Introduction We have developed a novel cough challenge methodology and previously showed that evoked maximal cough responses, defined as E_max, better discriminate health from disease than traditional endpoints.¹ It is unclear how other factors influence E_max or how it relates to the low cough rates observed in health. We therefore aimed to investigate the variability, repeatability and influences on E_max in a larger group of healthy volunteers.

Objective To assess maximum cough responses to capsaicin in a group of healthy adults representing a wide range of ages.

Method Doubling doses of capsaicin 0.49 to 1000[micro]M) were inhaled sequentially up to the maximum tolerated dose. Four inhalations of each dose were administered 30 seconds apart and the number of coughs evoked within 15 seconds was recorded. The maximum number of coughs evoked by any dose of capsaicin (E_max) and the dose that elicited half of the E_max, defined as ED₅₀, were calculated. General linear models were used to assess the influence of subject demographics on these endpoints.

Results Forty seven healthy volunteers performed the capsaicin challenge; median age 38 years (range 20–74), 17 males, median FEV₁ 103% predicted (97–115), median BMI 25.0 (22.2–28.6), and median total cough rate 0.2 c/h (0.0–0.1). The median E_max was 11 coughs (IQR, 8–19) with an ED₅₀ of 15.6[micro]M (7.8–109.4). The intraclass correlation coefficients for E_max and ED₅₀ were 0.89 and 0.96 respectively which were highly significant (p < 0.001). Age, gender, FEV₁ and BMI had no significant influence on E_max. In contrast, gender (p < 0.001) and BMI (p = 0.029) both significantly influenced ED₅₀ explaining 41.7% of the variation. Those subjects with a higher BMI and females tended to have a lower ED₅₀. Objective 24 h cough frequency did not correlate with either E_max or ED₅₀.

Conclusion Data collected to date has demonstrated that in healthy volunteers, E_max and ED₅₀ are stable measures over time however E_max has the advantage of being independent of patient factors. Intere stingly, objective cough frequency in healthy volunteers seems to be unrelated to capsaicin evoked coughing.

References

1. J Allergy Clin Immunol. 2013 Oct;132(4):847–55