Adenosine deaminase in pleural effusion: Bridging diagnosis and the pathophysiology of inflammation.

Abstract

This editorial underscores the importance of Maranhão et al's study, which investigates pleural adenosine deaminase (P-ADA) as a biomarker for inflammatory pleural effusions. Despite advances in imaging, distinguishing between inflammatory and non-inflammatory causes of pleural effusion remains a diagnostic challenge. The authors conducted a rigorous retrospective cohort analysis of 157 patients (124 with inflammatory exudates and 33 with non-inflammatory transudates), establishing a robust cutoff value of P-ADA ≥ 9.00 U/L for diagnosing inflammatory diseases using receiver operating characteristic curve analysis and internal statistical calibration. This is the first study to define a standardized P-ADA threshold in a Brazilian cohort, addressing previous inconsistencies in cutoff values. Furthermore, the authors delved into the pathophysiological mechanisms underlying elevated P-ADA, linking it to purinergic signaling pathways and immune cell activation, particularly emphasizing the role of ADA2 isoforms in macrophages and lymphocytes. Their findings support P-ADA as a non-invasive, cost-effective biomarker for early diagnosis, treatment stratification, and minimizing the need for invasive procedures such as thoracentesis. This has particular relevance in resource-limited settings, where streamlined diagnostics can reduce healthcare costs and improve patient outcomes. Future studies must prioritize global validation, explore the integration of adenosine deaminase with additional biomarkers (e.g., interleukin 6, C-reactive protein), and support the development of point-of-care technologies.