Obesity hypoventilation syndrome (OHS) is defined as a combination of obesity (body mass index ≥ 30 kg/m²), daytime hypercapnia (Pa_CO2 ≤ 45 mm Hg) and sleep-disordered breathing after ruling out other disorders that may cause alveolar hypoventilation. It is a chronic disease associated with respiratory and cardiometabolic impairments leading to a decrease in activities of daily life and social involvement, increased health-related costs, and higher risks of hospitalization and death (1, 2). Despite its established severity compared with eucapnic obesity, OHS is largely underrecognized, with only one-third of patients actually diagnosed when hospitalized for acute-on-chronic respiratory failure (3–6). In this issue of the Journal, Carrillo and colleagues (pp. ) describe the outcomes of 173 patients treated by noninvasive ventilation (NIV) for acute hypercapnic respiratory failure (AHRF) due to obesity hypoventilation (7). Only 9% of them were chronically treated at home by continuous positive airway pressure (CPAP)/NIV prior to admission, although 65% had already been admitted to an intensive care unit (ICU), probably for similar episodes of AHRF. These data emphasize the importance of a better awareness of OHS and systematic screening for hypercapnia in patients with obesity, particularly in primary care settings and obesity clinics. A sensitive and inexpensive marker in obese patients is serum bicarbonate: a level greater than 27 mmol/L is associated with a high prevalence of OHS and should lead to the patient’s referral to a respiratory physician (2). Early diagnosis is a crucial issue. Patients in whom NIV is initiated in acute conditions are more likely to have developed OHS-related cardiovascular complications, thus increasing the risk of multiple organ failure and death at the time of acute respiratory failure (5, 6).

There are no randomized controlled trials and very few well-designed studies addressing the question of efficacy of NIV in AHRF due to OHS. Available studies are retrospective and/or case studies including a limited numbers of patients. These studies, aiming to demonstrate the impact of NIV on mortality, included patients for whom NIV was initiated both in acute and chronic settings, which clearly correspond to distinct OHS phenotypes. Results cannot be extrapolated to an outcome analysis based on strict criteria of AHRF leading to ICU referral. Carrillo and colleagues prospectively assessed 716 consecutive patients (173 with OHS and 543 with chronic obstructive pulmonary disease [COPD]) with AHRF (7). NIV success was defined as avoidance of intubation and ICU survival at least 24 hours in the ward. Hospital survivors were followed for 1 year to assess hospital readmission rate and survival. This prospective study is by far the largest study in the field. Compared with COPD for whom NIV represents standard care in AHRF (8), patients with OHS exhibited less late NIV failure (7% vs. 13%, P = 0.037), less readmission to the ICU, and lower hospital and ICU mortality (6% vs. 18%, P < 0.001). Patients with OHS are thus clearly responsive to NIV. The pathophysiology of OHS results from complex interactions between various sleep breathing disorders (i.e., obstructive sleep apnea [OSA] and REM sleep hypoventilation), increased work of breathing as a result of a decreased thoracoabdominal compliance, and altered ventilatory drive. All these mechanisms are successfully addressed by NIV, and patients with OHS were even more effectively treated for their AHRF than are patients with COPD.

There are, however, a few unexpected findings in the study by Carrillo and coworkers. First, the investigators applied a similar protocol to titrate NIV pressure support in COPD and in patients with OHS. The bilevel positive airway pressure devices used in the study deliver adjustable inspiratory and expiratory positive airway pressure (EPAP). In OHS, 80 to 90% of the patients have associated obstructive sleep apnea, and EPAP levels are adjusted to maintain upper airway patency and to abolish obstructive events during sleep. For these patients, typical EPAP pressures range between 8 and 12 cm H₂O (9). In patients with COPD, OSA is not more frequent than in the general population, and titration of EPAP in acute conditions aims to counteract intrinsic positive end-expiratory pressure at values that do not usually exceed 6 to 8 cm H₂O (10). It is unclear, therefore, why the titration protocol was exactly the same for both groups of patients in the study by Carrillo and colleagues. Among patients with COPD included, 33.9% were obese, and 28% had associated OSA (“overlap syndrome”), which probably explains why the same titration protocol was in fact effective. Second, although in hospital mortality was lower in OHS, both 1-year adjusted survival and readmission rate following AHRF were similar to that of patients with COPD. The authors state that decisions as to long-term care were left to the attending physicians. However, only 55% of patients with OHS studied were put on a long-term positive pressure ventilatory support (CPAP or NIV) at home, and a very low 10% were treated by NIV. This is unexpected and probably not appropriate. Clinical guidelines and consensus statements recommend long-term NIV use in patients with OHS. Open studies show that long-term NIV for OHS suppresses respiratory events during sleep, normalizes sleep structure, and restores daytime vigilance (11, 12). Much higher survival rates (1-yr survival above 90%) have been reported for patients with OHS treated by NIV (4–6, 13, 14) (Figure 1), potentially explained by a decrease in incident cardiovascular events, and when comparative data were available, survival was much higher than for patients with COPD treated by NIV. Survival data from the study by Carrillo and coworkers are similar to those reported by Nowbar and colleagues (4) in untreated patients with OHS (Figure 1). This strongly suggests that long-term NIV should be systematically proposed at home after an acute-on-chronic failure in patients with OHS. Oxygen therapy alone is not appropriate when taking into account the underlying mechanisms for hypoventilation in OHS (15) but remains overused as demonstrated by the 39% of patients with OHS on long-term oxygen therapy before their admission for ARHF in the study by Carrillo and colleagues. After an acute respiratory failure, patients with OHS should be reevaluated on a regular basis. When normalization of Pa_CO2 and resetting of the respiratory centers is achieved by NIV, a proportion of OHS could be protected from respiratory failure by the use of simple CPAP therapy. ICU and respiratory physicians should favor the implementation of clinical pathways allowing an easy transition from ICU to home NIV treatment.

Figure 1. Survival rate in patients with obesity hypoventilation syndrome according to the condition of noninvasive ventilation (NIV) initiation and the long-term treatment with or without NIV. For the studies of Budweiser and colleagues (14), Priou and colleagues (6), Pérez de Llano and colleagues (5), and Borel and colleagues (13), survival rates are plotted at the mean observation time reported in each study. Symbols in white: NIV initiated in AHRF; symbols in black: NIV initiated in stable CRF; symbols in gray: NIV initiated in both conditions (AHRF + CRF). The size of the symbols is proportional to the sample size of the studies. AHRF = acute hypercapnic respiratory failure; CRF = chronic respiratory failure.

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The study by Carrillo and colleagues shows that better screening for patients with OHS is necessary to reduce the delay of NIV initiation and avoid acute-on-chronic respiratory failure. NIV appears at least as effective in acute conditions as in COPD. A step forward would be to improve the link between the acute initiation of NIV and long-term care. OHS requires a multimodal therapeutic approach including home NIV/CPAP, rehabilitation programs with physical training, weight loss, lifestyle changes, and appropriate medication to further control cardiovascular risk factors.

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