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。其他人和我们都发现，呼吸暂停通常会在一个晚上恶化，即使是在相同的睡眠阶段和躺姿下。我们最近的数据显示，大量内源性生物钟相关的变化在许多变量中可能影响呼吸暂停的严重程度，包括通气化学敏感性（高碳酸血症通气反应）、肺功能和从睡眠中唤醒的生理反应。昼夜节律起搏器以及睡眠本身会影响其中的一些变量，而这些影响以前从未被实验分离过。因此，本研究的目的是首次评估内源性昼夜节律因子在SAHS患者睡眠时呼吸障碍的发生和/或进展中的作用。为了实现这一目标，在为期10天的“强制非同步”方案中，当SAHS患者在昼夜周期的不同阶段睡眠时，将检查呼吸异常情况。如果昼夜节律系统对夜间呼吸暂停严重程度的增加负有责任，这可能揭示了导致呼吸暂停严重程度调节的新机制。可能的因素包括呼吸唤醒阈值和/或通气化学敏感性的昼夜变化。另一方面，如果呼吸暂停在白天睡眠时仍然恶化，这就表明昼夜节律系统不是造成夜间呼吸暂停恶化的原因。在这种情况下，其他假设也会出现，比如夜间开始时的呼吸暂停可能会影响随后的呼吸暂停（例如，通过解剖或生理上的不适应，这可以在随后的实验中进行探索）。这项研究应该有助于我们了解SAHS的自然历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使人衰弱的疾病，影响2-4%的成年人。本研究的目的是评估内源性昼夜节律因子在睡眠中呼吸障碍的发生和/或进展中的作用。这项研究应该有助于我们了解SAHS的自然历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.