ADA Levels in Pleural Fluid for Tuberculous Etiology
For pleural tuberculosis, use an ADA cutoff of 40 U/L or higher, which provides excellent sensitivity (87-100%) and specificity (89-100%) for diagnosis in the appropriate clinical context. 1, 2, 3
Recommended Diagnostic Thresholds
The optimal ADA cutoff depends on your clinical priorities:
ADA ≥40 U/L: This is the most widely validated threshold with sensitivity of 87-100% and specificity of 89-100% 4, 3, 5. The American Thoracic Society/Infectious Diseases Society of America/CDC guidelines support measuring ADA in suspected pleural TB, though they note it provides supportive rather than definitive evidence 1.
ADA >55.8 U/L: Provides slightly higher specificity (91.8%) with sensitivity of 87.3%, positive predictive value of 82.1%, and negative predictive value of 94.4% 4.
ADA <16.81 U/L: Essentially rules out tuberculous effusion with 100% sensitivity and 100% negative predictive value 4.
Maximizing Diagnostic Accuracy
Combine ADA with interferon-gamma for highest specificity:
The combination of ADA ≥40 IU/L AND IFN-γ ≥75 pg/mL yields 100% specificity for tuberculous pleurisy in lymphocyte-predominant effusions 3.
IFN-γ alone has 89% sensitivity and 97% specificity, with some studies showing 100% sensitivity and specificity when properly thresholded 1, 6.
Critical Clinical Context
ADA must be interpreted within the complete clinical picture 1, 2:
- Confirm lymphocyte-predominant exudate on cell count and chemistry 2
- ADA may be falsely elevated in empyema, parapneumonic effusions, and rheumatoid pleurisy 2
- ADA may be falsely low in HIV-positive patients with TB 2
- Local TB prevalence significantly affects predictive values 2
Tissue Diagnosis Remains Gold Standard
Pleural biopsy should be pursued for definitive diagnosis 2:
- Histological examination has 69-97% sensitivity, far superior to pleural fluid culture 2
- Send tissue for both histology (looking for granulomas) and mycobacterial culture with drug susceptibility testing 2
- Image-guided or thoracoscopic biopsy is preferred 2
Common Pitfalls to Avoid
- Do not rely on ADA alone - it provides supportive evidence requiring clinical correlation 1
- Do not use ADA in non-lymphocytic effusions - the test characteristics apply specifically to lymphocyte-predominant exudates 3
- Do not delay treatment while awaiting culture results if clinical suspicion is high and ADA is elevated, as AFB smear has only 0-10% sensitivity in pleural fluid 1