Studies of cough in Idiopathic Pulmonary Fibrosis

Hutchinson, Nicola-Xan 2016. Studies of cough in Idiopathic Pulmonary Fibrosis. MD Thesis, Cardiff University. Item availability restricted.

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Abstract

A dry cough is a common symptom described in patients with IPF and impairs quality of life. The exact mechanisms causing cough in IPF remain unclear, however there is evidence that altered cough neurophysiology and sensitisation plays a roleY IPF patients have an enhanced cough reflex sensitivity to the inhalation of capsaicin. It was hypothesised that IPF patients have increased airway expression of the capsaicin receptor TRPVF1 and a coFexpressed receptor TRPAF1. Bronchial biopsies were obtained in 16 IPF patients, 11 chronic cough patients and 8 controls. Quantitative PCR was used to detect TRPVF1 and TRPAF1 gene expression, with immunohistochemistry demonstrating protein expression. Mean TRPVF1 and TRPAF1 gene expression was higher in IPF patients compared with controls, but the difference did not reach statistical significance. Immunostaining supported these findings. Gastroesophageal reflux is common in IPF patients and has also been implicated. An inFvitro study using cultured pulmonary epithelial cells was conducted to assess the expression of these receptors in a cell model of gastric reflux. TRPVF1 and TRPAF1 gene expression was demonstrated in pulmonary epithelial cells of bronchial and alveolar origin. No significant difference in receptor expression level was seen in either cell line when exposed to the major constituents of gastric refluxate. This study suggests that a structural upFregulation of central airway TRP receptors is not the key mechanism for cough in IPF patients. Similarly, it does not support the role of the individual constituents of gastric refluxate resulting in cough hypersensitivity through a physical upFregulation of receptors in pulmonary epithelial cells. Overall this thesis outlines the complexity of the cough reflex. It is probable that cough in IPF results from the cumulative manifestation of various physiological changes and mechanisms.

Item Type:	Thesis (MD)
Date Type:	Completion
Status:	Unpublished
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Date of First Compliant Deposit:	14 September 2016
Last Modified:	23 Aug 2021 14:01
URI:	https://orca.cardiff.ac.uk/id/eprint/94471

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