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

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

The GLUCOLD Study Group consists of: H.F. Kauffman, D. de Reus, Dept. of Allergology; H.M. Boezen, D.F. Jansen, J. Vonk, Dept. of Epidemiology and Statistics; M.D.W. Barentsen, W. Timens, M. ZeinstraSmit, Dept. of Pathology; A.J. Luteijn, T. van der Molen, G. ter Veen, Dept. of General Practice; M.M.E. Gosman, N.H.T. ten Hacken, H.A.M. Kerstjens, M.S. van Maaren, D.S. Postma, C.A. Veltman, A. Verbokkem, I. Verhage, H.K. VinkKloosters, Dept. of Pulmonology; University Medical Centre Groningen, Groningen, The Netherlands. J.B. SnoeckStroband, H. Thiadens, Dept. of General Practice; J.K. Sont, Dept. of Medical Decision Making; I. Bajema, Dept. of Pathology; J. GastStrookman, P.S. Hiemstra, K. Janssen, T.S. Lapperre, K.F. Rabe, A. van Schadewijk, J.A. Schrumpf, J. SmitBakker, J. Stolk, A.C.J.A. Tiré, H. van der Veen, M.M.E. Wijffels and L.N.A. Willems, Dept. of Pulmonology; Leiden University Medical Centre, Leiden, The Netherlands; P.J. Sterk, Department of Pulmonology, Academic Medical Centre, University of Amsterdam, The Netherlands; T. Mauad, University of Sao Paulo, Sao Paulo, Brazil. The GLUCOLD Study Group applied for, and received grants from: the Netherlands Organization for Scientific Research (NWO) in a collaborative program with the Netherlands Asthma Foundation (grant 3.4.93.96.3), GlaxoSmithKline (The Netherlands), the University Medical Centre Groningen and the Leiden University Medical Centre.