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

一种测量和模拟导致睡眠呼吸暂停的生理特征的方法

基本信息

批准号：
8664909
负责人：
DAVID ANDREW WELLMAN
金额：
$ 42.29万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2016-03-31
项目状态：
已结题

项目摘要

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.

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) 解剖学上较小或可塌陷的上呼吸道，2) 不稳定的通气控制系统，3) 低睡眠中的呼吸唤醒阈值，以及 4) 睡眠期间上呼吸道肌肉反应不佳。这项研究的总体目标是更好地了解这些特征如何相互作用从而在个体患者中产生 OSA，然后利用这些信息设计新的治疗方法。具体来说，这笔赠款旨在验证一种测量和建模导致 OSA 的特征的新技术（目标 1），然后确定非连续气道正压治疗在控制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，以及通气稳定性和唤醒阈值指标的有效性。注意：上气道解剖/塌陷度测量之前已经过验证，不会重复。此外，上气道（肌肉）反应测量将不会得到验证，因为该方法很简单。通气稳定性指标（环路增益）将通过向个体施用低氧气体并将低氧环路增益与常氧环路增益进行比较（缺氧提高环路增益）来验证。由于测量环路增益没有黄金标准，因此正在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。新的唤醒阈值测量将通过与食管压力监测确定的唤醒阈值进行比较来验证。在目标 2 中，将测量多种干预措施对每个特征的影响。将测试的干预措施包括上呼吸道手术和口腔矫治器（以控制咽塌陷）、乙酰唑胺和补充氧气（以控制呼吸）以及艾司佐匹克隆（以控制觉醒阈值）。由于目前尚无良好的候选药物，因此不会测试操纵上呼吸道肌肉反应的干预措施。所提出的研究不仅将提高我们对 OSA 病理生理学的理解，而且可能真正导致新的治疗方法。