Neural ventilatory drive decline as a predominant mechanism of obstructive sleep apnoea events.

Abstract

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 <i>falling</i> 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. 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 <i>drive dependent</i> 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). 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 <i>drive-dependent</i> 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 (<i>classic</i> model). In contrast to the prevailing view, patients with OSA predominantly exhibit <i>drive-dependent</i> 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.