THORAXJNL151225 442..449

The global epidemic of obesity and the worldwide prevalence of obstructive sleep apnoea (OSA) are both increasing. Epidemiological studies reveal an association between obesity, weight gain and OSA. Metabolic or bariatric operations provide sustained weight loss and resolve or improve the symptoms of OSA in the majority of morbidly obese individuals. These operations also modulate the metabolic profile to improve glycaemic control, to decrease cardiovascular risk and obesityrelated mortality. The beneficial effects of metabolic operations on OSA include mechanical weight-dependent and metabolic weight-independent effects that are achieved through the BRAVE effects: (Bile flow alteration; Reduction of gastric size; Anatomical gut rearrangement and altered flow of nutrients; Vagal manipulation; and Enteric gut hormone modulation). These result in an improvement in insulin resistance, adipokines, cytokines and systemic inflammation. A literature analysis was performed with statistical pooling of available surgical and medical studies to determine whether the weighted mean decrease in body mass index and sleep apnoea severity (measured by the apnoea-hypopnoea index) are larger in metabolic surgical studies than in non-surgical weight loss studies (diet, exercise and medication). However, heterogeneity across available trials, poor follow-up measures and a deficiency in comparative studies between surgical and non-surgical therapy precludes definitive statements regarding the relative benefits of surgical therapy. Further research is required to quantify robustly the effects and mechanisms of sleep apnoea resolution by metabolic surgery, which may reveal novel non-surgical treatments or enhanced surgical strategies in the management of this multisystem sleep disorder. INTRODUCTION The global epidemic of obesity and the worldwide prevalence of sleep apnoea are both increasing. According to the WHO there are at least 300 million obese adults and an estimated 100 million individuals who suffer from sleep apnoea. Both conditions contribute to increased worldwide mortality and healthcare costs, and sleep apnoea is now considered as one of the most common organic sleep disorders. Obstructive sleep apnoea (OSA) syndrome is characterised by frequent episodes of apnoea and hypopnoea due to periods of upper airway collapse which can result in hypertension, increased cardiovascular mortality, stroke, decreased quality of life, sleepiness and morbidity associated with disordered sleep. The epidemiological association between obesity rates and sleep-disordered breathing has been progressively studied to identify obesity as a significant risk factor for the development of OSA. There are several other risk factors for sleep apnoea including sex, family history, race/ethnicity, craniofacial abnormalities, type 2 diabetes mellitus, menopause and behaviours including smoking and alcohol consumption. Several methods have been applied to reduce the burden of obesity, including disease prevention, lifestyle change, behavioural modification and pharmacotherapy. Patients have found the weight loss offered by these treatments difficult to maintain in the long term. Surgical modalities do, however, achieve longstanding weight loss in the severely obese population. The operations, initially called ‘bariatric’ procedures, have demonstrated a maintenance of weight loss for over 15 years 5 while also providing beneficial metabolic effects that include improved glycaemic control in the majority of morbidly obese patients. In view of their significant metabolic effects, these procedures are now known as ‘metabolic’ operations. Longitudinal studies on metabolic surgery have revealed that successful weight loss also results in lower sleep apnoea rates. In this review we describe the effects and potential mechanisms of sleep apnoea resolution by metabolic surgery. EPIDEMIOLOGY OF OBESITY AND OSA OSA is present in 4e9% of adult men and 1e2% of adult women in the general population when assessed by polysomnographic criteria (apnoeahypopnoea index (AHI) >5/h) and the presence of sleepiness. Its prevalence is highest in men aged 40e65 years although it is increasingly diagnosed in all age groups of both sexes. Based on polysomnography alone, the prevalence can be as high as 17e24% in men and 5e9% in women. The data from these studies were collected in the late 1980s and early 1990s when obesity was significantly less prevalent, rendering these values as a likely underestimation of the actual prevalence of OSA in the current era. The association of obesity with sleep apnoea was first described in the Ancient Ptolemaic dynasty (305e30 BC) and was regarded in the late 19th century as the Pickwickian syndrome. 20 Approximately 70% of patients with sleep apnoea present with obesity, and 40% of patients with obesity suffer from sleep apnoea. The ‘Sleep in America’ survey of the National Sleep Foundation revealed that 57% of obese individuals are at high risk of OSA, and its incidence in morbidly obese patients can be 12e30 times higher than the incidence in the general population. The prevalence The Department of Surgery and Cancer, Imperial College London, London, UK Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, UK National Heart and Lung Institute, Imperial College