Background: Exudative pleural effusion is a common clinical condition with diverse etiology, predominantly tuberculosis, malignancy, and parapneumonic infections. Differentiating these causes using routine pleural fluid analysis alone remains challenging. Pleural fluid adenosine deaminase (ADA) and serum C-reactive protein (CRP) are individually recognized biomarkers, but their combined ratio may offer superior diagnostic discrimination.

Objective: To assess the role of pleural fluid ADA to serum CRP (ADA/CRP) ratio in determining the etiological cause of exudative pleural effusion.

Methods: An observational cross-sectional study was conducted on 51 patients with confirmed exudative pleural effusion in the Department of Respiratory Medicine, National Institute of Medical Sciences and Research, Jaipur, over 18 months. Pleural fluid was analyzed for biochemical parameters, cytology, and ADA using a standard enzymatic colorimetric assay. Serum CRP was estimated using immunoturbidimetric method. The ADA/CRP ratio was calculated and compared among tubercular (TPE), malignant (MPE), and empyema/parapneumonic (PPE) groups using one-way ANOVA and post-hoc testing. Statistical analysis was performed with SPSS version 25.

Results: Among 51 patients (mean age 53.39 ± 17.26 years; 62.7% male), tubercular pleural effusion was the most common etiology (47.1%, n = 24), followed by empyema/parapneumonic effusion (31.4%, n = 16) and malignant pleural effusion (21.6%, n = 11). Mean pleural fluid ADA was highest in TPE (110.03 ± 21.15 U/L), intermediate in PPE (53.48 ± 25.20 U/L), and lowest in MPE (19.82 ± 6.29 U/L). Mean serum CRP was highest in PPE (109.17 ± 17.45 mg/L), reflecting acute bacterial inflammation. The ADA/CRP ratio showed the most significant discrimination: 1.97 ± 0.53 (TPE), 0.49 ± 0.23 (PPE), and 0.32 ± 0.08 (MPE) (p < 0.001). All malignant effusions had ADA/CRP ratio < 0.8, and most tubercular effusions had ratios > 1.5, forming a clear diagnostic gradient. Pleural fluid biochemical parameters — LDH, polymorphs, lymphocytes, total cell count, and glucose — differed significantly across groups (p < 0.001).

Conclusion: The pleural fluid ADA/serum CRP ratio is a simple, cost-effective, and reliable biomarker for differentiating tubercular from malignant and parapneumonic exudative pleural effusions. Its strong discriminatory gradient makes it a practical adjunct in clinical settings, particularly where invasive procedures or advanced diagnostics are not readily accessible.

KEYWORDS: Pleural Effusion, Adenosine Deaminase, C-reactive Protein, ADA/CRP Ratio, Tuberculosis, Exudative Effusion, Biomarker Diagnosis.