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）是一种常见的疾病，发生在大约1-3%的儿童中，是睡眠期间咽阻塞的结果。儿童时期睡眠呼吸暂停的流行与腺扁桃体肥大和肥胖症的日益流行有关。睡眠时的上气道阻塞是咽结构特性和/或代偿神经肌肉缺陷的结果。实践指南推荐腺扁桃体切除术作为其他方面健康的OSA患儿的一线治疗。然而，腺扁桃体切除术的治愈率是高度可变的，使许多儿童面临手术的风险，没有明确的临床益处。临床医生一直受到缺乏诊断测试来确定睡眠期间咽功能和预测治疗反应的阻碍。咽部结构特性和神经肌肉反应可以在睡眠中通过控制鼻压（Pcrit）来评估。然而，这些测量是费力的，幼儿或在快速眼动睡眠期间不能很好地忍受。然而，常规的睡眠呼吸暂停严重程度测量（AHI、唤醒指数、ETCO2 bb0 50mmHg和SaO2）并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，我们开发了儿童血流限制严重程度的敏感连续指标，将在本提案中用于评估咽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，简化的方法表征上呼吸道结构和神经肌肉特性将揭示儿童睡眠时上呼吸道阻塞的独特致病机制。为了解决这一假设，将在儿童睡眠期间评估咽机械和神经肌肉特性，并通过与金标准压力-流量关系（SA1）进行比较来验证。将OSA患儿与非打鼾对照者、腺扁桃体切除术（SA2）前后、肥胖患儿与非肥胖患儿（SA3）的咽部神经力学特性进行特征分析，以确定这些疾病调节剂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，以改善儿童阻塞性睡眠呼吸暂停的诊断和治疗。

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. PUBLIC HEALTH RELEVANCE: Obstructive sleep apnea is a common disorder in children that is linked to adenotonsillar hypertrophy and obesity. The proposal addresses underlying mechanisms of upper airway obstruction during sleep, and will develop novel clinically useful methods for diagnosing obstructive sleep apnea, elucidating its pathogenesis, and predicting responses to adenotonsillectomy.