NOVEL CAPSAICIN DOSE-RESPONSE PARAMETERS: INFLUENCES IN HEALTHY VOLUNTEERS

Abstract

IntroductionCapsaicin cough challenges have been used for many years to assess cough reflex sensitivity however traditional endpoints neither discriminate between health and disease nor predict spontaneous cough frequency. Consequently, normal reference ranges have never been established and no clinical test for cough hypersensitivity exists. We have developed a novel cough challenge method and have shown that maximal cough responses to capsaicin, Emax, better discriminates between health and disease. It is important to validate this challenge in large numbers and establish what factors influence such novel endpoints, in order to assess their clinical utility.AimsThis thesis aimed to investigate the variability, repeatability and influences on novel cough challenge endpoints, Emax and ED50, mainly in a large group of healthy volunteers, with a small group of chronic cough patients for comparison. MethodsAll participants recruited to the study were required to undergo 24 hour cough monitoring using the VitaloJAKTM cough recorder followed by a full dose-response capsaicin cough challenge within 2 weeks. Doubling doses of capsaicin (0.49 to 1000microM) 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. In a subset of participants, the cough challenge was repeated within 2 weeks. ResultsForty seven healthy volunteers and 11 patients with chronic cough completed the study. There was a highly significant difference between the groups for Emax (P

Date of Award	1 Aug 2015
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Jacky Smith (Supervisor) & Angela Kelsall (Supervisor)