Endotypic traits and hypoxic burden are associated with excessive daytime sleepiness in patients with moderate-to-severe obstructive sleep apnea.

INTRODUCTION: Excessive daytime sleepiness (EDS) is a common obstructive sleep apnea (OSA) phenotype and is linked to poor health outcome. This study aims to identify the pathological traits of EDS among patients with OSA. METHODS: We conducted a prospective study at a single sleep center between April 2020 and August 2024. Adults (≥20 years) undergoing full-night diagnostic polysomnography were enrolled. A total of 1130 patients with apnea-hypopnea index (AHI) ≥15 h-1 were enrolled and grouped by Epworth Sleepiness Scale (ESS) scores into EDS (>10) and non-EDS (≤10). Endotypic traits were estimated using polysomnographic signals during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep separately. We examined the association of ESS scores with each endotypic trait and with OSA severity (AHI and hypoxic burden) using linear regression models. RESULTS: Among the 1130 patients with OSA, 547 (48.4%) reported EDS. Compared with the non-EDS group, patients with EDS had a higher proportion of insomnia symptoms and had a higher body mass index, AHI, and hypoxic burden. In adjusted linear regression models, each one-point increase in the ESS score was associated with a 0.79%eupnea increase in arousal threshold and a 0.39%eupnea decrease in compensation (Vactive). Additionally, the ESS score was positively associated with hypoxic burden, and this association remained significant in REM sleep after adjustment for AHI. CONCLUSIONS: EDS among patients with OSA was characterized by elevated arousal threshold and poor upper airway dilator muscle function, potentially linking more severe desaturation with excessive sleepiness.