Year: 2026
Type: preprint
Study design: Observational Study
Abstract: The integrity of the pulmonary vasculature is a key determinant of lung health, yet challenges in visualisation and quantification have hindered interrogation of its pathophysiological role in chronic lung disease. Here, we align recent advances in microscale image acquisition with novel computer vision-based vessel segmentation models to demonstrate expansion of the bronchial and pulmonary veins across varying severities of tissue remodelling in idiopathic pulmonary fibrosis (IPF). Relating these imaging findings to molecular data in control, mild, and severe fibrosis, we show that bronchial venous endothelial cells expand beyond their physiological peribronchial niche even in mild disease, acquiring persistent angiogenic, inflammatory, and matrix-remodelling programmes that define a specialised fibrovascular-immune interface. Finally, we relate these microscale and molecular observations to clinical CT imaging, demonstrating that intrapulmonary vein enlargement independently associates with worsened survival across three IPF cohorts. Collectively, our multimodal, multiscale approach connects previously unresolved three-dimensional venous architecture to its molecular endothelial correlate, establishing venous enlargement as a prognostically significant and clinically relevant feature of IPF. Our analytical approach also demonstrates how biological discoveries made in intact ex vivo human organs can translate into measurable phenotypes in living patients, providing a template for other organs and diseases.
Authors: Daisuke Yamada, Huijuan Wang, Adam Szmul, Janik Riese, Ryoko Egashira, Coline H. M. van Moorsel, Nesrin Mogulkoc, Burak Gokce, Shahab Aslani, Daryl Cheng, Yunjie Chen, Rahel Bodenmann, Matthias Brunner, Birger Tielemans, Joseph Brunet, Theresa Urban, Joanna Purzycka, Hector Dejea, Paul Tafforeau, Marie Vermant, Frouke T. van Beek, Britta Maurer, Sara Krattli, Marco Kreuzer, Remy Bruggmann, Tine Follet, Marcel Veltkamp, Tinne Goos, Kenny Anseele, Maarten Vander Kuylen, Hendrik W van Es, Klaus Engel, Recep Savas, Jose Manuel Brenes, Jeroen MH Hendriks, Therese S Lapperre, Claire L Walsh, Danny Jonigk, Lavinia Neubert, Christopher Werlein, Hinrich Freitag, Sabine Dettmer, Jonas C Schupp, Laurens J de Sadeleer, Stephanie K. Robinson, Aurelie Fabre, Mark G. Jones, Francois Michel Carlier, Bart M Vanaudenaerde, Wim A Wuyts, Peter D Lee, Maximilian Ackermann, Stijn E Verleden, Janine Gote-Schniering, Joseph Jacob
Institutions: University College London, University of Bern, University Hospital of Bern, Universitätsklinikum Aachen, RWTH Aachen University, St. Antonius Ziekenhuis, Ege University, KU Leuven, European Synchrotron Radiation Facility, Universitair Ziekenhuis Leuven, SIB Swiss Institute of Bioinformatics, Université Libre de Bruxelles, Erasmus Hospital, Siemens Healthineers (Germany), Hospital de Sant Pau, University of Antwerp, Antwerp University Hospital, Medizinische Hochschule Hannover, German Center for Lung Research, University of Southampton, University College Dublin, UCLouvain, University Medical Center of the Johannes Gutenberg University Mainz
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Science Foundation, Silicon Valley Community Foundation, Oregon Health and Science University, University of Bern, Wellcome Trust, Cancer Research UK, National Institute for Health and Care Research, Royal Academy of Engineering, University College London, Rosetrees Trust, European Synchrotron Radiation Facility, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Robert Luff Foundation, Astellas Pharma, Université de Genève, Astellas Foundation for Research on Metabolic Disorders, University College London Hospitals NHS Foundation Trust, Deutsches Zentrum für Lungenforschung, Knight Cancer Institute, Oregon Health and Science University, Medical Research Council, Institute of Genetics and Genomics of Geneva
Awards: G1218620557, Imaging dynamics in biophysical/biochemical processes across the hierarchical scales (BioPro Network), The impact of mesenchymal stem cells on host immunity in bacterial lung infection and sepsis., Perovskite Accelerated Lifetime Assessment, degradation mechanism Comprehension for fast device reliability Enhancement, G339059223, Computer-based analysis of early fibrosing lung disease, Analysis of the Syringolin-Triggered Tranformation of Compatibility to Incompatibilty in Powdery Mildew-Infected Plants, Enhancing the characterisation of early respiratory disease to improve population health, G6158001132, G703488644, G7193505718, G7309960804, G7423961978, G7500717991, IMMUNOCODE - Decoding the Role of Immune Aging in Regenerative Cell State Dysfunction in Pulmonary Fibrosis, Enhancing the characterisation of early respiratory disease to improve population health, Computer-based analysis of early fibrosing lung disease, G8547529128, a) New Organic Chemistry with Sulfur Dioxide b) Asymmetric Synthesis of Glycomimetics and of Natural Products of Biological Interest
OpenAlex ID: W7213974063