Search

Idiopathic pulmonary fibrosis (IPF) is thought to result from aberrant tissue repair processes in response to chronic or repetitive lung injury. The origin and nature of the injury, as well as its cellular and molecular targets, are likely heterogeneous, which complicates accurate pre-clinical modelling of the disease and makes therapeutic targeting a challenge. Efforts are underway to identify central pathways in fibrogenesis which may allow targeting of aberrant repair processes regardless of the initial injury stimulus. Dysregulated endothelial permeability and vascular leak have long been studied for their role in acute lung injury and repair. Evidence that these processes are of importance to the pathogenesis of fibrotic lung disease is growing. Endothelial permeability is increased in non-fibrosing lung diseases, but it resolves in a self-limited fashion in conditions such as bacterial pneumonia and acute respiratory distress syndrome. In progressive fibrosing diseases such as IPF, permeability appears to persist, however, and may also predict mortality. In this hypothesis-generating review, we summarise available data on the role of endothelial permeability in IPF and focus on the deleterious consequences of sustained endothelial hyperpermeability in response to and during pulmonary inflammation and fibrosis. We propose that persistent permeability and vascular leak in the lung have the potential to establish and amplify the pro-fibrotic environment. Therapeutic interventions aimed at recognising and "plugging" the leak may therefore be of significant benefit for preventing the transition from lung injury to fibrosis and should be areas for future research., Competing Interests: Conflict of interest: C.K. Probst has nothing to disclose. Conflict of interest: S.B. Montesi reports fees paid to institution and participating in research from United Therapeutics Corporation and Promedior, outside the submitted work. Conflict of interest: B.D. Medoff has nothing to disclose. Conflict of interest: B.S. Shea reports personal fees from Genentech and Boehringer Ingelheim, outside the submitted work. Conflict of interest: R.S. Knipe has nothing to disclose., (Copyright ©ERS 2020.)

Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias and is characterised by progressive accumulation of scar tissue in the lungs. The objective of this study was to describe the current mortality rates due to IPF in Europe, based on the World Health Organization (WHO) mortality database.We used country-level data for IPF mortality, identified in the WHO mortality database using International Classification of Diseases 10th Edition (ICD-10) codes, for the period 2001-2013. Joinpoint analysis was performed to describe trends throughout the observation period.The median mortality was 3.75 per 100 000 (interquartile range (IQR) 1.37-5.30) and 1.50 per 100 000 (IQR 0.65-2.02) for males and females, respectively. IPF mortality increased in the majority of the European Union (EU) countries with the exceptions of Denmark, Croatia, Austria and Romania. There was a significant disparity in rates across Europe, in the range 0.41-12.1 per 100 000 for men and 0.24-5.63 per 100 000 for women. The most notable increases were observed in the United Kingdom and Finland. Rates were also substantially higher in males, with sex disparity increasing across the period.The reported IPF mortality appears to be increasing across the EU; however, there is substantial variation in mortality trends and overall reported mortality rates between countries., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2018.)