We sought to investigate capsaicin dose responses in different disease groups.
Two novel capsaicin cough challenges were compared in patients with chronic cough (CC; n?= 20), asthmatic patients (n?= 18), and healthy volunteers (HVs; n?= 20). Increasing doubling doses of capsaicin (0.48-1000 ¦Ìmol/L, 4 inhalations per dose) were administered in challenge 1, whereas the order of the doses was randomized in challenge 2. A?nonlinear mixed-effects model compared dose-response parameters by disease group and sex. Parameters were also correlated with objective cough frequency.
The model classified subjects based on maximum cough response evoked by any concentration of capsaicin (Emax) and the capsaicin dose inducing half-maximal response (ED50). HVs and asthmatic patients were not statistically different for either parameter and therefore combined for analysis (mean ED50, 38.6 ¦Ìmol/L [relative SE, 28 % ]; mean Emax, 4.5 coughs [relative SE, 11 % ]). Compared with HVs/asthmatic patients, patients with CC had lower ED50 values (14.7 ¦Ìmol/L [relative SE, 28 % ], P?= .008) and higher Emax values (8.6 coughs [relative SE, 11 % ], P?< .0001). Emax values highly correlated with 24-hour cough frequency (r?= 0.71, P?< .001) and were 37 % higher in female compared with male subjects, regardless of disease group (P?< .001).
Nonlinear mixed-effects modeling demonstrates that maximal capsaicin cough responses better discriminate health from disease and predict spontaneous cough frequency and therefore provide important insights into the mechanisms underlying CC.