Underlying mechanisms of obesity-induced obstructive sleep apnea

阻塞性睡眠呼吸暂停（OSA）是一种高度流行的疾病， 后遗症肥胖是OSA的主要危险因素，但其潜在机制尚不清楚。鉴于 肥胖症患病率的上升和一些患病患者缺乏足够的治疗，进一步机械化 工作是明确需要的。减肥手术越来越多地进行，令人信服的结果数据不断涌现; 然而，对体重减轻的临床反应是高度可变的。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在减肥手术后消退，而其他患者 尽管体重减轻，但OSA持续存在，并且还有其他患者可以在长时间内经历OSA的再次出现。 减肥手术后的长期随访研究。阻塞性睡眠呼吸暂停综合征的发生可归因于几个主要的病理生理因素 包括咽部解剖结构、咽扩张肌功能障碍、不稳定的吞咽控制、端- 呼气肺容量和唤醒阈值。因此，肥胖/OSA中存在相当大的复杂性， 关系，这表明需要进一步研究。首先，我们将进行基线评估， 减肥手术前肥胖人群的病理生理特征。因为有些人 OSA和一些不会，我们将定义OSA的潜在机制和潜在的保护作用。 无OSA的肥胖人群中的机制（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学的角度重新评估这些人。 在不同程度的体重减轻后，减肥手术后六个月的特征。我们预计一些OSA 患者将具有OSA的消退，而其他患者将具有疾病的持续。对于非OSA患者 进行减肥，我们将有一个阳性对照组，这将使我们能够解释非特异性 减肥的效果。这一目标将使我们能够测试咽力学是主要的假设， 体重减轻导致OSA改善的机制。第三，我们将进行磁共振 清醒期间功能残气量、总肺容量和残气量的成像， 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 结构/功能评估，以确定体重减轻对咽部解剖结构的影响， 并量化体重减轻前后上气道的肺容量依赖性。所获取的 数据还将用于计算建模，包括在治疗期间咽功能的动态评估。 潮式呼吸作为拟议研究的结果，我们有信心，我们将获得重大的见解， 目前还没有答案的问题“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为受折磨的患者提供个性化治疗。

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.