Cough desensitization treatment for patients with refractory chronic cough: results of a second pilot randomized control trial

Objective: The purpose of this study was to collect pilot efficacy data on a novel treatment for refractory chronic cough (RCC), which we call cough desensitization treatment (CDT). Design and methods: In this parallel cohort, sham-controlled, randomized controlled trial, 21 adults with RCC were randomly assigned to 12 sessions of either CDT (progressive doses of aerosolized capsaicin while behaviorally suppressing cough; n = 11) or a sham treatment (repeated exposure to aerosolized saline; n = 9). The Leicester Cough Questionnaire (LCQ) was the primary outcome measure. Perceived cough severity with a visual analogue scale and cough challenge testing (for measuring cough-reflex sensitivity) were secondary outcome measures. Data were analyzed with mixed effects linear regression and follow-up contrasts. Results: Results on all measures favored CDT. Excluding one sham participant, whose baseline LCQ scores were deemed unreliable, mean change in LCQ at 3-weeks post treatment was 6.35 and 2.17 in the CDT and sham groups, respectively. There was moderate to strong evidence of a greater improvement in the CDT group in total LCQ score (p =.058) and LCQ Psychological domain (p =.026) and Physical domain (p =.045) scores. Strong evidence was found for a greater reduction in urge-to-cough during CCT in the CDT group (p =.037) and marginal for a reduction in the capsaicin cough-reflex sensitivity (p =.094). There was weak evidence of a greater reduction in cough severity in the CDT group (p =.103). Discussion: Although the study is limited due to the small sample size, the data provide additional evidence supporting further research on CDT. CDT resulted in a greater change in the primary efficacy measure (LCQ) than both pharmaceutical and behavioral treatments currently found in the literature. Trial Registration: This trial (NCT05226299) was registered on Clinicaltrials.gov on 07/02/2022.