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

Chest. 2021 May;159(5):1998-2007. doi: 10.1016/j.chest.2020.10.080. Epub 2020 Nov 14.


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 (REMOSA) and NREM predominant OSA (NREMOSA).

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

Study design and methods: We recruited patients with three polysomnographic patterns. (1) REMOSA: twice as many respiratory events in REM sleep, (2) NREMOSA: 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 (NREMOSA, REMOSA, uniform OSA).

Results: Patients with NREMOSA 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 REMOSA 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 NREMOSA group (0.561 [0.429,0.675]) compared with the REMOSA 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 NREMOSA have a higher loop gain in NREM sleep; patients with REMOSA have a worsening of Vpassive in REM sleep.

Keywords: OSA; REM sleep; phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polysomnography
  • Sleep Apnea, Obstructive / physiopathology*
  • Sleep Stages*
  • Sleep, REM*