcysteine, which a...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Kim SW,Rhee CK,Kim YJ,Lee S,Kim HJ,Lee JW

    更新日期:2016-05-26 00:00:00

  • Impaired survival of regulatory T cells in pulmonary sarcoidosis.

    abstract:BACKGROUND:Impaired regulatory T cell (Treg) function is thought to contribute to ongoing inflammatory responses in sarcoidosis, but underlying mechanisms remain unclear. Moreover, it is not known if increased apoptotic susceptibility of Tregs may contribute to an impaired immunosuppressive function in sarcoidosis. The...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Broos CE,van Nimwegen M,Kleinjan A,ten Berge B,Muskens F,in 't Veen JC,Annema JT,Lambrecht BN,Hoogsteden HC,Hendriks RW,Kool M,van den Blink B

    更新日期:2015-09-16 00:00:00

  • Relation of exaggerated cytokine responses of CF airway epithelial cells to PAO1 adherence.

    abstract::In many model systems, cystic fibrosis (CF) phenotype airway epithelial cells in culture respond to P. aeruginosa with greater interleukin (IL)-8 and IL-6 secretion than matched controls. In order to test whether this excess inflammatory response results from the reported increased adherence of P. aeruginosa to the CF...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Kube DM,Fletcher D,Davis PB

    更新日期:2005-07-11 00:00:00

  • Serum biomarkers in interstitial lung diseases.

    abstract::The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The pas...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审


    authors: Tzouvelekis A,Kouliatsis G,Anevlavis S,Bouros D

    更新日期:2005-07-21 00:00:00

  • Azithromycin and cough-specific health status in patients with chronic obstructive pulmonary disease and chronic cough: a randomised controlled trial.

    abstract:BACKGROUND:Macrolides reduce exacerbations in patients with COPD. Their effects on health status has not been assessed as primary outcome and is less clear. This study assessed the effects of prophylactic azithromycin on cough-specific health status in COPD-patients with chronic productive cough. METHODS:In this rando...

    journal_title:Respiratory research

    pub_type: 杂志文章,随机对照试验


    authors: Berkhof FF,Doornewaard-ten Hertog NE,Uil SM,Kerstjens HA,van den Berg JW

    更新日期:2013-11-14 00:00:00

  • Therapeutic efficacy of α-1 antitrypsin augmentation therapy on the loss of lung tissue: an integrated analysis of 2 randomised clinical trials using computed tomography densitometry.

    abstract:BACKGROUND:Two randomised, double-blind, placebo-controlled trials have investigated the efficacy of IV alpha-1 antitrypsin (AAT) augmentation therapy on emphysema progression using CT densitometry. METHODS:Data from these similar trials, a 2-center Danish-Dutch study (n = 54) and the 3-center EXAcerbations and CT sca...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Stockley RA,Parr DG,Piitulainen E,Stolk J,Stoel BC,Dirksen A

    更新日期:2010-10-05 00:00:00

  • Perforin, granzyme B, and FasL expression by peripheral blood T lymphocytes in emphysema.

    abstract:BACKGROUND:It is generally accepted that emphysematous lungs are characterized by an increase in the numbers of neutrophils, macrophages, and CD8+ T lymphocytes, the lasts having increased cytotoxic activity. Because systemic inflammation is also a component of emphysema, we hypothesize that peripheral CD8+ T lymphocyt...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Morissette MC,Parent J,Milot J

    更新日期:2007-09-06 00:00:00

  • The bioavailability and airway clearance of the steroid component of budesonide/formoterol and salmeterol/fluticasone after inhaled administration in patients with COPD and healthy subjects: a randomized controlled trial.

    abstract:BACKGROUND:Airway absorption and bioavailability of inhaled corticosteroids (ICSs) may be influenced by differences in pharmacokinetic properties such as lipophilicity and patient characteristics such as lung function. This study aimed to further investigate and clarify the distribution of budesonide and fluticasone in...

    journal_title:Respiratory research

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Dalby C,Polanowski T,Larsson T,Borgström L,Edsbäcker S,Harrison TW

    更新日期:2009-10-31 00:00:00

  • DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease.

    abstract:BACKGROUND:Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in ...

    journal_title:Respiratory research

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Lee JH,McDonald ML,Cho MH,Wan ES,Castaldi PJ,Hunninghake GM,Marchetti N,Lynch DA,Crapo JD,Lomas DA,Coxson HO,Bakke PS,Silverman EK,Hersh CP,COPDGene and ECLIPSE Investigators.

    更新日期:2014-08-20 00:00:00

  • A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium.

    abstract:BACKGROUND:Pulmonary neuroendocrine cells (PNEC) are specialized epithelial cells that are thought to play important roles in lung development and airway function. PNEC occur either singly or in clusters called neuroepithelial bodies. Our aim was to characterize the three dimensional morphology of PNEC, their distribut...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Weichselbaum M,Sparrow MP,Hamilton EJ,Thompson PJ,Knight DA

    更新日期:2005-10-10 00:00:00

  • Prevalence and risk factors of moderate to severe obstructive sleep apnea syndrome in insomnia sufferers: a study on 1311 subjects.

    abstract:BACKGROUND:Several studies have investigated the prevalence and risk factors of insomnia in subjects with obstructive sleep apnea syndrome. However, few studies have investigated the prevalence and risk factors for obstructive sleep apnea syndrome in insomnia sufferers. Thus, the aim of this study was to examine the pr...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Hein M,Lanquart JP,Loas G,Hubain P,Linkowski P

    更新日期:2017-07-06 00:00:00

  • Role of PM2.5 in the development and progression of COPD and its mechanisms.

    abstract:BACKGROUND:A multitude of epidemiological studies have shown that ambient fine particulate matter 2.5 (diameter < 2.5um; PM2.5) was associated with increased morbidity and mortality of chronic obstructive pulmonary disease (COPD). However, the underlying associated mechanisms have not yet been elucidated. We conducted ...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Zhao J,Li M,Wang Z,Chen J,Zhao J,Xu Y,Wei X,Wang J,Xie J

    更新日期:2019-06-13 00:00:00

  • Outcome measures for airway clearance techniques in children with chronic obstructive lung diseases: a systematic review.

    abstract:BACKGROUND:Airway clearance techniques (ACTs) are an important aspect of the treatment of children with chronic obstructive lung diseases. Unfortunately, a sound evidence base is lacking and airway clearance strategies are largely based on clinical expertise. One of the reasons for the limited evidence is the lack of a...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审


    authors: Lauwers E,Ides K,Van Hoorenbeeck K,Verhulst S

    更新日期:2020-08-17 00:00:00

  • Sialic acid receptor detection in the human respiratory tract: evidence for widespread distribution of potential binding sites for human and avian influenza viruses.

    abstract:BACKGROUND:Influenza virus binds to cell receptors via sialic acid (SA) linked glycoproteins. They recognize SA on host cells through their haemagglutinins (H). The distribution of SA on cell surfaces is one determinant of host tropism and understanding its expression on human cells and tissues is important for underst...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Nicholls JM,Bourne AJ,Chen H,Guan Y,Peiris JS

    更新日期:2007-10-25 00:00:00