Total adenosine deaminase cases as an inflammatory biomarker of pleural effusion syndrome

Abstract

Background: Although inflammatory diseases commonly affect the pleura and pleural space, their mechanisms of action remain unclear. The presence of several mediators emphasizes the concept of pleural inflammation. Adenosine deaminase (ADA) is an inflammatory mediator detected at increased levels in the pleural fluid.

Aim: To determine the role of total pleural ADA (P-ADA) levels in the diagnosis of pleural inflammatory diseases.

Methods: 157 patients with inflammatory pleural effusion (exudates, n = 124, 79%) and non-inflammatory pleural effusion (transudates, n = 33, 21%) were included in this observational retrospective cohort study. The P-ADA assay was tested using a kinetic technique. The performance of the model was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). The ideal cutoff value for P-ADA in pleural inflammation was determined using the Youden index in the ROC curve.

Results: The transudates included congestive heart failure (n = 26), cirrhosis of the liver with ascites (n = 3), chronic renal failure (n = 3), and low total protein levels (n = 1). The exudate cases included tuberculosis (n = 44), adenocarcinoma (n = 37), simple parapneumonic effusions (n = 15), complicated parapneumonic effusions/empyema (n = 8), lymphoma (n = 7), and other diseases (n = 13). The optimal cutoff value of P-ADA was ≥ 9.00 U/L. The diagnostic parameters as sensitivity, specificity, positive and negative predictive values, positive and negative likelihood values, odds ratio, and accuracy were 77.69 (95%CI: 69.22-84.75); 68.75 (95%CI: 49.99-83.88); 90.38 and 44.90 (95%CI: 83.03-95.29; 30.67-59.77); 2.48 and 0.32 (95%CI: 2.21-11.2; 0.27-0.51); 7.65 (95%CI: 0.78-18.34), and 75.82 (95%CI: 68.24-82.37), respectively (χ² = 29.51, P = 0.00001). An AUC value of 0.8107 (95%CI: 0.7174-0.8754; P = 0.0000) was clinically useful. The Hosmer-Lemeshow test showed excellent discrimination.

Conclusion: P-ADA biomarker has high diagnostic performance for pleural inflammatory exudates.

Keywords: Adenosine deaminase; Biomarker; Exudate; Inflammation; Pleural effusion; transudate.

Figure 1

Nonparametric receiver operating characteristic curve of pleural adenosine deaminase for pleural inflammatory diseases. The selection criterion was the Youden index [J = 0.4644; distance to the receiver operating characteristic (ROC) curve corner = 0.3840]. The optimal cutoff value for ROC curve concavity was ≥ 9.00 U/L of pleural adenosine deaminase. Evaluation metric for checking the model’s performance: Area under the curve (AUC), 0.8107; 95%CI: 0.7174-0.8754; SE: 0.039; Z-value to test (AUC ≠ 0.5), 7.837; 2-Sided P-value, 0.0000.