BACKGROUND:Inhaled capsaicin elicits cough reproducibly in human subjects and is widely used in the study of cough and antitussive therapies. However, the traditional end points C2 and C5 (the concentrations of capsaicin inducing at least 2 or 5 coughs, respectively) display extensive overlap between health and disease and therefore might not best reflect clinically relevant mechanisms. OBJECTIVES: We sought to investigate capsaicin dose responses in different disease groups. METHODS: 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 μmol/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. RESULTS: 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 μmol/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 μmol/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). CONCLUSIONS: 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.
RCT Entities:
BACKGROUND: Inhaled capsaicin elicits cough reproducibly in human subjects and is widely used in the study of cough and antitussive therapies. However, the traditional end points C2 and C5 (the concentrations of capsaicin inducing at least 2 or 5 coughs, respectively) display extensive overlap between health and disease and therefore might not best reflect clinically relevant mechanisms. OBJECTIVES: We sought to investigate capsaicin dose responses in different disease groups. METHODS: 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 μmol/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. RESULTS: 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 μmol/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 μmol/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). CONCLUSIONS: 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.
Authors: Kian Fan Chung; Lorcan McGarvey; Woo-Jung Song; Anne B Chang; Kefang Lai; Brendan J Canning; Surinder S Birring; Jaclyn A Smith; Stuart B Mazzone Journal: Nat Rev Dis Primers Date: 2022-06-30 Impact factor: 65.038
Authors: Sara J Bonvini; Mark A Birrell; Jaclyn A Smith; Maria G Belvisi Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2015-01-10 Impact factor: 3.000
Authors: Maria G Belvisi; Mark A Birrell; Saifudin Khalid; Michael A Wortley; Rachel Dockry; Julie Coote; Kimberley Holt; Eric Dubuis; Angela Kelsall; Sarah A Maher; Sara Bonvini; Ashley Woodcock; Jaclyn A Smith Journal: Am J Respir Crit Care Med Date: 2016-06-15 Impact factor: 21.405
Authors: Jaclyn A Smith; Amélie Harle; Rachel Dockry; Kimberley Holt; Philip Russell; Alex Molassiotis; Janelle Yorke; Ryan Robinson; Mark A Birrell; Maria G Belvisi; Fiona Blackhall Journal: Am J Respir Crit Care Med Date: 2021-03-15 Impact factor: 21.405