Obstructive Sleep Apnea without Obesity Is Common and Difficult to Treat: Evidence for a Distinct Pathophysiological Phenotype

Study Objectives: To determine the proportion and physiological characteristics of nonobese patients with obstructive sleep apnea (OSA) and their response to prescribed therapy. Methods: Data from 163 consecutive in-laboratory diagnostic sleep studies for participants referred to an academic teaching-hospital sleep clinic for suspected OSA were assessed. Sleep and anthropometric parameters at baseline and follow-up (up to 22 mo) were examined and compared between obese and nonobese patients with a diagnosis of OSA (apnea-hypopnea index > 5 events/h sleep). A key nonanatomical contributor to OSA pathogenesis, the respiratory arousal threshold, was compared between groups. Results: Twenty-five percent of the participants with a diagnosis of OSA had a body mass index (BMI) within the normal range (BMI < 25 kg/m(2)) and 54% had a BMI < 30 kg/m(2) (nonobese). Of the patients prescribed continuous positive airway pressure (CPAP), more nonobese patients reported not using their CPAP machine at all at follow-up (36% vs. 13%, p = 0.03). Objective CPAP compliance was also lower in the nonobese patients with OSA (5.1 +/- 0.4 vs. 6.4 +/- 0.4 h/night, p < 0.03). A higher proportion of the nonobese patients had a low respiratory arousal threshold compared to obese OSA patients (86% vs. 60%, p < 0.001). Conclusions: A substantial proportion of patients with OSA are not obese. These patients are challenging to treat with existing therapies as they are less adherent and compliant with CPAP therapy. Nonanatomical contributors to OSA, such a low threshold for arousal, are likely to be particularly important in OSA pathogenesis in nonobese patients with OSA. These findings have important implications for the pathogenesis of OSA in nonobese patients and potential therapeutic targets for this group of patients.