Funding transnational collaborative research through joint transnational calls is one of the major objectives of E-Rare. This is the most important and effective joint activity to enhance the cooperation between European scientists working on rare diseases and thus reducing the fragmentation of research in this field. E-Rare launches calls on a yearly basis. The topic and eligibility criteria are specified every year and therefore may vary from one call to the other.

Acute Exacerbation of Idiopathic Pulmonary Fibrosis: Mechanism and Biomarkers

Project Coordinator

Pneumology, Albert Ludwigs University Freiburg University Medical centre


Eleni Papakonstantinou Lab of Pharmacology School of Medicine Aristotle University of Thessaloniki Thessaloniki, Greece
Dominique Valeyre Université Paris Nord PRES Sorbonne Paris Cité and Avicenne Universitary Hospital Service de Pneumologie Bobigny, France
Melanie Königshoff Comprehensive Pneumology Center Ludwig Maximillian University and Helmholtz Zentrum Munich Munich, Germany
Paola Rottoli Regione Toscana-Le Scotte Hospital Respiratory Diseases Section Depertment of Clinical Medicine and Immunology Sciences Siena, Italy
Venerino Poletti Regione Emilia Romagna-Ospedale GB Morgagni Department of Diseases of the Thorax Forli, Italy

Publications of the IPF-AE project

Major results of the project

By the E-rare project “IPF-AE” six European centres in Freiburg (Germany), Munich (Germany), Siena (Italy), Forli (Italy), Paris (France) and Thessaloniki (Greece) were funded to investigate pathomechanisms and biomarkers of acute exacerbation of idiopathic pulmonary fibrosis (IPF). Unfortunately due to the financial crisis the funding of the Greek and Italian centres was delayed and reduced. Moreover in the Munich centre personnel problems evolved. Finally, only 3 out of the 6 centres recruited actively patients to the study. However, the consortium with aid of an additional clinical center (Leuven, Belgium) managed to recruit 212 patients with IPF from whom samples and follow-up data were collected. The established biobank and databank were used in several studies testing biomarkers and pathomechanisms of IPF and particularly acute exacerbation (AE).

We were able to test BAL cell gene expression profiles in three indepedent cohorts of more than 200 patients with IPF. Using this dataset we found  a gene expression signature specifically up-regulated in acute exacerbation of IPF and a signature associated with high mortality in IPF. To our surprise, our data indicate an unexpected pathogenic role of airway epithelial cells in IPF. Based on these data we established several in vivo and in vitro models to test the functional role of airway epithelial cells in IPF. Our data suggest that airway epithlial progenitor cells are recruited to the alveolar compartment and participate in the fatal remodelling of the alveolar architecture. In addition, we studied the cytokine profile of BAL cells derived from stable IPF patients and patients suffering from acute exacerbation. The data were recently published and describe the BAL cytokine profile predictive of the evolution of acute exacerbation in patients with IPF. Moreover we tested the BAL proteome and glycosaminoglycan profile at baseline and during acute exacerbation. Based on the microarray studies we got also interested in the activation of the NLRP3 inflammasome of BAL macrophages. During acute exacerbation we found a tremendous increase in the NLRP3 inflammasome activation and studied potential mechanisms involved. In summary, although we encountered multiple obstacles we finally managed to generate a new biobank and databank for IPF which were already successfully used for several published studies and is the basis for multiple ongoing collaborative projects.

E-Rare 2012 - Created by Toussaint Biger