What is the cutoff of pleural fluid adenosine deaminase (ADA) at which pleural tuberculosis (TB) is diagnosed?

From the Guidelines

The cutoff value for pleural fluid adenosine deaminase (ADA) to diagnose pleural tuberculosis is generally 40 U/L (units per liter). When pleural fluid ADA levels exceed this threshold, it strongly suggests pleural TB, particularly in high-prevalence settings. This enzyme is released by activated T lymphocytes and macrophages during the immune response to mycobacterial antigens, making it a valuable biomarker for TB infection. The sensitivity and specificity of ADA at this cutoff are approximately 90-95% and 85-90%, respectively, as supported by a meta-analysis of 22 studies estimating the sensitivity and specificity of an elevated free IFN-γ level in pleural fluid are 89% and 97%, respectively 1. However, interpretation should consider the clinical context, as other conditions like empyema, lymphoma, and rheumatoid pleurisy can also elevate ADA levels. In low TB prevalence areas, a higher cutoff (50 U/L) may be used to increase specificity.

Key Points to Consider

• ADA testing is particularly valuable in resource-limited settings where more advanced diagnostic methods may be unavailable, offering a relatively quick and cost-effective diagnostic tool for pleural TB.
• The British Thoracic Society guideline for pleural disease recommends considering pleural fluid ADA and/or IFN-gamma tests for diagnosing tuberculous pleural effusion in high-prevalence populations 1.
• Tissue sampling for culture and sensitivity should be the preferred option for all patients with suspected tuberculous pleural effusion, as recommended by the British Thoracic Society guideline for pleural disease 1.
• It is essential to consider the clinical context and potential false-negative or false-positive results when interpreting ADA levels, as emphasized in the official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines 1.

From the Research

Cutoff Value for Pleural Fluid ADA in Diagnosing Pleural TB

• The cutoff value for diagnosing TB effusions was >55.8 U/L, with a sensitivity of 87.3% and specificity of 91.8% 2
• A pleural fluid ADA value <16.81 IU/L suggests that a tuberculous effusion is highly unlikely 2
• Other studies suggest a cutoff value of ≥40 IU/L for ADA in diagnosing TB pleurisy, with a specificity of 100% when combined with IFN-γ ≥ 75 pg/mL 3
• However, some cases of TB pleural effusion may show decreased ADA activity, and factors such as age, smoking status, and comorbid diseases can influence pleural ADA levels 4

Comparison of ADA Levels in Different Diseases

• Median ADA levels in patients with TB were 83.1 U/L, higher than those of patients with pleural infection, malignant pleural effusion, or autoimmune diseases 5
• Pleural fluid ADA levels of ≥40 U/L can be associated with other diseases, such as pleural infection, malignant pleural effusion, and nontuberculous mycobacteria 5
• A diagnostic flowchart for TB can be developed based on factors such as pleural fluid LDH, ADA/TP ratio, and neutrophil predominance or cell degeneration 5

Diagnostic Accuracy of ADA in Pleural TB

• The area under the ROC curve for ADA in diagnosing TB pleurisy was 0.933, indicating high diagnostic accuracy 2
• The combination of ADA ≥ 40 IU/L and IFN-γ ≥ 75 pg/mL yielded a specificity of 100% for TB pleurisy 3
• However, occult tuberculous pleurisy can occur in patients with pleural effusion ADA levels of 50 IU/L or less, highlighting the need for careful interpretation of ADA levels 6