Study Identifies Endotypic Traits Associated With Excessive Daytime Sleepiness in Obstructive Sleep Apnea

Newly published cross-sectional findings identified a distinct physiologic endotypic profile associated with excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA), characterized by elevated arousal threshold, higher loop gain, greater upper airway collapsibility, and reduced ventilatory compensation. Investigators also reported that arousal threshold appeared to play a central role in the expression of EDS, whereas loop gain remained the dominant contributor to overall OSA severity.¹

The study, conducted in Beijing, China, included 542 patients with confirmed OSA drawn from an initial cohort of 694 treatment-naïve adults referred for suspected sleep-disordered breathing between September 2022 and May 2025. EDS was defined as an Epworth Sleepiness Scale score greater than 10,² and endotypic traits were derived from full-night polysomnography using the Phenotyping Using Polysomnography method. Associations between traits and EDS were evaluated using multivariable logistic regression, with additional analyses examining relationships with apnea-hypopnea index (AHI) using linear regression models.

“In this study, we conducted logistic regression analyses to demonstrate the association of endotypic traits with comorbid EDS in patients with OSA,” lead author Yi Xiao, MD, professor in the Department of General Surgery at Peking Union Medical College Hospital in Beijing, China, and colleagues wrote.¹ “These findings emphasize the heterogeneity of OSA and underscore the importance of multidimensional trait profiling for risk stratification and individualized treatment.”

Across unadjusted models, the fourth quartiles of upper airway collapsibility, loop gain, and arousal threshold were all significantly associated with increased odds of comorbid EDS (all P <.01). However, after adjusting for covariates including age, sex, body mass index, alcohol use, smoking status, sleep quality measures, insomnia severity, AHI, oxygen saturation indices, and sleep architecture variables, only select associations remained significant.

In the fully adjusted model, the fourth quartile of arousal threshold was associated with more than a threefold increase in odds of EDS (OR, 3.12; 95% CI, 1.24–8.02; P = .016). The second quartile of loop gain was also significantly associated with EDS (OR, 1.81; 95% CI, 1.07–3.08; P = .027). When evaluated as continuous variables, however, no significant associations were observed between endotypic traits and comorbid EDS.

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Investigators also explored the relationship between endotypic traits and OSA severity as measured by AHI. In unadjusted analyses, all 4 traits were significantly associated with AHI in both patients with OSA without EDS and those with comorbid EDS (all P <.01), with higher loop gain consistently showing a strong association with disease severity across groups.

After adjusting for relevant covariates (excluding AHI), multiple traits remained significantly associated with AHI, though patterns differed by subgroup. In patients with OSA and EDS, all 4 traits remained significantly associated with AHI. In contrast, among patients without EDS, 3 traits (collapsibility, loop gain, and arousal threshold) retained significance, while ventilatory compensation did not.

The authors noted that loop gain appeared to be the strongest determinant of OSA severity overall, whereas arousal threshold was more closely linked to the presence of daytime sleepiness. Reduced ventilatory compensation was also identified as a factor contributing predominantly to severity in OSA with EDS.

In linear regression models, all 4 endotypic traits were significantly associated with AHI in unadjusted analyses for both OSA with and without EDS. For example, in patients with OSA and EDS, collapsibility (β = 0.53; 95% CI, 0.48–0.58), loop gain (β = 87.88; 95% CI, 77.07–98.70), arousal threshold (β = 0.34; 95% CI, 0.31–0.37), and ventilatory compensation (β = −0.19; 95% CI, −0.30 to −0.08) were all significantly associated with AHI (all P <.01).

After multivariable adjustment, these associations remained statistically significant for multiple traits in both groups, though effect estimates varied. In the adjusted model for patients with EDS, collapsibility, loop gain, arousal threshold, and ventilatory compensation all remained significantly associated with AHI. In patients without EDS, 3 traits remained significant, excluding ventilatory compensation.

“Incorporated relevant covariates into the regression model, four endotypic traits continued to show significant associations with AHI in patients with OSA and EDS,” Xiao et al wrote.¹ “However, three endotypic traits were significantly associated with AHI in OSA patients without EDS.”

Overall, the findings suggest that OSA is characterized by heterogeneity in physiologic mechanisms underlying both disease severity and symptom expression. Investigators emphasized that multidimensional trait profiling may improve risk stratification and support more individualized approaches to patient assessment. Authors concluded that future prospective studies are warranted to further clarify causal pathways linking endotypic traits to EDS and to evaluate whether targeting specific physiologic traits may have clinical utility in OSA.

REFERENCES
1. Wang L, Hui X, Huang R, Xiao Y. Differences in Endotypic Traits Between Obstructive Sleep Apnoea Patients With and Without Excessive Daytime Sleepiness. Respirology. Published online March 18, 2026. doi:10.1002/resp.70241
2. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14(6):540-545. doi:10.1093/sleep/14.6.540