Smoking may affect epithelial repair and differentiation differentially in smokers with and without chronic obstructive pulmonary disease (COPD). We hypothesized that epithelial repair is disturbed in patients with COPD owing to higher expression of epidermal growth factor (EGF)-like factors and/or receptors. We studied epithelial expression of EGF, transforming growth factor a, amphiregulin, heregulin (HRG), betacellulin (BTC), and their receptors, EGFR, HER-2, and HER-3, by immunohistochemical analysis in resected bronchial tissue from 20 subjects with (forced expiratory volume in 1 second [FEV(1)] <75% of predicted value) and 18 without (FEV(1) >85% predicted value) COPD. All subjects underwent surgery for lung cancer. The proportion of intact, damaged, goblet, or squamous metaplastic epithelium was similar in subjects with and without COPD. Regardless of smoking status, HRG expression was higher in intact epithelium of patients with COPD than in those without. Subgroup analysis showed higher EGFR expression in intact epithelium (1.4 times; P pound .04) and higher EGF, BTC, and HRG expression in damaged epithelium (1.4-1.8 times; P

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