Acetazolamide plus Atomoxetine Changed Chemosensitivity in Obesity Hypoventilation Syndrome

Some severe obese subjects develop hypoventilation defining the obesity-hypoventilation syndrome (OHS), due to altered ventilatory demand and drive, often associated with sleep apnoea. If left untreated, OHS is associated with increased morbidity and mortality. Blunted ventilatory responses to hypercapnia are one of the pathophysiological mechanisms behind the development of diurnal hypercapnia in OHS. We recently showed that 2 weeks treatment with atomoxetine plus acetazolamide (ato\acz) improved hypercapnia compared to placebo. However, the effects on chemosensitivity of ato\acz were not reported. <bold>Methods:</bold> We performed a randomized, double-blind crossover trial to compare 2 weeks of ato\acz with placebo in OHS. Subjects performed polysomnography with transcutaneous overnight measurement of CO₂ (PtcCO₂) and morning blood test. Ventilatory parameters were assessed during progressive hypercapnic stimulus, using the rebreathing technique after each treatment arm. CO₂ chemosensitivity was measured as VE/PetCO₂ slope and P01/PetCO₂ slope. <bold>Results:</bold> 15 subjects with (median [interquartile range]) age 54 [37-61] years, 8 females, BMI 44 [41-60] kg/m², baseline nocturnal PtcCO₂ 46.6 [42.2-51.9] mmHg and nocturnal SpO₂ 88 [81-92] % were randomized. Ato\acz improved VE/PetCO₂ slope and P01/PetCO₂ slope compared with placebo, with mean (95% confidence interval) increases by 0.8 (0.3-3.68) mmHg (p=0.003) and 0.2 (0.1-0.3) (p=0.002) respectively. <bold>Conclusion:</bold> The administration of ato\acz improved chemosensitivity in patients not previously treated for OHS. This study provides encouraging results for a potential pharmaco-therapy for OHS targeting its pathophysiology