BackgroundEmerging data suggest that determination of physiologic endotypic traits (eg, loop gain) may enable precision medicine in OSA.Research QuestionDoes a single-night assessment of polysomnography-derived endotypic traits provide reliable estimates in moderate to severe OSA?Study Design and MethodsTwo consecutive in-lab polysomnography tests from a clinical trial (n = 67; male, 69%; mean ± SD age, 61 ± 10 years; apnea-hypopnea index [AHI] 53 ± 22 events/h) were used for the reliability analysis. Endotypic traits, reflecting upper airway collapsibility (ventilation at eupneic drive [Vpassive]), upper airway dilator muscle tone (ventilation at the arousal threshold [Vactive]), loop gain (stability of ventilatory control, LG1), and arousal threshold (ArTh) were determined. Reliability was expressed as an intraclass correlation coefficient (ICC). Minimal detectable differences (MDDs) were computed to provide an estimate of maximum spontaneous variability. Further assessment across four repeated polysomnography tests was performed in a subcohort (n = 22).ResultsReliability of endotypic traits between the two consecutive nights was moderate to good (ICC: Vpassive= 0.82, Vactive= 0.76, LG1 = 0.72, ArTh = 0.83). Variability in AHI, but not in body position or in sleep stages, was associated with fluctuations in Vpassiveand Vactive(r= –0.49 andr= –0.41, respectively;P< .001 for both). MDDs for single-night assessments were: Vpassive= 22, Vactive= 34, LG1 = 0.17, and ArTh = 21. Multiple assessments (mean of two nights, n = 22) further reduced MDDs by approximately 20% to 30%.InterpretationEndotypic trait analysis using a single standard polysomnography shows acceptable reliability and reproducibility in patients with moderate to severe OSA. The reported MDDs of endotypic traits may facilitate the quantification of relevant changes and may guide future evaluation of interventions in OSA.