Clinical manifestations and diagnosis of obesity hypoventilation syndrome
- Amanda Piper, PhD
Amanda Piper, PhD
- Clinical Senior Lecturer
- Faculty of Medicine, University of Sydney
- Brendon Yee, MBChB, PhD
Brendon Yee, MBChB, PhD
- Associate Professor, University of Sydney
- Royal Prince Alfred Hospital Sydney, Woolcock Institute of Research
Obesity adversely impacts the respiratory system and in some circumstances is associated with the development of alveolar hypoventilation. When no better explanation for this hypoventilation can be found, the condition is referred to as the obesity hypoventilation syndrome (OHS). Although most patients with OHS present with chronic hypoventilation, in about a third of cases the diagnosis is made during a hospitalization for acute respiratory failure [1-3]. Individuals with OHS have considerably worse health status and access more health care resources compared to the general population, with differences apparent up to eight years before a diagnosis is made . Morbidity and mortality in untreated patients with OHS is high [1,2]. Even when sleep disordered breathing is treated with positive airway pressure therapy, mortality in those with severe OHS remains substantially worse than individuals with obstructive sleep apnea alone . The main cause of death is generally from cardiovascular disease [2,5]. Consequently, early diagnosis and commencement on appropriate therapy are considered crucial in order to minimize the adverse effects of this disorder.
The clinical manifestations and diagnosis of OHS are reviewed here, while the pathogenesis and treatment are discussed separately. (See "Pathogenesis of obesity hypoventilation syndrome" and "Treatment of the obesity hypoventilation syndrome" and "Noninvasive positive pressure therapy of the obesity hypoventilation syndrome".)
Obesity Hypoventilation Syndrome (OHS) exists when an obese individual (body mass index [BMI] >30 kg/m2) and sleep disordered breathing develops awake alveolar hypoventilation (PaCO2 >45 mmHg), which cannot be attributed to other conditions such as pulmonary disease, skeletal restriction, neuromuscular weakness, hypothyroidism, or pleural pathology [6,7].
The prevalence of OHS in the general population has not been studied. However, estimates based on rates of obesity and obstructive sleep apnea (OSA) in the community suggest 0.15 to 0.3 percent of the adult population in the United States are likely to have OHS . Obesity is the hallmark of OHS (BMI >30 kg/m2), and the prevalence of this disorder increases as BMI rises [8,9]. Prevalence rates among specific populations vary considerably, from around 8 percent in bariatric surgical patients to 16 percent of patients referred to sleep centers with symptoms of sleep apnea . In a study of hospitalized patients with a BMI >35kg/m2, the prevalence of OHS was 31 percent , while in another study of obese patients with hypoxemia, 51 percent were found to have OHS . In a single center study, 8 percent of ICU admissions fulfilled the criteria for OHS . Ethnic factors also affect prevalence rates. In Japanese patients presenting for investigation of OSA, 2.3 percent were found to have OHS  compared to 20 percent of predominantly African-American patients evaluated at a US sleep center .
About 90 percent of OHS individuals will have coexisting obstructive sleep apnea (OSA), and consequently the symptoms and many of the physical findings are indistinguishable from OSA [7,15]. These include excessive daytime sleepiness, loud snoring, choking during sleep, resuscitative snorting (ie, a loud snort that follows an apnea as the patient partially awakens and reopens the upper airway), fatigue, hypersomnolence, impaired concentration and memory, a small oropharynx, and a thick neck [7,15]. Unlike OSA, male gender does not appear to be a significant risk factor for OHS [5,13,16]. There is some evidence to suggest that women may be diagnosed later than men, and then only after presentation with acute respiratory failure [17,18]. (See "Clinical presentation and diagnosis of obstructive sleep apnea in adults".)
- Pérez de Llano LA, Golpe R, Ortiz Piquer M, et al. Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome. Chest 2005; 128:587.
- Borel JC, Burel B, Tamisier R, et al. Comorbidities and mortality in hypercapnic obese under domiciliary noninvasive ventilation. PLoS One 2013; 8:e52006.
- Priou P, Hamel JF, Person C, et al. Long-term outcome of noninvasive positive pressure ventilation for obesity hypoventilation syndrome. Chest 2010; 138:84.
- Jennum P, Kjellberg J. Health, social and economical consequences of sleep-disordered breathing: a controlled national study. Thorax 2011; 66:560.
- Castro-Añón O, Pérez de Llano LA, De la Fuente Sánchez S, et al. Obesity-hypoventilation syndrome: increased risk of death over sleep apnea syndrome. PLoS One 2015; 10:e0117808.
- Mokhlesi B, Kryger MH, Grunstein RR. Assessment and management of patients with obesity hypoventilation syndrome. Proc Am Thorac Soc 2008; 5:218.
- Mokhlesi B. Obesity hypoventilation syndrome: a state-of-the-art review. Respir Care 2010; 55:1347.
- Nowbar S, Burkart KM, Gonzales R, et al. Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome. Am J Med 2004; 116:1.
- Macavei VM, Spurling KJ, Loft J, Makker HK. Diagnostic predictors of obesity-hypoventilation syndrome in patients suspected of having sleep disordered breathing. J Clin Sleep Med 2013; 9:879.
- Chau EH, Lam D, Wong J, et al. Obesity hypoventilation syndrome: a review of epidemiology, pathophysiology, and perioperative considerations. Anesthesiology 2012; 117:188.
- Povitz M, James MT, Pendharkar SR, et al. Prevalence of Sleep-disordered Breathing in Obese Patients with Chronic Hypoxemia. A Cross-Sectional Study. Ann Am Thorac Soc 2015; 12:921.
