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

• 批准号: 8245082
• 负责人: DAVID ANDREW WELLMAN
• 金额: $ 41.97万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/8245082
• 关键词: Acetazolamide; Anatomy; Arousal; Breathing; Clinical; Continuous Positive Airway Pressure; Data; Disease; Effectiveness; Eszopiclone; Functional disorder; Future; Gases; Gold; Grant; Health; Hypoxia; Individual; Intervention; Lead; Measurement; Measures; Methodology; Methods; Metric; Modeling; Monitor; Muscle; Obstructive Sleep Apnea; Operative Surgical Procedures; Oral; Oral Surgical Procedures; Oxygen; Pathogenesis; Patients; Pharmaceutical Preparations; Physiological; Relative (related person); Research; Scientist; Sleep; Sleep Apnea Syndromes; System; Techniques; Testing; Validation; common treatment; design; drug candidate; effective therapy; esophagus pressure; improved; novel; novel diagnostics; novel therapeutic intervention; pharynx muscle; physiologic model; pressure; public health relevance; respiratory; response; sedative; standard measure; trait; treatment strategy

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.

描述（由申请人提供）：阻塞性睡眠呼吸暂停（OSA）是一种多因素障碍，可能有四个主要原因或生理特征：1）一条解剖上的小或可折叠的上呼吸道，2）不稳定的通气控制系统，3）3）在睡眠中遇到的低呼吸呼吸效果，以及睡眠不良的低呼吸症状，以及4）在睡眠期间的不良响应。这项研究的广义目标是更好地了解这些特征如何相互作用以在个别患者中产生OSA，然后使用这些信息来设计新的治疗方法。具体而言，该赠款旨在验证一种新的技术来测量和建模引起OSA的性状（AIM 1），然后确定在操纵性状（AIM 2）时如何有效的非连续阳性气道压力疗法。为了实现这些目标，将测试测量和模型的夜晚的重复性，以及通气稳定性和唤醒阈值指标的有效性。注意：上呼吸道解剖学/可折叠性测量以前已被验证，不会重复。同样，由于方法很简单，因此无法验证上呼吸道（肌肉）响应测量值。通气稳定性度量（LOOP增益）将通过对个体的低氧气体进行验证，并将低氧环路增益与常氧环的增益进行比较（缺氧增加了环路增益）。由于没有用于测量循环增益的黄金标准，因此通过确定是否可以检测环路增益的方向变化来验证新方法。将新的唤醒阈值测量将通过将其与食管压监测确定的唤醒阈值进行比较来验证。在AIM 2中，将测量几种干预措施对每个性状的影响。将要测试的干预措施包括上呼吸道手术和口服电器（操纵咽可折叠性），乙酰唑胺和补充氧气（操纵呼吸的控制）和埃斯波基隆（操纵唤醒阈值）。操纵上气道肌肉反应的干预措施将不会进行测试，因为目前没有良好的候选药物这样做。提出的研究不仅会改善我们对OSA病理生理学的理解，而且可以现实地导致新的治疗方法。 公共卫生相关性：该赠款描述了一种测量和建模引起睡眠呼吸暂停的一些重要病原特征的技术。非CPAP处理对每个性状的有效性也将进行测试。这些研究可能导致对睡眠呼吸暂停发病机理和潜在的新疗法有更好的了解。