Pleural fluid cell-free DNA in parapneumonic pleural effusion

Abstract

Objectives: To measure the accuracy of pleural fluid cell-free DNA (cfDNA) concentration for diagnosis of parapneumonic pleural effusions (PPE).

Design and methods: We studied pleural fluids obtained by thoracocentesis in patients with pleural effusion. DNA was automatically extracted from pleural fluid using the MagNa Pure Compact instrument (Roche Diagnostics), and was measured by a real-time quantitative PCR assay for the β-globin gene using a Light-Cycler 480 Real-Time PCR instrument (Roche Diagnostics). Patients were classified into two groups according to the etiology of pleural effusion: PPE and NOT PPE. The diagnostic accuracy was determined using receiver operating characteristic (ROC) techniques by analyzing the area under the ROC curve (AUC).

Results: We studied 78 patients with ages between 1 and 86 years old (median=64). Sixteen patients were PPE and 62 were NOT PPE (24 transudative, 30 malignant and 8 other etiology). Pleural fluid cfDNA concentration was higher in patients with PPE (median=46,240 ng/mL) than in those with NOT PPE (median=224 ng/mL). The AUC value was 0.907 (p<0.0001) and the optimal cut-off value was 6740 ng/mL exhibiting 87.5% sensitivity and 80.6% specificity. Also, there were significant differences between transudative and exudative effusions according to pleural fluid cfDNA concentration (p<0.0001). The AUC value was 0.994 and the optimal cut-off value was 162ng/mL exhibiting 100% sensitivity and 96.3% specificity.

Conclusions: Pleural fluid cfDNA concentration showed high accuracy for diagnosis of PPE and to discriminate between transudative and exudative effusions.

Keywords: Cell-free DNA; Parapneumonic effusion; Pleural effusion; Pleural fluid; Pneumonia.