Mechanistic insights into pleural effusions after lung transplantation

Background: Pleural effusions are common after lung transplantation and are associated with impaired allograft function and increased mortality. Previous proteomic analysis of lung transplant pleural effusions pointed towards a role for mesothelial-to-mesenchymal transition. However, the mechanisms behind this transition remain poorly understood. Methods: Resected pleural tissue from LTX recipients undergoing retransplantation as well as pleurectomy tissue from LTX recipients with recurrent effusions are analyzed by histology and immunofluorescence stainings for Collagen I/V, Fibronectin and Intelectin. Primary pleural fibroblasts and mesothelial cells are exposed to profibrotic stimulation with TGF-β, immunosuppressive agents (Tacrolimus, MMF), and supernatants from LTX pleural effusions to analyze transitions in cell phenotypes on morphology and protein expression (α-SMA, Collagen I/V, Fibronectin). Reversal is assessed with antifibrotic agents (Nintedanib, Nerandomilast). Ex vivo human pleural tissue slices undergo analogous stimulations, allowing direct assessment of structural changes and cell–matrix interactions in native tissue. Results: Preliminary histology shows pronounced pleural thickening with subpleural extracellular-matrix accumulation in recurrent-effusion samples. Initial comparative analyses suggest marked heterogeneity between patient groups. Comprehensive protein profiling, cellular phenotyping, and advanced in vitro modelling are ongoing to systematically reproduce and modulate these processes under controlled conditions. Conclusion: To our knowledge, this integrated clinic–bench approach is among the first to identify underlying mechanisms of lung transplant pleural effusions. The platform is designed to identify targetable pathways linking effusions to patient outcomes and to inform prospective validation and therapeutic strategies. Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany