Date Published: January 7, 2013
Publisher: Public Library of Science
Author(s): Chi-Li Chung, Shih-Hsin Hsiao, George Hsiao, Joen-Rong Sheu, Wei-Lin Chen, Shi-Chuan Chang, T. Mark Doherty. http://doi.org/10.1371/journal.pone.0053169
To investigate the relationship among angiogenic cytokines, fibrinolytic activity and effusion size in parapneumonic effusion (PPE) and their clinical importance.
From 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.
The 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. In 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.
Formation of parapneumonic effusion (PPE) involves increased vascular permeability of the pleura induced by the contiguous pneumonia. Exposure of pleural mesothelial cells to bacteria or lipopolysaccharide may increase release of angiogenic factors, including vascular endothelial growth factor (VEGF) and interleukin (IL)-8, induce vascular hyperpermeability and pleural fluid production, activate coagulation cascade, and repress fibrinolytic activity within the pleural cavity , , leading to the development of a “fibrinopurulent” or “complicated” PPE (CPPE) .
Our results demonstrated that effusion size reflected by radiological scores and effusion levels of 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-loculated 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, and VEGF, but not IL-8, had significant positive correlation with effusion size in all patients and in both UPPE and CPPE groups. Patients with higher effusion VEGF level or greater effusion size were prone to have medical treatment failure. Ten patients with RPT had larger effusion size and higher levels of VEGF and PAI-1/tPA ratio than did those without. To our knowledge, this is the first study to demonstrate that effusion angiogenic cytokines correlated significantly with pleural fibrinolytic activity, and that the elevated VEGF level or effusion size was associated with poor outcome in PPE.