"REM-related" obstructive sleep apnea: an epiphenomenon or a clinically important entity?

5 Commentary—Mokhlesi and Punjabi combination of both. Second, estimates of the AHIREM/AHINREM ratio can be highly imprecise, particularly if no consideration is given to the amount of REM sleep. For example, a patient with 6 minutes of REM sleep and 3 obstructive events during that period (AHIREM = 30 events/h) would be classified as having REM-related OSA, assuming that the AHINREM is 15 or fewer events/h. However, 6 minutes of REM sleep is not sufficient to precisely estimate the severity of disordered breathing during REM sleep. Thus, having a minimal requirement of REM-sleep duration is critical in assessing the presence of REM-related OSA. A third limitation with the use of the proposed ratio is that its numerator (AHIREM) and denominator (AHINREM) are highly correlated (r = 0.5-0.6). The strong correlation is not surprising given that disordered breathing events often manifest during both NREM and REM sleep. Defining a clinical entity based on a ratio of 2 rates (i.e., AHIREM and AHINREM) that are interdependent and correlated may not be possible because of the difficulty in separating out the NREM component of the underlying disease. In light of the aforementioned pitfalls, we propose the following criteria to designate the predominance of disordered breathing during REM sleep: (a) an AHINREM of fewer than 5 events/h and (b) an AHIREM of at least 5 events/h with at least 30 minutes of REM sleep. If the amount of REM sleep is less than 30 minutes, estimates of AHIREM should be considered imprecise, and decisions regarding disease classification should be made with caution. The threshold value of 30 minutes was based on the observation from the authors that 75% of all patients referred to the sleep laboratories for fullnight polysomnography at the University of Chicago and Johns Hopkins University have had REM sleep time of at least 30 minutes. Given the significant heterogeneity in defining REM-related OSA, it is not surprising that its epidemiology, natural history, and clinical significance are not well defined. A number of studies have shown that REM-related OSA is common in women and in younger patients.3-5,7,8 Aside from such basic descriptions, further characterization of its clinical attributes remains unclear, particularly regarding the possibility that patients with OSA only during REM sleep may differ in health outcomes when compared with those with disordered breathing events that are not strictly confined to REM sleep. To consider REM-related OSA as an entity with clinical significance, it is paramount that empiric evidence be collected to determine if it operates as a prescriptive element for adverse neurocognitive, cardiovascular, and metabolic outcomes. A number of clinicand community-based studies have suggested that only obstructive events during NREM sleep are associated with excessive daytime sleepiness or impaired quality Obstructive sleep apnea (OSA) is a prevalent sleep disorder characterized by recurrent episodes of complete or partial collapse of the upper airway that are associated with intermittent hypoxemia and recurrent arousals from sleep. Although upper airway collapse can occur in rapid eye movement (REM) and non-REM (NREM) sleep, the withdrawal of excitatory noradrenergic and serotonergic inputs to upper airway motor neurons during REM sleep further reduces pharyngeal muscle activity and substantially increases the propensity for upper airway collapse.1 Thus, REM sleep in patients with OSA is typically associated with increased frequency of obstructive events that are often prolonged and accompanied with severe oxyhemoglobin desaturation. The term “REM-related” OSA has been coined to denote the occurrence of disordered breathing events that predominantly or exclusively manifest during REM sleep—an observation that is common in clinical practice and well recognized by healthcare professionals in sleep medicine. The prevalence of REM-related OSA in clinical samples is highly variable, ranging from 10% to as much as 36%. 2-5 The variability in reported prevalence is due, in part, to the differences in sample characteristics and the definitions used for REM-related OSA.6 A commonly used diagnostic criterion is based on the ratio of the apnea-hypopnea index (AHI) during REM sleep to the AHI during NREM sleep (AHIREM/AHINREM), with a value of at least 2 indicating a predominance of disordered breathing during REM sleep. Although using a ratio of rates (i.e., events/h in REM sleep divided by events/h in NREM sleep) may have face validity, there are several inherent limitations. First, classifying patients with OSA based on the AHIREM/AHINREM ratio by itself is problematic because it will undoubtedly designate some patients as having REM-related OSA when, in fact, there is also substantial disease during NREM sleep. For example, a patient with an AHIREM of 70 events/h and an AHINREM of 35 events/h would be classified as having REM-related OSA when, in fact, the frequency of disordered breathing events during NREM sleep is not insignificant. In essence, the AHIREM/AHINREM ratio does not accurately depict the occurrence of disordered breathing events predominantly during REM sleep because it can be high either with (1) a high AHIREM, (2) a low AHINREM, or (3) a COMMENTARY