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：
10686814
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/10686814
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 Pharyngeal structure 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.

项目概要 OSA 的定义是上呼吸道反复塌陷，这一过程会导致短暂的低氧血症和睡眠中的觉醒，与各种心血管、代谢和神经认知有关 OSA 是最常见的呼吸系统疾病，影响大约 10% 的中年男性和女性。尽管持续气道正压通气 (PAP) 是一种治疗方法，但美国女性和全球多达 10 亿人。尽管治疗有效，但其耐受性并不总是良好，而且 OSA 的依从性也越来越不理想。被认为是一种多因素疾病，可能因不同原因而发生在不同的人身上，不仅仅是由于解剖学倾向（上呼吸道塌陷），但也与低唤醒阈值（醒来太容易），上呼吸道扩张肌功能障碍和通气控制不稳定。测量这些潜在因素和 OSA 经历的症状，该提案旨在了解 OSA 的不同机制（内型）如何导致不同的症状或后果 - 表型这些不同的表型范围从没有明显的症状到开车时睡着，经历心脏代谢后果。根本原因可能有助于个性化治疗、预测 PAP 的依从性以及了解哪些因素长期 PAP 治疗是否会改善症状是临床实践中的一个主要挑战。了解特定症状是否由 OSA 引起，以及这些症状是否会随着 OSA 的改善而改善此外，我们目前正在努力寻找 OSA 的替代疗法，这可能依赖于 OSA 的治疗。同样，我们目前不知道将哪些患者纳入临床试验，因为看起来似乎如此。例如，不太可能所有 OSA 患者都会因 PAP 治疗而获得心血管益处，因为并非所有人都面临以下风险：我们的目标是 1) 了解 OSA 的根本原因或内型对心脏病的影响。 OSA 患者所经历的症状，2) 阐明内型如何预测对非睡眠呼吸暂停的反应 CPAP 疗法，例如氧气或镇静催眠药，以及 3) 定义潜在的内型（机制）最终我们希望通过治疗 OSA 来介导表型（疾病的临床表现）的变化。我们的努力将推动 OSA 领域的发展，并有助于减轻痛苦或减少/预防疾病负担。