Elevated Pleural Fluid IL-9 as a Diagnostic Biomarker for Differentiating Tuberculous from Lung...

The differential diagnosis of tuberculous pleural effusion (TPE) and lung adenocarcinoma-associated malignant pleural effusion (LA-MPE) remains challenging. This study aimed to measure interleukin‑9 (IL‑9) levels in pleural fluid and evaluate its diagnostic utility in distinguishing between these two conditions.

The study enrolled 105 patients with PE (51 TPE and 54 LA-MPE). IL-9 levels in pleural fluid were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was employed to identify the optimal cutoff value and assess diagnostic performance, including area under the curve (AUC), sensitivity, and specificity, with adenosine deaminase (ADA) and carcinoembryonic antigen (CEA) as comparators. Internal cross-validation was conducted to examine model robustness, and decision curve analysis was used to evaluate the clinical net benefit of IL-9 alone and in combination with ADA and CEA.

IL-9 levels were significantly elevated in TPE compared with LA-MPE (2828.13 vs. 310.55 ng/L, P < 0.001). At a cutoff of 748.47 ng/L, IL-9 distinguished TPE from LA-MPE with a sensitivity of 98.0% and specificity of 92.59%, and an AUC of 0.987 (P < 0.001), exceeding both ADA and CEA. Decision curve analysis showed that, within a threshold probability range of 0.10-0.40, the IL‑9‑based model consistently yielded greater net clinical benefit than conventional markers. Cross-validation further confirmed the robustness of IL-9 for distinguishing TPE from LA-MPE.

IL-9 demonstrates promising diagnostic performance in differentiating TPE from LA-MPE, with favorable accuracy relative to ADA. It merits further investigation as a potential adjunctive diagnostic tool for pleural effusion.