Novel capsaicin cough endpoints effectively discriminate between healthy controls and patients with refractory chronic cough

Rationale: Chronic cough is a common problem, substantially affecting quality of life. Effective treatments and diagnostic clinical tools for refractory chronic cough are lacking which remains a diagnosis of exclusion. Objectives: To investigate capsaicin evoked cough responses in healthy volunteers and refractory chronic cough patients and assess the discriminatory ability of novel endpoints. Methods: Dose-response capsaicin cough challenges were performed, and receiver operating characteristic curves constructed to evaluate the discriminatory value of novel endpoints; Emax (maximum number of coughs evoked by any capsaicin concentration) and ED50 (capsaicin concentration evoking at least half of Emax). Measurements and main results: Ninety-three healthy volunteers (median age 39yrs(IQR; 29-52), 47 females) and 51 refractory chronic cough patients (59yrs(53-67), 31 females) were studied. Emax was significantly higher in the patient group compared to healthy volunteers (p < 0.001) and ED50 was significantly lower (p = 0.001). Both parameters were influenced by gender; females had a higher Emax (p = 0.009) and more sensitive ED50 (p < 0.001) but there were no correlations with other patient demographics. There was a significant relationship between Emax and cough frequency in the patient group (p < 0.001). Emax effectively discriminated between the groups (AUC = 0.83, 95% CI; 0.75-0.90, p < 0.001) independently of ED50 which was less favourable (AUC = 0.66, 95% CI; 0.57-0.76, p = 0.002). Emax and ED50 were shown to be repeatable, and the dose-response method well tolerated. Conclusion: Novel capsaicin dose-response endpoints effectively discriminate between healthy controls and refractory chronic cough patients, which may better represent pathophysiological mechanisms and show promise for development as a tool to identify patients with cough hyper-excitability.