Developing Novel Methods to Elucidate Mechanisms of Pediatric Sleep Apnea

描述(申请人提供)：阻塞性睡眠呼吸暂停(OSA)是一种常见的疾病，发生在大约1-3%的儿童中，是睡眠中咽部阻塞的结果。儿童时期睡眠呼吸暂停的流行与扁桃体肥大和日益流行的肥胖症有关。睡眠中的上呼吸道阻塞是咽部结构特性和/或代偿性神经肌肉功能障碍的结果。实践指南建议将腺体扁桃体切除术作为其他方面健康的阻塞性睡眠呼吸暂停儿童的一线治疗。然而，扁桃体切除术的治愈率是高度可变的，这使许多儿童面临手术的风险，而没有明确的临床益处。由于缺乏诊断测试来确定睡眠期间的咽部功能并预测治疗反应，临床医生一直受到阻碍。咽部结构特性和神经肌肉反应可以在睡眠期间通过调节鼻压来评估(Pcrit)。然而，这些测量是费力的，而且幼儿或快速眼动睡眠期间不能很好地忍受。儿童对多导睡眠图有很好的耐受性，然而，传统的睡眠呼吸暂停严重程度测量方法(AHI、觉醒指数、与ETCO2&GT；50 mmHg和SaO2共处的时间)不能充分衡量睡眠期间气流阻塞的严重程度，以表征咽部特性。为了克服这些缺陷，我们开发了儿童血流受限严重程度的敏感的连续测量标准，将在本提案中用于评估咽部结构特性和神经肌肉控制，并预测对手术的反应。我们的主要假设是，简化的方法来表征上呼吸道的结构和神经肌肉特性将揭示儿童睡眠期间上呼吸道阻塞的独特致病机制。为了解决这一假设，将评估儿童睡眠期间的咽部机械和神经肌肉特性，并通过与黄金标准压力-流量关系(SA1)的比较来验证。将对阻塞性睡眠呼吸暂停综合征儿童与非鼾症对照组、扁桃体切除术前后(SA2)以及肥胖儿童与非肥胖儿童(SA3)进行咽部神经机械特性的比较，以确定这些疾病修饰物对睡眠期间上呼吸道阻塞的影响。我们的方法将产生新的简化方法来改进儿童阻塞性睡眠呼吸暂停综合征的诊断和治疗。

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) is a common disorder, occurring in approximately 1-3% of children and is the result of pharyngeal obstruction during sleep. The prevalence of sleep apnea during childhood is linked to adenotonsillar hypertrophy and an increasing epidemic of obesity. Upper airway obstruction during sleep is the result of deficits in pharyngeal structural properties and/or compensatory neuromuscular. Practice guidelines recommend adenotonsillectomy as first-line therapy for otherwise healthy children with OSA. The cure rates for adenotonsillectomy, however, are highly variable exposing many children to the risks of surgery without clear clinical benefit. Clinicians have been hampered by a lack of diagnostic tests to determine pharyngeal function during sleep and to predict treatment responses. Pharyngeal structural properties and neuromuscular responses can be assessed during sleep by manipulating nasal pressure (Pcrit). These measurements, however, are laborious, and not well tolerated by young children or during REM sleep. Polysomnography is well tolerated by children, however, conventional measures of sleep apnea severity (AHI, arousal index, time spent with ETCO2>50mmHg and SaO2) do not adequately measure the severity of airflow obstruction during sleep to characterize pharyngeal properties. To overcome these deficiencies we have developed sensitive continuous metrics of flow limitation severity in children that will be used in this proposal to assess the pharyngeal structural properties and neuromuscular control, and to predict responses to surgery. Our primary hypothesis is that streamlined methods to characterize upper airway structural and neuromuscular properties will reveal unique pathogenic mechanisms of upper airway obstruction in children during sleep. To address this hypothesis, pharyngeal mechanical and neuromuscular properties will be assessed in children during sleep and validated by comparison to the gold standard pressure-flow relationships (SA1). Pharyngeal neuromechanical properties will be characterized in children with OSA compared to non snoring controls, before and after adenotonsillectomy (SA2) and in obese compared to non obese children (SA3) to determine the impact of these disease modifiers on upper airway obstruction during sleep. Our approach will yield novel streamlined methods to improve the diagnosis and treatment of OSA in children.