Circadian Mechanisms in Progression of Obstructive Apnea in Humans

描述（由申请人提供）：阻塞性睡眠呼吸暂停低通气综合征（SAHS）是一种影响2-4%成年人的衰弱性疾病。其他人和我们发现，呼吸暂停通常持续一个晚上，即使在相同的睡眠阶段和躺姿。我们最近的数据显示，大量内源性生物钟相关的变化，可能会影响呼吸暂停的严重程度，包括呼吸暂停的化学敏感性（高碳酸血症的呼吸反应），肺功能和生理反应，从睡眠中觉醒。昼夜节律起搏器和睡眠本身可以影响其中一些变量，这些影响以前从未被实验分离。因此，本研究的目的是进行第一次评估的内源性昼夜因素的发生和/或睡眠期间的呼吸阻塞的进展SAHS患者的贡献。为了实现这一目标，在10天的“强迫睡眠”方案中，当SAHS受试者在昼夜节律周期的不同阶段睡眠时，将检查呼吸异常。如果昼夜节律系统是导致夜间呼吸暂停严重程度增加的原因，这可能揭示了导致呼吸暂停严重程度调节的新机制。其中可能的因素，将被检查的是昼夜节律改变呼吸唤醒阈值和/或化疗敏感性。另一方面，如果在白天发生睡眠时，呼吸暂停仍然在整个睡眠期间持续，这表明昼夜节律系统不是夜间呼吸暂停恶化的原因。在这种情况下，会出现其他假设，例如夜间开始时的呼吸暂停影响随后的呼吸暂停的可能性（例如，通过解剖学或生理学上的适应不良，这可以在随后的实验中探索）。这项研究应该帮助我们理解SAHS的自然史和潜在的病理生理机制。公共卫生相关性：阻塞性睡眠呼吸暂停低通气综合征是一种影响2-4%成年人的衰弱性疾病。本研究的目的是评估内源性昼夜因素在睡眠呼吸阻塞的发生和/或进展中的作用。这项研究应该帮助我们理解SAHS的自然史和潜在的病理生理机制。

DESCRIPTION (provided by applicant): Obstructive sleep apnea-hypopnea syndrome (SAHS) is a debilitating condition affecting 2-4% of adults. Others and we have found that apnea usually worsens across a single night even when in the same sleep stage and lying posture. Our recent data show large endogenous circadian clock related changes in numerous variables that could affect apnea severity including ventilatory chemosensitivity (hypercapnic ventilatory response), pulmonary function, and physiological responses to arousal from sleep. The circadian pacemaker as well as sleep itself can affect some of these variables, and these effects have never before been experimentally separated. Thus, the aims of this study are to perform the first assessment of the contribution of endogenous circadian factors in the genesis and/or progression of obstructed breathing during sleep in patients with SAHS. To achieve this aim, breathing abnormalities will be examined when subjects with SAHS sleep at varied phases of the circadian cycle throughout a 10 day 'forced desynchrony' protocol. If the circadian system is responsible for increases in apnea severity across the night, this may reveal novel mechanisms causing modulation of apnea severity. Among the likely factors that will be examined are circadian alterations in respiratory arousal thresholds and/or ventilatory chemosensitivity. On the other hand, if apnea still worsens across the sleep period when sleep occurs during the day, this would suggest that the circadian system is not responsible for the worsening of apnea across the night. In this case other hypotheses would emerge, such as the possibility that apneas at the beginning of the night affect subsequent apneas (e.g., via anatomical or physiological maladaptations, which could be explored in subsequent experiments). This study ought to aid our understanding of the natural history and underlying pathophysiological mechanisms of SAHS. PUBLIC HEALTH RELEVANCE: Obstructive sleep apnea-hypopnea syndrome is a debilitating condition affecting 2-4% of adults. The aims of this study are to assess the contribution of endogenous circadian factors in the genesis and/or progression of obstructed breathing during sleep. This study ought to aid our understanding of the natural history and underlying pathophysiological mechanisms of SAHS.