Diagnostic utility of pleural fluid adenosine deaminase in tuberculous pleural effusion in patients with exudative effusion: a retrospective multicenter study (ADATPE)

Background: Tuberculous pleural effusion (TPE) remains a diagnostic challenge, particularly in tuberculosis-endemic regions. Pleural fluid adenosine deaminase (pfADA) is widely used as a diagnostic biomarker; however, its optimal cutoff value may vary depending on the epidemiological context. This study aimed to optimise the diagnostic performance of pfADA by determining a new local cutoff, evaluating the conventional threshold (≥40 U/L), and assessing the diagnostic value of the pleural fluid lactate dehydrogenase (LDH)/ADA ratio. Methods: The ADATPE study was a retrospective, observational, multicenter analysis involving 276 patients with exudative pleural effusion from three tertiary Malaysian hospitals. Patients were categorized into definite, clinical, and non-TPE groups based on microbiological, histopathological, and clinical criteria. Receiver operating characteristic curve analysis and the Youden Index were used to identify an optimal local pfADA threshold. Results: PfADA demonstrated excellent diagnostic accuracy with an area under the receiver operating characteristic curve (AUC) of 0.852. A new local cutoff of ≥36 U/L improved sensitivity to 82.9% while maintaining specificity at 80.6%, outperforming the conventional threshold of ≥40 U/L. The combination of ADA ≥36 U/L and LDH/ADA ratio ≤16 yielded the highest diagnostic specificity (90.78%), positive predictive value (69.84%), and overall accuracy (83.70%). Conclusions: A revised pfADA cutoff of ≥36 U/L enhances diagnostic accuracy for TPE in Malaysian patients. PfADA remains a valuable diagnostic tool, but it should be interpreted in conjunction with other clinical and laboratory parameters. The LDH/ADA ratio is a valuable adjunct, particularly in cases that are borderline or inconclusive.