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An investigation into the mechanism of inhalational cough challenge

Fowles, Helen Elizabeth


Helen Elizabeth Fowles


Alyn H. Morice


Chronic cough is a common problem. Historically treatments have focussed on treating underlying physiological causes. More recently an overarching theory of cough hypersensitivity syndrome has developed. In-vitro models of cough have not successfully translated into human studies. Testing the cough reflex in humans via inhalational cough challenge has been utilised since the 1950s. The mechanisms of cough challenge are poorly understood. This thesis sets out to investigate these mechanisms further in three different experiments. By altering pH in a citric acid challenge and measuring cough response, I show that cough hypersensitivity is not due purely to a shift in the dose response curve to pH, but also an alteration in the pattern of response to a given stimulus. Designing a cough challenge with a novel agent (ATP) revealed that the cough response to ATP is clearly delineated from that of AMP. The response to ATP in chronic cough is heightened, but not to such a degree as to implicate the acute response to inhalation of ATP in the pathophysiology of cough hypersensitivity syndrome. Comparing four cough challenges – the commonly used citric acid and capsaicin; the slightly less utilised distilled water fog challenge; and the new ATP challenge – proved that all challenges show less intra-patient reproducibility in chronic cough patients. Inhaled ATP cough challenge responses correlated with citric acid and capsaicin challenge suggesting overlap in mode of action. All experiments explore the cough challenge further in a group who have had little previous cough challenge investigation: the patient with chronic cough. They reveal that patients with cough hypersensitivity syndrome have not only a heightened but an unpredictable cough reflex, and that this is not due solely to upregulation of the cough receptors at peripheral nerve endings. Inhalational cough challenge plays an important role in further elucidating the mechanisms of chronic cough.


Fowles, H. E. (2018). An investigation into the mechanism of inhalational cough challenge. (Thesis). Hull York Medical School, the University of Hull and the University of York. Retrieved from

Thesis Type Thesis
Deposit Date Oct 19, 2018
Publicly Available Date Feb 23, 2023
Keywords Medicine
Public URL
Additional Information Hull York Medical School, The University of Hull and The University of York
Award Date Jan 1, 2018


Thesis (2.6 Mb)

Copyright Statement
© 2018 Fowles, Helen Elizabeth. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.

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