Long-term continuous positive airway pressure treatment ameliorates biological clock disruptions in obstructive sleep apnea

BACKGROUND: Obstructive Sleep Apnea (OSA) is a highly prevalent and underdiagnosed sleep disorder. Recent studies suggest that OSA might disrupt the biological clock, potentially causing or worsening OSA-associated comorbidities. However, the effect of OSA treatment on clock disruption is not fully understood. METHODS: The impact of OSA and short- (four months) and long-term (two years) OSA treatment, with Continuous Positive Airway Pressure (CPAP), on the biological clock was investigated at four time points within 24 h, in OSA patients relative to controls subjects (no OSA) of the same sex and age group, in a case-control study. Plasma melatonin and cortisol, body temperature and the expression levels and rhythmicity of eleven clock genes in peripheral blood mononuclear cells (PBMCs) were assessed. Additional computational tools were used for a detailed data analysis. FINDINGS: OSA impacts on clock outputs and on the expression of several clock genes in PBMCs. Neither short- nor long-term treatment fully reverted OSA-induced alterations in the expression of clock genes. However, long-term treatment was able to re-establish levels of plasma melatonin and cortisol and body temperature. Machine learning methods could discriminate controls from untreated OSA patients. Following long-term treatment, the distinction between controls and patients disappeared, suggesting a closer similarity of the phenotypes. INTERPRETATION: OSA alters biological clock-related characteristics that differentially respond to short- and long-term CPAP treatment. Long-term CPAP was more efficient in counteracting OSA impact on the clock, but the obtained results suggest that it is not fully effective. A better understanding of the impact of OSA and OSA treatment on the clock may open new avenues to OSA diagnosis, monitoring and treatment.