Pathophysiology of Childhood Obstructive Sleep Apnea

描述（由申请人提供）：阻塞性睡眠呼吸暂停综合征（OSAS）是儿童期发病的常见原因。然而，其病理生理学知之甚少。据推测，上气道神经运动张力在发展过程中的变化发挥了重要作用，在睡眠期间的上气道通畅的维护，睡眠呼吸障碍的表达。以下假设将在睡眠期间进行检验：（1）在正常受试者中，上气道通透性在儿童期最低，并随年龄增长而增加，在青春期发生关键转变。在儿童时期注意到的呼吸能力下降主要是由于上呼吸道反射神经运动张力增加。具体而言，在正常、无打鼾的受试者中，我们将（a）确定低渗条件下儿童和成人之间UA功能的基线差异;（B）检查正常儿童与成人相比UA反射对UA通畅性的影响;（c）确定青春期对UA可耐受性的影响。(2)阻塞性睡眠呼吸暂停综合症是在缺乏这些保护性上呼吸道反射的儿童身上发生的。特别是，在正常儿童和OSAS儿童中，我们将（a）建立低渗条件下UA功能的基线差异，（B）确定REM睡眠对UA可耐受性的作用，（c）检查UA反射对UA通畅性的影响。(3)神经运动张力的调节，以及中枢对上气道负荷的反应，解释了儿童OSAS特有的睡眠呼吸障碍的多导睡眠图特征。具体而言，我们将（a）检查阻塞性通气不足（OH）儿童与离散性周期性阻塞性呼吸暂停（OA）儿童的UA反射对UA通畅性的影响，（B）测量OH与OA儿童的吸气阻力负荷唤醒阈值，以及（c）测量OA儿童与OH儿童和对照儿童在睡眠期间对吸气阻塞的反应的呼吸相关诱发电位（RREP）。这些研究将有助于阐明儿童OSAS的潜在病理生理学，从而更好地理解和改善这种疾病的管理。

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.