Endotypic traits and lung function in patients with obstructive sleep apnea comorbid with obesity hypoventilation syndrome.

PURPOSE: Obesity hypoventilation syndrome (OHS) frequently coexists with obstructive sleep apnea (OSA) and is linked to lung function impairment and poor outcomes. However, its underlying pathology remains unclear. This study compares lung function and endotypic traits in obese OSA patients with and without OHS. METHODS: We prospectively collected polysomnographic data from 186 obese patients with OSA who underwent lung function and blood gas tests. Eighteen patients were identified as having OHS, as defined by body mass index ≥ 30 kg/m² with daytime hypercapnia (PaCO₂ ≥ 45 mmHg). Endotypic traits were assessed using polysomnographic signals and compared between patients with and without OHS. Lung function was compared between the two patient groups, and the association with endotypic traits was examined. RESULTS: Compared to the non-OHS group, the OHS group showed higher Epworth Sleepiness Scale scores, higher loop gain (LG1; 0.66 vs. 0.59), and a lower FEV₁/FVC ratio (80.4% vs. 81.9%). Adjusted linear regression analysis showed that OHS was associated with a lower FEV₁/FVC ratio and a lower FEF₂₅–₇₅, but not associated with specific endotypic traits. Pearson correlation revealed a negative association (r = -0.25, p = 0.002) between loop gain (LGn) and FEV₁/FVC ratio. CONCLUSIONS: Compared to patients with simple OSA, those with coexisting OHS exhibited more unstable breathing patterns and reduced lung function. Future studies are needed to explore the biological mechanisms underlying the association between high loop gain and ventilatory impairment.