Abstract
Rationale: Obstructive sleep apnea (OSA) is a heterogeneous syndrome with various endotypic traits and symptoms. A link among symptoms, endotypes, and disease prognosis has been proposed but remains unsupported by empirical data. Objectives: To link symptom profiles and endotypes by clustering endotypic traits estimated using polysomnographic signals. Methods: We recruited 509 patients with moderate to severe OSA from a single sleep center. Polysomnographic data were collected between May 2020 and January 2022. Endotypic traits, namely arousal threshold, upper airway collapsibility, loop gain, and upper airway muscle compensation, were retrieved using polysomnographic signals during non-rapid eye movement periods. We used latent class analysis to group participants into endotype clusters. Demographic and polysomnographic parameter differences were compared between clusters, and associations between endotype clusters and symptom profiles were examined using logistic regression analyses. Results: Three endotype clusters were identified, characterized by high collapsibility/loop gain, low arousal threshold, and low compensation, respectively. Patients in each cluster exhibited similar demographic characteristics, but those in the high collapsibility/loop gain cluster had the highest proportion of obesity and severe oxygen desaturation observed in polysomnographic studies. The low compensation cluster was characterized by fewer sleepy symptoms and exhibited a lower rate of diabetes mellitus. Compared with the excessively sleepy group, disturbed sleep symptoms were associated with the low arousal threshold cluster (odds ratio, 1.89; 95% confidence interval, 1.16-3.10). Excessively sleepy symptoms were associated with the high collapsibility/loop gain cluster (odds ratio, 2.16; 95% confidence interval, 1.39-3.37) compared with the minimally symptomatic group. Conclusions: Three pathological endotype clusters were identified among patients with moderate to severe OSA, each exhibiting distinct polysomnographic characteristics and clinical symptom profiles.