PROJECT SUMMARY/ABSTRACT Chronic cough affects millions of people in the US and around the world, and has a significant negative impact on quality of life, especially when it is refractory to treatment. Existing treatments for chronic cough can help, but up to 50% of patients have persistent cough symptoms despite receiving standard treatments. Identifying effective treatments for refractory chronic cough aligns with the mission of the NHLBI to advance the treatment of lung and related diseases, enhancing “the health of all individuals so that they can live longer and more fulfilling lives.” A promising approach to treating refractory chronic cough is laryngeal vibrotactile stimulation, which changes sensory input to the larynx with the goal to break the vicious cycle of cough causing laryngeal irritation and increased sensitivity, which in turn causes more cough. Chronic cough is associated with abnormalities in laryngeal sensorimotor cortex activity in areas that can be modulated by the use of laryngeal vibrotactile stimulation. In preliminary findings, the use of laryngeal vibrotactile stimulation was associated with an improvement in cough-related quality of life and cough counts, and participants expressed interest in increased laryngeal vibrotactile stimulation dosing. In Aim 1 of this proposal, dose refinement for vibrotactile stimulation will be performed, using a series of escalating dose conditions. The most favorable dosing will be identified, taking into account acceptability and tolerability for participants as well as changes in cough-related quality of life and objective cough counts. In Aim 2, a pilot randomized controlled trial will be conducted to measure the effect of 4 weeks of laryngeal vibrotactile stimulation use on key cough outcomes. Data on acceptance of randomization and retention will be collected. Changes in cough-related quality of life, cough severity, and objective cough counts will be measured. These aims will be conducted by a multidisciplinary research team with expertise in pulmonology, laryngeal physiology and function, clinical trials, biostatistics, and medical devices, in partnership with an extensive and engaged network of referring providers. Completion of these aims will provide necessary and sufficient information about the feasibility and acceptability of a subsequent randomized clinical trial to definitively test the effect of laryngeal vibrotactile stimulation on refractory chronic cough. In addition, the proposed project will provide a preliminary estimate of the effect of laryngeal vibrotactile stimulation on cough-related quality of life as well as an estimate of the resources needed to conduct a subsequent definitive clinical trial. This study has the potential to lead to a non-invasive, portable, repeatable treatment free of systemic side effects for the millions of people who suffer from refractory chronic cough.