Obesity and obstructive sleep apnea: pathogenic mechanisms and therapeutic approaches.
Obesity and obstructive sleep apnea: pathogenic mechanisms and therapeutic approaches.
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DOI：
10.1513/pats.200708-137mg
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发表时间：
2008-02-15
期刊：
影响因子：
--
通讯作者：
Smith, Philip L
中科院分区：
文献类型：
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作者：
Schwartz, Alan R;Patil, Susheel P;Smith, Philip L
阻塞性睡眠呼吸暂停是一种常见的疾病，其流行与西方社会肥胖的流行有关。睡眠呼吸暂停是由于睡眠期间上呼吸道阻塞的反复发作，这是由于睡眠期间上呼吸道塌陷性升高引起的。上呼吸道神经肌肉控制的基础解剖改变和/或障碍可增加塌陷性，两者在阻塞性睡眠呼吸暂停的发病机制中发挥关键作用。肥胖，特别是中心性肥胖，是睡眠呼吸暂停的潜在危险因素。它们可以通过对咽部软组织和肺体积的机械作用，以及可能影响呼吸道神经肌肉控制的中枢神经系统作用信号蛋白(脂肪因子)来增加咽部的塌陷性。特定的分子信号通路编码脂肪组织分布和代谢活性的差异。这些差异会导致上呼吸道塌陷的机械和神经控制的改变，这决定了睡眠呼吸暂停的易感性。虽然减肥可以降低睡眠期间上呼吸道的塌陷性，但目前尚不清楚其作用主要是通过改善上呼吸道的机械性能还是通过神经肌肉控制来实现的。通过对局部脂肪储备的质量和活动的不同影响，各种行为、药物和手术减肥方法可能对睡眠呼吸暂停患者有益。研究对特定减肥策略的反应将提供对肥胖和睡眠呼吸暂停联系机制的关键洞察，并有助于阐明减肥反应的体液和分子预测因素。
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. Collapsibility can be increased by underlying anatomic alterations and/or disturbances in upper airway neuromuscular control, both of which play key roles in the pathogenesis of obstructive sleep apnea. Obesity and particularly central adiposity are potent risk factors for sleep apnea. They can increase pharyngeal collapsibility through mechanical effects on pharyngeal soft tissues and lung volume, and through central nervous system-acting signaling proteins (adipokines) that may affect airway neuromuscular control. Specific molecular signaling pathways encode differences in the distribution and metabolic activity of adipose tissue. These differences can produce alterations in the mechanical and neural control of upper airway collapsibility, which determine sleep apnea susceptibility. Although weight loss reduces upper airway collapsibility during sleep, it is not known whether its effects are mediated primarily by improvement in upper airway mechanical properties or neuromuscular control. A variety of behavioral, pharmacologic, and surgical approaches to weight loss may be of benefit to patients with sleep apnea, through distinct effects on the mass and activity of regional adipose stores. Examining responses to specific weight loss strategies will provide critical insight into mechanisms linking obesity and sleep apnea, and will help to elucidate the humoral and molecular predictors of weight loss responses.