Mechanisms underlying Cough in Health and Disease

Abstract

Introduction: Refractory chronic cough (CC) is a debilitating condition where the majority of patients complain of noxious somatic airway sensations (e.g. throat irritation) which precedes coughing. I propose these sensations drive the urge to cough (UTC) and cough. Furthermore, I hypothesise that low-dose, slow-release morphine sulphate (MST) works by modulating these sensations. I also hypothesise that patients respond differently to tussive agents dependent on the transient receptor potential (TRP) receptors triggered and their own demographics. Methods We devised a novel cough challenge study in healthy volunteers (HV) to identify if VAS rated somatic airway sensations were associated with UTC and cough. This study was repeated using opioid responsive CC patients who withdrew from their MST therapy. The CC patients subsequently entered a placebo controlled randomised control trial assessing the effect of MST on these sensations and UTC. Morphine's antitussive efficacy was assessed simultaneously. I performed another randomised control trial involving four different tussive agents (each acting on a distinct combination of TRP receptors) in both CC and HV. The cough response to each agent was compared by group and other variables in order to determine influencing factors. Results: Somatic sensations/UTC were rated higher per dose citric acid in CC patients versus HV. Somatic sensations were perceived more potently than UTC at low citric acid doses and predicted the UTC and cough in the CC cohort. MST reduced somatic sensations in the CC cohort. This effect was negated at the point of coughing twice (C2). MST reduced both 24-hour cough frequency (-72.4%, p

Date of Award	31 Dec 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Jacky Smith (Supervisor) & Douglas Corfield (Supervisor)