Circadian Mechanisms in Progression of Obstructive Apnea in Humans

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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.