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P1 A Novel Capsaicin Cough Challenge In Healthy Adults; Beyond The C5
  1. K Holt1,
  2. C Gibbard1,
  3. K Ahern2,
  4. JA Smith1
  1. 1University of Manchester, Manchester, UK
  2. 2University Hospital of South Manchester, Manchester, UK

Abstract

Introduction We have developed a novel cough challenge methodology and previously showed that evoked maximal cough responses, defined as Emax, better discriminate health from disease than traditional endpoints.1 It is unclear how other factors influence Emax or how it relates to the low cough rates observed in health. We therefore aimed to investigate the variability, repeatability and influences on Emax 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 (Emax) and the dose that elicited half of the Emax, 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 Emax was 11 coughs (IQR, 8–19) with an ED50 of 15.6[micro]M (7.8–109.4). The intraclass correlation coefficients for Emax 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 Emax. 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 Emax or ED50.

Conclusion Data collected to date has demonstrated that in healthy volunteers, Emax and ED50 are stable measures over time however Emax 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

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