The global obesity pandemic contributes to an increase in the prevalence of obesity hypoventilation syndrome (OHS). OHS is associated with poor prognosis and early mortality. Definitions of OHS and disease severity classifications differ between international guidelines, and consideration of polysomnographic features is often lacking. To address this, the European Respiratory Society has proposed a severity classification approach. It is also important to consider the possibility that patients with OHS might have multiple factors contributing to hypercapnia, including obesity-related changes in the respiratory system, alterations in central respiratory drive, and different sleep-disordered breathing (SDB) abnormalities. There are also multiple health trajectories that occur before an OHS diagnosis. Positive airway pressures such as continuous positive airway pressure or non-invasive ventilation are the mainstay of OHS treatment. The choice of therapy needs to be guided by appropriate SDB phenotyping and daytime hypercapnia severity. Comorbidities are common in patients with OHS and these trigger and increase the risk of acute on chronic respiratory failure. Appropriate management of comorbidities, and weight loss management, are essential (including behavioral interventions, physical activity, pharmacotherapy, and metabolic/bariatric procedures, as appropriate for each individual). Newer pharmacological treatments such as glucagon-like peptide-1 receptor agonists, recombinant human leptin, and orexin receptor antagonists are promising, but have not yet been specifically investigated in OHS populations. Overall, there is a need for a significant redesign in assessment and care to facilitate the evidence-based management of the complex and diverse OHS presentations in clinical practice.
