Background In the classic model of obstructive sleep apnoea (OSA), respiratory events occur with sleep-related dilator muscle hypotonia, precipitating increased neural ventilatory ‘drive’. By contrast, a drive-dependent model has been proposed, whereby falling drive promotes dilator muscle hypotonia to precipitate respiratory events. Here we determine the extent to which the classic versus drive-dependent models of OSA are best supported by direct physiological measurements. Methods In 50 OSA patients (5–91 events/hour), we recorded ventilation (‘flow’, oronasal mask and pneumotach) and ventilatory drive (calibrated intraoesophageal diaphragm electromyography, EMG) overnight. Flow and drive during events were ensemble averaged; patients were classified as drive dependent if flow fell/rose simultaneously with drive. Overnight effects of lower drive on flow, genioglossus muscle activity (EMGgg) and event risk were quantified (mixed models). Results On average, ventilatory drive fell (rather than rose) during events (−20 (−42 to 3)%baseline, median (IQR)) and was strongly correlated with flow (R=0.78 (0.24 to 0.94)). Most patients (30/50, 60%) were classified as exhibiting drive-dependent event pathophysiology. Lower drive during sleep was associated with lower flow (−17 (−20 to –14)%/drive) and EMGgg (−3.5 (−3.8 to –3.3)%max/drive) and greater event risk (OR: 2.2 (1.8 to 2.5) per drive reduction of 100%eupnoea); associations were concentrated in patients with drive-dependent OSA (ie, flow: −37 (−40 to –34)%/drive, OR: 6.8 (5.3 to 8.7)). Oesophageal pressure—without tidal volume correction—falsely suggested rising drive during events ( classic model). Conclusions In contrast to the prevailing view, patients with OSA predominantly exhibit drive-dependent event pathophysiology, whereby flow is lowest at nadir drive, and lower drive raises event risk. Preventing ventilatory drive decline is therefore considered a target for OSA intervention. Data are available on reasonable request. A summary table of individual participant data can be made available on request for the purposes of data review. Deidentified (pseudonymised) raw signals data may be made available to qualified scientists pending a data use agreement with the Brigham and Women’s Hospital.

中文翻译：

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神经通气驱动力下降是阻塞性睡眠呼吸暂停事件的主要机制

背景 在阻塞性睡眠呼吸暂停 (OSA) 的经典模型中，呼吸事件与睡眠相关的扩张肌肌张力减退一起发生，导致神经通气“驱动”增加。相比之下，已经提出了一种依赖驱动的模型，即下降的驱动会促进扩张肌肌张力减退，从而引发呼吸事件。在这里，我们确定 OSA 的经典模型与驱动依赖模型在多大程度上得到直接生理测量的最佳支持。方法 在 50 名 OSA 患者（5-91 次/小时）中，我们记录通气（“流量”、口鼻面罩和呼吸机）和通气驱动（校准的食管内隔膜肌电图，EMG）过夜。事件期间的流量和驱动力是整体平均的；如果流量与驱动同时下降/上升，则患者被归类为依赖驱动。量化较低驱动力对流量、颏舌肌活动 (EMGgg) 和事件风险的夜间影响（混合模型）。结果 平均而言，通气驱动在事件期间下降（而不是上升）（-20（-42 至 3）％基线，中位数 (IQR)）并且与流量密切相关（R = 0.78（0.24 至 0.94））。大多数患者 (30/50, 60%) 被归类为表现出驱动依赖事件病理生理学。睡眠期间较低的驱动力与较低的流量（-17（-20 至 –14）％/驱动器）和 EMGgg（-3.5（-3.8 至 –3.3）％最大/驱动器）和较高的事件风险（OR：2.2（1.8至 2.5) 每驱动减少 100% 正常呼吸)；相关性集中在驾驶依赖性 OSA 患者中（即，流量：-37（-40 至 –34）%/驾驶，OR：6.8（5.3 至 8.7））。食管压力——没有潮气量校正——错误地建议在事件期间上升驱动（经典模型）。结论 与普遍观点相反，OSA 患者主要表现出驱动依赖性事件病理生理学，即最低点驱动时血流最低，较低的驱动会增加事件风险。因此，防止通气驱动下降被认为是 OSA 干预的目标。可应合理要求提供数据。出于数据审查的目的，可应要求提供个人参与者数据的汇总表。在与布莱根妇女医院达成数据使用协议之前，可以向合格的科学家提供去识别化（假名化）的原始信号数据。因此，防止通气驱动下降被认为是 OSA 干预的目标。可应合理要求提供数据。出于数据审查的目的，可应要求提供个人参与者数据的汇总表。在与布莱根妇女医院达成数据使用协议之前，可以向合格的科学家提供去识别化（假名化）的原始信号数据。因此，防止通气驱动下降被认为是 OSA 干预的目标。可应合理要求提供数据。出于数据审查的目的，可应要求提供个人参与者数据的汇总表。在与布莱根妇女医院达成数据使用协议之前，可以向合格的科学家提供去识别化（假名化）的原始信号数据。