No Cover Image

E-Thesis 74 views 52 downloads

Applying metabolomics in diagnosing and monitoring Obstructive Sleep Apnoea Hypopnoea Syndrome / SCOTT O'ROURKE

Swansea University Author: SCOTT O'ROURKE

  • O'Rourke_Scott_MD_Thesis_Final_Cronfa.pdf

    PDF | E-Thesis – open access

    Copyright: The Author, Scott O’Rourke, 2025.

    Download (4.66MB)

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...

Full description

Published: Swansea, Wales, UK 2025
Institution: Swansea University
Degree level: Doctoral
Degree name: M.D
Supervisor: Lewis, Keir ; Conlan, Steve
URI: https://cronfa.swan.ac.uk/Record/cronfa69227
first_indexed 2025-04-04T12:46:58Z
last_indexed 2025-04-05T04:44:36Z
id cronfa69227
recordtype RisThesis
fullrecord <?xml version="1.0"?><rfc1807><datestamp>2025-04-04T14:03:02.9755413</datestamp><bib-version>v2</bib-version><id>69227</id><entry>2025-04-04</entry><title>Applying metabolomics in diagnosing and monitoring Obstructive Sleep Apnoea Hypopnoea Syndrome</title><swanseaauthors><author><sid>5c3c9fee660e1fd456201b305ce8b4c3</sid><firstname>SCOTT</firstname><surname>O'ROURKE</surname><name>SCOTT O'ROURKE</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2025-04-04</date><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&lt;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.</abstract><type>E-Thesis</type><journal/><volume/><journalNumber/><paginationStart/><paginationEnd/><publisher/><placeOfPublication>Swansea, Wales, UK</placeOfPublication><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic/><keywords>Obstructive sleep apnoea, metabolomics</keywords><publishedDay>27</publishedDay><publishedMonth>3</publishedMonth><publishedYear>2025</publishedYear><publishedDate>2025-03-27</publishedDate><doi>10.23889/SUthesis.69227</doi><url/><notes/><college>COLLEGE NANME</college><CollegeCode>COLLEGE CODE</CollegeCode><institution>Swansea University</institution><supervisor>Lewis, Keir ; Conlan, Steve</supervisor><degreelevel>Doctoral</degreelevel><degreename>M.D</degreename><apcterm/><funders/><projectreference/><lastEdited>2025-04-04T14:03:02.9755413</lastEdited><Created>2025-04-04T13:43:25.4906871</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Biomedical Science</level></path><authors><author><firstname>SCOTT</firstname><surname>O'ROURKE</surname><order>1</order></author></authors><documents><document><filename>69227__33951__b1dec973f0cb450b94951e19a8429792.pdf</filename><originalFilename>O'Rourke_Scott_MD_Thesis_Final_Cronfa.pdf</originalFilename><uploaded>2025-04-04T14:00:53.8224091</uploaded><type>Output</type><contentLength>4884723</contentLength><contentType>application/pdf</contentType><version>E-Thesis &#x2013; open access</version><cronfaStatus>true</cronfaStatus><documentNotes>Copyright: The Author, Scott O&#x2019;Rourke, 2025.</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language></document></documents><OutputDurs/></rfc1807>
spelling 2025-04-04T14:03:02.9755413 v2 69227 2025-04-04 Applying metabolomics in diagnosing and monitoring Obstructive Sleep Apnoea Hypopnoea Syndrome 5c3c9fee660e1fd456201b305ce8b4c3 SCOTT O'ROURKE SCOTT O'ROURKE true false 2025-04-04 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. E-Thesis Swansea, Wales, UK Obstructive sleep apnoea, metabolomics 27 3 2025 2025-03-27 10.23889/SUthesis.69227 COLLEGE NANME COLLEGE CODE Swansea University Lewis, Keir ; Conlan, Steve Doctoral M.D 2025-04-04T14:03:02.9755413 2025-04-04T13:43:25.4906871 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science SCOTT O'ROURKE 1 69227__33951__b1dec973f0cb450b94951e19a8429792.pdf O'Rourke_Scott_MD_Thesis_Final_Cronfa.pdf 2025-04-04T14:00:53.8224091 Output 4884723 application/pdf E-Thesis – open access true Copyright: The Author, Scott O’Rourke, 2025. true eng
title Applying metabolomics in diagnosing and monitoring Obstructive Sleep Apnoea Hypopnoea Syndrome
spellingShingle Applying metabolomics in diagnosing and monitoring Obstructive Sleep Apnoea Hypopnoea Syndrome
SCOTT O'ROURKE
title_short Applying metabolomics in diagnosing and monitoring Obstructive Sleep Apnoea Hypopnoea Syndrome
title_full Applying metabolomics in diagnosing and monitoring Obstructive Sleep Apnoea Hypopnoea Syndrome
title_fullStr Applying metabolomics in diagnosing and monitoring Obstructive Sleep Apnoea Hypopnoea Syndrome
title_full_unstemmed Applying metabolomics in diagnosing and monitoring Obstructive Sleep Apnoea Hypopnoea Syndrome
title_sort Applying metabolomics in diagnosing and monitoring Obstructive Sleep Apnoea Hypopnoea Syndrome
author_id_str_mv 5c3c9fee660e1fd456201b305ce8b4c3
author_id_fullname_str_mv 5c3c9fee660e1fd456201b305ce8b4c3_***_SCOTT O'ROURKE
author SCOTT O'ROURKE
author2 SCOTT O'ROURKE
format E-Thesis
publishDate 2025
institution Swansea University
doi_str_mv 10.23889/SUthesis.69227
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 1
active_str 0
description 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.
published_date 2025-03-27T17:19:32Z
_version_ 1832113482376413184
score 11.05923

Similar Items