Long-term nocturnal non-invasive mechanical ventilation (NIMV) is an effective treatment for obesity-hypoventilation syndrome (OHS), improving central carbon dioxide (CO₂) sensitivity. Leptin might contribute to sustain adequate ventilation in obesity. The aim of the study was to investigate the role of leptin in the OHS pathogenesis looking at its relationship to CO₂ sensitivity before and after NIMV in OHS patients.

In six obese patients (3F/3M; aged 63±9yr; BMI 47.0±4.5kg/m²) with OHS and without obstructive sleep apnoea–hypopnoea (OSAH) diurnal arterial blood gases, fasting plasma leptin concentration and CO₂ chemosensitivity were determined before and after 10.3±5.6 (range 6–20) months of NIMV.

After NIMV improvements were observed in gas exchange (PaO₂ from 51.3±6.7 to 75.0±10.3mmHg, p<0.01; PaCO₂ from 55.5±4.8 to 43.7±1.2mmHg, p<0.01; [HCO₃⁻] from 33.3±3.8 to 29.8±1.7mmol/l, p<0.05) and CO₂ chemosensitivity, measured as P_0.1/PetCO₂ slope (from 0.09±0.07 to 0.18±0.07cmH₂O/mmHg, p<0.05) and V_E/PetCO₂ slope (from 0.4±0.3 to 0.9±0.5l/min/mmHg,  ). Plasma leptin increased from 34.5±21.1ng/ml to 50.2±22.9ng/ml (p<0.01) after NIMV and changes of the P_0.1/PetCO₂ slope correlated with percent changes of plasma leptin ( , p<0.05).

These findings suggest a possible role of leptin in the recovery of neuromuscular response to hypercapnia obtained during long-term nocturnal NIMV in OHS patients without OSAH.