PROJECT SUMMARY/ABSTRACT Upper aerodigestive functions, including swallowing and airway clearance, are critical for airway protection. In people with sporadic inclusion body myositis (IBM), swallowing impairment, or dysphagia, is recognized as the primary contributor to early mortality, given its association with aspiration pneumonia. Further, upper aerodigestive dysfunction is linked to reduced quality of life and substantial economic healthcare burden in people with IBM. While these poor outcomes are well recognized in the literature, the project team has found that the mechanism underlying these impairments is poorly understood in IBM and has yet to be well-defined using well-tested measures. Preliminary data analyzed by the project team has begun to address this issue by applying the standardized and validated Modified Barium Swallow Impairment Profile (MBSImP) approach. Specifically, data of 13 patients with IBM revealed significantly worse and widespread dysfunction across 11 physiologic swallow components, primarily within the pharyngeal domain, when compared to an age- and sex-matched healthy cohort. Such efforts need to be further applied to define IBM's gestalt and nuanced impact on swallowing physiology. Moreover, airway clearance ability has not been investigated despite it being the first line defense mechanism to aspiration. Through a cross-sectional design and by leveraging methods that are well-tested in diseases with similar clinical phenotypes to IBM, the research premise is to uncover IBM’s impact on swallowing physiology (Aim 1) and airway clearance ability (Aim 2). For Aim 1, the following will be applied: 1) MBSImP for comprehensive physiologic swallowing analysis across oral, pharyngeal, and esophageal domains; and 2) selected Analysis of Swallowing Physiology: Events, Kinematics & Timing Method for nuanced biomechanical measures. Relationships between dysphagia severity and airway clearance ability in IBM will also be mapped (Aim 2) through links between global dysphagia severity (derived from swallow safety and efficiency measures), voluntary and reflexive cough function, and respiratory muscle strength. This project will yield the first and most comprehensive upper aerodigestive profile for IBM to date. By employing well-tested methods, patient performance will be compared to published normative reference values to interpret IBM’s impact on upper aerodigestive function. The proposed study will also provide new insight into the interplay between respiratory-swallowing processes in IBM, which may lead to more timely dysphagia work-up, improve diagnostic accuracy, and promote the employment of targeted interventions. This proposal integrates well-tested upper aerodigestive analysis methods, an interdisciplinary team, and a focused research plan to accelerate the application’s long-term goal: developing best practice clinical guidelines for managing upper aerodigestive dysfunction in IBM.