RT Journal Article
SR Electronic
T1 Neural ventilatory drive decline as a predominant mechanism of obstructive sleep apnoea events
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 707
OP 716
DO 10.1136/thoraxjnl-2021-217756
VO 77
IS 7
A1 Laura K Gell
A1 Daniel Vena
A1 Raichel M Alex
A1 Ali Azarbarzin
A1 Nicole Calianese
A1 Lauren B Hess
A1 Luigi Taranto-Montemurro
A1 David P White
A1 Andrew Wellman
A1 Scott A Sands
YR 2022
UL http://thorax.bmj.com/content/77/7/707.abstract
AB 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.