AJM theme issue: Obesity and diabetes
Review
The obesity hypoventilation syndrome

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Abstract

The obesity hypoventilation syndrome, which is defined as a combination of obesity and chronic hypoventilation, utimately results in pulmonary hypertension, cor pulmonale, and probable early mortality. Since the classical description of this syndrome nearly fifty years ago, research has led to a better understanding of the pathophysiologic mechanisms involved in this disease process, and to the development of effective treatment options. However, recent data indicate the obesity hypoventilation syndrome is under-recognized, and under-treated. Because obesity has become a national epidemic, it is critical that physicians are able to recognize and treat obesity-associated diseases. This article reviews current definitions of the obesity hypoventilation syndrome, clinical presentation and diagnosis, present understanding of the pathophysiology, and treatment options.

Section snippets

History and definitions

Obesity hypoventilation syndrome was classically described as “Pickwickian syndrome” in a 1956 case report by Burwell.10 This patient resembled a character depicted by Dickens in his story, The Posthumous Papers of the Pickwick Club, because both were obese with excessive hypersomnolence. Further, Burwell’s patient had hypoventilation during wakefulness, with hypoxemia-induced erythrocytosis, pulmonary hypertension, and cor pulmonale.

Subsequent investigation of patients with Pickwickian

Epidemiology

Although the prevalence of obesity hypoventilation syndrome is unknown, a recent study of severely obese (body mass index ≥35 kg/m2) hospitalized patients found that 31% had daytime hypercapnia unexplained by other disorders.6 Although weight alone did not predict the presence of hypoventilation, almost half of the patients with a body mass index 50 kg/m2 or greater had chronic daytime hypoventilation. Although data have shown men to be at higher risk for obstructive sleep apnea-hypopnea

Overview

Despite significant research, the exact pathophysiologic mechanisms leading to obesity hypoventilation syndrome have not been clearly defined. The syndrome may result from complex interactions among impaired respiratory mechanics, abnormal central ventilatory control, possible sleep-disordered breathing, and neurohormonal aberrancies (Figure 1).7, 28

Respiratory system mechanics

Significant impairment in respiratory system mechanics is present when individuals with obesity hypoventilation syndrome are compared with

Weight loss

The ideal treatment for obesity hypoventilation syndrome is weight loss, which improves most of the physiologic abnormalities thought to be involved in the pathogenesis and ultimately leads to the restoration of daytime eucapnia.7, 18, 38

Weight loss of at least 10 kg results in a significant improvement in vital capacity and maximum voluntary ventilation, and a significant reduction in daytime Paco2.38 Although data are limited, weight loss has also been shown to significantly increase central

Progesterone

Medroxyprogesterone has been shown to increase hypercapnic chemosensitivity and improve ventilation in patients with obesity hypoventilation syndrome.68, 69 However, it does not improve apnea frequency or symptoms of sleepiness,70 and there are limited data regarding adverse effects and outcomes of long-term use. As a result, experts do not currently recommend progesterone therapy.28

Conclusion

Because obesity has become a national epidemic, it is imperative that physicians are able to recognize and treat obesity-associated diseases. Evidence suggests that obesity hypoventilation syndrome is under-recognized, under-treated, and associated with a significant increase in mortality. These findings are particularly disturbing because effective treatment options exist. Further investigations are needed to completely understand the prevalence, pathophysiology, morbidity, and long-term

Acknowledgment

The authors thank Ms. Jacklyn Martinez for her assistance with article preparation.

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