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Obesity hypoventilation syndrome: current theories of pathogenesis

Pierce, Aaron M.a; Brown, Lee K.a,b

Current Opinion in Pulmonary Medicine: November 2015 - Volume 21 - Issue 6 - p 557–562
doi: 10.1097/MCP.0000000000000210
SLEEP AND RESPIRATORY NEUROBIOLOGY: Edited by Lee K. Brown and Adrian Williams

Purpose of review To summarize recent primary publications and discuss the impact these finding have on current understanding on the development of hypoventilation in obesity hypoventilation syndrome (OHS), also known as Pickwickian syndrome.

Recent findings As a result of the significant morbidity and mortality associated with OHS, evidence is building for pre-OHS intermediate states that can be identified earlier and treated sooner, with the goal of modifying disease course. Findings of alterations in respiratory mechanics with obesity remain unchanged; however, elevated metabolism and CO2 production may be instrumental in OHS-related hypercapnia. Ongoing positive airway pressure trials continue to demonstrate that correction of nocturnal obstructive sleep apnea and hypoventilation improves diurnal respiratory physiology, metabolic profiles, quality of life, and morbidity/mortality. Finally, CNS effects of leptin on respiratory mechanics and chemoreceptor sensitivity are becoming better understood; however, characterization remains incomplete.

Summary OHS is a complex multiorgan system disease process that appears to be driven by adaptive changes in respiratory physiology and compensatory changes in metabolic processes, both of which are ultimately counter-productive. The diurnal hypercapnia and hypoxia induce pathologic effects that further worsen sleep-related breathing, resulting in a slowly progressive worsening of disease. In addition, leptin resistance in obesity and OHS likely contributes to blunting of ventilatory drive and inadequate chemoreceptor response to hypercarbia and hypoxemia.

aDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of New Mexico School of Medicine

bDepartment of Electrical and Computer Engineering, University of New Mexico School of Engineering, Albuquerque, New Mexico, USA

Correspondence to Lee K. Brown, MD, Professor and Senior Vice Chair, Clinical Affairs, Department of Internal Medicine, Professor of Pediatrics, University of New Mexico School of Medicine, Professor of Electrical and Computer Engineering, University of New Mexico School of Engineering, 1101 Medical Arts Avenue NE, Building #2, Albuquerque, NM 87102, USA. Tel: +1 505 272 6110; fax: +1 505 272 6112; e-mail:

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