Cough reflex sensitivity has not been studied extensively in patients with chronic obstructive pulmonary disease (COPD). The aim of the study was to evaluate cough reflex sensitivity to capsaicin in current and former smokers with COPD and examine its association with potentially protussive mediators. Fifteen active smokers and 18 ex-smokers with moderate to severe COPD, 14 healthy active smokers, and 13 healthy never smokers were enrolled. Capsaicin aerosol was administered in order of ascending concentration until the concentrations inducing two or more coughs (C(2)) and five or more coughs (C(5)) were attained. The concentrations of leukotriene E(4) (LTE(4)), leukotriene B(4) (LTB(4)), and interleukin-8 (IL-8) in bronchoalveolar lavage (BAL) fluid were analyzed by ELISA. Cough reflex sensitivity in COPD smokers [mean log C(2) = 1.20 +/- 0.23 (SEM) microM; log C(5) = 1.85 +/- 0.21 microM] did not differ from that in COPD ex-smokers (log C(2) = 1.15 +/- 0.14 microM; log C(5) = 2.10 +/- 0.19 microM; p > 0.05). Mean C(2) and C(5) in both COPD groups were significantly lower than in healthy active smokers, but higher compared with the healthy never-smokers. BAL fluid concentrations of LTE(4) and LTB(4) were similar in all groups. IL-8 concentrations did not differ between COPD smokers, COPD ex-smokers, and healthy active smokers, but were significantly higher in all three groups compared with healthy never smokers. Cough reflex sensitivity to capsaicin does not differ between smokers and ex-smokers with COPD.