Novel physiologiC prEdictors of Positive Airway Pressure effectiveness: NICE-PAP study. - Candidate. My goal is to become an independent physician-scientist who merges physiology and patient-ori- ented research methods to personalize care for patients with obstructive sleep apnea (OSA). My training as an engineer and a doctor in Pulmonary, Critical Care and Sleep Medicine (PCCSM), complemented by research training in epidemiology, have given me the background necessary to pursue this goal. I propose training activ- ities that will allow me to personalize treatments for one of the most pressing problems for OSA patients- effec- tiveness of continuous positive airway pressure (CPAP). Through coursework, externships and mentored expe- rience in physiologic and patient-oriented research, this training program will build skills and knowledge in 1) physiologic characterization of OSA, 2) treatment adherence, efficacy and patient-oriented outcomes, 3) conduct of clinical studies, 4) advanced biostatistics and 5) leading a research program. Executing this program will bridge current knowledge gaps related to the role of physiologic traits in CPAP effectiveness and set me up for success as an independent investigator. Mentors and Environment. I have engaged an exceptional team of mentors with expertise tailored for this proposal. My primary mentor, Dr. Yaggi, is a national expert in OSA epidemiology and clinical study conduct. My co-mentors are Dr. Wellman, a pioneer in translational OSA physiology, and Dr. Redeker, a leader in patient- centered outcomes sleep research. This proposal leverages a wealth of resources across institutions, including Yale’s Center for Precision Pulmonary Medicine and Clinical Epidemiology Research Center, Centers for Sleep Medicine, PCCSM Section and Internal Medicine Department. The Sleep Disordered Breathing laboratory led by Dr. Wellman at Harvard is a renowned OSA physiology center. This environment provides methodologic expertise, research tools and a venue to conduct cutting-edge patient-oriented research in sleep. Mentored Research Project. Most patients with OSA who are prescribed the gold-standard therapy, CPAP, are ineffectively treated. This is due to 1) poor CPAP adherence, 2) high residual apnea in 20% of users (low efficacy) and 3) inconsistent symptom improvement. To improve CPAP effectiveness, we propose to address novel phys- iologic targets that cause OSA in each individual: arousability, ventilatory control sensitivity and pharyngeal mus- cle compensation. Our overall objective is to determine the contribution of these traits to CPAP effectiveness independently of established biological, psychological and social predictors. This work leverages state-of-the art sleep study analysis tools and validated measures of the determinants of CPAP effectiveness to create a prag- matic, prospective cohort (n=267) of OSA patients. This unique dataset will help determine whether physiologic causes of OSA influence CPAP adherence, efficacy, sleep quality, symptoms, function and quality of life. The results will inform design and conduct of a randomized clinical trial designed to modify physiologic traits such as easy arousability to improve CPAP effectiveness and other patient-centered outcomes in OSA patients.
