Differences in physiological endotypes between non-positional and positional obstructive sleep apnea: Results from Shanghai Sleep Health Study cohort

BACKGROUND:Positional obstructive sleep apnea (POSA) is a recognized subtype of obstructive sleep apnea (OSA) that exhibits distinct endotypic characteristics when compared to non-positional OSA (NPOSA). The basis for the disparity in endotypes between these subtypes remains poorly understood. RESEARCH QUESTIONS:(1) Do individuals with NPOSA and POSA have different underlying OSA endotypes? (2) Which endotypic characteristics are critical in determining NPOSA and POSA severity? STUDY DESIGN AND METHODS:Within the Shanghai Sleep Health Study cohort, individuals with OSA were recruited and classified as POSA or NPOSA. Endotypes were calculated using polysomnography. RESULTS:Endotype analysis was conducted in 1,036 individuals with OSA. Compared to individuals with NPOSA, those with POSA had lower LGAll (0.55 [0.46-0.66] VS 0.68 [0.52-0.90], p<0.001), lower ArTHAll (138.67 [118.94-180.87] %Veupnea VS 189.00 [129.71-257.76] %Veupnea, p<0.001), higher VpassiveAll (91.85 [83.13-95.15] %Veupnea VS 76.38 [23.77-92.08] %Veupnea, p<0.001) and higher VcompAll (6.50 [-6.77-16.39] %Veupnea VS 3.65 [-10.47-12.14] %Veupnea, p=0.003). Logistic regression analyses indicated that higher VpassiveAll was associated with increased odds of POSA versus NPOSA. In NPOSA, fully adjusted linear regression analyses indicated that VpassiveAll (β [95% confidence interval, 95% CI], -0.55[-0.68-[-0.42]], p<0.001) and LGAll (β [95% CI], 0.19[0.08-0.30], p<0.001) were significant independent predictors of AHI, with VpassiveAll being the most critical factor. In contrast, in POSA, collapsibility appeared to be less influential (β [95% CI], -0.09[-0.21-0.03], p=0.138). Non-anatomical endotypic characteristics (LGAll, β [95% CI], 0.29 [0.18-0.41], p<0.001; ArTHAll, β [95% CI], 0.15 [0.01-0.28], p=0.031; VcompAll, β [95% CI], -0.21[-0.29-[-0.12]], p<0.001) were significant in determining the severity of POSA, with LG being the most crucial factor. INTERPRETATION:This study highlights the differences in endotypes between NPOSA and POSA. In Chinese individuals, anatomical factors were more significant in determining the severity of NPOSA, while non-anatomical traits were more likely to determine the severity of POSA. Future research should focus on developing personalized management strategies for individuals with NPOSA and POSA based on their endotypes. CLINICAL TRIAL REGISTRATION NUMBER:The study was approved by the Ethics Committee of Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Approval No: 2019-KY-050[K]) and registered at the Chinese Clinical Trial Registry (No. ChiCTR1900025714).