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

Thérèse S Lapperre, Jacob K Sont, Annemarie van Schadewijk, Margot Me Gosman, Dirkje S Postma, Ingeborg M Bajema, Wim Timens, Thais Mauad, Pieter S Hiemstra, GLUCOLD Study Group, Thérèse S Lapperre, Jacob K Sont, Annemarie van Schadewijk, Margot Me Gosman, Dirkje S Postma, Ingeborg M Bajema, Wim Timens, Thais Mauad, Pieter S Hiemstra, GLUCOLD Study Group

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 (> or =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.

Figures

Figure 1
Figure 1
Epithelial phenotype in smokers (S) and ex-smokers with COPD. Individual values of: (A) % PAS/AB+ area of intact epithelium, (B) Ki-67+ cells (/mm basement membrane = BSM) in intact epithelium, (C) % squamous cell metaplasia (SCM) of intact epithelium (note: in a large % of patients no SCM was observed), (D) % EGFR+ area of intact epithelium. Data are grouped by COPD smokers (S), COPD ex-smokers who quit < 3.5 years ago (<3.5 yr), and who quit ≥3.5 years ago (≥3.5 yr). Horizontal bars represent median values, * p < 0.05.

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