The role of vascularity and the fibrovascular interface in interstitial lung diseases.

Jana Dietrich, Alice Kang, Tobias Welte, Stijn E Verleden, Michael Dreher, Birger Tielemans, Hassan Khalil, Florian Länger, Philipp Bruners, Steven J Mentzer, Danny D Jonigk, Maximilian Ackermann

Journal: European respiratory review : an official journal of the European Respiratory Society 2025;34(175):

PMID: 39909504

Abstract

Interstitial lung disease (ILD) is a clinical term that refers to a diverse group of non-neoplastic lung diseases. This group includes idiopathic and secondary pulmonary entities that are often associated with progressive pulmonary fibrosis. Currently, therapeutic approaches based on specific structural targeting of pulmonary fibrosis are limited to nintedanib and pirfenidone, which can only slow down disease progression leading to a lower mortality rate. Lung transplantation is currently the only available curative treatment, but it is associated with high perioperative mortality. The pulmonary vasculature plays a central role in physiological lung function, and vascular remodelling is considered a hallmark of the initiation and progression of pulmonary fibrosis. Different patterns of pulmonary fibrosis commonly exhibit detectable pathological features such as morphomolecular changes, including intussusceptive and sprouting angiogenesis, vascular morphometry, broncho-systemic anastomoses, and aberrant angiogenesis-related gene expression patterns. Dynamic cellular interactions within the fibrovascular interface, such as endothelial activation and endothelial-mesenchymal transition, are also observed. This review aims to summarise the current clinical, radiological and pathological diagnostic algorithm for different ILDs, including usual interstitial pneumonia/idiopathic pulmonary fibrosis, non-specific interstitial pneumonia, alveolar fibroelastosis/pleuroparenchymal fibroelastosis, hypersensitivity pneumonitis, systemic sclerosis-related ILD and coronavirus disease 2019 injury. It emphasises an interdisciplinary clinicopathological perspective. Additionally, the review covers current therapeutic strategies and knowledge about associated vascular abnormalities.

Copyright ©The authors 2025.

Address: Institute of Pathology, University Clinics Aachen, RWTH University of Aachen, Aachen, Germany.; J. Dietrich and A. Kang share first authorship.; Department of Pneumology and Intensive Care Medicine, University Hospital RWTH Aachen, Aachen, Germany.; J. Dietrich and A. Kang share first authorship.; Institute of Pathology, University Clinics Aachen, RWTH University of Aachen, Aachen, Germany.; Antwerp Surgical Training, Anatomy and Research Centre (ASTARC), University of Antwerp, Edegem, Belgium.; Department of Respiratory Medicine, University Hospital Antwerp, Edegem, Belgium.; Laboratory of Adaptive and Regenerative Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Department of Thoracic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Aachen, Germany.; Department of Respiratory Medicine and Infectious Disease, Hannover Medical School, Hannover, Germany.; Department of Pneumology and Intensive Care Medicine, University Hospital RWTH Aachen, Aachen, Germany.; Institute of Pathology, University Clinics Aachen, RWTH University of Aachen, Aachen, Germany.; Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany.; Institute of Pathology, Hannover Medical School, Hannover, Germany.; D.D. Jonigk and M. Ackermann share senior authorship.; Institute of Pathology, University Clinics Aachen, RWTH University of Aachen, Aachen, Germany [email protected].; Institute of Pathology and Molecular Pathology, Helios University Clinic Wuppertal, University of Witten/Herdecke, Wuppertal, Germany.; Institute of Anatomy, University Medical Center of Johannes Gutenberg University Mainz, Mainz, Germany.; D.D. Jonigk and M. Ackermann share senior authorship.
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