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Principal Investigator: ANDREY ZINCHUK
Organization: YALE UNIVERSITY
Fiscal Year: 2024
Award: $172,260
Funding agency: National Heart Lung and Blood Institute
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.
Terms: <21+ years old><Accounting><Acetazolamide><Address><Adherence><Adult><Adult Human><Affect><Age><American><Anatomic Sites><Anatomic structures><Anatomy><Apnea><Apoplexy><Arousal><Atrial Fibrillation><Auricular Fibrillation><Automobile Driving><Biological><Biometrics><Biometry><Biostatistics><Brain Vascular Accident><Breathing><CPAP><CPAP Ventilation><Cardiac infarction><Catheters><Cerebral Stroke><Cerebrovascular Apoplexy><Cerebrovascular Stroke><Clinical Paths><Clinical Pathways><Clinical Research><Clinical Study><Clinical Trials Design><Compensation><Continuous Positive Airway Pressure><Critical Care><Data><Data Set><Development Plans><Diabetes Mellitus><Diagnosis><Drowsiness><Effectiveness><Engineering><Environment><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology><Epidemiology Research><Equipment><Exhibits><Expectancy><Future><Generalized Growth><Goals><Growth><Heart failure><Hour><Hypertension><Impairment><Individual><Infrastructure><Insomnia><Insomnia Disorder><Institution><Internal Medicine><Investigators><K23 Award><K23 Mechanism><K23 Program><Knowledge><Laboratories><Link><Lung><Lung Respiratory System><Measurement><Measures><Medicine><Mentored Patient-Oriented Research Career Development Award><Mentored Patient-Oriented Research Career Development Award (K23)><Mentors><Methodology><Modification><Morbidity><Morbidity - disease rate><Motor carrier accident><Myocardial Infarct><Myocardial Infarction><O element><O2 element><Obstructive Sleep Apnea><Outcome><Oxygen><Pathogenesis><Patient Care><Patient Care Delivery><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Pharyngeal Muscles><Pharyngeal structure><Pharynx><Physicians><Physiologic><Physiological><Physiology><Pneumology><Pneumonology><Polysomnography><Precision care><Predisposition><Prospective cohort><Psychological Factors><Psychosocial Factor><Pulmonary Medicine><Pulmonology><QOL><Quality of life><R-Series Research Projects><R01 Mechanism><R01 Program><Randomization trial><Research><Research Grants><Research Methodology><Research Methods><Research Personnel><Research Project Grants><Research Projects><Research Resources><Research Training><Researchers><Residual><Residual state><Resources><Respiratory Aspiration><Respiratory Inspiration><Risk><Role><Science><Scientist><Self Efficacy><Sleep><Sleep Apnea><Sleep Apnea Syndromes><Sleep Hypopnea><Sleep Monitoring><Sleep-Disordered Breathing><Sleeplessness><Social support><Somnography><Somnolence><Stroke><Susceptibility><Symptoms><Syndrome, Sleep Apnea, Obstructive><Techniques><Throat><Tissue Growth><Training><Training Activity><Training Programs><Translating><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Work><adulthood><ages><biologic><brain attack><cardiac failure><cardiac infarct><care for patients><care of patients><career development><caring for patients><cerebral vascular accident><cerebrovascular accident><clinical applicability><clinical application><clinical epidemiology><cohort><common treatment><coronary attack><coronary infarct><coronary infarction><design><designing><diabetes><driving><epidemiologic><epidemiologic investigation><epidemiological><epidemiology study><experience><externship><heart attack><heart infarct><heart infarction><high blood pressure><hyperpiesia><hyperpiesis><hypertensive disease><hypertensive disorder><hypnotic><improve symptom><improved><individualized care><individualized patient care><ineffective therapies><ineffective treatment><inspiration><mortality><motor vehicle accident><new approaches><novel><novel approaches><novel strategies><novel strategy><ontogeny><patient centered><patient oriented><patient oriented outcomes><patient oriented research><patient oriented study><personalization of treatment><personalized care><personalized medicine><personalized patient care><personalized therapy><personalized treatment><pharynx muscle><polysomnographic><poor sleep><positive airway pressure><pressure><prevent><preventing><programs><prospective><psychologic><psychological><psychosocial variables><pulmonary><quality of sleep><randomized trial><randomized, clinical trials><remote monitoring><research and methods><response><sex><skills><sleep measurement><sleep polysomnography><sleep position><sleep quality><sleep-related breathing disorder><sleepiness><social><social factors><social role><social support network><stroked><strokes><success><symptom improvement><symptomatic improvement><tool><training module><trait><treatment adherence><treatment compliance><vehicular accident>