Flow Limitation Is Associated with Excessive Daytime Sleepiness in Individuals without Moderate or Severe Obstructive Sleep Apnea, 2024, Mann et al.

[nataliezzz]

Flow Limitation Is Associated with Excessive Daytime Sleepiness in Individuals without Moderate or Severe Obstructive Sleep Apnea
Dwayne L. Mann, Eric Staykov, Thomas Georgeson, Ali Azarbarzin, Samu Kainulainen, Susan Redline, Scott A. Sands, Philip I. Terrill
https://www.atsjournals.org/doi/full/10.1513/AnnalsATS.202308-710OC (PDF available)

Rationale
Moderate-severe obstructive sleep apnea (OSA) (apnea–hypopnea index [AHI], >15 events/h) disturbs sleep through frequent bouts of apnea and is associated with daytime sleepiness. However, many individuals without moderate-severe OSA (i.e., AHI <15 events/h) also report sleepiness.

Objectives
To test the hypothesis that sleepiness in the AHI <15 events/h group is a consequence of substantial flow limitation in the absence of overt reductions in airflow (i.e., apnea/hypopnea).

Methods
A total of 1,886 participants from the MESA sleep cohort were analyzed for frequency of flow limitation from polysomnogram-recorded nasal airflow signal. Excessive daytime sleepiness (EDS) was defined by an Epworth Sleepiness Scale score ⩾11. Covariate-adjusted logistic regression assessed the association between EDS (binary dependent variable) and frequency of flow limitation (continuous) in individuals with an AHI <15 events/h.

Results
A total of 772 individuals with an AHI <15 events/h were included in the primary analysis. Flow limitation was associated with EDS (odds ratio, 2.04; 95% confidence interval, 1.17–3.54; per 2–standard deviation increase in flow limitation frequency) after adjusting for age, sex, body mass index, race/ethnicity, and sleep duration. This effect size did not appreciably change after also adjusting for AHI.

Conclusions
In individuals with an AHI <15 events/h, increasing flow limitation frequency by 2 standard deviations is associated with a twofold increase in the risk of EDS. Future studies should investigate addressing flow limitation in low-AHI individuals as a potential mechanism for ameliorating sleepiness.

 

[nataliezzz]

EDS = excessive daytime sleepiness (Epworth Sleepiness Scale [ESS] ≥11 here); the ESS isn't a great measure of true objective sleepiness (i.e. how quickly one falls asleep, as measured by mean sleep latency on multiple sleep latency testing) and measures an uninterpretable mix of objective sleepiness and fatigue (I will share the data on that when it is published).

Participants:

We analyzed PSG data from the MESA study (15, 16). Briefly, MESA is a large multicenter longitudinal study with a focus on investigating factors associated with incident subclinical and clinical cardiovascular disease (17). The study includes Black, White, Hispanic, and Chinese American men and women. Participants were enrolled between 2000 and 2002, when they were aged 45–84 years, and were free of known clinical cardiovascular disease. Participants were studied at examinations conducted every 2 to 4 years thereafter. In conjunction with exam 5 (2010–2012), participants were enrolled in a sleep examination (2010–2013), when they underwent unattended PSG.

Although there was nearly even representation of males and females in the full dataset (53.0% females), there was a higher proportion of females in the AHI <15 events/h sample (66.2%), and a female predominance of the lower AHI sample was observed in both the EDS and non-EDS subgroups.

In primary analyses (i.e., individuals with AHI <15 events/h), our main model revealed a 2.04 increase in odds for EDS (CI95%, 1.17–3.54; P = 0.011) for each 2-SD increase in flow limitation (+19.2% of sleep in this group). In all three sensitivity models, flow limitation remained significantly associated with EDS. In sensitivity model 1, which included both flow limitation and AHI, only flow limitation was associated with EDS (OR, 2.08; CI95%, 1.19–3.64; P = 0.010). In sensitivity model 2, which included additional covariates (hypoxic burden and arousal index), flow limitation remained associated with EDS (OR, 1.95; CI95%, 1.10–3.46; P = 0.022). Finally, in sensitivity model 3, which included additional precision variables (insomnia, depression, and diabetes), flow limitation remained associated with EDS (OR, 2.08; CI95%, 1.19–3.64; P = 0.010).

 

[nataliezzz]

Regarding flow limitation driving symptoms like self-reported sleepiness, and decreased psychomotor vigilance (as shown in the study below - S4ME link), there needs to be some additional factor accounting for how flow limitation is driving these symptoms beyond flow limitation itself, since many asymptomatic people have significant flow limitation (for ex, see: A comparison of inspiratory airflow dynamics during sleep between upper airway resistance syndrome patients and healthy controls, Gold et al. 2013 - multiple controls [who were rigorously screened to be free of any medical conditions, fatigue/pain/etc.] had >90% of their breaths flow limited during stage 2 non-REM sleep).

Increased Flow Limitation During Sleep Is Associated With Increased Psychomotor Vigilance Task Lapses in...Suspected OSA, 2024, Staykov et al.

This is where Dr. Gold's theory of UARS/OSAS being driven by a stress response in the brain to inspiratory flow limitation comes in (S4ME link - AI Summary)