Cough-reflex sensitivity to inhaled capsaicin in COPD associated with increased exacerbation frequency

Background and objective: The causes of exacerbations in COPD patients are poorly understood. This study examined the association between cough-reflex sensitivity in patients with stable COPD and the frequency of subsequent exacerbations. Methods: The sampling frame for cases and controls for this study was patients attending a hospital outpatient clinic. cough-reflex sensitivity was evaluated using the log concentration of capsaicin causing five or more coughs (log C-5). Subsequent COPD exacerbations were identified prospectively via symptom-based diaries over a 12-month period. Results: The study group comprised 45 COPD subjects and 10 controls. Mean log C-5 was lower in the COPD group than in the control group (0.97 (95% confidence interval (CI): 0.76-1.18) versus 1.26 (95% CI: 0.81-1.71), P = 0.095). In the COPD group, log C-5 was negatively correlated with serum CRP level (r = -0.36, P = 0.02) and significantly associated with the exacerbation frequency (r = -0.38, P = 0.01). Stepwise multiple regression analysis showed that cough-reflex sensitivity was significantly associated with exacerbation frequency (r(2) = 0.15, P = 0.01). Conclusions: Hypersensitivity of the cough reflex to inhaled capsaicin might reflect airway inflammation in stable COPD patients, which predisposes to frequent exacerbations.