Sleep Apnea Endophenotypes: One Size Does Not Fit All

项目摘要 阻塞性睡眠呼吸暂停的定义是上呼吸道的反复塌陷，这是一个导致短暂低氧血症的过程， 从睡眠中唤醒，并与各种心血管，代谢和神经认知有关 后果OSA是最常见的呼吸系统疾病，影响大约10%的中年男性， 在美国和全球多达10亿的女性。虽然持续气道正压通气（PAP）是一种有效的治疗方法， 然而，尽管它是一种有效的治疗方法，但并不总是耐受良好，并且依从性也不理想。OSA越来越多 被认为是一种多因素的疾病，可以发生在不同的人，不同的原因，不仅是由于 解剖学倾向（上呼吸道的可呼吸性），但也与低唤醒阈值（唤醒）有关 太容易）、上呼吸道扩张肌功能障碍和呼吸控制不稳定。通过仔细 为了测量这些潜在因素和OSA中经历的症状，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。这些不同的表型从没有明显的症状， 在开车时睡着，到经历心脏代谢的后果。此外，解决 潜在原因可能有助于个性化治疗，预测PAP的依从性，并了解 长期PAP治疗可改善或不改善症状。临床实践中的一个主要挑战是 了解特定的症状是否是由于OSA，以及这些症状是否会改善， 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 潜在机制同样，我们目前也不知道哪些患者应该进行临床试验，因为 不太可能，例如，PAP治疗对所有OSA患者都有心血管益处，因为并非所有OSA患者都有 心脏病我们的目标是：1）了解OSA的潜在病因或内型对 2）为了阐明内型如何预测对非阻塞性睡眠呼吸暂停综合征的反应， CPAP治疗，如氧气或镇静催眠药，以及3）定义潜在的内型（机制） 通过OSA的治疗介导表型（疾病的临床表现）的变化。最终我们希望 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。

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.