1. Spanish Paediatric Interstitial Lung Diseases Registry Spanish Rare Diseases Registries Research Network (SpainRDR) Antonio Moreno Galdó Unidad de Neumología Pediátrica y Fibrosis quística Hospital Universitari Vall d’Hebron Barcelona, Spain

2. Acknowledgments Collaboration and financial support of the Research Integrated Project in Diffuse Interstitial Lung Diseases (PII-EPID) of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) (www.separ.es) The Little Lungs Foundation (http://www.pequenospulmones.org)http://www.pequenospulmones.org Institute of Rare Diseases Research (IIER), Instituto de Salud Carlos III ( https://spainrdr.isciii.es ) Dr. Robin Deterding. USA chILD registry

3. Introduction  The Spanish Society of Paediatric Pulmonology Justification  Why a registry about Paediatric interstitial lung diseases? Which type of diseases are included? Current Developments Future projects – National and International collaborations Summary

4. Founded in 1977 Members number: 250 Paediatric Pulmonologists, Paediatricians and nurses (associated members) with interest in Paediatric Pulmonology Aims To spread knowledge about children respiratory health among Paediatricians, Health providers and general population To promote research in Paediatric Pulmonology To collaborate with the Spanish Paediatric Association in aspects related to children lung diseases To collaborate with other national and international associations interested in children respiratory health To collaborate in the design of training programs in Paediatric Pulmonology for training Paediatricians Spanish Society of Paediatric Pulmonology

5. Why a Registry about Paediatric Interstitial Lung Diseases? Adult ILD: 30% chronic pulmonary diseases Children: represent very rare diseases Clement A. Task force on chronic interstitial lung disease in immunocompetent children. Eur Respir J 2004; 24:686-697. Onset year European Survey 1997 – 2002 185 cases 1/3 < 2 years

6. Neonates (> 36 weeks of gestation) to children less than 17 years of age Survey was performed with the help of the German Surveillance Unit for Rare Paediatric Disorders Monthly postcards or e-mails to all paediatric hospitals. Overall return rate was 97% M. Griese, et al. Orphanet Journal of Rare Diseases 2009, 4:26 N= 38 cases 2005-2006 The incidence of DPLD was 1.32 new cases per 1 million of children per year The incidence of DPLD was 1.32 new cases per 1 million of children per year

7. Why a Registry about Paediatric Interstitial Lung Diseases? Paediatric interstitial lung disease (ILD) is rare and diverse, meaning no single centre will see sufficient children to perform the studies needed to make progress Recent description of interstitial Recent description of interstitial disorders typical or more prevalent in infancy and different of those seen in adult patients Cellular interstitial pneumonitis Schroeder 1992 Chronic pneumonitis of infancy Katzenstein 1995 Surfactant protein B mutationsNogee 1993 Surfactant protein C mutations Nogee 2001 ABCA-3 mutations Shulenin 2004 Pulmonary interstitial glycogenosisCanakis 2002 Neuroendocrine cell hyperplasia of infancy Deterding 2005

8. Why a Registry about Paediatric Interstitial Lung Diseases? To establish the prevalence and incidence of Paediatric Interstitial Lung Diseases in Spain To improve the knowledge about the natural history and prognosis of these diseases To establish common protocols for diagnosis and management of these rare diseases To establish common protocols for diagnosis and management of these rare diseases To validate properly the diagnosis of cases To validate properly the diagnosis of cases To establish collaboration with international projects To establish collaboration with international projects To establish a Biobank ¿? for future studies To establish a Biobank ¿? for future studies Aims

9. Which type of diseases are included? Interstitial lung diseases Heterogenous group of diseases (> 150), with low incidence Inflammation of lung interstitium (alveolar septa and perialveolar tissues)

10. Diffuse developmental disorders Acinar dysplasia Congenital alveolar dysplasia Alveolar capillary dysplasia with misalignment of pulmonary veins Growth abnormalities reflecting deficient alveolarization Pulmonary hypoplasia Chronic neonatal lung disease (prematurity) Related to chromosomal disorders Related to congenital heart disease Children’s Interstitial Lung Disease (chILD) Network Classification of Diffuse Lung Disease in Children Disorders more prevalent in infancy (1)

