Underlying mechanisms of obesity-induced obstructive sleep apnea

肥胖引起的阻塞性睡眠呼吸暂停的潜在机制

• 批准号: 10636633
• 负责人: Atul Malhotra
• 金额: $ 65.17万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10636633
• 关键词: Anatomy; Apnea; Arousal; Autonomic Pathways; Behavior; Body Weight; Body Weight decreased; Body fat; Breathing; Cardiovascular system; Catecholamines; Clinical; Computer Models; Control Groups; Data; Dependence; Dilator; Disease; Epidemic; Evaluation; Exclusion; Fatty acid glycerol esters; Follow-Up Studies; Functional Residual Capacity; Functional disorder; Health; Hypercapnia; Hypoxemia; Hypoxia; Image; Imaging Techniques; Impairment; Individual; Inflammatory; Lead; Life Expectancy; Link; Literature; Longterm Follow-up; Magnetic Resonance Imaging; Mechanics; Medical; Morbid Obesity; Muscle; Neurocognitive; Obesity; Obstructive Sleep Apnea; Operative Surgical Procedures; Outcome; Participant; Pathogenesis; Pathway interactions; Patients; Pattern; Persons; Pharmaceutical Preparations; Pharyngeal structure; Population; Positioning Attribute; Predictive Value; Prevalence; Prevention; Public Health; Recommendation; Recurrence; Research; Residual volume; Resolution; Risk; Risk Factors; Role; Sleep; Sleep Apnea Syndromes; Structure; Testing; Therapeutic; Thinness; Time; Tongue; Total Lung Capacity; Traction; Wakefulness; Weight maintenance regimen; Work; bariatric surgery; diet and exercise; experience; improved; individualized medicine; insight; lung volume; novel therapeutic intervention; obese person; personalized approach; pharyngeal critical pressure; poor health outcome; pressure; primary outcome; recruit; response; trait

Obstructive sleep apnea (OSA) is a highly prevalent disease with major neurocognitive and cardiovascular sequelae. Obesity is a major risk factor for OSA, but the underlying mechanisms remain unclear. Given the rising prevalence of obesity and the lack of adequate therapies for some afflicted patients, further mechanistic work is clearly required. Bariatric surgery is being done increasingly with compelling outcome data emerging; however, clinical response to weight loss is highly variable. In some patients, OSA is not present at baseline, despite morbid obesity, in other patients, OSA resolves following bariatric surgery, while other patients have persistence of OSA despite weight loss, and still other patients can experience re-emergence of OSA in long term follow-up studies after bariatric surgery. OSA can occur due to several major pathophysiological factors including pharyngeal anatomy, pharyngeal dilator muscle dysfunction, unstable ventilatory control, end- expiratory lung volume and arousal threshold. As a result considerable complexity exists in the obesity/OSA relationship, suggesting the need for further research. First, we will perform a baseline evaluation of pathophysiological traits among obese people prior to weight loss surgery. Because some people will have OSA and some will not, we will define the potential mechanisms underlying OSA and potential protective mechanisms among obese people without OSA (pharyngeal critical closing pressure Pcrit primary outcome). Second, we will re-evaluate these same individuals from the standpoint of sleep study and pathophysiological traits six months following bariatric surgery after a variable degree of weight loss. We anticipate that some OSA patients will have resolution of OSA whereas others will have persistence of disease. For non-OSA patients undergoing weight loss, we will have a positive control group which will allow us to account for non-specific effects of weight loss. This aim will allow us to test the hypothesis that pharyngeal mechanics is the predominant mechanism whereby weight loss leads to improvement in OSA. Third, we will perform magnetic resonance imaging during wakefulness at functional residual capacity, total lung capacity and residual volume on participants at baseline and 6months following bariatric surgery. This aim will allow us to perform structure/function assessments in our participants, to define the impact of weight loss on pharyngeal anatomy, and to quantify the lung volume dependence of the upper airway before and after weight loss. The acquired data will also be used for computational modeling including dynamic assessment of pharyngeal function during tidal breathing. As a result of the proposed research, we are confident that we will gain major insights into the as yet unanswered question “why does obesity (sometimes) cause sleep apnea”. This research will have major therapeutic implications as it will allow us to individualize therapy for afflicted patients.

阻塞性睡眠呼吸暂停(OSA)是一种以神经认知和心血管疾病为主的高发疾病 后遗症。肥胖是阻塞性睡眠呼吸暂停综合征的主要风险因素，但其潜在机制尚不清楚。给定 肥胖率的上升和一些患者缺乏适当的治疗，进一步机械地 显然，这方面的工作是必要的。随着令人信服的结果数据出现，减肥手术正在越来越多地进行； 然而，临床上对减肥的反应是高度不同的。在一些患者中，OSA在基线时不存在， 尽管有病态肥胖，但在其他患者中，OSA在减肥手术后痊愈，而其他患者 尽管体重减轻，但OSA仍持续存在，还有其他患者可能在很长时间内再次出现OSA 减肥手术后的定期随访研究。阻塞性睡眠呼吸暂停综合征的发生有多种主要的病理生理因素 包括咽解剖、咽扩张肌功能障碍、呼吸控制不稳定、 呼气肺容量和觉醒阈值。因此，肥胖/阻塞性睡眠呼吸暂停综合征存在相当大的复杂性 关系，表明有必要进行进一步的研究。首先，我们将对 肥胖者减肥手术前的病理生理学特征。因为有些人会有 OSA和一些不会，我们将定义OSA潜在的机制和潜在的保护 无阻塞性睡眠呼吸暂停的肥胖者的发病机制(咽部临界关闭压Pcrit主要结果)。 其次，我们将从睡眠研究和病理生理的角度对这些人进行重新评估 减重程度不同的减肥手术后6个月的特征。我们预计会有一些OSA 患者会有OSA的消退，而其他人会有疾病的持久性。适用于非阻塞性睡眠呼吸暂停患者 在减肥期间，我们将有一个积极的对照组，这将允许我们解释非特定的 减肥的效果。这一目标将使我们能够检验咽部力学是主要的假设 体重减轻导致OSA改善的机制。第三，我们将进行磁共振 清醒时的功能残气量、总肺活量和残气量 参与者在基线和减肥手术后6个月。这一目标将使我们能够执行 我们的参与者的结构/功能评估，以确定体重减轻对咽部解剖的影响， 并量化减重前后上呼吸道的肺容量依赖关系。被收购的 数据还将用于计算建模，包括动态评估咽部功能 潮气呼吸。作为拟议研究的结果，我们有信心我们将获得对 尚未解答的问题是：为什么肥胖(有时)会导致睡眠呼吸暂停？这项研究将具有重大意义 治疗意义，因为它将使我们能够对受影响的患者进行个性化治疗。