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

基本信息

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
项目类别：
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

项目摘要

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）是一种高度流行的疾病，主要影响神经认知和心血管疾病肥胖是 OSA 的主要危险因素，但其潜在机制仍不清楚。肥胖患病率不断上升，并且一些受影响的患者缺乏适当的治疗，进一步的机制随着令人信服的结果数据不断涌现，减肥手术显然是必要的；然而，在一些患者中，体重减轻的临床反应变化很大，OSA 在基线时并不存在。尽管有病态肥胖，但其他患者的 OSA 在减肥手术后得到缓解，而其他患者则尽管体重减轻，但 OSA 仍持续存在，还有一些患者可能会在很长一段时间内再次出现 OSA 减肥手术后的长期随访研究可能是由于几个主要的病理生理因素而发生的。包括咽部解剖结构、咽部扩张肌功能障碍、不稳定的通气控制、终末期因此，肥胖/OSA 存在相当大的复杂性。关系，表明需要进一步研究。首先，我们将进行基线评估。减肥手术前肥胖者的病理生理特征，因为有些人会有。 OSA 和有些不会，我们将定义 OSA 的潜在机制和潜在的保护作用无 OSA（咽部临界闭合压 Pcrit 主要结果）的肥胖人群的机制。其次，我们将从睡眠研究和病理生理学的角度重新评估这些人减肥手术后六个月的特征我们预计，某些 OSA 会出现不同程度的体重减轻。对于非 OSA 患者，患者的 OSA 会得到缓解，而其他患者的疾病会持续存在。在减肥期间，我们将有一个阳性对照组，这将使我们能够解释非特异性这个目标将使我们能够检验咽部力学是主要作用的假设。减肥导致 OSA 改善的机制第三，我们将进行磁共振检查。清醒时对功能残气量、肺总容量和残气量进行成像基线和减肥手术后 6 个月的参与者这一目标将使我们能够执行。对参与者进行结构/功能评估，以确定减肥对咽部解剖结构的影响，并量化减肥前后上呼吸道的肺容量依赖性。数据还将用于计算建模，包括在期间动态评估咽部功能作为拟议研究的结果，我们相信我们将获得对潮汐呼吸的重要见解。尚未解答的问题“为什么肥胖（有时）会导致睡眠呼吸暂停”这项研究将有重大意义。治疗意义，因为它将使我们能够对患病患者进行个体化治疗。