Introduction Numerous studies have assessed the diagnostic ability of pleural adenosine deaminase (ADA) in detecting tuberculous pleural effusions, with good specificity and sensitivity reported. However, in the UK (UK) ADA is not routinely used in the investigation of a patient with a pleural effusion, mainly due to a lack of evidence as to its utility in areas where tuberculosis (TB) incidence is low.
Methods Patients presenting with an undiagnosed pleural effusion to a tertiary pleural centre in South-West England over a 3 year period, were prospectively recruited to a pleural biomarker study, in which baseline pleural fluid samples were collected and stored. Samples from consecutive patients with robust 12-month follow up data and confirmed diagnoses were sent for ADA analysis.
Results Of 338 patients enrolled, 7 had confirmed tuberculous pleural effusion (2%). All 7 TB effusions were lymphocyte predominant with a median ADA of 72.0 IU/L (range- 26.7 to 91.5) compared to a population median of 12.0 IU/L (range- 0.3 to 568.4). Using the established cut off of 35 IU/L, ADA was shown to have a negative predictive value (NPV) of 99.7% (95% CI; 98.2–99.9%) for the exclusion of TB, and sensitivity of 85.7% (95% CI; 42.2–97.6%) with an area under the curve of 0.88 (95% CI; 0.732–1.000). In the context of a lymphocytic effusion an ADA over 35 IU/L had a sensitivity and positive predictive value of 85.7% (95% CI; 42.2–97.6%), see figure. Bacterial pleural infection was the main alternative cause of raised ADA in our cohort.
Discussion This is the first study examining the diagnostic utility of pleural fluid ADA in a low TB incidence area. The chance of an effusion with an ADA under 35 IU/L being of tuberculous aetiology was negligible and empirical anti-TB therapy could be avoided in such cases. A pleural ADA of over 35 IU/L in lymphocyte-predominant pleural fluid gives a strong suspicion of tuberculous aetiology. In patients who are unsuitable for more invasive procedures this could be used as an indication to start therapy.