Night-to-Night Variability of Polysomnography-Derived Physiologic Endotypic Traits in Patients With Moderate to Severe OSA

BACKGROUND: Emerging data suggest that determination of physiologic endotypic traits (eg, loop gain) may enable precision medicine in OSA.RESEARCH QUESTION: Does a single-night assessment of polysomnography-derived endotypic traits provide reliable estimates in moderate to severe OSA?STUDY DESIGN AND METHODS: Two 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 pro-vide an estimate of maximum spontaneous variability. Further assessment across four repeated polysomnography tests was performed in a subcohort (n = 22). RESULTS: Reliability 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 Vpassive and Vactive (r = -0.49 and r = -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%. INTERPRETATION: Endotypic trait analysis using a single standard polysomnography shows acceptable reliability and reproducibility in patients with moderate to severe OSA. The re-ported MDDs of endotypic traits may facilitate the quantification of relevant changes and may guide future evaluation of interventions in OSA. CHEST 2023; 163(5):1266-1278