"eurIPFreg: A European Registry and Biobank for Patients with Idiopathic Pulmonary Fibrosis " Drakopanagiotakis Fotios Universities of Giessen and Marburg Lung Center Giessen, Germany

On behalf of the European IPF Registry (www.pulmonary-fibrosis.net)

Idiopathic Pulmonary Fibrosis Why do we need an IPF Registry? • Usually affects individuals at the age of 50 or older

• Presents with dyspnea on exertion and at rest • IPF is deadly, with a median survival rate of 2-3 years. • Not easy to diagnose, needs expert evaluation • Idiopathic` disease (cause unknown)

• Not common disease, many centers need to collaborate for sufficient patient numbers • Course of an individual patient largely unpredictable • Numerous treatment failures, significant side-effects with

`treatment`

INTERSTITIAL LUNG DISEASES Connective Tissue Diseases Scleroderma Polymyositis-Dermatomyositis Systemic Lupus Erythematosus Rheumatoid Arthritis Mixed Connective Tissue Disease Ankylosing Spondyitis Primary (Unclassified) Sarcoidosis Langerhans cell histiocytosis Amyloidosis Pulmonary vasculitis Lipoid pneumonia Lymphangitic carcinomatosis Bronchoalveolar carcinoma Pulmonary lymphoma Gaucher’s Disease Niemann-Pick Disease Hermansky-Pudlak syndrome Neurofibromatosis Lymphangioleiomyomatosis Tuberous Sclerosis ARDS AIDS Bone Marrow Transplantation Postinfectious Eosinophilic pneumonia Alveolar Proteinosis Diffuse Alveolar Hemorrhage Syndromes Alveolar microlithiasis Metastatic calcification

Treatment-Related / Drug-Induced Antibiotics – nitrofurantoin, sulfasalazine Antiarrhythmics – amiodarone, propanolol Anti-inflammatories – gold, penacillamine Anti-convulsants – dilantin Chemotherapeutic agents – bleomycin, cyclophosphamide, methotrexate, azathioprine Therapeutic radiation Oxygen toxicity Narcotics

Occupational and Environmental Diseases Inorganic

Organic

Silicosis Asbestosis Hard-metal pneumoconiosis Coal worker’s pneumoconiosis Berylliosis Aluminum oxide fibrosis Talc pneumoconiosis Siderosis (arc welder) Stannosis (tin)

Bird breeder’s lung Farmer’s lung Bacteria – e.g. NTB mycobacteria Fungi – e.g. Aspergillus Animal protein – e.g. Avian Chemical sensitizers e.g. isocyanates

Idiopathic Fibrotic Disorders Acute interstitial pneumonitis (Hamman-Rich syndrome) Idiopathic Pulmonary Fibrosis Familial Idiopathic Pulmonary Fibrosis Desquamative intersitial pneumonitis Respiratory bronchiolitis Cryptogenic organizing pneumonia Nonspecific interstitial pneumonitis Lymphocytic interstitial pneumonia (Sjögrens Syndrome, AIDS, Hashimoto’s) Autoimmune pulmonary fibrosis (inflammatory bowel disease, PBC, ITP, AIHA)

Lung microinjuries Beginning of symptoms

Acute exacerbations

Rapid progressive

Slowly progressive

Asymptomatic period

Years unknown

0

1

2

Diagnosis

3

4

5

6

7

8

Years

9

10

Open questions • • • • • •

Epithelium versus mesenchyme or both? Second hits: which ones, how many, how severe? When actually does IPF start? Early markers of IPF and their potential use? Is IPF reversible at all? Overlap and differences between different forms of IPF? • Intraindividual response pattern to given treatment modalities?

How to answer these questions?

European IPF Network and Registry / Biobank

European IPF network Natural Course, Pathomechanism and Novel Treatment Options in Idiopathic Pulmonary Fibrosis Funded through FP7 from 01.01.08 until 30.06.11 (EU)

European IPF Registry and Biobank - opened 04/09 by eurIPFnet - open to all interested scientists

• Tight collaboration with German Center for Lung Research (DZL)

What is the European IPF Registry? • A European database of longitudinal data from IPF patients • Includes control groups of patients with other lung diseases • Born out of the EU 7th Framework Programme funded project European IPF Network (eurIPFnet)

Beginnings of the Registry and Biobank

eurIPFnet members at the Kick-Off Meeting in Giessen, February 2008

Administrative Structure Funding Entities

Ethics Committee

Steering Committee: Coordinator – main

2 voted members from eurIPFnet + 2 voted members from eurIPFreg + Coordinator

point of contact for outside entities

Parties of the Consortium Agreement

GENERAL ASSEMBLY

Registered Site Investigators

European IPF registry

Data included in the European IPF Registry

European IPF registry

Patient´s baseline questionnaire: Nature and history of complaints Coughing and expectoration Concomitant complaints Smoking history Previous Airway or lung disease Concomitant diseases Medication at the time of evolution of symptoms Family history Environmental aspects Professional activities Quality of Life EQ5D VAS Mahler SF 36

European IPF registry

Patient´s follow-up questionnaire: Change of overall condition Infectious episodes, criteria Hospitalizations (duration, reasons) Lung transplantation status Professional activities Quality of Life EQ5D VAS Mahler SF 36

