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、重度阻塞性睡眠呼吸暂停(OSA)不能耐受正压 谁正在接受药物诱导的睡眠内窥镜检查(DISE)，包括测量上 呼吸道闭合压(PCLOSE)和软腭组织再定位手术。之前和6 手术后几个月，我们将通过睡眠研究来测量OSA的严重程度(呼吸暂停-低呼吸指数 (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(与腭部阻塞一致)。预计将有90名与会者，但没有解决 手术后OSA(手术失败)将参加试验性随机交叉 乙酰唑胺(1个月)和乙酰唑胺/埃索匹克隆联合用药(1个月)。 每次治疗都将进行多导睡眠图检查，并基于算法确定 特征。本研究的目标是：(1)明确机械性特征是如何影响工作绩效的 解剖治疗(手术)和(2)检查手术的疗效 结合内型控制(尤其是环路增益和唤醒阈值控制) 治疗。目的1：确定影响软组织影响的机制因素 腭部手术治疗呼吸道塌陷。假设：组织重新定位腭部手术将 降低呼吸道的塌陷性，仅腭部阻塞的下降幅度更大(基于 DISE和无创气流形态分析)。目的2：评价机械性因素 软腭手术对阻塞性睡眠呼吸暂停综合征严重程度的影响。假设：手术疗效将 独立地与纯腭部梗阻(DISE)和以下症状相关 手术：较小的气道塌陷性、较小的环路增益和较大的觉醒阈值。目标3：实现 环路增益和觉醒阈值联合手术的疗效评价 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的严重程度(预期应答率=40%)；疗效将是 与术后(用药前)较小的气道塌陷和较大的气道塌陷有关 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/埃索匹克隆)将进一步减轻OSA的严重程度(预期应答率=60%)； 疗效将与术后较小的呼吸道塌陷性和联合应用 较大的术后环路增益和较小的术后觉醒阈值。

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.