Abstract

Dry cough is a common symptom described in patients with Idiopathic Pulmonary Fibrosis (IPF) and impairs quality of life. The exact mechanisms causing cough in IPF remain unclear, however evidence suggests altered cough neurophysiology and sensitisation plays a role; IPF patients have an enhanced cough reflex sensitivity to inhaled capsaicin. The Transient Receptor Potential Vanniloid-1 channel (TRPV-1) has a role in the cough reflex and airway expression is increased in patients with chronic cough. The Ankyrin-1 receptor (TRPA-1) is often co-expressed. It was hypothesised that, like chronic cough patients, IPF patients have increased airway TRP receptor expression. Bronchial biopsies were obtained from 16 patients with IPF, 11 patients with idiopathic chronic cough and 8 controls without cough. All other causes of cough were rigorously excluded. Real-time quantitative Polymerase Chain Reaction was used to detect TRPV-1 and TRPA-1 mRNA expression with Immunohistochemistry demonstrating protein expression. Mean TRPV-1 and TRPA-1 gene expression was higher in IPF patients compared with controls, but the difference did not reach statistical significance. Immunostaining supported these findings. This study suggests that structural up-regulation of central airway TRP receptors is not the key mechanism for cough in IPF patients. It is probable that IPF cough results from altered neuronal sensitivity at multiple levels of the cough pathway.

Highlights

  • Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrotic interstitial lung disease of unknown aetiology [1]

  • We have shown that Transient Receptor Potential Vanniloid-1 channel (TRPV-1) and Transient Receptor Potential Ankyrin 1 (TRPA-1) receptor expression is not significantly increased in the central airways of patients with IPF at gene or protein level when compared with patients with chronic cough and normal controls

  • Cough was the predominant symptom in all IPF and chronic cough (CC) patients, there was no significant association between the level of airway transient receptor potential (TRP) receptor expression and cough severity measured by Visual Analogue Score (VAS) and Leicester Cough Questionnaire (LCQ)

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Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrotic interstitial lung disease of unknown aetiology [1]. Despite new therapeutic strategies the prognosis for the majority of patients remains poor with a median survival of less than 4 years and supportive therapy remains the mainstay of treatment for many [2]. A debilitating dry cough is described in more than 70% of IPF patients [2]. Patients have been shown to have higher 24-hour cough counts compared with controls [3] and this symptom impairs quality of life [4].

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