R01HL154926

Sleep Apnea Endophenotypes: One Size Does Not Fit All - Project Summary

OSA is defined by repetitive collapse of the upper airway, a process which leads to transient hypoxemia and arousals from sleep, and is associated with various cardiovascular, metabolic, and neurocognitive consequences. OSA is the most common respiratory disorder, affecting roughly 10% of middle-aged men and women in the USA and up to 1 billion globally.

Although continuous positive airway pressure (PAP) is an efficacious therapy, it is not always well tolerated and adherence is less than ideal. OSA is increasingly recognized as a multifactorial disorder that can occur in different people for different reasons, not only due to anatomical predisposition (collapsibility of the upper airway), but also related to low arousal threshold (wake up too easily), dysfunction in upper airway dilator muscles, and instability in ventilatory control.

Through careful measurement of these underlying factors and the symptoms experienced in OSA, this proposal seeks to understand how different mechanisms underlying OSA – endotypes – lead to different symptoms or consequences – phenotypes. These different phenotypes range from having no appreciable symptoms, to falling asleep at the wheel, to experiencing cardiometabolic consequences.

Additionally, addressing the underlying cause might be useful to personalize therapy, to predict adherence to PAP, and to understand which symptoms will or will not improve with long-term PAP therapy. A major challenge in clinical practice is understanding whether particular symptoms are due to OSA, and whether these symptoms will improve with treatment. Moreover, we are currently struggling to find alternative therapies for OSA which will likely depend on underlying mechanism.

Similarly, we do not currently know which patients to put into clinical trials since it seems unlikely that, e.g., all OSA patients will have cardiovascular benefits to PAP therapy since not all are at risk of heart disease. Our goals are 1) to understand the contribution of the underlying cause, or endotype, of OSA to the symptoms experienced by people with OSA, 2) to elucidate how the endotype predicts response to non-CPAP therapies, such as oxygen or sedative hypnotics, and 3) to define how underlying endotype (mechanism) mediates changes in phenotype (clinical manifestations of disease) with treatment of OSA.

Ultimately, we hope that our efforts will advance the OSA field and help to alleviate suffering or reduce/prevent disease burden.

San Diego University Of California

THE NATIONAL CENTER ON SLEEP DISORDERS RESEARCH (NCSDR) SUPPORTS RESEARCH AND RESEARCH TRAINING RELATED TO SLEEP DISORDERED BREATHING, AND THE FUNDAMENTAL FUNCTIONS OF SLEEP AND CIRCADIAN RHYTHMS. THE CENTER ALSO STEWARDS SEVERAL FORUMS THAT FACILITATE THE COORDINATION OF SLEEP RESEARCH ACROSS NIH, OTHER FEDERAL AGENCIES AND OUTSIDE ORGANIZATIONS, INCLUDING THE SLEEP DISORDERS RESEARCH ADVISORY BOARD AND AN NIH-WIDE SLEEP RESEARCH COORDINATING COMMITTEE. THE CENTER ALSO PARTICIPATES IN THE TRANSLATION OF NEW SLEEP RESEARCH FINDINGS FOR DISSEMINATION TO HEALTH CARE PROFESSIONALS AND THE PUBLIC. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

La Jolla, California 920930001 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Required) (PA-19-055)

Amendment Since initial award the total obligations have increased 444% from $610,256 to $3,318,435.