Pathophysiology of Childhood Obstructive Sleep Apnea

阻塞性睡眠呼吸暂停综合征（OSAS）是儿童常见的疾病， 该提案将整合上呼吸道（UA）神经运动控制的研究 和UA结构，以提供所有病理生理风险的综合评估 在同一个人的OSAS的因素，并将这些知识应用于高风险的儿科 患者该提案的重点是肥胖在2010年过渡期的影响。 青春期总的假设是，OSAS的发展时，结构负荷是收购 由具有UA神经运动功能的潜在损伤的个体进行。这将是一个1：1：1 配对病例-双对照研究，具有补充干预成分。UA反射 将通过测量UA压力-流量响应之间的差异来确定， 在激活状态和低渗状态下睡眠。将使用MRI确定UA大小和结构。 在目标1中，我们将确定UA反射对呼吸暂停低通气指数（AHI）的贡献。 通过进行一项横断面病例对照研究， 与（i）非打鼾、BMI匹配的肥胖对照组和（ii）非肥胖、非打鼾对照组相比， 对照我们推测肥胖青少年OSAS患者UA反射降低 与肥胖对照组相比，肥胖对照组的UA反射比非肥胖对照组大 对照.在目标2A中，我们将确定结构性UA缩小对 嗨。我们假设肥胖青少年OSAS患者的UA比正常人更窄， 肥胖对照组。在目标2B中，我们将确定导致 上呼吸道狭窄我们假设扁桃体腺组织和扁桃体的区域分布 脂肪组织是青少年UA大小的主要决定因素。在目标3中，我们 确定减肥对OSAS的影响。在目标3A中，我们将确定 体重减轻与AHI的变化相关。我们假设重量越大 越是亏损，AHI的跌幅就越大。在目标3B中，我们将确定AHI的降低是否 体重减轻后的变化主要是由于UA反射的变化或UA大小的变化。我们 假设体重减轻后AHI的改善主要是由于 UA大小而不是UA反射的变化。在目标3C中，我们将确定 UA结构的重量损失。我们假设减肥主要会导致 在咽旁脂肪垫的大小，但也可能影响舌头和软腭的大小。 这些研究将有助于阐明肥胖青少年OSAS的病理生理学， 从而改善对这种疾病的管理。

The obstructive sleep apnea syndrome (OSAS) is a common cause of morbidity in the pediatric population This proposal will integrate studies of neuromotor control of the upper airway (UA) and UA structure in order to provide a comprehensive assessment of all pathophysiologic risk factors for OSAS in the same individual, and to apply this knowledge to high risk pediatric patients. The proposal focuses on the effects of obesity during the transitional period of adolescence. The overall hypothesis is that OSAS develops when a structural load is acquired by an individual with an underlying impairment of UA neuromotor function. This will be a 1:1:1 matched case-dual control study with a complementary interventional component. UA reflexes will be determined by measuring the difference between the UA pressure-flow response during sleep in the activated vs the hypotonic state. UA size and structure will be determined using MRI. In Aim 1, we will determine the contribution of UA reflexes to the apnea hypopnea index (AHI) by conducting a cross-sectional, case control study that will compare obese, adolescent cases with OSAS to (i) non-snoring, BMI-matched obese controls and to (ii) non-obese, non-snoring controls. We hypothesize that UA reflexes will be decreased in obese adolescents with OSAS compared to obese controls, and that UA reflexes will be greater in obese controls than in nonobese controls. . In Aim 2A, we will determine the contribution of structural UA narrowing to the AHI. We hypothesize that the UA will be narrower in obese adolescents with OSAS compared to obese controls. In Aim 2B, we will identify the most important structural factors leading to upper airway narrowing. We hypothesize that adenotonsillar tissue and regional distribution of adipose tissue are the prime determinants of UA size in adolescents. In Aim 3, we will determine the effects of weight loss on OSAS. In Aim 3A, we will determine whether the degree of weight loss correlates with the change in AHI. We hypothesize that the greater the weight loss, the greater the fall in AHI. In Aim 3B, we will determine whether the decrease in AHI following weight loss is due primarily to a change in UA reflexes or a change in UA size. We hypothesize that the improvement in AHI following weight loss is due primarily to an increase in UA size rather than to a change in UA reflexes. In Aim 3C, we will determine the effect of weight loss on UA structure. We hypothesize that weight loss will result primarily in a decrease in the size of the parapharyngeal fat pads, but may also affect tongue and soft palate size. These studies will help elucidate the pathophysiology of OSAS in obese adolescents, ultimately resulting in improved management of this disease.