Novel approaches to identify biomarkers associated with respiratory disease in patient biofluids

Abstract

Rationale:
Chronic respiratory conditions cause around four million deaths each year and respiratory infections are the leading cause of death in most developing countries. The yearly economic burden of these conditions on the NHS adds up to 11 billion pounds. Metabolomics may provide new clinical insights and lead to development of cheap and fast point-of-care tests which could allow for early screenings of some diseases and use in remote places with no access to modern healthcare.

Research question:
This project assessed if metabolomics methods on various biofluids from respiratory disease patients could inform disease pathophysiology and suggest potential biomarkers for informed therapeutics.

Evidence and methods:
The diseases examined represented oncogenic changes, chronic conditions, viral infections, and bacterial infections. The biofluids used differed for each disease but included plasma, urine, stool. Metabolomic assessment employed flow injection electrospray mass spectrometry and multivariate and univariate analyses. The Human Metabolome Database (HMDB) was used to identify the specific metabolites from their ionised masses.

Results:
For lung cancer, the urine metabolomes could suggest the presence of cancer including early stage (I and II), as well as tentatively distinguishing between NSCLC vs SCLC and adenocarcinoma vs squamous cell carcinoma (SCC). COPD results showed systemic changes and the potential in COPD staging. Plasma showed metabolic differences of COVID-19 and controls as well as between the COVID-19 strains. Urine and plasma of human tuberculosis patients suggested pathways and metabolites related to coordinated responses that may have an impact on immune responses of TB patients.

Conclusion:
Metabolomics methods were able to uncover changes in metabolomes related to various types of respiratory conditions which could be used for both diagnostics/typing and informing clinicians about potential therapeutic strategies.

Implications of the findings:
Using metabolomic approaches has potential to give deeper insights into various respiratory conditions and help with diagnostics and therapeutic approaches.

Date of Award	2024
Original language	English
Awarding Institution	Aberystwyth University
Supervisor	Manfred Beckmann (Supervisor) & Luis Mur (Supervisor)