- Marik PE, Desai H. Characteristics of patients with the "malignant obesity hypoventilation syndrome" admitted to an ICU. J Intensive Care Med 2013; 28:124.
- Harada Y, Chihara Y, Azuma M, et al. Obesity hypoventilation syndrome in Japan and independent determinants of arterial carbon dioxide levels. Respirology 2014; 19:1233.
- Mokhlesi B, Tulaimat A, Faibussowitsch I, et al. Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea. Sleep Breath 2007; 11:117.
- Olson AL, Zwillich C. The obesity hypoventilation syndrome. Am J Med 2005; 118:948.
- BaHammam AS. Prevalence, clinical characteristics, and predictors of obesity hypoventilation syndrome in a large sample of Saudi patients with obstructive sleep apnea. Saudi Med J 2015; 36:181.
- Carrillo A, Ferrer M, Gonzalez-Diaz G, et al. Noninvasive ventilation in acute hypercapnic respiratory failure caused by obesity hypoventilation syndrome and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012; 186:1279.
- Palm A, Midgren B, Janson C, Lindberg E. Gender differences in patients starting long-term home mechanical ventilation due to obesity hypoventilation syndrome. Respir Med 2016; 110:73.
- Basoglu OK, Tasbakan MS. Comparison of clinical characteristics in patients with obesity hypoventilation syndrome and obese obstructive sleep apnea syndrome: a case-control study. Clin Respir J 2014; 8:167.
- Kessler R, Chaouat A, Schinkewitch P, et al. The obesity-hypoventilation syndrome revisited: a prospective study of 34 consecutive cases. Chest 2001; 120:369.
- Castro-Añón O, Golpe R, Pérez-de-Llano LA, et al. Haemodynamic effects of non-invasive ventilation in patients with obesity-hypoventilation syndrome. Respirology 2012; 17:1269.
- Kauppert CA, Dvorak I, Kollert F, et al. Pulmonary hypertension in obesity-hypoventilation syndrome. Respir Med 2013; 107:2061.
- Held M, Walthelm J, Baron S, et al. Functional impact of pulmonary hypertension due to hypoventilation and changes under noninvasive ventilation. Eur Respir J 2014; 43:156.
- Borel JC, Roux-Lombard P, Tamisier R, et al. Endothelial dysfunction and specific inflammation in obesity hypoventilation syndrome. PLoS One 2009; 4:e6733.
- Berg G, Delaive K, Manfreda J, et al. The use of health-care resources in obesity-hypoventilation syndrome. Chest 2001; 120:377.
- Jennum P, Ibsen R, Kjellberg J. Morbidity prior to a diagnosis of sleep-disordered breathing: a controlled national study. J Clin Sleep Med 2013; 9:103.
- Manuel AR, Hart N, Stradling JR. Is a raised bicarbonate, without hypercapnia, part of the physiologic spectrum of obesity-related hypoventilation? Chest 2015; 147:362.
- Mandal S, Suh ES, Boleat E, et al. A cohort study to identify simple clinical tests for chronic respiratory failure in obese patients with sleep-disordered breathing. BMJ Open Respir Res 2014; 1:e000022.
- Bingol Z, Pıhtılı A, Cagatay P, et al. Clinical predictors of obesity hypoventilation syndrome in obese subjects with obstructive sleep apnea. Respir Care 2015; 60:666.
- Budweiser S, Riedl SG, Jörres RA, et al. Mortality and prognostic factors in patients with obesity-hypoventilation syndrome undergoing noninvasive ventilation. J Intern Med 2007; 261:375.
- Heinemann F, Budweiser S, Dobroschke J, Pfeifer M. Non-invasive positive pressure ventilation improves lung volumes in the obesity hypoventilation syndrome. Respir Med 2007; 101:1229.
- Hollier CA, Maxwell LJ, Harmer AR, et al. Validity of arterialised-venous P CO2, pH and bicarbonate in obesity hypoventilation syndrome. Respir Physiol Neurobiol 2013; 188:165.
- Littleton SW. Impact of obesity on respiratory function. Respirology 2012; 17:43.
- Hart N, Mandal S, Manuel A, et al. Obesity hypoventilation syndrome: does the current definition need revisiting? Thorax 2014; 69:83.
- Piper AJ. Obesity hypoventilation syndrome--the big and the breathless. Sleep Med Rev 2011; 15:79.
- Kaw R, Hernandez AV, Walker E, et al. Determinants of hypercapnia in obese patients with obstructive sleep apnea: a systematic review and metaanalysis of cohort studies. Chest 2009; 136:787.
- Banerjee D, Yee BJ, Piper AJ, et al. Obesity hypoventilation syndrome: hypoxemia during continuous positive airway pressure. Chest 2007; 131:1678.
- Resta O, Foschino-Barbaro MP, Bonfitto P, et al. Prevalence and mechanisms of diurnal hypercapnia in a sample of morbidly obese subjects with obstructive sleep apnoea. Respir Med 2000; 94:240.
- Wijesinghe M, Perrin K, Healy B, et al. Pre-hospital oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease. Intern Med J 2011; 41:618.
- Hollier CA, Harmer AR, Maxwell LJ, et al. Moderate concentrations of supplemental oxygen worsen hypercapnia in obesity hypoventilation syndrome: a randomised crossover study. Thorax 2014; 69:346.
- CLINICAL MANIFESTATIONS
- DIAGNOSTIC TESTS
- Serum bicarbonate
- Oxygen saturation by pulse oximetry
- Other blood tests
- Arterial blood gases
- Pulmonary function tests
- Chest radiograph
- Cardiac studies
- DIAGNOSTIC APPROACH
- SUMMARY AND RECOMMENDATIONS