Understanding Parapneumonic Pleural Effusion
Parapneumonic pleural effusion (PPE) is a common complication in patients with community-acquired pneumonia (CAP). It occurs in about 10% to 60% of CAP cases. Prompt diagnosis is crucial to improve treatment outcomes and prevent potential complications like empyema. However, diagnosing PPE can be challenging, especially when pleural effusion is not immediately apparent. This article delves into the study comparing two biomarkers, C-reactive protein (CRP) and procalcitonin (PCT), for their diagnostic accuracy in identifying PPE.
The Role of Biomarkers
Among various pleural biomarkers, CRP and PCT are the most extensively studied. CRP, a non-specific inflammatory marker, and PCT, derived from calcitonin precursor, have both been evaluated for their diagnostic capabilities in PPE. However, the comparison between these two markers has not been comprehensively analyzed head-to-head. The current study aims to fill this gap and evaluate the diagnostic efficacy of CRP and PCT for PPE using a rigorous design.
Study Design and Participants
The study utilized participants from the SIMPLE trial, a prospective and pre-registered initiative. Patients were recruited from the Department of Respiratory and Critical Care Medicine in the Affiliated Hospital of Inner Mongolia Medical University from September 2018 to July 2021. The trial included patients over 18 with undiagnosed pleural effusion. Patients were excluded if they had known conditions like lung cancer or had developed effusion during the hospital stay.
Measurement of Pleural Fluid CRP and PCT
In December 2021, the researchers measured CRP and PCT levels in pleural fluid samples. PCT was measured using the Beckman DXI800, and CRP using the Beckman AU5800. Laboratory personnel were blinded to patient characteristics to avoid bias. High precision was achieved with coefficients of variation as low as 0.31% and 1.40% for CRP and PCT, respectively.
Statistical Analysis
The study employed a range of statistical tests to compare continuous and categorical variables. A logistic regression model was used to integrate CRP and PCT levels, and diagnostic accuracy was assessed using ROC curves. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were also calculated for each marker.
Results
Figure 1 illustrates the participant selection process. Out of 170 initially recruited, 153 were included in the final analysis, with 32 having PPE and 121 non-PPE cases.
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Figure 1 A flowchart of the participant selection process. Abbreviations: PPE, parapneumonic pleural effusion; MPE, malignant pleural effusion; TPE, tuberculous pleural effusion; HF, heart failure. |
The median CRP level in PPE patients was significantly higher than in non-PPE patients, 16.3 mg/L compared to 4.9 mg/L (p < 0.001, Mann–Whitney U-test). In contrast, median PCT levels were not statistically different between groups, 0.10 ng/mL for PPE and 0.08 ng/mL for non-PPE (p = 0.185, Mann–Whitney U-test). Notably, a positive correlation was found between CRP and PCT levels in pleural fluid.
Diagnostic Accuracy
Figure 3 presents ROC curves for CRP and PCT in diagnosing PPE. The area under the curve (AUC) for CRP was 0.73 (95% CI: 0.63–0.83), indicating moderate diagnostic accuracy. The sensitivity and specificity were 0.71 (95% CI: 0.55–0.87) and 0.68 (95% CI: 0.59–0.77), respectively, at a threshold of 10 mg/L. In contrast, the AUC for PCT was 0.58 (95% CI: 0.46–0.69), with sensitivity and specificity of 0.50 (95% CI: 0.33–0.67) and 0.65 (95% CI: 0.56–0.74) at a threshold of 0.1 ng/mL. A logistic regression model combining CRP and PCT had an AUC of 0.73, similar to CRP alone. Decision curve analysis indicated better net benefit for CRP than PCT.
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Figure 3 Receiver operating characteristic curves of CRP and PCT for parapneumonic pleural effusion. Abbreviations: CRP, C-reactive protein; PCT, procalcitonin; AUC, the area under the curve; CI, confidence interval. |
Interpreting Results
The findings suggest that CRP outperforms PCT in diagnosing PPE. CRP has moderate diagnostic accuracy with an AUC of 0.73, while PCT’s AUC is only 0.58. The combination of CRP and PCT did not significantly enhance diagnostic performance over CRP alone. At a threshold of 10 mg/L, CRP has a PLR of 2.24 and an NLR of 0.42, indicating that while it is neither perfect in ruling in nor ruling out PPE, it has utility when combined with clinical findings.
Implications for Practice
The study highlights the utility of CRP as a diagnostic biomarker for PPE, with limited role for PCT. The moderate diagnostic accuracy of CRP suggests it is valuable but not definitive in diagnosing PPE. Clinicians should use CRP in conjunction with a comprehensive clinical evaluation. The results also indicate that measuring both CRP and PCT together is not beneficial and may increase unnecessary testing.
Conclusion
In conclusion, pleural fluid CRP has moderate diagnostic utility for identifying PPE, while PCT offers limited benefit. The study supports using CRP as the biomarker of choice for diagnosing PPE and suggests that combining CRP and PCT does not improve diagnostic performance. This information is crucial for optimizing treatment strategies in patients with pneumonia and undiagnosed pleural effusion, enhancing patient outcomes.
Ethics Approval and Consent
This study was approved by the Ethics Committee of Inner Mongolia Medical University Hospital (No. 2018011). All participants provided informed consent. Patient details were de-identified in accordance with the Declaration of Helsinki.
Funding
The research was funded by the Scientific Project of Inner Mongolia Healthcare Committee (202201340). The funder had no role in study design, data analysis, or paper preparation.
Disclosure
The authors declare no conflicts of interest.
Figures
Figure 2 shows the comparison of pleural fluid CRP and PCT levels between PPE and non-PPE patients.
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Figure 2 Comparison of pleural fluid CRP (A) and PCT (B) levels between PPE and non-PPE. Data were log-transformed. Abbreviations: CRP, C-reactive protein; PCT, procalcitonin; PPE, parapneumonic pleural effusion. |
Figure 4 presents decision curves for CRP and PCT.
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Figure 4 Decision curves of CRP and PCT for parapneumonic pleural effusion. |
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