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Impaired cough suppression in chronic refractory cough
Sabtu, 20 Apr 2019 17:12:47
Peter S. P. ChoHannah V. FletcherRichard D. TurnerCaroline J. JolleySurinder S. Birring
European Respiratory Journal 2019; DOI: 10.1183/13993003.02203-2018

Abstract

Functional brain imaging in individuals with chronic cough demonstrates reduced activation in cortical regions associated with voluntary cough suppression. Little is known about the ability of patients with chronic cough to suppress cough. This study aimed to compare the ability to voluntarily suppress cough during inhaled capsaicin challenge in participants with chronic refractory cough with that in healthy controls. This study also aimed to assess the repeatability of capsaicin challenge test with voluntary cough suppression.

Participants with chronic refractory cough and healthy controls underwent inhaled capsaicin challenge tests whilst attempting to suppress their cough responses. After 5 days either a conventional capsaicin challenge test with no cough suppression attempt, or a repeat test with an attempt at cough suppression was performed. Threshold capsaicin concentrations required to elicit 1, 2 and 5 coughs were calculated by interpolation. Objective 24-hour cough frequency was measured in individuals with chronic refractory cough.

Healthy controls were able to suppress capsaicin-evoked cough whilst participants with chronic refractory cough were not. Geometric mean (sd) capsaicin dose thresholds for 5 coughs with (CS5) and without (C5) suppression attempts were 254.40 (3.78) versus 45.89 (3.95) µmol.L−1respectively in healthy controls (p=0.033) and 3.34 (5.04) versus 3.86 (5.13) µmol.L−1 in patients (p=0.922). Capsaicin dose thresholds for triggering 5 coughs with self-attempted cough suppression were significantly lower in participants with chronic refractory cough than in healthy controls; geometric mean (sd) 4.94 (4.43) versus 261.10 (4.34) µmol.L−1 respectively; mean difference (95% CI) 5.72 (4.54–6.91) doubling doses (p<0.001). Repeatability of cough suppression test in both patients and healthy controls was high; intraclass correlation coefficients of log(CS5) values 0.81 and 0.87 respectively. CS5 was associated with objective cough frequency (ρ=−0.514, p=0.029).

Participants with chronic refractory cough were less able to voluntarily suppress capsaicin-evoked cough compared to healthy controls. This may have important implications for the pathophysiology and treatment of chronic cough.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Cho reports a grant from Merck outside the submitted work.

Conflict of interest: Dr. Fletcher has nothing to disclose.

Conflict of interest: Dr. Turner has nothing to disclose.

Conflict of interest: Dr. Jolley has nothing to disclose.

Conflict of interest: Dr. Birring reports grants from Merck, personal fees from Merck, personal fees from Bayer, personal fees from GSK, personal fees from Menlo, personal fees from Sanofi, other from Boehringer Ingleheim, outside the submitted work.