Mechanisms of Sleep Apnea in Severe Obesity

严重肥胖症睡眠呼吸暂停的机制

• 批准号: 7727751
• 负责人: Alan R. Schwartz
• 金额: $ 41.83万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7727751
• 关键词: Address; Adipocytes; Adipose tissue; Anatomy; Antisense Oligonucleotides; Biological Markers; Body Weight decreased; Central Nervous System Depressants; Central obesity; Data; Defect; Development; Diagnostic; Disease; Early Diagnosis; Enzymes; Epidemic; Fatty acid glycerol esters; Functional disorder; Human; Inflammation Mediators; Inflammatory; Intervention; Lead; Leptin; Link; Mechanics; Mediating; Metabolic; Metabolic Pathway; Modeling; Morbid Obesity; Morbidity - disease rate; Mus; Obese Mice; Obesity; Obstruction; Obstructive Sleep Apnea; Operative Surgical Procedures; Pathogenesis; Pathway interactions; Pattern; Pharyngeal structure; Physiological; Play; Predisposition; Prevalence; Property; Recurrence; Resources; Risk Factors; Role; Signal Transduction; Sleep; Sleep Apnea Syndromes; Societies; Stearoyl-CoA Desaturase; Therapeutic; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Woman; airway obstruction; cytokine; dietary restriction; lung volume; men; mortality; mouse model; neuromuscular; novel; pharyngeal critical pressure; pressure; public health relevance; research study; response; restoration; sex; weight loss intervention

DESCRIPTION (provided by applicant): Obstructive sleep apnea is a common disorder whose prevalence is linked to an epidemic of obesity in Western society. Sleep apnea is due to recurrent episodes of upper airway obstruction during sleep that are caused by elevations in upper airway collapsibility during sleep. Current evidence indicates that anatomic alterations and disturbances in upper airway neuromuscular control play key roles in the pathogenesis of obstructive sleep apnea. Obesity and particularly central adiposity are potent risk factors for sleep apnea. Our primary hypothesis is that metabolic and inflammatory dysregulation in obesity produce specific defects in upper airway mechanical and neuromuscular control during sleep. To address this hypothesis, human and murine models will be probed to characterize the mechanisms of upper airway dysfunction during sleep in obesity. Dramatic surgical weight loss and specific nocturnal interventions will be implemented to elucidate specific physiologic, metabolic and inflammatory mechanisms causing upper airway dysfunction during sleep (SA 1 & 2). Complementary murine experiments are proposed to establish specific adipocytokines and metabolic pathways in the pathogenesis of upper airway obstruction during sleep (SA3). An inter-disciplinary team will leverage scientific and institutional resources in this project to: (1) define distinct physiologic, metabolic and inflammatory mediators of sleep apnea susceptibility, and (2) lay the groundwork for targeting novel biomarkers and pathways for diagnostic and therapeutic purposes. PUBLIC HEALTH RELEVANCE: Obstructive sleep apnea is a common disorder associated with substantial morbidity and mortality whose prevalence is linked to an epidemic of obesity in Western society. This proposal addresses the underlying physiologic, metabolic and inflammatory causes of sleep apnea in obesity. It promises to uncover new strategies for early diagnosis and treatment of this disorder.

描述（由申请人提供）：阻塞性睡眠呼吸暂停是一种常见疾病，其患病率与西方社会的肥胖症流行有关。睡眠呼吸暂停是由于睡眠期间的上呼吸道障碍物的复发性发作是由于睡眠期间的上呼吸道可折叠性的高度引起的。当前的证据表明，上气道神经肌肉控制的解剖学改变和干扰在阻塞性睡眠呼吸暂停的发病机理中起关键作用。肥胖，尤其是中心肥胖是睡眠呼吸暂停的有效危险因素。我们的主要假设是，在睡眠期间，肥胖症的代谢和炎症失调在上气道机械和神经肌肉控制中会产生特定的缺陷。为了解决这一假设，将探测人类和鼠模型以表征肥胖症睡眠期间上呼吸道功能障碍的机制。将实施戏剧性的手术减肥和特定的夜间干预措施，以阐明在睡眠期间引起上呼吸道功能障碍的特定生理，代谢和炎症机制（SA 1和2）。提出了互补的鼠实验，以在睡眠期间上呼吸道阻塞的发病机理中建立特定的脂肪细胞因子和代谢途径（SA3）。一个跨学科的团队将利用该项目的科学和机构资源来：（1）定义睡眠呼吸暂停易感性的独特的生理，代谢和炎症介体，以及（2）为瞄准新型的生物标志物以及诊断和治疗用途的新型生物标志物和途径。 公共卫生相关性：阻塞性睡眠呼吸暂停是一种与大量发病率和死亡率相关的常见疾病，其患病率与西方社会的肥胖症流行有关。该建议涉及肥胖症中睡眠呼吸暂停的潜在生理，代谢和炎症原因。它有望发现这种疾病的早期诊断和治疗的新策略。