The Biological Role of Pleural Fluid PAI-1 and Sonographic Septations in Pleural Infection: Analysis of a Prospectively Collected Clinical Outcome Study.
Bedawi EO., Kanellakis NI., Corcoran JP., Zhao Y., Hassan M., Asciak R., Mercer RM., Sundaralingam A., Addala DN., Miller RF., Dong T., Condliffe AM., Rahman NM.
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.