11. Specific conditions of uncertain aetiology Neuroendocrine cell hyperplasia of infancy Pulmonary interstitial glycogenosis Surfactant dysfunction disorders Surfactant protein B (SFTPB) mutations Surfactant protein C (SFTPC) mutations ABCA3 mutations Congenital GMCSF receptor deficiency TITF-1 (NKX2-1) mutations Histology consistent with Surfactant dysfunction disorders without known genetic aetiology Pulmonary alveolar proteinosis Chronic pneumonitis of infancy Desquamative interstitial pneumonia Non-specific interstitial pneumonia Children’s Interstitial Lung Disease (chILD) Network Classification of Diffuse Lung Disease in Children Disorders more prevalent in infancy (2)

12. Disorders related to systemic disease processes Immune-mediated/collagen vascular disorders Storage disease Sarcoidosis Langerhans cell histiocytosis Disorders of the normal host (non-immunocompromised) Related to environmental agents Hypersensitivity pneumonitis; Toxic inhalation Aspiration syndromes Eosinophilic pneumonia Disorders of the immunocompromised host Related to therapeutic intervention Diffuse alveolar damage, unknown aetiology Disorders masquerading as interstitial lung disease Lymphatic disorders Children’s Interstitial Lung Disease (chILD) Network Classification of Diffuse Lung Disease in Children

13. Term newborn Neonatal respiratory distress Mechanical ventilation 8 days Tachypnoea Persistent hypoxemia 6 months Treatment with monthly high dose steroids O 2 was retired at age 10 months PAS-D Pulmonary interstitial glycogenosis

14. Lung transplant at age 5 months Good evolution 10 y post lung Tx Full term newborn Respiratory distress begining at 6 days Mechanical ventilation Chronic pneumonitis of infancy

15. Current development May 2012: Signed agreement between the Research Insitute Carlos III – Institute of Rare Diseases Research (IIER) and the Spanish Society of Paediatric Pulmonology September – December 2012: Design of the database January 2013 – March 2013: Software Development Registry coordinator Antonio Moreno. Hospital Vall d’Hebron Advisory committee Amparo Escribano. Hospital Clínic, Valencia María Isabel Barrio. Hospital La Paz, Madrid Javier Korta. Hospital Donostia, San Sebastián Borja Osona, Hospital Son Espases, Mallorca

16. Current development General information (demographics) Diagnostic evaluation (Pulmonary function, chest X ray, CT scan, bronchoalveolar lavage, lung biopsy, genetics) Clinical data (clinical presentation, comorbidities, treatment) Diagnostic classification Follow up Database structure Inclusion of retrospective and prospective cases

17. Current development General information (demographics)

18. Current development Diagnostic evaluation

19. Current development Diagnostic classification and Follow-up

20. Future projects – National collaborations SPANISH EPID-chILD Group Group driven by Dr. Julio Ancoechea (PII-EPID Director): Workgroup formed in the Integrated Research Program in Interstitial and Diffuse Lung diseases (PII-EPID) of SEPAR Coordinators: - Amparo Escribano Montaner (Hospital Clinico Universitario de Valencia) - Antonio Moreno Galdo (Hospital Universitari Vall d'Hebron in Barcelona) -Members: 18 pediatric pulmonologists, 2 Pulmonologists adults, 3 pathologists, 1 Pediatric radiologist, 1 molecular biologist Goals: - Encourage and promote clinical and basic research in the EPID - Creation of a Spanish Register for EPID-chILD cases. - Promote the participation of researchers and groups in national and international multicentre studies. - Stimulate interest in research into childhood ILD, within SEPAR. - Additional training / development of researchers in ILD in childhood. - Active participation in the development of guides, reports, papers, etc.

21. Bush A, …. Griese M on behalf of the ch-ILD EU collaboration; Research in progress: put the orphanage out of business. Thorax doi:10.1136/thoraxjnl-2012-203201 This EU FP-7 grant will standardise the evaluation of these rare conditions by establishing pan-European multidisciplinary expert panels and establish consensus on treatment protocols and standard operating procedures across Europe We will work with patient groups to determine optimal treatment end-points and biomarkers. A biobank will be established as a Europe-wide resource for mechanistic studies Ultimately we aim to do the first randomised controlled trial of a pharmacological treatment in paediatric ILD. ch-ILD EU collaboration Future projects - International collaborations We are not partners of the FP-7 grant Invitation to collaborate