Longitudinal Trajectories and Incidence of Obesity-Hypoventilation Syndrome Over Three Years in Obese Adults (The Cohypob Study)

Background Obesity hypoventilation syndrome (OHS) is defined by daytime hypercapnia in obese individuals and is often considered the consequence of progressive nocturnal hypoventilation. However, the natural history of obesity-related nocturnal hypoventilation (ONH) and its progression toward OHS remain poorly understood. Methods COHYPOB is a prospective multicentre cohort study including obese adults without daytime hypercapnia or obstructive sleep apnoea requiring CPAP at baseline. Participants underwent comprehensive clinical, respiratory, metabolic and sleep assessments at inclusion and during a 3-year follow-up. ONH was defined using elevated morning serum bicarbonate (≥27 mmol·L⁻ 1 ) in the absence of daytime hypercapnia, according to current ERS Task Force recommendations. The primary outcome was the occurrence of OHS, defined by daytime PaCO₂ ≥45 mmHg. Results A total of 162 participants were included (74% women, mean age 48±14 years, mean BMI 37.3±4.9 kg·m⁻ 2 ). Among the 144 participants with available baseline serum bicarbonate measurements, 67 (46.5%) met the criterion for bicarbonate-defined ONH. Compared with those without ONH, affected individuals were older and showed mild alterations in daytime gas exchange and nocturnal oxygenation despite similar body mass index. Over the 3-year follow-up, body weight remained stable, whereas bicarbonate-defined ONH demonstrated marked temporal variability. Five participants developed OHS, corresponding to an incidence of 5.4% among those completing follow-up. Conclusions In this prospective cohort of obese adults without daytime hypercapnia and without OSA requiring CPAP, bicarbonate-defined ONH was common and showed substantial temporal variability over three years, whereas incident OHS remained uncommon. These observations suggest that the evolution towards OHS may be more heterogeneous than traditionally proposed. Because ONH was defined using morning serum bicarbonate, longitudinal studies incorporating direct nocturnal CO₂ monitoring are required.