Sex differences and predictors of objective cough frequency in chronic cough

Background: Women are consistently over-represented in specialist cough clinics and known to have a more sensitive cough reflex than men. Whether female sex and other patient characteristics are associated with higher cough rates is not known. A study was conducted to determine the predictors of objective cough frequency in patients presenting to a tertiary referral clinic with chronic cough. Methods: 100 subjects (65 women) of mean (SD) age 55.8 (11.0) years and median cough duration 4 years (IQR 2.0-10.0) with unexplained chronic cough completed flow-volume loops (mean (SD) forced expiratory volume in 1 s 103 (15.2)% predicted; forced expiratory flow (FEF50) 68.8 (24.1)% predicted), methacholine challenge (42% positive), citric acid cough reflex sensitivity (C5; 0.12 M (IQR 0.06-0.50)) and the Leicester Cough Questionnaire. 24-h ambulatory cough monitoring was performed in 86 subjects; manually counted coughs were quantified as the number of explosive cough sounds per hour. Results: Women coughed significantly more than men (geometric mean 16.6 coughs/h (95% CI 13.1 to 21.0) vs 9.4 coughs/h (95% CI 6.4 to 13.9), p=0.01)). The cough reflex was also more sensitive in women than in men (median logC5 -0.9 M vs 20.6 M, p=0.002), but cough-related quality of life was similar in women and men (12.0 (3.6) and 12.2 (3.2), respectively, p=0.76). Linear regression analysis showed that 38.6% of the variation in cough rate was predicted by sex (p=0.01), logC5 (p < 0.001) and age (p=0.002) but not lung function or bronchial hyper-reactivity. Conclusions: Ambulatory objective cough monitoring provides novel insights into factors modulating chronic cough. These findings suggest that effects of sex and age must be taken into account in the study of cough and when designing clinical trials testing novel antitussive agents.