Crynodeb
Introduction: Respiratory diseases affect 1 out of 5 people and is the 3rd biggest killer in the UK. The current diagnostic tools available for respiratory diseases are limited by cost, invasiveness and lack of accuracy. Therefore, the use of biomarkers could be beneficial to create a non-invasive cheap diagnostic tool detecting changes in the biofluids of people suffering with IPF, COPD and TB/HIV co-morbidity. The test could both be used for diagnostics and disease progression tracking.Methods: The study consists of three parts; a COPD study, IPF study and TB/HIV study. For the IPF study 32 urine samples (16 HC and 16 IPF), 11 lavages (6 HC and 5 IPF) and 40 plasmas (15 HC and 25 IPF) was analysed. For the COPD metabolomic study 390 urine samples (117 HC and 273 COPD, where 64 was early stage and 60 late stage), 155 sputum samples (11 GOLD 1, 32 GOLD 2, 38 GOLD 3 and 34 GOLD 4) and for the proteomic COPD study 100 samples (14 GOLD 1, 25 GOLD 2, 22 GOLD 3 and 21 GOLD 4) were analysed. For the TB/HIV study there were 438 urine samples (34 HIV + TB +, 48 HIV + TB -, 119 HIV – TB + and 237 HIV – TB -), 426 stool samples (34 HIV + TB +, 56 HIV + TB -, 96 HIV – TB + and 240 HIV – TB -) and plasma samples (36 HIV + TB +, 52 HIV + TB -, 122 HIV – TB + and 248 HIV – TB -) analysed. The data was assessed using metaboanalyst, an R based platform, presenting principal component analyses (PCA), partial least squares discriminant analysis (PLS-DA), the receiver operating characteristics (ROC) curves and pathway analysis.
Results: For the IPF study comparing IPF and HC the PCA and PLSDA showed clear separation between the groups for the urine, plasma and lavage group. The most common biomarkers seen separating the groups were Lipids, Fatty acids, Amino acids, Glycerol, prostaglandins and Phosphatic acids.
For the HIV/TB co-morbidity study we saw little to no separation in any of the PCA for any of the biofluids, but a clear separation in all of the PLS-Das. The major groups seen to separate the HIV-TB+ and HIV-TB- were carboxylic acids, lipids, glucosamine, amino acids, folate, bile acid, malic acid, hydroxy acid, adenosine and arachidonic acid. When comparing to HIV+TB- and HIV+ TB+ groups we see that there is a lack of the groups involved in the inflammatory processes and are left with some fatty acids.
For the COPD study we see some separation in the PCA groups and PLS-DA groups, and in the graphs focusing on GOLD 1-4 we see a gradient separating the disease according to severity. The main groups found in the metabolomic study is short chain fatty acids, long chain fatty acids, pyrimidine, purine, sphingolipids, phospholipids and steroids. In the proteomics study the pathways seen to separate the disease were proteolysis, signal transduction, cell adhesion, innate immune responses, inflammatory responses, extracellular exosome, plasma membrane, protein binding, calcium binding, glycolytic process, glycosphingolipid biosynthesis and cholesterol efflux.
Conclusions: There are currently poor diagnostic tools available for respiratory diseases. Metabolomic and proteomic analyses have been proven useful in the diagnostic of certain respiratory diseases. Our analysis identified significant changes in fatty acids, amino acids, steroids, and inflammation processes. Both sputum and urine are minimally invasive compared to the methods already available and has great potential in a future diagnostic test for COPD and IPF, as well as in creating an understanding for the effect HIV has on TB illness.
| Dyddiad Dyfarnu | 2025 |
|---|---|
| Iaith wreiddiol | Saesneg |
| Sefydliad Dyfarnu |
|
| Goruchwyliwr | Manfred Beckmann (Goruchwylydd) & Luis Mur (Goruchwylydd) |
Dyfynnu hyn
- Standard