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Review
. 2011 Mar;20(119):7-22.
doi: 10.1183/09059180.10010610.

Update on the roles of distal airways in COPD

P-R Burgel  1 , A Bourdin, P Chanez, F Chabot, A Chaouat, T Chinet, J de Blic, P Devillier, A Deschildre, A Didier, G Garcia, G Jebrak, F Laurent, H Morel, T Perez, C Pilette, N Roche, I Tillie-Leblond, S Verbanck, D Dusser
Affiliations
Review

Update on the roles of distal airways in COPD

P-R Burgel et al. Eur Respir Rev. 2011 Mar.

Erratum in

  • Eur Respir Rev. 2011 Jun;20(120):123

Abstract

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.

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Conflict of interest statement

Statement of Interest

D. Dusser received fees for consultancy, advisory board participation or lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis and Nycomed. Industry-sponsored grants for education were received from GlaxoSmithKline and Boerhinger-Ingelheim. The present article is the result of a workshop organised with the support of Chiesi for which honorarium were received as speaker. P-R. Burgel received fees for advisory board participation or lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis and Nycomed. The present article is the result of a workshop organised with the support of Chiesi for which honorarium were received as speaker. A. Bourdin received a €1,500 fee for speaking from Chiesi during a workshop in 2009 and 2010. P. Chanez has provided consultancy services for Almirall, BI, Centocor, GlaxoSmithKline, MSD, AstraZeneca and Novartis, Teva, Chiesi, and Schering Plough. He has served on advisory boards for Almirall, BI, Centocor, GSK, AstraZeneca, Novartis, Teva, Chiesi, Schering Plough and MSD. He has received lecture fees from Almirall, BI, Centocor, GSK, AstraZeneca, Novartis, Teva, Chiesi, Schering Plough and MSD. He has received industry-sponsored grants from Almirall, BI, Centocor, GSK, AstraZeneca, Novartis, Teva, Chiesi and Schering Plough. F. Chabot has received fees for speaking from Chiesi. Travel to the ERS and SPLF Congresses were funded by Altana, Boehringer Ingelheim, Chiesi and GSK. T. Chinet has received reimbursements for attending meetings and symposia and/or fees for speaking from Chiesi, Pfizer, Boehringer Ingelheim, Novartis, AstraZeneca and GSK. J. de Blic has received consulting fees from Merck, GSK, Chiesi, Stallergenes and ALK; lecture fees from Merck, Chiesi, GSK, Stallergènes and ALK; and has received grant support from GSK. Travel to the ERS and ATS Congresses were funded by GSK and Chiesi. P. Devillier has received fees for speaking or for participating in research boards from Almirall, AstraZeneca, Bioprojet Pharma, Boehringer Ingelheim, Chiesi, GSK, Merck Sharp and Dohme, Nycomed, Sanofi-Aventis, Schering-Plough and Stallergènes. He has received grants for research in fundamental pharmacology from Boehringer Ingelheim, Pierre Fabre, Novartis, Nycomed and Servier. A. Deschildre has relationships with drug companies including GSK, MSD and Novartis, relationships include consultancy and membership of scientific advisory boards. Travel to the ERS and ATS Congresses was funded by GSK. A. Didier has a consulting arrangement with GSK, Stallergenes, ALK, Novartis, MSD and Chiesi, and has received honoraria from AstraZeneca and Schering-Plough. G. Jebrak has received a fee for speaking during a meeting about the subject prior to publication. F. Laurent has received fees for speaking and reimbursement for attending a symposium from Chiesi. H. Morel has received reimbursement for attending a symposium from Boehringer Ingelheim, Chiesi and Novartis. T. Perez was a paid speaker for GSK, AstraZeneca, Novartis, Boehringer Ingelheim and Chiesi, and a consultant for Novartis, Nycomed, Chiesi. He also received funding for clinical research by Boehringer Ingelheim. C. Pilette's travel and accommodation to the “Small airways in COPD” meeting in Vence (France) was funded by Chiesi. I. Tillie-Leblond has received reimbursement for attending a symposium, fees for speaking, funds for research and fees for consultancy from AstraZeneca, GSK, Chiesi, Novartis and Boehringer Ingelheim. N. Roche has received fees for speaking, organising education or consulting from Altana Pharma, Nycomed, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, MEDA, Mundipharma, Novartis, Pfizer and Teva.

Figures

Figure 1.
Figure 1.
Representative photomicrograph of small airways abnormalities in a subject with chronic obstructive pulmonary disease. A narrowed small conducting airway with thickened airway wall (W) is shown. The airway lumen (L) is filled with mucins and inflammatory cells. The arrowheads indicate loss of alveolar attachments. Scale bar = 50 μm.
Figure 2.
Figure 2.
Representative computed tomography (CT) and magnetic resonance imaging (MRI) images showing small airways abnormalities. a) Axial CT image in a 45-yr-old smoker showing areas of low attenuation (arrows) related to early centrilobular emphysema. b) Coronal minimum intensity projection (minIP) image (5 mm thick) in the same subject showing the same lesions with a better conspicuity (arrows). c) Axial CT image in a 56-yr-old smoker with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III chronic obstructive pulmonary disease (COPD). Small airways findings are seen as multiple small micronodules, with some of them showing a typical branched (tree-in-bud) pattern (arrows). Dilated bronchiolectases (arrowheads) are present in the right lower lobe. d) Coronal minIP inspiratory image (5 mm thickness) of a 63-yr-old smoker with GOLD stage III COPD showing multiple areas of hypoattenuation of various size throughout the lung consistent with a mosaic pattern. There is no visual mean for separating emphysema from hypoattenuation areas related to small airways involvement. e) Axial CT image of a 52-yr-old smoker with GOLD stage II COPD showing areas of hypoattenuation in both the upper segments of the lower lobes (#) and thickened large airways (arrows). f) Coronal MRI images after inhalation of hyperpolarised 3He in a 42-yr-old COPD subject showing the heterogeneous distribution of gas within airspaces. Peripheral areas of hypointensity (arrows) are probably related to emphysema or areas of obstructed small airways. (MRI images provided by Y. Cremilleux, Universitie de Lyon, Lyon, France; personal communication).
See this image and copyright information in PMC

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