Significance of Lysozyme as a Biomarker in Differentiating Tubercular Pleural Effusions From Non-tubercular Effusions

Pleural effusion, defined as the abnormal buildup of fluid within the pleural cavity, arises from a wide range of causes. In countries with a high tuberculosis (TB) burden, such as India, tubercular pleural effusion (TPE) is particularly common. Adenosine deaminase (ADA) is widely used in TB-endemic regions due to its low cost and high diagnostic accuracy, although its specificity may be reduced in certain conditions, such as empyema, lymphoma, and rheumatoid pleuritis. Molecular diagnostic tools such as polymerase chain reaction (PCR) and cartridge-based nucleic acid amplification tests (CBNAAT) are increasingly accessible through national tuberculosis programs and offer improved specificity; however, their sensitivity may be limited in paucibacillary pleural disease. Therefore, there remains a need for additional adjunctive biomarkers to improve diagnostic accuracy, particularly in borderline or inconclusive cases. Recent studies continue to highlight the diagnostic challenges of tubercular pleural effusion, particularly in differentiating it from malignant and parapneumonic effusions, emphasizing the need for additional biomarkers to improve diagnostic accuracy. Pleural fluid lysozyme was evaluated as a diagnostic biomarker to differentiate tubercular from non-tubercular pleural effusions. This study evaluated pleural fluid lysozyme as a diagnostic indicator for TPE and compared its performance with ADA. A case-control study was carried out over 18 months, enrolling 50 patients (25 with TPE and 25 with non-TPE). Pleural fluid samples were analyzed for ADA and lysozyme using an enzyme-linked immunosorbent assay (ELISA)-based method. Data were statistically assessed for sensitivity, specificity, and diagnostic accuracy using receiver operating characteristic (ROC) curve analysis. The mean pleural fluid lysozyme level was 7714.21 ± 1793.17 ng/mL in the TPE group and 9285.37 ± 3403.90 ng/mL in the non-TPE group (p = 0.038). Despite higher absolute values in the non-TPE group, ROC curve analysis demonstrated good diagnostic performance of lysozyme in differentiating TPE. When used in combination with ADA, lysozyme appeared to improve diagnostic accuracy. ADA levels were markedly elevated in the TPE group (mean: 84.95 U/L versus 21.45 U/L). ROC analysis suggested good diagnostic performance of lysozyme, which further improved when used in combination with ADA. Pleural fluid lysozyme may serve as a useful adjunct biomarker in differentiating tubercular from non-tubercular pleural effusions. Its diagnostic utility is enhanced when used alongside ADA, making it particularly valuable in settings with limited resources. Larger studies are warranted to confirm these findings and define standardized diagnostic thresholds.