PROJECT SUMMARY/ABSTRACT Cough hypersensitivity syndrome (CHS) is a disorder characterized by chronic coughing, which leads to serious health sequelae such broken ribs, unintended urine leakage, and fainting. Because coughing is a respiratory symptom across a variety of chronic lung diseases, the investigation of CHS aligns with the research priorities identified in the Strategic Vision of the National Heart, Lung, and Blood Institute. A critical barrier to progress is that clinical practice presents two distinct treatment approaches for CHS. Pharmacologic options include neuromodulating medications and nerve block injections, while nonpharmacologic options rely on cognitive behavioral principles via speech therapy. The lack of empirical evidence to guide which of these extremely different treatments to recommend for an individual patient results in a trial-and-error approach, resulting in increased misdiagnosis and unnecessary, risky, and expensive treatments. The exact components of nonpharmacologic speech therapy that target underlying mechanisms of change in CHS remain unknown, presenting a barrier to future treatment optimization. The central rationale for the proposed research is that cough symptomology can identify CHS patient subgroups, which will more accurately predict which patients respond to different CHS treatments. Preliminary work demonstrates that the symptom of the urge-to-cough using the general Labeled Magnitude Scale successfully detects changes in healthy adults, which needs to be trialed as a metric of cough symptomology in patients with CHS. The current project addresses these critical gaps by (Aim 1) investigating whether cough symptoms predict responses to treatments for CHS, and (Aim 2) determining the feasibility of a pilot randomized controlled trial of a nonpharmacologic treatment, acceptance and commitment therapy, in patients with CHS. Aim 1 will provide essential clinical guidance by establishing a scientifically informed approach to predict which patients with CHS are candidates for pharmacologic versus nonpharmacologic treatments. Aim 2 will demonstrate feasibility, acceptability, and preliminary data for pursuing larger randomized controlled trials in specific nonpharmacologic interventions for CHS. The proposed K23 award will address these research needs by focusing on essential career development training in the areas of clinical trials, cough neurobiology, respiratory psychology, and scientific leadership. Taken together, completion of the proposed project will logically lead to an independent patient-oriented research program focused on improving symptom burden and quality of life in patients with CHS across the spectrum of chronic lung disease.