Data included in the European IPF Registry

Data included in the European IPF Registry

Research in eurIPFreg „bottom up“ from the test tube to humans Clinical Trials Patient Biomaterials Pharmacology Animal experiment

„top down“ from humans to the cell / animals Clinical Observations Human Biomaterial

~omics, NGS

Cell culture

Pathomechanistic concept

Molecular biology Protein / Lipid chemistry

gain-of-function loss-of-function in vitro/vivo

European IPF registry

Multi-level

Informed Consent Procedure

Patient recruitment in the eurIPFreg (only IPF)

Publications resulting from the work of Amara N, et al. Thorax. 2010 Aug;65(8):733-8 Avcuoglu S, et al. Am J Respir Cell Mol Biol. 2011 Oct;45(4):76880 Bantsimba-Malanda C, et al. Am J Respir Crit Care Med. 2010 Aug 1;182(3):385-95 Cigna N, et al. Am J Pathol. 2012 Dec;181(6):2126-37 **Conte E, et al. Lab Invest. 2013 May;93(5):566-76 Conte E, et al. PLoS One. 2011;6(10):e24663 Datta A, et al. Br J Pharmacol. 2011 May;163(1):141-72 Decologne N, et al. Eur Respir J. 2010 Jan;35(1):176-85 Decologne N, et al. Bull Acad Natl Med. 2010 Feb;194(2):383-9. Ecker J, et al. Chemistry of Physics of Lipids. 2009 160:S20 Failla M, et al. Am J Respir Cell Mol Biol. 2009 Jul;41(1):50-8. Fagone E, et al. Exp Lung Res. 2011 Apr;37(3):162-74. Gupte VV, et al. Am J Respir Crit Care Med. 2009 Sep 1;180(5):424-36. **Guenther A, et al. 2008 Sept;Thorax 36:9. Günther A, et al. Eur Respir Rev. 2012 Jun 1;21(124):152-60. **A. Guenther on behalf of the European IPF Network, Eur Respir J 37:1-3, 2011. Janssen W, et al. J Pathol 2013 229(2):242-249. Königshoff M, Ket al. J Clin Invest. 2009 Apr;119(4):772-87. **Korfei M, et al. J Proteomics. 2013 Jun 24;85:109-28. **Korfei M, et al. J Proteome Res. 2011 May 6;10(5):2185-205. **Mahavadi P, et al. Am J Respir Crit Care Med. 2010 Jul 15;182(2):207-19. Markart P, et al. J Aerosol Med Pulm Drug Deliv. 2010 Jun;23(3):161-72. **Nikolova S, et al. Respir Res. 2010 Oct 27;11:146.

**Nkyimbeng T, et al. PLoS One. Accepted for publication July 2013 Ortiz-Stern A, et al. J Cell Physiol. 2012 Nov;227(11):3575-84. **Plantier L, et al. Thorax. 2011 Aug;66(8):651-7. Pfaff EM, et al. Eur Respir J. 2011 Jan;37(1):79-87. Phin S, et al. Am J Respir Cell Mol Biol. 2010 Mar;42(3):286-93. **Pullamsetti SS, et al. Sci Transl Med. 2011 Jun 15;3(87):87ra53. Quesnel C,et al. Crit Care Med. 2012 Jan;40(1):21-8. Quesnel C, et al. Eur Respir J. 2010 Jun;35(6):1312-21. Ruppert C, et al. Crit Care Med. 2010 Jul;38(7):1584-91. Scherer M, et al. J Lipid Res. 2010 Jul;51(7):2001-11. **Scotton CJ, et al. J Clin Invest. 2009 Sep;119(9):2550-63. Scotton CJ, et al. Am J Physiol Lung Cell Mol Physiol. 2010 Oct;299(4):L439-41. Comment on Repetitive intratracheal bleomycin models several features of idiopathic pulmonary fibrosis. Shetty S, et al. Am J Respir Crit Care Med. 2010 Jun 15;181(12):1355-66. Taillé C, et al. Am J Respir Crit Care Med. 2011 Mar 15;183(6):759-66. Udalov S, et al. BMC Pulm Med. 2010 May 5;10:26. **Wettstein G, et al. FASEB J. 2013 Apr;27(4):1549-60. Wettstein G, et al. Int J Biochem Cell Biol. 2012 Oct;44(10):16806 Wygrecka M, et al. Am J Respir Crit Care Med. 2011 Jun 15;183(12):1703-14.

** indicates joint publication of consortium members

Visibility of the Registry

Research goals of the European IPF Registry • a) Future development of non-invasive, air- or blood-borne biomarkers in IPF allowing safe diagnosis, sub-grouping of IPF subjects and identification of therapy-responders • b) Quality of Life assessment • c) Description of epigenetic changes in IPF lung epithelial cells and fibroblasts • d) Genome profiling in IPF subjects • e) Isolation of progenitor cells and different parenchymal cell populations from IPF and other lungs

eurIPFreg Project manager (Sandy Jones)

eurIPFreg Coordinator (Andreas Guenther)

eurIPFreg Steering Committee

Physicians and nurses providing clinical care

UKGMTransMIT

Industry

External Site Investigators European PATIENTS IPF Registry and Biobank

Scientists involved in IPF research Scientific Collaborators and Advisors

Staff of the eurIPFreg (Sabine Heinemann, Stefan Kuhn, Bettina Paul, Conny Scheld)

Thank you!