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

Abstract

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. Keywords: arousal threshold, continuous positive airway pressure therapy, nonobese, sleep apnea pathogenesis, upper airway Citation: Gray EL, McKenzie DK, Eckert DJ. Obstructive sleep apnea without obesity is common and difficult to treat: evidence for a distinct pathophysiological phenotype. J Clin Sleep Med. 2017;13(1):81-88.

Ten-year adherence to continuous positive airway pressure treatment in patients with moderate-to-severe obstructive sleep apnea

“…Patients with a high BMI may experience the benefits of CPAP treatment more easily. One study comparing obese patients with OSA with non-obese patients with OSA shows that OSA non-obese patients have a lower arousal threshold for airway stenosis, which may limit CPAP resistance and contribute to reduced CPAP compliance [26]. It should be recognized that it may be difficult to treat OSA with CPAP in patients with low BMI.…”

Role of common hypnotics on the phenotypic causes of obstructive sleep apnoea: paradoxical effects of zolpidem

“…30-50% of OSA patients [16][17][18] and up to ∼85% in some patient groups (e.g. non-obese individuals) [19] have a low respiratory arousal threshold. Thus, some hypnotics may promote breathing stability for certain people with OSA.…”

Qualitative Phenotyping of Obstructive Sleep Apnea and Its Clinical Usefulness for the Sleep Specialist

“…Neural respiratory drive as an electrical index of ventilation and AT activating the respiratory muscle pump has also been tested in experimental settings [79]. A simple estimate of the arousal threshold from standard PSG parameters which was validated by using Pepi signals during respiratory events has also been proposed and used in follow-up studies [85][86][87].…”

“…Recently, novel methods of PT analysis have been introduced using clinical PSG and mathematical models [72,85,91]. So far, laboratory procedures to determine PT are mostly limited to the research setting and are unavailable in routine clinical practice.…”