Effects of sex and fat distribution on sleep disordered breathing

睡眠呼吸障碍的主要特征是睡眠期间部分或全部上气道阻塞。睡眠呼吸障碍最常见的形式是阻塞性睡眠呼吸暂停，这是由于睡眠状态开始时上气道反复塌陷造成的。与睡眠呼吸暂停相关的主要危险因素是肥胖、男性和绝经后状态。目前，我们的总体假设是，性别和脂肪分布预测睡眠呼吸暂停的易感性，由于上气道机械负荷代偿性神经肌肉控制的改变。基于我们最近的研究结果，我们证明肥胖与上气道负荷（被动Pcrit）升高相关，上气道负荷（被动Pcrit）由代偿性上气道神经反应抵消。此外，我们发现，女性，外周性肥胖，和年轻的年龄与增加的代偿性神经肌肉反应，而男性，中枢性肥胖，和老年与钝化的代偿反应。代偿性神经肌肉反应的丧失导致阻塞性睡眠呼吸暂停，睾酮替代可能逆转老年男性的机械和神经代偿性改变。在具体目标1中，我们将定义性别和年龄状态对正常个体上气道代偿反应的影响。我们假设：女性将比男性表现出更大的补偿性神经肌肉反应，并且这些补偿性反应中与年龄相关的下降将在两性中发生。在具体目标2中，我们将确定身体成分对上气道神经肌肉反应的影响。我们假设内脏肥胖是老年男性神经肌肉反应下降的主要决定因素。本研究旨在阐明阻塞性睡眠呼吸暂停的病理生理基础。 新的生理技术已经发展到允许在睡眠期间上呼吸道控制的机械和神经调节的分区。这些研究也为上呼吸道功能的神经体液调节提供了新的见解。

Sleep-disordered breathing is characterized primarily by partial or total upper airway obstruction during sleep. The most common form of sleep-disordered breathing is obstructive sleep apnea due to recurrent collapse of the upper airway with the onset of sleep state. The major risk factors associated with the development of sleep apnea are obesity, male sex, and post menopausal status. Currently, our overall hypothesis is that sex and fat distribution predict sleep apnea susceptibility due to alterations in upper airway mechanical load compensatory neuromuscular control. Based on our most recent findings, we demonstrate that obesity is associated with elevations in the upper airway load (passive Pcrit) that are counterbalanced by compensatory upper airway neural responses. Moreover, we show that female sex, peripheral adiposity, and younger age are associated with increased compensatory neuromuscular responses, while male sex, central adiposity, and older age are associated with blunted compensatory responses. The loss of the compensatory neuromuscular responses leads to obstructive sleep apnea and testosterone replacement may reverse both the mechanical and neurocompensatory alterations in aging men. In Specific Aim 1, we will define the effects of sex and age status on upper airway compensatory responses normal individuals. We hypothesize that: women will demonstrate greater compensatory neuromuscular responses than men, and that age-related declines in these compensatory responses will occur in both sexes. In Specific Aim 2, we will determine the effects of body composition on upper airway neuromuscular responses. We hypothesize that visceral adiposity is the major determinate of decrement in neuromuscular responses in older men compared to women The proposed studies are designed to elucidate the pathophysiologic basis for the development of obstructive sleep apnea. Novel physiologic techniques have been developed to allow partitioning of the mechanical and neural regulation of upper airway control during sleep. The studies also provide insights into the neurohumoral regulation of upper airway function.