Upper airway collapsibility, loop gain and arousal threshold: an integrative therapeutic approach to obstructive sleep apnea

上气道塌陷、循环增益和唤醒阈值：阻塞性睡眠呼吸暂停的综合治疗方法

• 批准号: 10516957
• 负责人: ERIC JAMES KEZIRIAN
• 金额: $ 73.78万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2023-06-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10516957
• 关键词: Acetazolamide; Address; Air Movements; Algorithms; Anatomy; Apnea; Arousal; Breathing; Cardiovascular system; Cross-Over Studies; Dilator; Disease; Drowsiness; Effectiveness; Endoscopy; Eszopiclone; Evaluation; Failure; Functional disorder; Goals; Intervention; Investigation; Measurement; Measures; Morbidity - disease rate; Multiple Abnormalities; Muscle; Neurocognitive; Observational Study; Obstruction; Obstructive Sleep Apnea; Operative Surgical Procedures; Palate; Participant; Patients; Pattern; Pharmaceutical Preparations; Polysomnography; Postoperative Period; Procedures; Prospective cohort; Public Health; Quality of life; Randomized; Research; Resolution; Sedation procedure; Severities; Shapes; Sleep; Soft Palate; Source; Therapeutic; Tissues; Treatment Efficacy; airway obstruction; alternative treatment; base; efficacy evaluation; experience; improved; indexing; innovation; mortality; novel therapeutics; positive airway pressure; pressure; response; shape analysis; signal processing; success; surgery outcome; trait; ventilation

We propose to conduct a prospective cohort (observational) study of 150 participants with moderate to severe obstructive sleep apnea (OSA) unable to tolerate positive airway pressure who are undergoing drug-induced sleep endoscopy (DISE), including measurement of upper airway closing pressure (Pclose), and tissue-repositioning soft palate surgery. Before and 6 months after surgery, we will measure OSA severity (apnea-hypopnea index) with sleep studies (polysomnograms). Using our recently-validated polysomnography-based signal processing algorithm, we will systematically assess the underlying mechanisms of OSA (traits) and airflow shape (consistent with palate obstruction). The expected 90 participants without resolution of OSA after surgery (surgery failures) will participate in an experimental randomized crossover study of acetazolamide (1 month) and acetazolamide/eszopiclone combination (1 month). Polysomnograms will be performed with each treatment, with algorithm-based determination of traits. The research goals are: (1) to define how mechanistic traits modify effectiveness of anatomic treatment (surgery) and (2) to examine the therapeutic efficacy of surgery in combination with endotype-directed (especially loop gain- and arousal threshold-directed) treatment. Aim 1: To determine the mechanistic factors modifying the impact of soft palate surgery on airway collapsibility. Hypothesis: tissue-repositioning palate surgery will decrease airway collapsibility, with the decrease greater with palate-only obstruction (based on DISE and non-invasive airflow shape analysis). Aim 2: To evaluate the mechanistic factors modifying efficacy of soft palate surgery on OSA severity. Hypotheses: surgery efficacy will be independently associated with palate-only obstruction (DISE) and the following prior to surgery: lesser airway collapsibility, lesser loop gain, and greater arousal threshold. Aim 3: To evaluate the efficacy of combining surgery with loop gain and arousal threshold interventions. Hypotheses: In surgery failures (non-responders), lowering loop gain (acetazolamide) will lower OSA severity (expected response rate = 40%); efficacy will be associated with lesser postoperative (prior to medication) airway collapsibility and greater postoperative loop gain. Lowering loop gain and raising arousal threshold together (acetazolamide/eszopiclone) will further reduce OSA severity (expected response rate = 60%); efficacy will be associated with lesser postoperative airway collapsibility and the combination of greater postoperative loop gain and lesser postoperative arousal threshold.

我们建议对 150 名参与者进行前瞻性队列（观察）研究 中度至重度阻塞性睡眠呼吸暂停 (OSA) 无法耐受气道正压通气 正在接受药物诱导睡眠内窥镜检查 (DISE) 的人，包括测量上肢 气道闭合压 (Pclose) 和组织重新定位软腭手术。之前和 6 手术后几个月，我们将通过睡眠研究来测量 OSA 严重程度（呼吸暂停低通气指数） （多导睡眠图）。使用我们最近验证的基于多导睡眠图的信号处理 算法，我们将系统地评估 OSA（特征）和气流的潜在机制 形状（与上腭阻塞一致）。预计 90 名参与者没有解决 手术后（手术失败）的 OSA 将参加实验性随机交叉 乙酰唑胺（1 个月）和乙酰唑胺/艾司佐匹克隆组合（1 个月）的研究。 每次治疗都会进行多导睡眠图，并根据算法确定 特征。研究目标是：（1）定义机械特征如何改变有效性 解剖治疗（手术）和（2）检查手术的治疗效果 与内型导向（特别是循环增益和唤醒阈值导向）相结合 治疗。目标 1：确定改变软影响的机械因素 腭手术治疗气道塌陷。假设：组织重新定位腭手术将 减少气道塌陷，仅腭部阻塞时减少幅度更大（基于 DISE 和非侵入式气流形状分析）。目标 2：评估机械因素 改变软腭手术对 OSA 严重程度的疗效。假设：手术疗效将 与仅上腭阻塞 (DISE) 和以下之前的情况独立相关 手术：较小的气道塌陷、较小的环增益和较高的唤醒阈值。目标 3： 评估手术与环路增益和唤醒阈值相结合的疗效 干预措施。假设：在手术失败（无反应者）中，降低环路增益 （乙酰唑胺）将降低 OSA 严重程度（预期缓解率 = 40%）；功效将是 与术后（用药前）气道塌陷程度较低和较大程度相关 术后环路增益。降低环路增益并提高唤醒阈值 （乙酰唑胺/艾司佐匹克隆）将进一步降低 OSA 严重程度（预期缓解率 = 60%）； 疗效与术后气道塌陷的减轻以及以下因素的结合有关： 术后环增益更大，术后唤醒阈值更小。