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

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_OSA) and NREM predominant OSA (NREM_OSA).

(1) How does OSA physiologic condition change with sleep stage in patients with NREM_OSA and REM_OSA? (2) Do patients with NREM_OSA and REM_OSA have different underlying OSA pathophysiologic conditions?

We recruited patients with three polysomnographic patterns. (1) REM_OSA: twice as many respiratory events in REM sleep, (2) NREM_OSA: 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_OSA, REM_OSA, uniform OSA).

Patients with NREM_OSA 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_OSA 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_OSA group (0.561 [0.429,0.675]) compared with the REM_OSA group (0.459 [0.388,0.539]; P = .0033).

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