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: 7841754
• 负责人: STEVEN A SHEA
• 金额: $ 26.7万
• 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 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7841754
• 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呼吸症综合征（SAHS）是影响2-4％成年人的衰弱状况。其他人，我们发现即使在同一个睡眠阶段和躺着的姿势时，呼吸暂停通常会在一个晚上恶化。我们最近的数据表明，大量的内源性昼夜节律与许多变量相关的变化可能会影响呼吸暂停严重程度，包括通气化学敏感性（高碳水化合物通气反应），肺功能和对唤醒的生理反应。昼夜节律起搏器以及睡眠本身会影响其中的某些变量，而这些效果从未经过实验分离。因此，这项研究的目的是首先评估内源性昼夜节律因素在SAHS患者睡眠期间受阻呼吸中受阻呼吸中的贡献和/或进展。为了实现这一目标，当SAHS的受试者在整个10天的“强迫Dephthrony”方案中以不同的阶段入睡时，将检查呼吸异常。如果昼夜节日系统整个夜间负责呼吸暂停严重程度的增加，则可能揭示了引起呼吸暂停严重程度调节的新机制。在将要研究的可能因素中，均是呼吸唤醒阈值和/或通气化学敏感性的昼夜节律改变。另一方面，如果在白天发生睡眠时呼吸暂停在整个睡眠期间仍然恶化，这表明昼夜节律系统对整个晚上的呼吸暂停不断恶化概不负责。在这种情况下，其他假设将出现，例如，夜晚初期呼吸暂停会影响随后的呼吸暂停（例如，通过解剖学或生理疾病疾病，可以在随后的实验中探索）。这项研究应该有助于我们对SAHS的自然历史和潜在的病理生理机制的理解。公共卫生相关性：阻塞性睡眠呼吸暂停呼吸症综合征是影响2-4％成年人的令人衰弱的疾病。这项研究的目的是评估内源性昼夜节律因素在睡眠期间受阻呼吸受到阻塞的进展中的贡献。这项研究应该有助于我们对SAHS的自然历史和潜在的病理生理机制的理解。