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Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional study

Thérèse S Lapperre1*, Jacob K Sont2, Annemarie van Schadewijk1, Margot ME Gosman5, Dirkje S Postma5, Ingeborg M Bajema3, Wim Timens6, Thais Mauad1,4, Pieter S Hiemstra1 and the GLUCOLD Study Group7

Author Affiliations

1 Dept. of Pulmonology, Leiden University Medical Centre, Leiden, The Netherlands

2 Dept. of Medical Decision Making, Leiden University Medical Centre, Leiden, The Netherlands

3 Dept. of Pathology, Leiden University Medical Centre, Leiden, The Netherlands

4 Dept. of Pathology, University of Sao Paulo, Sao Paulo, Brazil

5 Dept. of Pulmonology, University Medical Centre Groningen, The Netherlands

6 Dept. of Pathology, University Medical Centre Groningen, The Netherlands

7 The GLUCOLD Study Group: Groningen Leiden Universities and Corticosteroids in Obstructive Lung Disease, a full list of members is listed at the back

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Respiratory Research 2007, 8:85 doi:10.1186/1465-9921-8-85

Published: 26 November 2007

Abstract

Background

Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia. These features are partially attributed to activation of the epidermal growth factor receptor (EGFR). Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists. We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation.

Methods

114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 ± 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV1 63 ± 9% predicted. Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue+) area (%), proliferating (Ki-67+) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies.

Results

Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression. Epithelial features were not different between short-term quitters (<3.5 years) and current smokers. Long-term quitters (≥3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs. 14.4%, p = 0.005; 7.9% vs. 13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs. 18.6%, p < 0.001).

Conclusion

Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years).

Trial registration

NCT00158847