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

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.