Role of pleural fluid biomarkers-ADA, ADA2 & interferon gamma in the diagnosis of tuberculous pleural effusion

OBJECTIVES: To study the role of pleural fluid biomarkers- ADA, ADA2 and Interferon gamma alone and in combination for the diagnosis of tuberculous pleural effusion. METHODS: 154 patients, between May 2012 and July 2013 with exudative pleural effusion were included in the study after informed consent. All patients underwent pleural fluid aspiration and closed pleural biopsy and these samples were sent for analysis. The pleural fluid was analyzed for biomarkers in addition to routine tests. The frequencies and percentages are calculated for the detection of biomarkers and the sensitivity, specificity; positive predictive, negative predictive values were calculated and an ROC analysis was performed. The area under the curve and cutoff values for biomarkers were calculated. RESULTS: Among the 154 patients, 68 patients had tuberculosis. The mean age of the patients was 44.8 years with a male predominance (74%) and 94% were unilateral effusions. Tuberculous effusion was commonly seen in age group less than 40 years with male predominance and 80% of the patients had lymphocytic effusion. Also those with TB had higher protein levels (mean=5.4mg/dl). The yield of mycobacterial cultures was low and pleural biopsy culture had a better yield than pleural fluid culture. ADA had a sensitivity of 70.1% with a specificity of 71.1%. ADA2 had a better sensitivity than ADA but lacks specificity. Interferon gamma had a better specificity and specificity than ADA and ADA2. The sensitivity was 80% and specificity was 87%. The combination of biomarkers improved the sensitivity but failed to improve the specificity. A combination of ADA > 40U/L with Interferon gamma >3.12IU/L in pleural fluid improves the diagnostic yield in tuberculous pleural effusion but may not replace the gold standard, culture and histopathology. CONCLUSION: Tuberculous pleural effusion is one of the common causes for pleural effusion with a diagnostic challenge. The pleural fluid biomarkers, combination of tests and scoring system have an important role in diagnosing TB effusion but are not sufficient to replace the conventional gold standard methods for diagnosis.