ORPNR has been used extensively in group studies to determine if different demographics and clinical disorders are associated with different sleep depth. High group averages (shallower sleep) were associated with age (1), male gender (1), increasing OSA severity (1-3), Parkinson’s disease (4), adolescents with attention deficit hyperactivity disorder (ADHD) (5), sleep under noisy conditions (6), Narcolepsy (7), a subtype of insomnia (8), and a subtype of idiopathic hypersomnia (9). 

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Group averages of ORPNR are lower after sleep deprivation (10) and higher in the latter part of the night (10,11), indicating that ORPNR is sensitive to sleep pressure. Low average values (<0.60) can be seen at all ages but mostly in asymptomatic young subjects (10,12) and sleepy older subjects, including a subgroup of patients with idiopathic hypersomnia (9). 

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The range of individual ORPNR values is very wide (0.30-1.60) in all cohorts studied so far, regardless of demographics or presence or absence of sleep disorders or symptoms, and the difference in cohort averages in symptomatic vs. asymptomatic subjects is very small relative to the range in different cohorts, such that there is substantial overlap in the cohort ranges (1). There are, accordingly, no values that can be considered normal or abnormal. Even in subjects with bona fide idiopathic hypersomnia, ORPNR ranges from low to very high values (9). ORPNR is, accordingly, not very helpful when assessed in isolation in the diagnosis and management of individual patients. However, as will be discussed in later sections, it is a very common member of biomarker clusters that are fairly specific to underlying mechanisms of sleep complaints and disorders. Reference has already been made to the use of associated ORPW in determining the mechanism of elevated ORPNR.

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ORPNR is negatively associated with quality of life after adjusting for age, gender, and BMI. In a preliminary analysis of the relation between ORPNR and the 36-Item Short Form Survey (SF-36) in SHHS participants, an increase in ORPNR of 1 unit was associated with 3-point decrease in physical (SF36-P) and 4-point decrease in mental (SF36-M) quality of life. Both relations were significant whether or not participants with OSA were included (M Younes, unpublished observations). Higher ORPNR was associated with all-cause mortality (13).

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The relation between ORPNR and excessive sleepiness is most interesting. Subjects with very high or very low ORPNR could be very sleepy or not sleepy at all. In the aforementioned study on SHHS participants, there was no correlation between ORPNR and the Epworth Sleepiness Scale (ESS) despite the very large number of participants (>5000). Furthermore, Keenan et al found no differences in ORPNR among SAGIC participants with OSA who were not sleepy (n=485), excessively sleepy (n=533), or moderately sleepy (n=500) (14) 

 

A possible explanation is that shallow sleep may be an expression of a disorder with low sleep pressure, where EDS is not expected or seen, or the result of a disorder that interferes with progression to deep sleep (e.g., OSA), where EDS may be expected.

 

Likewise, excessive deep sleep may be a manifestation of a primary disorder of excessive sleepiness, or the deep sleep during the PSG may be the result of sleep deprivation in prior nights in subjects who are not otherwise sleepy (as indicated by questionnaires performed separately).

Properly controlled studies are needed to address this important issue.