Endotypic Traits Characterizing Obesity and Sleep-Related Hypoventilation in Patients with Obstructive Sleep Apnea

<b>Rationale:</b> Sleep-related hypoventilation disorder (SHD) is common among obese patients with obstructive sleep apnea (OSA), but the pathological endotypes associated with obesity and SHD remain unclear. <b>Objectives:</b> To investigate the relationship between endotypes with body mass index (BMI) among patients with OSA and to explore endotypic traits of patients with comorbid SHD. <b>Methods:</b> We prospectively collected polysomnographic studies of 1,364 patients with OSA and overnight transcutaneous CO₂ measurements among 420 obese patients. Endotypic traits were estimated using polysomnographic signals. SHD was determined using transcutaneous CO₂ > 55 mm Hg for ⩾10 minutes. We illustrated the nonlinear relationship between BMI and endotypic traits. Differences in endotypic traits between nonobese patients with OSA, obese patients with simple OSA, and obese patients with comorbid OSA and SHD were examined using Kruskal-Wallis tests and multiple regression analysis. <b>Results:</b> A unit increase in BMI was associated with a 1.02%eupnea increase in arousal threshold, 1.16%eupnea increase in collapsibility, 0.01 increase in loop gain, and 0.48%eupnea increase in compensation, with a ceiling effect. SHD was observed in 18-36% of obese patients with OSA, depending on the criteria. Among obese patients with OSA, those with SHD exhibited a 0.06 higher loop gain than those with simple OSA, after adjusting for BMI. <b>Conclusions:</b> A ceiling effect of upper airway compensation function coupled with worse collapsibility and high loop gain characterizes pathological endotypes of obese patients with OSA. Patients with SHD exhibited a more sensitive respiratory pattern, indicated by increased loop gain.