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Published ahead of print on June 1, 2004, doi:10.1164/rccm.200401-112OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 5, September 2004, 499-504

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Submitted on January 26, 2004
Accepted on May 20, 2004

Dissociation of Lung Function and Airway Inflammation in Chronic Obstructive Pulmonary Disease

Therese S Lapperre1*, Jiska B Snoeck-Stroband2, Margot M E Gosman3, Jan Stolk1, Jaap K Sont4, Desiree F Jansen5, Huib A M Kerstjens3, Dirkje S Postma3, Peter J Sterk1, and The GLUCOLD Study Group1

1 Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands, 2 General Practice, Leiden University Medical Center, Leiden, The Netherlands, 3 Department of Pulmonology, University of Groningen, Groningen, The Netherlands, 4 Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands, 5 Department of Epidemiology and Statistics, University of Groningen, Groningen, The Netherlands

* To whom correspondence should be addressed. E-mail: t.s.lapperre{at}lumc.nl.

Chronic obstructive pulmonary disease (COPD) is defined by progressive, irreversible airflow limitation and an inflammatory response of the lungs, usually to cigarette smoke. However, COPD is a heterogeneous disease in terms of clinical, physiological and pathological presentation. We aimed to evaluate whether airflow limitation, airway responsiveness and airway inflammation are separate entities underlying the pathophysiology of COPD by using factor analysis. 114 patients (M/F: 99/15, age 62±8 yrs, 42 pack years smoking, no inhaled or oral steroids >6 months) with irreversible airflow limitation (postbronchodilator FEV1 63±9 %pred, FEV1/IVC 48±9 %) and symptoms of chronic bronchitis or dyspnea were studied in a cross-sectional design. Postbronchodilator FEV1 and FEV1/IVC, reversibility to inhaled b2-agonists, diffusion capacity (KCO), PC20 methacholine, total serum IgE, exhaled nitric oxide (eNO) and induced sputum cell counts (% eosinophils, % neutrophils) were collected. Factor analysis yielded 4 separate factors that accounted for 63.6% of the total variance. Factor 1 comprised FEV1, FEV1/IVC and RV/TLC. Factor 2 included reversibility, IgE, PC20 and KCO. Factor 3 contained eNO and factor 4 sputum % neutrophils and % eosinophils. We conclude that airflow limitation, airway inflammation and features commonly associated with asthma are separate and largely independent factors in the pathophysiology of COPD.
Key words: induced sputum, bronchial hyperreactivity, bronchodilator reversibility, nitric oxide, factor analysis




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