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

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 an inhaled substance designed to enhance the effect of BCS treatment. The active inhaled substance used in the study 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. Inhalation of this substance has been shown to be safe across multiple studies. The investigators will recruit 135 participants diagnosed with RCC. 100 participants will be randomized into one of two treatment arms -- BCS combined with an active inhaled substance, and BCS combined with an inactive inhalant. A non-randomized no-treatment control group (n=35) will be included to provide a control comparison to fMRI. Participants in the treatment arms 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 (CS Thresh Diff): the ability to suppress cough when instructed, quantified by 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 (UTC S-M Thresh Diff): 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. The following patient-report outcome measures (PROMS) will be included as secondary outcomes: * Leicester Cough Questionnaire (LCQ): Assesses patient-reported cough-related quality of life, relevant for assessing the broader impact of treatment. * PROMIS-Global Health: Assesses patient-reported generalized quality of life, relevant for assessing the broader impact of treatment. * Voice Handicap Index-10 (VHI-10): Assesses patient-reported impact of voice problems and is relevant for assessing the broader impact of treatment. * Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ): Assesses patient-reported laryngeal sensory symptoms and is relevant for assessing the broader impact of treatment * Multidimensional Assessment of Interoceptive Awareness (MAIA-2): Assesses patient-reported awareness and regulation of bodily sensations and is relevant for assessing the broader impact of treatment * Patient Global Impression of Severity (PGI-S): Assesses patient-reported overall perception of cough severity and is relevant for assessing the broader impact of treatment * Patient Global of Impression of Change (PGI-C): Assesses patient-reported impression of change related to treatment and is relevant for assessing the broader impact of treatment * PROMIS-Sleep: Assesses patient-reported sleep quality and is relevant for assessing the broader impact of treatment Ambulatory cough frequency monitoring will also be included as a secondary outcome. This data will be collected with the CoughMonitor smartwatch by Hyfe, Inc. The investigators hypothesize that both treatments will lead to desensitization of cough sensitivity (i.e., increase in C5). We further hypothesize that the combination of BCS+active inhaled treatment will provide the greatest therapeutic benefit on all outcome measures due to simultaneous peripheral desensitization and central sensory-motor modulation. Regarding fMRI, we hypothesize that both treatments will result in increased activity in areas responsible for motor inhibition (e.g., prefrontal cortex).