Discipline of Physiology, School of Medical Sciences, University of Adelaide , Adelaide, South Australia , Australia.
Adelaide Institute for Sleep Health: A Flinders Centre of Research Excellence, Repatriation General Hospital, Daw Park, South Australia, Australia.
J Appl Physiol (1985). 2018 Nov 1;125(5):1490-1497. doi: 10.1152/japplphysiol.00175.2018. Epub 2018 Aug 30.
Reduced ventilatory control stability (elevated loop gain) is a key nonanatomical, pathological trait contributing to obstructive sleep apnea (OSA), yet the mechanisms responsible remain unclear. We sought to identify the key factors contributing to elevated loop gain in OSA (controller vs. plant contributions) and to examine whether abnormalities in these factors persist after OSA treatment. In 15 males (8 OSA, 7 height, weight- and age -matched controls), we measured loop gain, controller gain, and plant gain using a pseudorandom binary CO stimulation method during wakefulness. Factors potentially influencing plant gain were also assessed (supine lung volume via helium dilution and spirometry). Measures were repeated 2 and 6 wk after initiating continuous positive airway pressure treatment. Loop gain (LG) was higher in OSA versus controls (LG at 1 cycle/min 0.28 ± 0.04 vs. 0.16 ± 0.04, P = 0.046, respectively), and the controller exhibited a greater peak response to CO and faster roll-off in OSA. OSA patients also exhibited reduced forced expiratory volume in the first second and forced vital capacity compared with controls (92.2 ± 1.7 vs. 102.9 ± 3.5% predicted, P = 0.021; 93.4 ± 3.1 vs. 106.6 ± 3.6% predicted, P = 0.015, respectively). There was no effect of treatment on any variable. These findings confirm loop gain is higher in untreated OSA patients than in matched controls; however, this was not affected by treatment. NEW & NOTEWORTHY Elevated loop gain contributes to obstructive sleep apnea (OSA) pathophysiology. However, whether loop gain is inherently elevated in OSA or induced by OSA itself, whether it is elevated due to increased chemoreflex sensitivity or obesity-dependent reduced lung volume, and whether it is treatment reversible, are all currently uncertain. This study found loop gain was elevated in OSA versus age-, sex-, height-, and weight-matched controls. However, this was not altered by 6-wk continuous positive airway pressure treatment.
通气控制稳定性降低(升高的环路增益)是导致阻塞性睡眠呼吸暂停(OSA)的一个关键的非解剖学、病理学特征,但导致这种情况的机制仍不清楚。我们试图确定导致 OSA 中环路增益升高的关键因素(控制器与植物贡献),并检查这些因素在 OSA 治疗后是否仍然存在异常。在 15 名男性(8 名 OSA,7 名身高、体重和年龄匹配的对照)中,我们使用伪随机二进制 CO 刺激方法在清醒时测量环路增益、控制器增益和植物增益。还评估了可能影响植物增益的因素(通过氦稀释和肺活量计测量仰卧位肺容积)。在开始持续气道正压通气治疗后 2 周和 6 周重复测量。与对照组相比,OSA 中的环路增益(LG)更高(LG 在 1 个循环/分钟时分别为 0.28±0.04 和 0.16±0.04,P=0.046),并且控制器对 CO 的峰值反应更大,CO 衰减更快。与对照组相比,OSA 患者的第一秒用力呼气量和用力肺活量也降低(92.2±1.7%和 102.9±3.5%预测值,P=0.021;93.4±3.1%和 106.6±3.6%预测值,P=0.015)。治疗对任何变量均无影响。这些发现证实,未经治疗的 OSA 患者的环路增益高于匹配对照组;然而,这不受治疗的影响。新发现和值得注意的是:升高的环路增益有助于阻塞性睡眠呼吸暂停(OSA)的病理生理学。然而,环路增益在 OSA 中是否固有升高,或者是否由 OSA 本身引起,是由于化学感受器反射敏感性增加还是肥胖相关的肺容积减少引起,以及它是否可以通过治疗逆转,目前都还不确定。本研究发现,OSA 患者的环路增益高于年龄、性别、身高和体重匹配的对照组。然而,6 周的持续气道正压通气治疗并没有改变这一点。