TY - JOUR
T1 - Ventilatory Drive Withdrawal Rather Than Reduced Genioglossus Compensation as a Mechanism of Obstructive Sleep Apnea in REM Sleep
AU - Messineo, Ludovico
AU - Eckert, Danny J.
AU - Taranto-Montemurro, Luigi
AU - Vena, Daniel
AU - Azarbarzin, Ali
AU - Hess, Lauren B.
AU - Calianese, Nicole
AU - White, David P.
AU - Wellman, Andrew
AU - Gell, Laura
AU - Sands, Scott A.
PY - 2022/1/15
Y1 - 2022/1/15
N2 - Rationale: REM sleep is associated with reduced ventilation and greater obstructive sleep apnea (OSA) severity than non-REM (nREM) sleep for reasons that have not been fully elucidated. Objectives: Here, we use direct physiological measurements to determine whether the pharyngeal compromise in REM sleep OSA is most consistent with 1) withdrawal of neural ventilatory drive or 2) deficits in pharyngeal pathophysiology per se (i.e., increased collapsibility and decreased muscle responsiveness). Methods: Sixty-three participants with OSA completed sleep studies with gold standard measurements of ventilatory “drive” (calibrated intraesophageal diaphragm EMG), ventilation (oronasal “ventilation”), and genioglossus EMG activity. Drive withdrawal was assessed by examining these measurements at nadir drive (first decile of drive within a stage). Pharyngeal physiology was assessed by examining collapsibility (lowered ventilation at eupneic drive) and responsiveness (ventilation–drive slope). Mixed-model analysis compared REM sleep with nREM sleep; sensitivity analysis examined phasic REM sleep. Measurements and Main Results: REM sleep (>10 min) was obtained in 25 patients. Compared with drive in nREM sleep, drive in REM sleep dipped to markedly lower nadir values (first decile, estimate [95% confidence interval], 221.8% [231.2% to 212.4%] of eupnea; P, 0.0001), with an accompanying reduction in ventilation (225.8% [231.8% to 219.8%] of eupnea; P, 0.0001). However, there was no effect of REM sleep on collapsibility (ventilation at eupneic drive), baseline genioglossus EMG activity, or responsiveness. REM sleep was associated with increased OSA severity (110.1 [1.8 to 19.8] events/h), but this association was not present after adjusting for nadir drive (14.3 [24.2 to 14.6] events/h). Drive withdrawal was exacerbated in phasic REM sleep. Conclusions: In patients with OSA, the pharyngeal compromise characteristic of REM sleep appears to be predominantly explained by ventilatory drive withdrawal rather than by preferential decrements in muscle activity or responsiveness. Preventing drive withdrawal may be the leading target for REM sleep OSA.
AB - Rationale: REM sleep is associated with reduced ventilation and greater obstructive sleep apnea (OSA) severity than non-REM (nREM) sleep for reasons that have not been fully elucidated. Objectives: Here, we use direct physiological measurements to determine whether the pharyngeal compromise in REM sleep OSA is most consistent with 1) withdrawal of neural ventilatory drive or 2) deficits in pharyngeal pathophysiology per se (i.e., increased collapsibility and decreased muscle responsiveness). Methods: Sixty-three participants with OSA completed sleep studies with gold standard measurements of ventilatory “drive” (calibrated intraesophageal diaphragm EMG), ventilation (oronasal “ventilation”), and genioglossus EMG activity. Drive withdrawal was assessed by examining these measurements at nadir drive (first decile of drive within a stage). Pharyngeal physiology was assessed by examining collapsibility (lowered ventilation at eupneic drive) and responsiveness (ventilation–drive slope). Mixed-model analysis compared REM sleep with nREM sleep; sensitivity analysis examined phasic REM sleep. Measurements and Main Results: REM sleep (>10 min) was obtained in 25 patients. Compared with drive in nREM sleep, drive in REM sleep dipped to markedly lower nadir values (first decile, estimate [95% confidence interval], 221.8% [231.2% to 212.4%] of eupnea; P, 0.0001), with an accompanying reduction in ventilation (225.8% [231.8% to 219.8%] of eupnea; P, 0.0001). However, there was no effect of REM sleep on collapsibility (ventilation at eupneic drive), baseline genioglossus EMG activity, or responsiveness. REM sleep was associated with increased OSA severity (110.1 [1.8 to 19.8] events/h), but this association was not present after adjusting for nadir drive (14.3 [24.2 to 14.6] events/h). Drive withdrawal was exacerbated in phasic REM sleep. Conclusions: In patients with OSA, the pharyngeal compromise characteristic of REM sleep appears to be predominantly explained by ventilatory drive withdrawal rather than by preferential decrements in muscle activity or responsiveness. Preventing drive withdrawal may be the leading target for REM sleep OSA.
KW - Drive withdrawal
KW - Pharyngeal muscle responsiveness
KW - Phasic
KW - REM sleep hypotonia
KW - REM sleep pathogenesis
KW - Tonic REM sleep
UR - http://www.scopus.com/inward/record.url?scp=85123812517&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/1116942
UR - http://purl.org/au-research/grants/NHMRC/1196261
U2 - 10.1164/rccm.202101-0237OC
DO - 10.1164/rccm.202101-0237OC
M3 - Article
C2 - 34699338
AN - SCOPUS:85123812517
VL - 205
SP - 219
EP - 232
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 2
ER -