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The Biological Role of Pleural Fluid PAI-1 and Sonographic Septations in Pleural Infection: Analysis of a Prospectively Collected Clinical Outcome Study

Bedawi, Eihab O; Kanellakis, Nikolaos I; Corcoran, John P; Zhao, Yu; Hassan, Maged; Asciak, Rachelle; Mercer, Rachel M; ... Rahman, Najib M; + view all (2023) The Biological Role of Pleural Fluid PAI-1 and Sonographic Septations in Pleural Infection: Analysis of a Prospectively Collected Clinical Outcome Study. American Journal of Respiratory and Critical Care Medicine , 207 (6) pp. 731-739. 10.1164/rccm.202206-1084OC. Green open access

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Abstract

RATIONALE: Sonographic septations are assumed to be important clinical predictors of outcome in pleural infection but the evidence for this is sparse. The inflammatory and fibrinolysis-associated intrapleural pathway(s) leading to septation formation have not been studied in a large cohort of pleural fluid (PF) samples with confirmed pleural infection, matched with ultrasound and clinical outcome data. OBJECTIVES: To assess the presence and severity of septations against baseline PF Plasminogen-Activator Inhibitor-1 (PAI-1) and other inflammatory and fibrinolysis-associated proteins as well as to correlate these with clinically important outcomes. METHODS: We analysed 214 pleural fluid samples from the PILOT study, a prospective observational pleural infection study, for inflammatory and fibrinolysis-associated proteins using the Luminex platform. Multivariate regression analyses were utilised to assess association of pleural biological markers with septation presence and severity (on ultrasound), and clinical outcomes. RESULTS: PF PAI-1 level was the only protein independently associated with septation presence (p=<0.001) and septation severity (p=0.003). PF PAI-1 levels were associated with increased length of stay (LOS) (p=0.048) and increased 12-month mortality (p=0.003). Sonographic septations alone had no relation to clinical outcomes. CONCLUSIONS: In a large and well characterised cohort, this is the first study to associate pleural biological parameters with a validated sonographic septation outcome in pleural infection. PF PAI-1 is the first biomarker to demonstrate an independent association with mortality. While PF PAI-1 plays an integral role in driving septation formation, septations themselves are not associated with clinically important outcomes. These novel findings now require prospective validation.

Type: Article
Title: The Biological Role of Pleural Fluid PAI-1 and Sonographic Septations in Pleural Infection: Analysis of a Prospectively Collected Clinical Outcome Study
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1164/rccm.202206-1084OC
Publisher version: https://doi.org/10.1164/rccm.202206-1084OC
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: empyema, fibrinolysis, pleural infection, septations
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10156829
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