Assessing the Physiologic Endotypes Responsible for REM- and NREM-Based OSA.

Background: Patients with OSA can have the majority of their respiratory events in rapid eye movement (REM) sleep or in non-rapid eye movement (NREM) sleep. No previous studies have linked the different physiologic conditions in REM and NREM sleep to the common polysomnographic patterns seen in everyday clinical practice, namely REM predominant OSA (REM) and NREM predominant OSA (NREM).

Research Question: (1) How does OSA physiologic condition change with sleep stage in patients with NREM and REM? (2) Do patients with NREM and REM have different underlying OSA pathophysiologic conditions?

Study Design And Methods: We recruited patients with three polysomnographic patterns. (1) REM: twice as many respiratory events in REM sleep, (2) NREM: twice as many events in NREM sleep, and (3) uniform OSA: equal number of events in NREM/REM sleep. We deployed a noninvasive phenotyping method to determine OSA endotype traits (Vpassive, Vactive, loop gain, arousal threshold) in NREM sleep, REM sleep, and total night sleep in each group of patients (NREM, REM, uniform OSA).

Results: Patients with NREM have significantly worse ventilatory control stability in NREM sleep compared with REM sleep (loop gain, 0.546 [0.456,0.717] in NREM vs 0.365 [0.238,0.459] in REM sleep; P = .0026). Patients with REM displayed a significantly more collapsible airway (ie, lower Vpassive) in REM compared with NREM sleep (98.4 [97.3,99.2] %Veupnea in NREM vs 95.9 [86.4,98.9] %Veupnea in REM sleep; P < .0001). The major between-group difference across the whole night was a significantly higher loop gain in the NREM group (0.561 [0.429,0.675]) compared with the REM group (0.459 [0.388,0.539]; P = .0033).

Interpretation: This study is the first to link long-recognized polysomnographic patterns of OSA to underlying physiologic differences. Patients with NREM have a higher loop gain in NREM sleep; patients with REM have a worsening of Vpassive in REM sleep.