Current perspectives on the obesity hypoventilation syndrome

PURPOSE OF REVIEW: Identifying and treating obesity hypoventilation syndrome is an important therapeutic goal, especially given the high morbidity and mortality associated with untreated disease. Significant weight loss or effective treatment of upper airway obstruction will reverse daytime hypoventilation, suggesting that these two mechanisms play key roles in the development and progression of this disorder. Only a subset of morbidly obese patients will develop awake hypercapnia, however, even in the presence of sleep disordered breathing. This implies that complex interplay between a number of known and unknown mechanisms is needed to produce daytime respiratory failure in this patient population. RECENT FINDINGS: Work in the mouse model of obesity has been central in advancing our understanding of the role leptin plays in stimulating ventilation. Leptin deficiency or development of leptin resistance in obesity leads to alterations in central respiratory drive and reduced ventilatory responsiveness, permitting development of carbon dioxide retention. Changes in neuromodulators resulting from the effects of hypoxia may further exacerbate the problem by depressing arousal from sleep in the face of abnormal breathing. SUMMARY: Understanding the various mechanisms contributing to development of obesity hypoventilation is important in order to identify new approaches to effective long-term management of this disorder.