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）是一种高度普遍的疾病，具有主要的神经认知和心血管后遗症。肥胖是OSA的主要危险因素，但潜在的机制尚不清楚。鉴于肥胖症患病率上升和一些患者缺乏足够的疗法，进一步的机理显然需要工作。随着引人注目的结果数据的出现，减肥手术正在越来越多地进行；但是，对减肥的临床反应是高度可变的。在某些患者中，OSA在基线时不存在，尽管病态肥胖症，但在其他患者中，软骨手术后仍能解决OSA，而其他患者则具有 OSA目的地减肥的持久性，还有其他患者可以长期体验OSA的重新出现减肥手术后的术语随访研究。 OSA可能由于几个主要的病理生理因素而发生包括咽解剖，咽部扩张肌功能障碍，不稳定的通风控制，末端呼气肺体积和唤醒阈值。结果，肥胖/OSA中存在相当大的复杂性关系，表明需要进一步研究。首先，我们将对减肥手术前肥胖者的病理生理特征。因为有些人会 OSA和某些人不会，我们将定义OSA的潜在机制和潜在的保护没有OSA的肥胖者的机制（咽临界关闭压力PCRIT主要结果）。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相同的个体减肥程度可变后，减肥手术后六个月的特征。我们预计会有一些OSA 患者将分辨出OSA，而其他患者将持续存在疾病。对于非OSA患者减肥，我们将拥有一个阳性对照组，这将使我们能够考虑非特异性体重减轻的影响。这个目标将使我们能够检验咽部机制是主要主导的假设体重减轻会导致OSA改善的机制。第三，我们将执行磁共振在唤醒期间以功能残留能力，总肺容量和剩余体积的成像成像减肥手术后基线和6个月的参与者。这个目标将使我们能够执行参与者中的结构/功能评估，以定义减肥对咽解剖学的影响，并量化体重减轻之前和之后的上呼吸道的肺体积依赖性。获得的数据还将用于计算建模，包括对咽功能的动态评估潮汐呼吸。由于拟议的研究，我们有信心我们将获得对尚未解决的问题“肥胖症（有时）为什么会导致睡眠呼吸暂停”。这项研究将有重大治疗意义将使我们能够为患者的患者个性化治疗。