Pathophysiology of Childhood Obstructive Sleep Apnea

描述(申请人提供)：阻塞性睡眠呼吸暂停综合征(OSAS)是儿童发病的常见原因。然而，人们对其病理生理学知之甚少。假设发育过程中上呼吸道神经运动张力的变化在睡眠期间维持上呼吸道通畅以及睡眠障碍呼吸的表达中起主要作用。以下假设将在睡眠期间进行检验：(1)在正常受试者中，上呼吸道的塌陷性在童年时期最低，并随着年龄的增长而增加，关键的转变发生在青春期。儿童时期的塌陷性降低主要是由于上呼吸道反射神经运动张力增加所致。具体地说，在正常、不打呼的受试者中，我们将(A)建立低张状态下儿童和成人之间UA功能的基线差异；(B)与成人相比，检查正常儿童UA反射对UA开放程度的影响；以及(C)确定青春期对UA崩溃能力的影响。(2)OSAS发生在缺乏这些保护性上呼吸道反射的儿童中。具体地说，在正常儿童和OSAS儿童中，我们将(A)建立低张状态下UA功能的基线差异，(B)确定REM睡眠对UA崩溃的作用，以及(C)检查UA反射对UA开放的影响。(3)神经运动张力的调节，以及对上呼吸道负荷的中枢反应，解释了儿童OSAS特有的睡眠障碍呼吸的多导睡眠图特征。具体地说，我们将(A)检测阻塞性低通气症(OH)儿童与离散周期性阻塞性呼吸暂停(OA)儿童UA反射对UA通畅性的影响，(B)测量OHvsOA儿童对吸气阻力负荷的唤醒阈值，以及(C)在OVOVS和对照组儿童睡眠中测量呼吸相关诱发电位(RREP)对吸气阻塞的反应。这些研究将有助于阐明儿童阻塞性睡眠呼吸暂停综合征的潜在病理生理机制，从而更好地了解和改善对这种疾病的治疗。

DESCRIPTION (provided by applicant): The obstructive sleep apnea syndrome (OSAS) is a common cause of morbidity in childhood. However, its pathophysiology is poorly understood. It is hypothesized that changes in upper airway neuromotor tone during development play a major role in the maintenance of upper airway patency during sleep, and the expression of sleep-disordered breathing. The following hypotheses will be tested during sleep: (1) That, in normal subjects, upper airway collapsibility is lowest during childhood and increases with age, with a critical transition occurring during adolescence. The decreased collapsibility noted during childhood is due primarily to increased upper airway reflex neuromotor tone. Specifically, in normal, non-snoring subjects, we will (a) Establish baseline differences in UA function between children and adults in the hypotonic condition; (b) Examine the effects of UA reflexes on UA patency in normal children compared to adults, and (c) Determine the effect of puberty on UA collapsibility. (2) That OSAS develops in children lacking these protective upper airway reflexes. Specifically, in normal children compared to children with OSAS, we will (a) Establish baseline differences in UA function in the hypotonic condition, (b) Determine the role of REM sleep on UA collapsibility, and (c) Examine the effects of UA reflexes on UA patency. (3) That regulation of neuromotor tone, and the central response to an upper airway load, accounts for the polysomnographic characteristics of sleep-disordered breathing unique to childhood OSAS. Specifically, we will (a) Examine the effects of UA reflexes on UA patency in children with obstructive hypoventilation (OH) vs children with discrete, cyclical obstructive apneas (OA), (b) Measure the arousal threshold to an inspiratory resistive load in children with OH vs OA, and (c) Measure the respiratory-related evoked potentials (RREP) in response to inspiratory occlusion during sleep in children with OA vs OH and controls. These studies will help elucidate the underlying pathophysiology of childhood OSAS, resulting in better understanding and improved management of this disease.