Sleep Apnea Endophenotypes: One Size Does Not Fit All

睡眠呼吸暂停内表型：一种方法并不适用于所有情况

基本信息

批准号：
10404911
负责人：
Atul Malhotra
金额：
$ 66.34万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-15 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10404911
关键词：
Address Adherence Affect Aging Alternative Therapies Anatomy Apnea Arousal Cardiovascular system Clinical Clinical Trials Cognition Continuous Positive Airway Pressure Data Diagnosis Dilator Disease Drowsiness Endothelium Eszopiclone Functional disorder Goals Heart Diseases Hypercapnia Hypoxemia Individual Intervention Laboratories Lead Measurement Measures Mediating Metabolic Methods Muscle Neurocognitive Newly Diagnosed Obesity Obstructive Sleep Apnea Outcome Oxygen Patients Pattern Performance Persons Phenotype Physiological Polysomnography Population Predisposition Prevalence Process Randomized Recurrence Reporting Research Respiration Disorders Risk Risk Factors Severities Severity of illness Sleep Sleep Apnea Syndromes Symptoms Testing Therapeutic United States National Institutes of Health Woman actigraphy arterial tonometry burden of illness cardiometabolism clinical practice efficacious treatment endophenotype endothelial dysfunction experience falls heart disease risk hypnotic improved inattention individualized medicine insight men middle age pain perception pandemic disease personalized care personalized medicine positive airway pressure precision medicine predicting response prevent primary outcome randomized trial response sedative supplemental oxygen symptom cluster symptomatic improvement treatment as usual vehicular accident vigilance

项目摘要

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.

项目摘要 OSA由上呼吸道的重复崩溃来定义，这一过程导致短暂性低氧血症和来自睡眠的唤醒，与各种心血管，代谢和神经认知有关结果。 OSA是最常见的呼吸障碍，影响了大约10％的中年男性和美国妇女在全球范围内最多10亿。尽管连续的正气道压力（PAP）是有效的治疗，它并不总是能够宽容，并且依从性不理想。 OSA越来越多由于不同的原因，被公认为可以在不同的人中发生的多因素障碍，不仅是由于解剖倾向（上呼吸道的可折叠性），但也与低唤醒阈值有关（唤醒太容易），上呼吸道扩张肌的功能障碍和通风控制中的不稳定性。小心这些基本因素和OSA中症状的测量，该提议试图了解OSA（内型）潜在的不同机制如何导致不同的症状或后果 - 表型。这些不同的表型从没有欣赏的符号到在方向盘上入睡，体验心脏代谢后果。另外，解决根本原因可能对个性化治疗，预测遵守PAP并了解哪个是有用的长期的子宫颈抹片疗法将有或不会改善症状。临床实践中的一个主要挑战是了解特定症状是否是由于OSA引起的，以及这些症状是否会随着OSA而改善治疗。此外，我们目前正在努力寻找OSA的替代疗法，这可能取决于基本机制。同样，我们目前不知道要投入哪些患者，因为例如，所有OSA患者都会对PAP疗法具有心血管益处，因为并非所有人都有心脏病。我们的目标是1）了解OSA的根本原因或内型的贡献 OSA患者经历的症状，2）阐明内型预测如何反应非 CPAP疗法，例如氧或镇静催眠药，3）定义了基础内型（机制）通过治疗OSA的治疗，介导表型的变化（疾病的临床表现）。最终我们希望我们的努力将推进OSA领域，并有助于减轻伯恩的痛苦或减少/预防疾病。