An observational study in Pleural Infection, Pleural Diseases and Pleural Effusion, sponsored by University of Oxford. Completed at 1 site in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-07-22.
Sponsored by University of Oxford · Observational
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.
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.
51 studies on the registry are indexed under Pleural Diseases; 12 are open to participants now.
This study's enrollment of 80 is below the median of 200 across 17 observational studies indexed under Pleural Diseases.
Browse Pleural Diseases studies →University of Oxford is the lead sponsor of 812 studies on the registry; 119 are open to participants now.
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Patients with evidence of pleural infection
Samples collected for the PILOT clinical trial (DOI: 10.1183/13993003.00130-2020) used for the TORPIDS-2 study.
Patients were included if they had a clinical presentation consistent with pleural infection and any of the following criteria: 1. pleural fluid that was macroscopically purulent; or 2. pleural fluid that was positive on culture for bacterial infection; or 3. pleural fluid that demonstrated bacteria on Gram staining; or 4. pleural fluid with a pH ≤7.2 (measured by blood gas analyser) or low glucose level (≤3 mmol·L-1 or ≤55 mg·dL-1) in a patient with clinical evidence of infection; or 5. contrast-enhanced computed tomography (CT) evidence of pleural infection (consolidation of underlying lung with enhancing pleural collection) in a patient with clinical evidence of infection, alongside exclusion of other sources of infection. Evidence of infection was assessed by the recruiting physician on the basis of fever, an elevated peripheral blood white-cell count, or elevated serum inflammatory markers such as C-reactive protein (CRP). Study exclusion criteria were as follows: 1. age \<18 years; 2. no pleural fluid available for analysis; 3. previous pneumonectomy on the side of pleural infection; and 4. expected survival of \<3 months due to co-morbid disease, as judged by the recruiting physician.
All samples were collect at patient enrolment for the PILOT study (PMID: 32675200, ISRCTN 50236700)
Pleural infection endotypes
Discovery of pleural infection biological endotypes
Time frame: 12 months
Association between endotypes and microbiology
Investigate the association between pleural infection endotypes and microbiology
Time frame: 12 months
Association between endotypes and one-year survival
Investigate the association between pleural infection endotypes and one-year survival
Time frame: 12 months
Association between endotypes and need for surgical treatment
Investigate the association between pleural infection endotypes and need for surgical treatment
Time frame: 12 months
Association between levels of pleural fluid plasminogen and neutrophil elastase
Investigate the association between pleural fluid plasminogen and neutrophil elastase protein levels
Time frame: 12 months
Plan to share: Yes — Anonymised and non-identifiable data could be shared with other researchers. The mass spectrometry data are deposited in PRIDE to share with other researchers.
Supporting information: Study protocol, Informed consent form
Ran from Jun 2021 to primary completion in Jun 2023, 24 months.
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