From the Guidelines
Adenosine deaminase (ADA) levels in pleural fluid are a valuable diagnostic tool for tuberculous pleural effusion, with levels above 40 U/L strongly suggesting tuberculosis, as evidenced by a meta-analysis of studies estimating a sensitivity of 88% and specificity of 83% for an elevated ADA level in pleural fluid 1. The optimal cutoff value ranges between 40-60 U/L, providing a sensitivity of approximately 90% and specificity of 85-95% 1. This enzyme is released by activated T lymphocytes and macrophages during the cell-mediated immune response against Mycobacterium tuberculosis. ADA testing is particularly useful in resource-limited settings where more sophisticated tests may be unavailable. However, elevated ADA levels can also occur in empyema, lymphoma, and rheumatoid arthritis, so results should be interpreted alongside clinical presentation, radiological findings, and other laboratory tests. Some key points to consider when interpreting ADA levels in pleural fluid include:
- The American Thoracic Society recommends measuring ADA levels in fluid collected from patients with suspected pleural TB, as it provides supportive evidence for diagnosis 1.
- A meta-analysis of 22 studies estimated that the sensitivity and specificity of an elevated free IFN-γ level in pleural fluid are 89% and 97%, respectively, but the test characteristics of free IFN-γ levels have not been as extensively studied as ADA levels 1.
- When TB is confirmed, standard treatment includes a four-drug regimen of isoniazid, rifampin, ethambutol, and pyrazinamide for two months, followed by isoniazid and rifampin for an additional four months.
- In patients with pleural TB, corticosteroids may sometimes be added to reduce inflammation and prevent pleural thickening, though this remains controversial. It is essential to note that neither ADA nor IFN-γ levels provide a definitive diagnosis of extrapulmonary TB disease, and results must be interpreted in the entire clinical context, considering the potential consequences of false-negative and false-positive results 1.
From the Research
Significance of Adenosine Deaminase (ADA) Levels in Pleural Fluid
- ADA levels in pleural fluid are a useful marker for diagnosing tuberculous pleurisy, with high levels arguing strongly for TB in areas with high TB prevalence 2
- A pleural fluid ADA level greater than 40 U/l has a high positive predictive value for TB, while low levels have a high negative predictive value in low-prevalence countries 2
- The specificity of ADA increases if only lymphocytic exudates are considered, and a cutoff value of >55.8 U/L has been suggested for diagnosing TB effusions with a sensitivity of 87.3% and specificity of 91.8% 3
Diagnostic Accuracy and Validation
- A diagnostic flowchart incorporating pleural fluid ADA levels, lactate dehydrogenase, and total protein ratio has been validated for diagnosing tuberculous pleurisy, with a diagnostic accuracy rate of 77.7% and sensitivity of 86.2% 4
- The flowchart has been revised to enhance its utility, and its effectiveness has been confirmed in settings with a low incidence of tuberculosis 4
Factors Influencing ADA Levels
- Older age and current smoking have been identified as predictive factors for low ADA levels in patients with TB pleurisy, and physicians should be cautious when interpreting ADA levels in these patients 5
- A history of tuberculosis and hypertension have also been found to be more common in patients with low ADA levels 5
Clinical Implications
- Pleural fluid ADA levels should be interpreted in conjunction with other clinical and laboratory findings, such as lymphocyte predominance and parenchymal involvement on chest imaging 6
- In areas with high TB prevalence, a lymphocyte-predominant exudate with a high ADA level has a positive predictive value of 98% for TB, while in low-prevalence areas, the absence of an elevated ADA and lymphocyte predominance makes TB unlikely 6