A method for measuring and modeling the physiologic traits causing sleep apnea

描述（由申请人提供）：阻塞性睡眠呼吸暂停（OSA）是一种多因素疾病，可能有四个主要原因或生理特征：1）解剖学上小或可塌陷的上气道，2）不稳定的呼吸控制系统，3）睡眠时呼吸唤醒阈值低，以及4）睡眠期间上气道肌肉反应差。这项研究的广泛目标是更好地了解这些特征如何相互作用，在个体患者中产生OSA，然后利用这些信息设计新的治疗方法。具体来说，这项资助旨在验证一种新的技术，用于测量和建模导致OSA的特征（目标1），然后确定非连续气道正压通气治疗在操纵这些特征方面的有效性（目标2）。为了实现这些目标，将测试测量和模型的夜间和夜间重复性，沿着睡眠稳定性和觉醒阈值指标的有效性。注：上气道解剖结构/可扩展性测量先前已经过确认，将不再重复。此外，上气道（肌肉）反应测量将不会得到验证，因为该方法是直接的。将通过向个体施用低氧气体并将低氧回路增益与常氧回路增益进行比较（低氧提高回路增益）来验证呼吸稳定性指标（回路增益）。由于没有测量环路增益的黄金标准，因此通过确定新方法是否可以检测环路增益的方向变化来验证新方法。将通过将新的觉醒阈值测量值与食管压力监测确定的觉醒阈值进行比较来验证新的觉醒阈值测量值。在目标2中，将衡量几种干预措施对每种特征的影响。将测试的干预措施包括上呼吸道手术和口腔器具（以操纵咽部可吸收性）、乙酰唑胺和辅助供氧（以操纵呼吸控制）和右佐匹克隆（以操纵唤醒阈值）。将不测试操纵上气道肌肉反应的干预措施，因为目前还没有很好的候选药物。提出的研究不仅将提高我们对OSA病理生理学的理解，而且可能实际导致新的治疗方法。 公共卫生相关性：该资助描述了一种测量和建模导致睡眠呼吸暂停的一些重要致病特征的技术。还将测试非CPAP治疗对每种性状的有效性。这些研究可能会导致更好地了解睡眠呼吸暂停的发病机制和潜在的新治疗方法。

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) is a multifactorial disorder with probably four main causes or physiologic traits: 1) an anatomically small, or collapsible, upper airway, 2) an unstable ventilatory control system, 3) a low respiratory arousal threshold from sleep, and 4) a poor upper airway muscle response during sleep. The broad term objective of this research is to better understand how these traits interact to produce OSA in individual patients, and then to use this information to design new treatments. Specifically, this grant aims to validate a novel technique for measuring and modeling the traits causing OSA (Aim 1), and then determine how effective non-continuous positive airway pressure therapies are at manipulating the traits (Aim 2). To achieve these objectives, the within-night and between-night repeatability of the measurements and model will be tested, along with the validity of the ventilatory stability and arousal threshold metrics. Note: the upper airway anatomy/collapsibility measurement has been previously validated and will not be repeated. Also, the upper airway (muscle) response measurement will not be validated because the methodology is straightforward. The ventilatory stability metric (loop gain), will be validated by administering hypoxic gas to individuals and comparing the hypoxic loop gain to the normoxic loop gain (hypoxia raises the loop gain). As there is not a gold standard for measuring loop gain, the new method is being validated by determining if it can detect a directional change in loop gain. The new arousal threshold measurement will be validated by comparing it to the arousal threshold determined from esophageal pressure monitoring. In Aim 2, the effect of several interventions on each trait will be measured. The interventions that will be tested include upper airway surgery and oral appliances (to manipulate pharyngeal collapsibility), acetazolamide and supplemental oxygen (to manipulate the control of breathing), and eszopiclone (to manipulate the arousal threshold). Interventions to manipulate the upper airway muscle response will not be tested since currently there are not good candidate drugs for doing this. The studies proposed will not only improve our understanding of OSA pathophysiology, but could realistically lead to new therapeutic approaches. PUBLIC HEALTH RELEVANCE: This grant describes a technique for measuring and modeling some of the important pathogenic traits causing sleep apnea. The effectiveness of non-CPAP treatments on each trait will also be tested. These studies could lead to a better understanding of sleep apnea pathogenesis and potentially new treatments.