Spanish Paediatric Interstitial Lung Diseases Registry

Spanish Rare Diseases Registries Research Network (SpainRDR)

Antonio Moreno GaldóUnidad de Neumología Pediátrica y Fibrosis quísticaHospital Universitari Vall d’HebronBarcelona, Spain

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)

• Institute of Rare Diseases Research (IIER), Instituto de Salud Carlos III(https://spainrdr.isciii.es)

• Dr. Robin Deterding. USA chILD registry

• 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

• 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

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 cases1/3 < 2 years

• 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 yearThe incidence of DPLD was 1.32 new cases per 1 million of children per year

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 mutations Nogee 1993

• Surfactant protein C mutations Nogee 2001

• ABCA-3 mutations Shulenin 2004

• Pulmonary interstitial glycogenosis Canakis 2002

• Neuroendocrine cell hyperplasia of infancy Deterding 2005

Why a Registry about Paediatric Interstitial Lung Diseases?

• To establish the prevalence and incidence of Paediatric Interstitial Lung Diseasesin 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 To establish common protocols for diagnosis and management of these rare diseases diseases

• To validate properly the diagnosis of casesTo validate properly the diagnosis of cases

• To establish collaboration with international projects To establish collaboration with international projects

• To establish a Biobank ¿? for future studiesTo establish a Biobank ¿? for future studies

Aims

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)

Diffuse developmental disordersAcinar dysplasiaCongenital alveolar dysplasiaAlveolar capillary dysplasia with misalignment of pulmonary veins

Growth abnormalities reflecting deficient alveolarizationPulmonary hypoplasiaChronic neonatal lung disease (prematurity)Related to chromosomal disordersRelated to congenital heart disease

Children’s Interstitial Lung Disease (chILD) Network Classificationof Diffuse Lung Disease in Children

Disorders more prevalent in infancy (1)

Specific conditions of uncertain aetiologyNeuroendocrine cell hyperplasia of infancyPulmonary interstitial glycogenosis

Surfactant dysfunction disordersSurfactant protein B (SFTPB) mutationsSurfactant protein C (SFTPC) mutationsABCA3 mutationsCongenital GMCSF receptor deficiencyTITF-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 Classificationof Diffuse Lung Disease in Children

Disorders more prevalent in infancy (2)

Disorders related to systemic disease processesImmune-mediated/collagen vascular disordersStorage diseaseSarcoidosisLangerhans cell histiocytosis

Disorders of the normal host (non-immunocompromised)Related to environmental agentsHypersensitivity pneumonitis; Toxic inhalationAspiration syndromesEosinophilic pneumonia

Disorders of the immunocompromised hostRelated to therapeutic interventionDiffuse alveolar damage, unknown aetiology

Disorders masquerading as interstitial lung diseaseLymphatic disorders

Children’s Interstitial Lung Disease (chILD) Network Classificationof Diffuse Lung Disease in Children

Term newbornNeonatal respiratory distressMechanical ventilation 8 days

TachypnoeaPersistent hypoxemia 6 months

Treatment with monthly high dose steroidsO2 was retired at age 10 months

PAS-D

Pulmonary interstitial glycogenosis

Lung transplant at age 5 monthsGood evolution 10 y post lung Tx

Full term newbornRespiratory distress begining at 6 daysMechanical ventilation

Chronic pneumonitis of infancy

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 coordinatorAntonio Moreno. Hospital Vall d’Hebron

Advisory committeeAmparo Escribano. Hospital Clínic, Valencia María Isabel Barrio. Hospital La Paz, MadridJavier Korta. Hospital Donostia, San Sebastián Borja Osona, Hospital Son Espases, Mallorca

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

Current development

General information (demographics)

Current development

Diagnostic evaluation

Current development

Diagnostic classification and Follow-up

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.

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 grantInvitation to collaborate