Abstract
Patients with pneumonia and parapneumonic effusion (PPE) have elevated mortality and a poor prognosis. The aim of this study was to discover novel biomarkers to help distinguish between uncomplicated PPE (UPPE) and complicated PPE (CPPE). Using an iTRAQ-based quantitative proteomics, we identified 766 proteins in pleural effusions from PPE patients. In total, 45 of these proteins were quantified as upregulated proteins in CPPE. Four novel upregulated candidates (BPI, NGAL, AZU1, and calprotectin) were selected and further verified using enzyme-linked immunosorbent assays (ELISAs) on 220 patients with pleural effusions due to different causes. The pleural fluid levels of BPI, NGAL, AZU1, and calprotectin were significantly elevated in patients with CPPE. Among these four biomarkers, BPI had the best diagnostic value for CPPE, with an AUC value of 0.966, a sensitivity of 97%, and a specificity of 91.4%. A logistic regression analysis demonstrated a strong association between BPI levels > 10 ng/ml and CPPE (odds ratio = 341.3). Furthermore, the combination of pleural fluid BPI levels with LDH levels improved the sensitivity and specificity to 100% and 91.4%, respectively. Thus, our findings provided a comprehensive effusion proteome data set for PPE biomarker discovery and revealed novel biomarkers for the diagnosis of CPPE.
Highlights
A parapneumonic effusion (PPE) is an accumulation of exudative pleural fluid that occurs in association with an ipsilateral pulmonary infection
The combination of pleural fluid bactericidal permeability-increasing protein (BPI) levels with lactate dehydrogenase (LDH) levels improved the sensitivity to 100% for identifying complicated PPE (CPPE)
We provided a comprehensive proteome profiling of uncomplicated PPE (UPPE) and CPPE fluid specimen samples
Summary
A parapneumonic effusion (PPE) is an accumulation of exudative pleural fluid that occurs in association with an ipsilateral pulmonary infection. When CPPE and empyema are present, pleural space drainage is mandatory[2]. For conditions such as patients with loculated pleural collection or poor clinical progress during treatment with antibiotics alone, drainage treatment will be required[3]. We aimed to investigate useful biomarkers for the differential diagnosis of UPPE and CPPE, with the goal of identifying specific proteins and pathways important for the molecular mechanisms of PPE progression. Using the comprehensive proteomics approach, we generated the PPE proteome data set for biomarker research and verified the levels of four novel proteins (BPI, NGAL, AZU1, and calprotectin) in PPE. We identified novel biomarkers for the diagnosis of CPPE
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