Urinary Metabolomic Profiling in Obstructive Sleep Apnoea Hypopnoea Syndrome

We examined the urinary metabolome of those with obstructive sleep apnoea hypopnoea syndrome (OSAHS), and how continuous positive airway pressure (CPAP) affects it. We compared it with their non-OSAHS counterparts to identify any distinguishing biomarkers that could be used to diagnose and monitor, as well as highlight those at increased cardiometabolic risk. Observational, prospective and longitudinal study including 70 consecutive attenders referred to our sleep service. OSAHS was defined as apnoea-hypopnoea index ≥ 15 events/h and Epworth sleepiness score (ESS) > 10. Patients treated with CPAP were followed up 6-10 weeks following treatment set-up. Untargeted urinary metabolomic profiling was performed using high-throughput flow-infusion electrospray high-resolution mass spectrometry (FIE-MS). A panel of metabolites was identified (mainly glycerophospholipids, acylcarnitines and fatty acids), with a single metabolite, octadecanamide, being able to differentiate between OSAHS and non-OSAHS with an accuracy (95% CI) of 0.86 [0.76-0.93]. Levels of the panel of metabolites were significantly lower with CPAP, with the effect on 2-anilino-6-cyclohexylmethoxypurine (a hypoxanthine) being particularly marked (AUC 0.93 [0.858-0.971]). Metabolomics in urine offers a promising and non-invasive way to differentiate and diagnose OSAHS from non-OSAHS, while identifying pathways activated by chronic intermittent hypoxia, oxidative stress and inflammation. Correlation of these key metabolites with the known cardiometabolic consequences of OSAHS could potentially highlight those at an increased risk of adverse complications and provide areas for future personalised targeted treatments that CPAP is unable to impact currently, whilst also being a surrogate marker of treatment compliance.