The Oxford Pleural Infection Endotyping Study
- Conditions
- Pleural InfectionPleural DiseasesPleural Infections and InflammationsPleural EmpyemaPleural Infection BacterialPleural Effusion
- Registration Number
- NCT06513689
- Lead Sponsor
- University of Oxford
- Brief Summary
Pleural infection is a severe disease with increasing incidence worldwide. The subphenotypes of pleural infection remain unknown.We designed a study to endotype the disease and assess the association between patient phenotype, microbiology and clinical outcome.
We subjected 80 pleural fluid samples to unlabelled mass spectrometry.
Pathway analysis of the differentially expressed proteins identified the neutrophil degranulation, glycolysis, pentose phosphate pathway, and the liver and retinoid X receptors (LXR-RXR) activation. Higher neutrophil degranulation was associated with increased glycolysis and pentose phosphate activation.
Pleural infection patients exhibit proteomic signatures indicating diverse responses of neutrophil mediated immunity, glycolysis, and pentose phosphate activation.
- Detailed Description
Pleural infection is a common and severe disease with increasing incidence worldwide. The endotypes of pleural infection remain unknown. A better understanding of patient variation in underlying biological response to infection may lead to improved treatments and clinical outcomes. We designed a study with the aim to endotype the disease and assess the association between patient phenotype, microbiology and clinical outcome.
We subjected 80 pleural fluid samples from the PILOT study, a prospective study on pleural infection, to unlabelled mass spectrometry. Proteins were retained if they were detected in at least 50% of the samples resulting in a total of 449 proteins. Unsupervised hierarchical clustering and UMAP analyses were used to cluster samples, Spearman and exact Fischer's methods were used for correlation assessment and protein expression was correlated with clinical outcomes.
UMAP plotting separated the samples in to two different and distinct cohorts. Pathway analysis of the differentially expressed proteins identified neutrophil degranulation, glycolysis, the pentose phosphate pathway, and the liver and retinoid X receptors (LXR-RXR) activation. Higher neutrophil degranulation was associated with increased glycolysis and pentose phosphate activation. Specimens dominated by Streptococcus Pneumoniae exhibited high neutrophil degranulation. Increased activity of the LXR-RXR pathway was associated with better survival.
Pleural infection patients exhibit proteomic signatures indicating diverse responses of neutrophil mediated immunity, glycolysis, and pentose phosphate activation which were associated with microbiology. Therapeutic targeting the LXR-XRX pathway with agonists may improve survival.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 80
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Pleural infection endotypes 12 months Discovery of pleural infection biological endotypes
Association between endotypes and microbiology 12 months Investigate the association between pleural infection endotypes and microbiology
Association between endotypes and one-year survival 12 months Investigate the association between pleural infection endotypes and one-year survival
- Secondary Outcome Measures
Name Time Method Association between endotypes and need for surgical treatment 12 months Investigate the association between pleural infection endotypes and need for surgical treatment
Association between levels of pleural fluid plasminogen and neutrophil elastase 12 months Investigate the association between pleural fluid plasminogen and neutrophil elastase protein levels
Trial Locations
- Locations (1)
Laboratory of Pleural Translational Research, Nuffield Department of Medicine, University of Oxford
🇬🇧Oxford, Oxfordshire, United Kingdom