Mechanisms of Change in Behavioral Cough Suppression Therapy for Refractory Chronic Cough

Overview

This study is testing new ways to help people who have chronic cough that has not improved with typical treatments. One approach is called behavioral cough suppression (BCS) therapy, which teaches people techniques to stop themselves from coughing. Another approach uses capsaicin, the substance that makes chili peppers hot, to help reduce the body's sensitivity to cough triggers. In this study, we will test three treatments: * BCS therapy with capsaicin (BCS+CAP), * BCS therapy with a placebo (BCS+Sham), * Capsaicin stimulation alone (CAP). The investigators will enroll 150 adults with chronic cough and randomly assign them to one of the three treatments. Each person will attend 12 treatment sessions. The investigators want to find out how these treatments affect: * How sensitive someone is to things that make them cough, * How well they can hold back a cough when they try, * How their brain responds to things that cause an urge-to-cough, * And how much their coughing affects their quality of life. The investigators believe all treatments may reduce sensitivity to cough stimulants, but BCS treatments will also improve how people sense and control the urge to cough. The investigators think combining BCS with capsaicin will work the best overall.

Refractory chronic cough (RCC) is a persistent and costly condition that is difficult to treat, often persisting despite appropriate treatment of underlying causes. While behavioral cough suppression (BCS) therapy has shown effectiveness in reducing cough frequency and improving quality of life in controlled studies, it remains underutilized, and the mechanisms by which it works are not well understood. This multi-site randomized controlled trial will investigate the effects and mechanisms of BCS therapy with and without the addition of capsaicin desensitization, compared to capsaicin stimulation alone. Capsaicin, a known cough stimulant, has demonstrated desensitization effects on sensory pathways in conditions such as chronic rhinitis and pain syndromes, suggesting potential utility in modulating cough-related neural pathways. The investigators will recruit 150 participants diagnosed with RCC and randomize them into one of three treatment arms: * BCS combined with capsaicin stimulation (BCS+CAP), * BCS combined with sham stimulation (BCS+Sham), * Capsaicin stimulation alone (CAP). Participants will undergo 12 treatment sessions over several weeks. The study will evaluate both behavioral and neural markers of treatment response. Primary outcome measures will include: * Cough sensory threshold (C5): the lowest concentration of citric acid causing five or more coughs, * Cough suppression ability: the ability to suppress cough when instructed (the difference between the dose of capsaicin causing five or more coughs when trying to suppress cough (CS5) and C5, * Urge-to-cough (UTC) sensory-motor threshold difference: a measure of how perception of the need to cough relates to actual coughing behavior, * Blood oxygen level dependent (BOLD) neural responses using whole-brain functional MRI (fMRI) during UTC stimulation. Secondary outcomes will include patient-reported measures such as the Leicester Cough Questionnaire (LCQ) and objective ambulatory cough frequency monitoring. The investigators hypothesize that all three treatments will lead to desensitization of cough sensitivity (i.e., increase in C5), but only the BCS-based interventions will alter UTC thresholds, suppression ability, and brain network activity. We further hypothesize that the combination of BCS and capsaicin (BCS+CAP) will provide the greatest therapeutic benefit due to simultaneous peripheral desensitization and central sensory-motor modulation.