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Applying metabolomics in diagnosing and monitoring Obstructive Sleep Apnoea Hypopnoea Syndrome / SCOTT O'ROURKE
Swansea University Author: SCOTT O'ROURKE
DOI (Published version): 10.23889/SUthesis.69227
Abstract
Obstructive sleep apnoea hypopnoea syndrome (OSAHS) is associated with adverse cardiometabolic risk and a chronic inflammatory metabolic state. Current sleep tests are limited by waiting times, are labour intensive, and have ongoing controversies regarding the optimal physiological parameter(s). Met...
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Swansea, Wales, UK
2025
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| Institution: | Swansea University |
| Degree level: | Doctoral |
| Degree name: | M.D |
| Supervisor: | Lewis, Keir ; Conlan, Steve |
| URI: | https://cronfa.swan.ac.uk/Record/cronfa69227 |
| Abstract: |
Obstructive sleep apnoea hypopnoea syndrome (OSAHS) is associated with adverse cardiometabolic risk and a chronic inflammatory metabolic state. Current sleep tests are limited by waiting times, are labour intensive, and have ongoing controversies regarding the optimal physiological parameter(s). Metabolomics is the study of multiple chemical processes simultaneously of the small molecule substrates, intermediates, and products of cell metabolism. It provides a chemical fingerprint of an organism at a precise timepoint. Metabolomics has mainly been applied to plasma in OSAHS, with inconsistent methods and results and remains far from clinical application. By applying untargeted metabolomic profiling on the plasma, serum, and urine of consecutive attenders to our sleep service, I demonstrated a panel of 5 biologically plausible urinary metabolites that could distinguish between those with OSAHS and their non-OSAHS counterparts with an AUC of 0.77 (0.52-0.93). Furthermore, I found a single urinary metabolite, octadecanamide, could differentiate groups with an AUC 0.86 (0.76-0.93), 84% sensitivity, and 78% specificity. Furthermore, the same patients profiled for OSAHS were followed-up and re-sampled after a period of treatment with CPAP to assess the effect of CPAP on their circulating metabolomic profile. I found significant down-regulation in again biologically plausible metabolites following treatment with CPAP (p<0.05), with 2-anilino-6-cyclohexylmethoxypurine differentiating between pre- and post-CPAP groups with an AUC of 0.93 [0.858-0.971]. Metabolomics in urine offers a promising and non-invasive way to differentiate OSAHS from non-OSAHS, whilst identifying pathways activated by chronic intermittent hypoxia, oxidative stress, and inflammation. Furthermore, correlation of these key metabolites with the known cardiometabolic consequences of OSAHS could potentially highlight those at an increased risk of future adverse complications and provide areas for future targeted treatments that CPAP is unable to impact currently. |
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| Keywords: |
Obstructive sleep apnoea, metabolomics |
| College: |
Faculty of Medicine, Health and Life Sciences |