Pleural fluid cytokines in malignant pleural effusion: associations with lung expandability and prediction of pleurodesis outcome

Background/Aims: Lung expandability is a key determinant of successful pleurodesis in malignant pleural effusion (MPE). Although pleural elastance is widely used to assess expandability, pleurodesis may still fail in some patients with low elastance. This study investigated pleural fluid cytokines as potential biomarkers for lung expandability and pleurodesis outcome in MPE.Methods: Sixty-eight patients with MPE were prospectively enrolled and categorized into expandable lung (n = 34; pleural elastance ≤ 14.5 cmH2O/L or pleural apposition ≥ 75%) and non-expandable lung (n = 34; pleural elastance > 14.5 cmH2O/L and pleural apposition < 75%) groups. Pleural fluid concentrations of 28 cytokines, including transforming growth factor-β1 (TGF-β1), were measured using multiplex immunoassays and compared between groups. Among patients with expandable lungs, pleurodesis outcomes were recorded, and the discriminative performance of cytokines was evaluated.Results: Cytokine levels, including TGF-β1, did not differ significantly between expandable and non-expandable lungs, and no significant correlations were observed between pleural elastance and cytokine concentrations. Among the 28 patients undergoing pleurodesis, those with pleurodesis failure (25%) had significantly higher TGF-β1 levels than those with successful pleurodesis (median [interquartile range]: 5,779.83 [3,924.54–9,705.53] pg/mL vs. 2,598.93 [1,425.35–3,294.35] pg/mL; p = 0.0016). TGF-β1 demonstrated good discriminative performance for predicting pleurodesis outcome (area under the curve 0.884).Conclusions: Pleural fluid TGF-β1 does not reflect lung expandability in MPE but is associated with pleurodesis outcome in patients with expandable lungs. These findings suggest a potential role for biological factors beyond mechanical assessment, although further validation is required.