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


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


BACKGROUND
NCT00158847.
Lapperre
Thérèse S
TS
Dept. of Pulmonology, Leiden University Medical Centre, Leiden, The Netherlands. t.s.lapperre@lumc.nl
Sont
Jacob K
JK
van Schadewijk
Annemarie
A
Gosman
Margot Me
MM
Postma
Dirkje S
DS
Bajema
Ingeborg M
IM
Timens
Wim
W
Mauad
Thais
T
Hiemstra
Pieter S
PS
D000368:Aged; D001980:Bronchi / Q000473:pathology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology*; D020545:Respiratory Mucosa / Q000473:pathology*; D016540:Smoking Cessation