0500 Understanding Contributions of Upper Airway Anatomy to OSA Risk in Lean and Obese Patients: Results from the EXPO Study

Abstract Introduction Obstructive sleep apnea (OSA) is strongly influenced by upper-airway anatomy, with increased soft tissue size thought to be particularly important in obese patients and craniofacial restriction thought to be more important in lean patients. However, obesity alone do not fully explain disease susceptibility: many obese individuals remain unaffected and lean individuals without craniofacial restriction can develop OSA. The present study, Mechanisms of Extreme Phenotypes in OSA (EXPO), compared lean and obese individuals with and without OSA to identify anatomical characteristics that may confer risk in lean patients and protection in obese individuals. Methods Adults ≥18 years-old were enrolled from the University of Pennsylvania and University of Iceland and classified into one of four groups: lean OSA (AHI≥15 events/hour; BMI≤27.5 kg/m2), lean controls (AHI≤5; BMI≤27.5 kg/m2), obese OSA (AHI≥15; BMI≥32.5 kg/m2), and obese controls (AHI≤5; BMI≥32.5 kg/m2). All participants underwent standardized magnetic resonance imaging (MRI) of the upper airway to quantify soft-tissue volumes and craniofacial dimensions. Anatomical differences across groups were evaluated using analysis of covariance adjusting for age, sex, race, and site, following by comparisons between apneics and controls within BMI strata. Results The study sample included 263 participants (64 lean apneics, 64 lean controls, 94 obese apneics, 41 obese controls). Among lean participants, apneics had a smaller retropalatal airway and greater tongue fat and pharyngeal fat pads than controls, suggesting increased upper airway fat deposition increases OSA risk even without general obesity. Among obese participants, controls demonstrated a larger retropalatal airway and smaller lateral pharyngeal wall and tongue volumes than obese apneics, as well as less craniofacial restriction, suggesting a more favorable soft-tissue to craniofacial ratio protects from OSA despite obesity. Conclusion Soft tissue and craniofacial anatomy contribute to OSA risk in both lean and obese individuals, which can inform personalized medicine approaches. In obese individuals, less retrognathia and smaller pharyngeal soft tissues protect against OSA, consistent with weight loss being effective in these patients. In lean individuals, localized soft tissue enlargement (including tongue fat) increases OSA risk, suggesting that use of weight-loss medications targeting soft-tissue reduction may also be effective in lean patients. Support (if any) National Institutes of Health (P01 HL094307; P01 HL160471).