Cough desensitization treatment: A randomized, sham-controlled pilot trial for patients with refractory chronic cough

Abstract

Background: The purpose of this study was to determine feasibility of treating refractory chronic cough (RCC) with progressive doses of capsaicin paired with cough suppression.

Methods: In this sham-controlled, parallel RCT, 14 adults with RCC were randomly assigned to either behavioral cough suppression therapy (BCST) plus 6 treatment sessions involving exposure to nebulized capsaicin in progressively larger concentrations while actively suppressing cough (n = 8), or BCST plus 6 sessions of exposure to a single subthreshold dose of capsaicin (sham; n = 6). The Leicester Cough Questionnaire (LCQ) was the primary outcome measure. Urge-to-cough (UTC) testing, measuring both UTC and cough frequency, served as secondary outcome measures. Data was analyzed with mixed effects linear regression and follow-up contrasts.

Results: Results on all measures favored the treatment group; however, there was only strong evidence of a difference in treatment effect on cough frequency during UTC testing. Mean change in LCQ at 3-weeks post treatment was 2.95 and 1.75 (p = .23), in the treatment and sham groups, respectively. Cough frequency during UTC testing reduced by 97% and 56% (p < .0001) at three weeks post, respectively. Within-group comparisons revealed strong evidence of change in the treatment group (p < .001) and moderate evidence of a change in the sham group (p = .08) in LCQ.

Conclusions: Conclusions from this study are limited due to the very small sample size; however, the study provides feasibility and proof-of-concept evidence to support further investigation of treating RCC with repeated exposure to nebulized capsaicin paired with BCST.

Trial registration: ClinicalTrials.gov NCT04256733.

Keywords: Capsaicin; Chronic cough; Cough hypersensitivity; Cough suppression; Desensitization; Refractory chronic cough.

Conflict of interest statement

Conflict of interest/Competing interests: The authors declare no conflicts of interest associated with this submission.

Copyright © 2022 Elsevier Ltd. All rights reserved.

Figures

Figure 1.

Study Flow Diagram CCT = cough challenge testing; LCQ = Leciester Cough Questionnaire; UTC = urge-to-cough testing;PT1 = post-test 1; PT2 = post-test 2.

Figure 2:

LCQ scores at baseline, 1-week post-treatment and 3-weeks post-treatment per group.

Figure 3:

Number of coughs elicited during urge-to-cough (UTC) testing at baseline, 1-week post-treatment, and 3-weeks post-treatment per group.

Figure 4.

Sum of urge-to-cough (UTC) scores at baseline, 1-week post-treatment, and 3-weeks post-treatment per group.