Investigation in BAL and blood eosinophilia in lung transplant recipients

Background: Chronic lung allograft dysfunction (CLAD) remains the major obstacle to long-term survival after lung transplantation (LTX). Eosinophilic episodes, defined by elevated eosinophil counts in bronchoalveolar lavage fluid (BALF) and/or blood, are increasingly recognized as potential biomarkers for CLAD. Increased expression of T2-associated genes (IL13, IL13RA1, IL33, CL11, CCL24, and TSLP) has been detected in explanted lungs at the end stage of CLAD. However, their role in early CLAD development and their potential link to eosinophilic episodes remain unexplored. As T2 inflammation is therapeutically targetable in asthma and COPD using biologics (anti-IL5/IL5Ra, anti-TSLP, anti-IL4Ra), defining its role in CLAD could pave the way for novel targeted interventions. Results: We characterized 8 LTX recipients with one or more episodes of BAL and/or blood eosinophilia during the first year after transplantation with a total of 31 BAL samples from these patients. We compared these to a matched control group of 48 patients without BAL and blood eosinophilia during the first year after transplantation. 4 patients received anti-IL5 or anti-IL5R medication as off-label use in the setting of pronounced eosinophilia and concomitant graft failure. Of all patients, clinical characteristics including BAL differential cell counts, BAL microbiological findings, the ISHLT classification of concomitant transbronchial biopsies, blood parameters, HLA antibody findings, and medication, in particular the administration of immunosuppressants, azithromycin, and antibiotics were analyzed. Cytokine expression in BAL samples were analyzed by 15-plex human cytokine ELISA. Conclusion: This study investigates whether T2 cytokines may serve as CLAD biomarkers, providing early risk stratification and giving novel pathophysiological insights into CLAD development in LTX recipients. Furthermore, by studying patients treated with anti-IL5/IL5Ra, we aim to determine whether these therapies can reduce T2 inflammatory profiles also in the context of LTX. This research could thus indicate if T2 biologics should be further investigated as CLAD-preventive therapeutics in LTX recipients with eosinophilia. Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany