Developing Novel Methods to Elucidate Mechanisms of Pediatric Sleep Apnea

描述（由申请人提供）：阻塞性睡眠呼吸暂停（OSA）是一种常见疾病，发生在大约1-3%的儿童中，是睡眠期间咽部阻塞的结果。儿童期睡眠呼吸暂停的患病率与扁桃体肥大和肥胖症的流行有关。睡眠中的上呼吸道阻塞是咽部结构特性和/或代偿性神经肌肉缺陷的结果。实践指南建议将腺样体扁桃体切除术作为其他健康的OSA儿童的一线治疗。然而，腺样体扁桃体切除术的治愈率是高度可变的，使许多儿童暴露于手术的风险中，而没有明确的临床益处。临床医生一直受到缺乏诊断测试，以确定在睡眠期间的咽功能和预测治疗反应。咽部结构特性和神经肌肉反应可以在睡眠期间通过操纵鼻压（Pcrit）来评估。然而，这些测量是费力的，并且幼儿或在REM睡眠期间不能很好地耐受。儿童对多导睡眠图的耐受性良好，然而，睡眠呼吸暂停严重程度的常规测量（AHI、觉醒指数、ETCO 2> 50 mmHg和SaO 2的时间）不能充分测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，我们已经开发了灵敏的连续指标的流动限制的严重程度，在儿童中，将用于本建议，以评估咽部的结构特性和神经肌肉控制，并预测手术的反应。我们的主要假设是，简化的方法来表征上气道结构和神经肌肉特性将揭示儿童睡眠期间上气道阻塞的独特致病机制。为了解决这一假设，将在睡眠期间对儿童的咽部机械和神经肌肉特性进行评估，并通过与黄金标准压力-流量关系（SA 1）进行比较进行验证。将在腺样体扁桃体切除术前后（SA 2）和肥胖儿童与非肥胖儿童（SA 3）中比较，对OSA儿童与非打鼾对照儿童的咽部神经力学特性进行表征，以确定这些疾病修饰物对睡眠期间上气道阻塞的影响。我们的方法将产生新的简化方法，以改善儿童OSA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.