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

我们建议对150名参与者进行前瞻性队列（观察性）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）的患者，包括测量上 气道闭合压（Pclose）和组织复位软腭手术。之前和6 术后3个月，我们将通过睡眠研究来测量OSA的严重程度（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（特质）和气流的潜在机制 形状（与腭阻塞一致）。预计将有90名与会者， 手术后OSA（手术失败）将参与一项实验性随机交叉研究 乙酰唑胺（1个月）和乙酰唑胺/右佐匹克隆联合用药（1个月）研究。 将对每种治疗进行多导睡眠图，并基于算法确定 性状本研究的目的是：（1）明确机制性特质如何影响行为的有效性， 解剖治疗（手术）和（2）检查手术的治疗效果， 结合内型导向（特别是环路增益和唤醒阈值导向） 治疗目的1：确定改变软组织影响的机械因素 腭部手术对气道通畅性的影响假设：组织复位腭手术将 降低气道可膨胀性，仅腭阻塞的降低幅度更大（基于 DISE和无创气流形状分析）。目的2：评价机械因素 改变软腭手术对OSA严重程度的影响。假设：手术疗效将 与仅腭阻塞（DISE）和以下疾病独立相关， 手术：气道可膨胀性更低，环路增益更低，唤醒阈值更高。目标3： 评估手术与环路增益和唤醒阈值联合使用的疗效 干预措施。假设：在手术失败（无应答者）中，环路增益降低 （乙酰唑胺）将降低OSA的严重程度（预期应答率= 40%）;疗效将 与术后（用药前）气道可扩张性较低相关， 术后环路增益。同时降低环路增益和提高唤醒阈值 （乙酰唑胺/右佐匹克隆）将进一步降低OSA严重程度（预期缓解率= 60%）; 有效性与术后气道可扩张性较低相关， 术后环路增益更大，术后唤醒阈值更低。

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.