Effects of sex and fat distribution on sleep disordered breathing

性别和脂肪分布对睡眠呼吸障碍的影响

• 批准号: 7895691
• 负责人: PHILIP L SMITH
• 金额: $ 42.51万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-01-20 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7895691
• 关键词: Age; Aging; Body Composition; Body Weight decreased; Body fat; Central obesity; Data; Development; Dose; Fatty acid glycerol esters; Female; Gases; Gonadal Steroid Hormones; Individual; Lead; Mechanics; Menopausal Status; Modeling; Muscle; Obesity; Obstructive Sleep Apnea; Pathogenesis; Pathologic; Peripheral; Physiological; Play; Postmenopause; Predisposition; Recurrence; Regulation; Research Design; Risk Factors; Role; Severities; Sex Characteristics; Sleep; Sleep Apnea Syndromes; Sturnus vulgaris; Techniques; Testosterone; Visceral; Woman; age related; airway obstruction; base; improved; insight; male; men; neuromuscular; neuroregulation; novel; older men; pharyngeal critical pressure; pressure; relating to nervous system; response; sex; sleep onset

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.

睡眠呼吸的呼吸主要由睡眠期间部分或总呼吸道阻塞。睡眠呼吸的最常见形式是由于上呼吸道的复发性塌陷而导致睡眠状态的折断。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，性别和脂肪分布可以预测由于上呼吸道机械载荷补偿性神经肌肉控制的改变而导致的睡眠呼吸暂停敏感性。根据我们的最新发现，我们证明肥胖与上呼吸道负荷（被动PCRIT）的高程有关，这些高度与补偿性上呼吸道神经反应相抵消。此外，我们表明女性，外周肥胖和年轻年龄与补偿性神经肌肉反应的增加有关，而男性性别，中心肥胖和年龄较大，与补偿性反应有关。补偿性神经肌肉反应的丧失导致阻塞性睡眠呼吸暂停和睾丸激素的替代可能会逆转衰老男性的机械和神经反应改变。在特定目标1中，我们将定义性别和年龄状况对正常人的上空补偿反应的影响。我们假设这一点：女性将表现出比男性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。在特定的目标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与女性相比，老年男性神经肌肉反应降低的主要确定性，拟议的研究旨在阐明阻塞性睡眠呼吸暂停发展的病理生理基础。 已经开发了新型的生理技术，以允许在睡眠期间对上气道控制的机械和神经调节进行分配。这些研究还提供了对上气道功能的神经肿瘤调节的见解。

项目成果

Response to inspiratory resistive loading during sleep in normal children and children with obstructive apnea.

正常儿童和患有阻塞性呼吸暂停的儿童在睡眠期间对吸气阻力负荷的反应。

• DOI: 10.1152/jappl.1999.87.4.1448
• 发表时间: 1999
• 期刊: Journal of applied physiology (Bethesda, Md. : 1985)
• 作者: Marcus,CL;Moreira,GA;Bamford,O;Lutz,J
• 通讯作者: Lutz,J

Obstructive sleep apnea syndrome: differences between children and adults.

阻塞性睡眠呼吸暂停综合征：儿童和成人之间的差异。

• 发表时间: 2000
• 期刊: Sleep
• 影响因子: 5.6
• 作者: Marcus,CL

Inspiratory duty cycle responses to flow limitation predict nocturnal hypoventilation.

吸气占空比对流量限制的反应可预测夜间通气不足。

• DOI: 10.1183/09031936.00063008
• 发表时间: 2009
• 期刊: The European respiratory journal
• 作者: Schneider,H;Krishnan,V;Pichard,LE;Patil,SP;Smith,PL;Schwartz,AR
• 通讯作者: Schwartz,AR

The association between daytime sleepiness and sleep-disordered breathing in NREM and REM sleep.

• DOI: 10.1093/sleep/25.3.307
• 发表时间: 2002-05
• 期刊: Sleep
• 影响因子: 5.6
• 作者: N. Punjabi;K. Bandeen-Roche;Jason J. Marx;D. Neubauer;Philip L. Smith;A. Schwartz

Childhood obstructive sleep apnea associates with neuropsychological deficits and neuronal brain injury.

• DOI: 10.1371/journal.pmed.0030301
• 发表时间: 2006-08
• 期刊: PLoS medicine
• 影响因子: 15.8
• 作者: Halbower AC;Degaonkar M;Barker PB;Earley CJ;Marcus CL;Smith PL;Prahme MC;Mahone EM
• 通讯作者: Mahone EM