Clinical Importance of Angiogenic Cytokines, Fibrinolytic Activity and Effusion Size in Parapneumonic Effusions

Chi-Li Chung,George Hsiao,Shih-Hsin Hsiao,Shi-Chuan Chang,Joen-Rong Sheu,Wei-Lin Chen,T. Mark Doherty

doi:10.1371/journal.pone.0053169

Abstract

ObjectiveTo investigate the relationship among angiogenic cytokines, fibrinolytic activity and effusion size in parapneumonic effusion (PPE) and their clinical importance.MethodsFrom January 2008 through December 2010, 26 uncomplicated (UPPE) and 38 complicated (CPPE) PPE were studied. Based on chest ultrasonography, there were non-loculated in 30, uni-loculated in 12, and multi-loculated effusions in 22 patients. The effusion size radiological scores, and effusion vascular endothelial growth factor (VEGF), interleukin (IL)-8, plasminogen activator inhibitor type-1 (PAI-1) and tissue type plasminogen activator (tPA) were measured on admission. Treatment outcome and pleural fibrosis, defined as radiological residual pleural thickening (RPT), were assessed at 6-month follow-up.ResultsThe effusion size and effusion VEGF, IL-8 and PAI-1/tPA ratio were significantly higher in CPPE than in UPPE, and significantly higher in multi-loculated PPE than in non-locualted and uni-loculated PPE, respectively. VEGF (cutoff value 1975 pg/ml) and IL-8 (cutoff value 1937 pg/ml) seemed best to discriminate between UPPE and CPPE. VEGF, IL-8 and effusion size correlated positively with PAI-1/tPA ratio in both UPPE and CPPE. Moreover, the level of VEGF, but not IL-8, correlated positively with effusion size in all patients (r = 0.79, p<0.001) and in UPPE (r = 0.64, p<0.001) and CPPE (r = 0.71, p<0.001) groups. The patients with higher VEGF or greater effusion were prone to have medical treatment failure (n = 10; VEGF, odds ratio 1.01, p = 0.02; effusion size, odds ratio 1.26, p = 0.01). Additionally, ten patients with RPT had larger effusion size and higher levels of VEGF and PAI-1/tPA ratio than did those without.ConclusionsIn PPE, VEGF and IL-8 levels are valuable to identify CPPE, and higher VEGF level or larger effusion is associated with decreased fibrinolytic activity, development of pleural loculation and fibrosis, and higher risk of medical treatment failure.

Highlights

Formation of parapneumonic effusion (PPE) involves increased vascular permeability of the pleura induced by the contiguous pneumonia
Fibrin turnover in the pleural cavity is affected by fibrinolytic activity mediated by plasmin, which is regulated by the equilibrium between plasminogen activators (PAs) and plasminogen activator inhibitors (PAIs) [6]
Our results demonstrated that effusion size reflected by radiological scores and effusion levels of vascular endothelial growth factor (VEGF), IL-8 and plasminogen activator inhibitor type-1 (PAI-1)/type plasminogen activator (tPA) ratio were significantly higher in complicated’’ PPE (CPPE) than in uncomplicated PPE (UPPE), and significantly higher in multi-loculated PPE than in non-loculated and uniloculated PPE, respectively

Summary

Introduction

Formation of parapneumonic effusion (PPE) involves increased vascular permeability of the pleura induced by the contiguous pneumonia. Previous studies reported that VEGF might play a role in the modulation of tPA and PAI-1 [9], and that anti-VEGF antibody could attenuate pleurodesis and reduced fluid volume of inflammatory pleural effusion in experimental models [10,11,12]. These findings suggest that VEGF may be involved in the regulation of fibrin turnover and fluid loculation in the pleural cavity and subsequent residual pleural thickening (RPT) or fibrosis [8]. The aim of the present study was to evaluate the relationship among angiogenic cytokines (VEGF, IL-8), fibrinolytic parameters (tPA and PAI-1) and effusion size in PPE, and their clinical importance

Methods

Results

Conclusion