CLINICAL REVIEW Obesity hypoventilation syndrome e The big and the breathless Amanda J. Piper * Royal Prince Alfred Hospital, Department of Respiratory and Sleep Medicine, Level 11, E Block, Missenden Rd., Camperdown, NSW 2050, Australia article info Article history: Received 1 March 2010 Received in revised form 18 April 2010 Accepted 19 April 2010 Available online 6 July 2010 Keywords: Morbid obesity Hypercapnia Leptin Ventilatory control Sleep hypoventilation Respiratory failure Bilevel ventilation summary Daytime hypercapnia that develops in morbidly obese individuals in the absence of concurrent lung or neuromuscular disease is referred to as the obesity hypoventilation syndrome (OHS). The characteristic polysomnographic (PSG) abnormality is marked sleep hypoxemia. Although the likelihood of hypo- ventilation increases with increasing body mass index (BMI), it is too simplistic to think of this disorder arising merely from chest wall restriction due to excess weight. Rather, this is a disorder which emerges when the compensatory mechanisms that normally operate to maintain ventilation appropriate for the level of obesity are impaired. OHS develops from a complex interaction between abnormal respiratory function, sleep disordered breathing and diminished respiratory drive. Irrespective of the mechanisms underlying the development of this disorder, early recognition of the problem and institution of effective therapy is important to reduce the significant clinical and societal repercussions of OHS. While therapy directed at improving sleep disordered breathing is effective in reversing daytime respiratory failure, it is not universally successful and information regarding longer term clinical outcomes is limited. Attention to weight reduction strategies are also necessary to reduce comorbid conditions and improve quality of life, but data regarding how successful and sustained this is in obesity hypoventilation are sparse. Ó 2010 Elsevier Ltd. All rights reserved. Introduction A substantial body of literature now exists highlighting the significant impact obesity has on upper airway function and the development of obstructive sleep apnea (OSA). More recently, the potential links between OSA and a range of cardiometabolic disorders have received considerable attention. 1 As obesity increases so do health problems, requiring greater utilisation of healthcare resources. 2,3 Current estimates suggest not only rising rates of obesity, but the emergence of an increasing population of morbidly obese (Body Mass Index: BMI  40 kg/m 2 ) and super obese (BMI  50 kg/m 2 ) individuals. 4 Greater degrees of obesity have more significant consequences for the respiratory system. The most critical of these consequences is the development of alveolar hypoventilation and daytime respira- tory failure (awake arterial carbon dioxide (PaCO 2 )  45 mmHg) in patients with a BMI  30 kg/m 2 . Termed obesity hypoventilation syndrome (OHS), this disorder is diagnosed after other possible causes of hypoventilation such as lung, neuromuscular or chest wall deformities have been excluded. The incidence of OHS rises signif- icantly as obesity increases, 5 with a reported prevalence of around 10e20% in outpatients presenting to sleep clinics, to almost 50% of hospitalised patients with a BMI  50 kg/m. 26 The prevalence of OHS in the general population is unknown, as one of the major measures to identify this disorder (namely a raised PaCO 2 on arterial blood gas measurements) is not routinely performed in epidemio- logical studies. However, a current estimate suggests around 0.37% of the US population may have OHS, 7 equating to several hundred thousand individuals. 8 In light of the rapidly increasing numbers of individuals joining the ranks of the morbidly obese, and the signif- icantly greater need they have for medical care, OHS needs to be considered as a significant clinical and societal problem. Unfortu- nately it is also one that is frequently overlooked, 6 despite the significant comorbidities 3,9 and higher hospitalisation rates these individuals experience. 3,6 To breathe or not to breathe The sources of respiratory abnormality in OHS have been cat- egorised into three main areas: alterations in pulmonary function; changes in ventilatory control; and the presence of sleep breathing abnormalities. There is no doubt that obesity in its own right has a significant impact on each of these factors. However, the majority of morbidly obese individuals are able to compensate for the abnormalities imposed by their excessive weight, maintaining daytime eucapnia. Consequently, it appears that OHS emerges only when compensatory mechanisms fail or become overwhelmed. 10e13 It is important to realise that these various respiratory abnormalities * Tel.: þ61 2 9515 8708; fax: þ61 2 9515 7196. E-mail address: ajp@med.usyd.edu.au Contents lists available at ScienceDirect Sleep Medicine Reviews journal homepage: www.elsevier.com/locate/smrv 1087-0792/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.smrv.2010.04.002 Sleep Medicine Reviews 15 (2011) 79e89