Circadian Mechanisms in Progression of Obstructive Apnea in Humans

人类阻塞性呼吸暂停进展的昼夜节律机制

• 批准号: 7589472
• 负责人: STEVEN A SHEA
• 金额: $ 22.17万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7589472
• 关键词: Accounting; Acute; Adult; Affect; Aging; Apnea; Arousal; Body Size; Body Temperature; Breathing; Chemicals; Circadian Rhythms; Clinical; Data; Disease; Edema; Frequencies; Future; Gender; Hand; Hour; Human; Hypercapnia; Hypoxia; Inflammation; Lead; Length; Measurement; Measures; Mechanics; Movement; Natural History; Newly Diagnosed; Obstructive Sleep Apnea; Oxygen; Patients; Phase; Physiological; Plethysmography; Positioning Attribute; Posture; Predisposing Factor; Protocols documentation; Research; Schedule; Severities; Severity of illness; Sleep; Sleep Apnea Syndromes; Sleep Stages; Sleep Wake Cycle; Snoring; Stimulus; Suction; Surface; Syndrome; System; Temperature; Time; Tissues; Trauma; circadian pacemaker; day length; novel; pressure; public health relevance; pulmonary function; research study; respiratory; response

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.

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%成年人的衰弱疾病。其他人和我们发现，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卧姿。我们最近的数据显示，许多可能影响呼吸暂停严重程度的变量发生了巨大的内源性昼夜节律相关的变化，包括呼吸化学敏感性(高二氧化碳呼吸反应)、肺功能和对睡眠唤醒的生理反应。昼夜节律起搏器和睡眠本身都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，这项研究的目的是首次评估内源性昼夜节律因素在SAHS患者睡眠期间呼吸障碍的发生和/或发展中的作用。为了实现这一目标，当SAHS患者在整个10天的强制去同步方案中，在昼夜周期的不同阶段睡眠时，将检查呼吸异常。如果昼夜节律系统导致夜间呼吸暂停严重程度的增加，这可能揭示导致呼吸暂停严重程度调节的新机制。可能要检查的因素包括呼吸觉醒阈值和/或呼吸性化疗敏感性的昼夜变化。另一方面，如果呼吸暂停在白天睡眠期间仍在恶化，这表明昼夜呼吸暂停的恶化并不是昼夜节律系统造成的。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可能会影响随后的呼吸暂停(例如，通过解剖学或生理学的适应不良，这可以在随后的实验中探索)。这项研究应该有助于我们理解SAHS的自然历史和潜在的病理生理机制。公共卫生意义：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。这项研究的目的是评估内源性昼夜节律因素在睡眠期间呼吸障碍的发生和/或发展中的作用。这项研究应该有助于我们理解SAHS的自然历史和潜在的病理生理机制。