Surfactant Disorders and Chronic Lung Disease (APSE)

Surfactant Disorders Associated With Chronic Lung Disease in Children.

Interstitial lung diseases (ILD) in children represent a heterogeneous group of rare and not well defined disorders. Genetic abnormalities of surfactant proteins B (SFTPB) and more recently C (SFTPC) have been shown to be related to these pathologies. However, variability in the lung disease phenotype suggests the involvement of other surfactant-associated genes such as ABCA3 (ATP-binding cassette, sub-family A, member, 3). Thus, the aim of this project is: 1) to assess the prevalence of SFTPC mutation in children with chronic lung diseases, 2) to precise clinical and radiological features of children with SFTPC mutation, and 3) to identify environmental or genetic factors that may explain the extreme variability of this disease.

Study Overview

• Status: Completed
• Conditions: Chronic Lung Disease
• Intervention / Treatment: Other: whole blood sample

Detailed Description

The first stage of this project will be to constitute a clinical, radiological, biological database of children (1 moth-17 years) with severe respiratory distress and/or an unexplained chronic ILD. Mutations in SFTPC, SFTPB and ABCA3 will be further identified by sequencing and documented with using the parents blood samples.

• Study Type: Observational
• Enrollment (Actual): 58

Contacts and Locations

Study Locations

• France
  • Paris, France, 75012
    • Hôpital Trousseau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

French pulmonary units participating to the study

Description

Inclusion Criteria:

• Children from 1 month to 17 years old with radiological alveola-interstitial syndrome and:
• Oxygen weaning failure > 1 month in term newborn babies(>37th week of PCA)or> 40 weeks of PCA in preterm babies
• or
• Chronic respiratory disease define by chronic hypoxia and/or clinical signs of respiratory distress (cough, retractions, crackle)

Exclusion criteria:

• informed consent denied
• absence of social security

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; Children with chronic lung disease	Other: whole blood sample; 2 ml of whole blood for children 5 ml of whole blood for parents that will be used only if 1 mutation is found in children

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess the prevalence of SFTPC mutation in children with chronic lung diseases	At the inclusion visit

Secondary Outcome Measures

Outcome Measure	Time Frame
To precise clinical and radiological features of children with SFTPC mutation	At the inclusion visit
To identify environmental or genetic factors that may explain the extreme variability of this disease	At the inclusion visit

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Ralph Epaud, MD, Hopital Trousseau, APHP

Publications and helpful links

General Publications

• Epaud R, Delestrain C, Louha M, Simon S, Fanen P, Tazi A. Combined pulmonary fibrosis and emphysema syndrome associated with ABCA3 mutations. Eur Respir J. 2014 Feb;43(2):638-41. doi: 10.1183/09031936.00145213. Epub 2013 Oct 17. No abstract available.
• Delestrain C, Flamein F, Jonard L, Couderc R, Guillot L, Fanen P, Epaud R. [Lung diseases in children associated with inherited disorders of surfactant metabolism]. Rev Pneumol Clin. 2013 Aug;69(4):183-9. doi: 10.1016/j.pneumo.2013.05.002. Epub 2013 Jul 12. French.
• Flamein F, Riffault L, Muselet-Charlier C, Pernelle J, Feldmann D, Jonard L, Durand-Schneider AM, Coulomb A, Maurice M, Nogee LM, Inagaki N, Amselem S, Dubus JC, Rigourd V, Bremont F, Marguet C, Brouard J, de Blic J, Clement A, Epaud R, Guillot L. Molecular and cellular characteristics of ABCA3 mutations associated with diffuse parenchymal lung diseases in children. Hum Mol Genet. 2012 Feb 15;21(4):765-75. doi: 10.1093/hmg/ddr508. Epub 2011 Nov 7.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ACTUAL): June 1, 2012
• Study Completion (ACTUAL): June 1, 2012

Study Registration Dates

• First Submitted: October 31, 2008
• First Submitted That Met QC Criteria: October 31, 2008
• First Posted (ESTIMATE): November 2, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): November 19, 2012
• Last Update Submitted That Met QC Criteria: November 16, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: lung; Children; Interstitial; Surfactant protein C
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases
• Other Study ID Numbers: AOM 07019