PROJECT SUMMARY/ABSTRACT Generalized approaches for laryngopharyngeal reflux (LPR), a prevalent and heterogeneous syndrome in which laryngeal symptoms are attributed to gastroesophageal reflux, have led to poor health outcomes, inappropriate resource utilization, and tremendous healthcare costs. The long-term career goal is to discover phenotype guided care paradigms for LPR, focused on distinct disease mechanism. Our preliminary findings have generated the central hypothesis that identification of distinct LPR phenotypes is feasible and that psychological processes such as hypervigilance and anxiety impact symptom burden in LPR. Thus, the overall objectives in this proposal are to establish a validated method to measure levels of hypervigilance and anxiety surrounding laryngeal symptoms and understand whether distinct LPR phenotypes report differing levels of hypervigilance and anxiety. The rationale for this project is that it will highlight the impact of cognitive-affective processes on LPR symptom burden and generate hypotheses surrounding the role of behavioral interventions in LPR. Thus, two specific aims will be pursued: 1) validate the laryngeal hypervigilance and anxiety scale [LHAS] self-report instrument, and 2) measure levels of hypervigilance and anxiety across distinct LPR phenotypes. Under the first aim, 200 symptomatic patients and 40 healthy volunteers will complete the LHAS and a set of validated instruments measuring psychological distress and health related quality of life. Psychometric properties of the LHAS will be assessed and a preliminary cutoff for the LHAS will be determined. Under the second aim, the 200 symptomatic patients will be categorized into LPR phenotypes utilizing our prior model from discriminant analysis of principal components. Levels of laryngeal hypervigilance and anxiety will be measured and compared across LPR phenotypes, as well as the healthy volunteers. The proposed research is significant as it is expected to fill a key evidence gap about the interplay of psychological stressors on LPR symptom burden. This research is innovative as it will provide a novel clinical tool to evaluate cognitive affective processes in patients with LPR as well as inform the framework of a first-of- its-kind phenotype stratified randomized controlled trial to assess efficacy of behavioral interventions compared to traditional anti-reflux therapy such as proton pump inhibitors in patients with LPR.