Genetic Causes and Clinical Features of Childhood Interstitial Lung Diseases in China

Genetic Testing Clinical Trial

Official title:

Genetic Causes and Clinical Features of Childhood Interstitial Lung Diseases in China

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03869515
• Other study ID #: CHFudanU-02
• Status: Active, not recruiting
• Start date: March 25, 2019
• Est. completion date: December 30, 2025

Study information

• Verified date: March 2024
• Source: Children's Hospital of Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Recruitment of a carefully characterized cohort of chILD patients, to generate a database and biobank via collecting data on chILD in China. Importantly, compatibility with ongoing United States and Europe chILD data base developments will be factored in.

Description:

Children Interstitial lung disease (chILD) is a heterogeneous group of rare respiratory disorders of known and unknown etiologies that are mostly chronic and associated with high morbidity and mortality. ILD are characterized by inflammatory and fibrotic changes of the lung parenchyma structure that typically result in the presence of diffuse infiltrates on lung imaging, and abnormal pulmonary function tests with evidence of a restrictive ventilatory defect and/or impaired gas exchange.

Genetic factors are important contributors to chILD. Genetic variations have been mainly described in genes encoding (or interacting with) the surfactant proteins (SP): SP-C (SFTPC) and the ATP-binding cassette-family A-member 3 (ABCA3) (ABCA3), and less frequently in the genes encoding NKX homeobox 2 (NKX2)-1 (NKX2-1), SP-B (SFTPB), SP-A (SFTPA) ,MARS and other genes.

To investigate genetic defects and clinical features of chILD in China, wide recruitment and interdisciplinary critical peer review of all diagnoses from discharge diagnosis coding system of Children's Hospital of Fudan University will be included. Each case will be given a diagnosis independently; if no firm diagnosis is possible, the investigators will review the case periodically as new information becomes available. During the first year of the study, clinicians´ decisions according to clinical practice and outcomes will be independently monitored and assessed.

The investigators will systematically optimize and clarify the relative weight of a large spectrum of single and composite clinical outcomes, sequential limited chest CT (to minimise radiation exposure), lung function testing, histopathological categorization of lung biopsies, serum markers and genetic tests. Variability, reproducibility and the effects of training on reading images will be investigated.

This project will analyse in detail treatment and outcomes within and between subjects using data collected. Analysis of the collected data will support the definition of trial protocols planned in the future.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 271
• Est. completion date: December 30, 2025
• Est. primary completion date: December 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• The chILD syndrome exists when a child with DLD has had the common causes of DLD excluded as the primary diagnosis and has at least three of the following four criteria: (1) respiratory symptoms (e.g., cough, rapid and/or difficult breathing, or exercise intolerance);(2) respiratory signs (e.g., resting tachypnea, adventitious sounds, retractions, digital clubbing, failure to thrive, or respiratory fail- ure); (3) hypoxemia; and (4) diffuse abnormalities on CXR or a CT scan.

Exclusion Criteria:

• These include cystic fibrosis, congenital or acquired immunodeficiency, congenital heart disease, bronchopulmonary dysplasia, pulmonary infection, primary ciliary dyskinesia presenting with newborn respiratory distress and recurrent aspiration.

Related Conditions & MeSH terms

• Genetic Testing
• Interstitial Lung Diseases of Childhood
• Lung Diseases
• Lung Diseases, Interstitial

Intervention

Other:
• No intervention
It's an observational study, so no intervention will be carried out.

Locations

Country	Name	City	State
China	Children's hospital of Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital of Fudan University

Country where clinical trial is conducted

China, 

References & Publications (5)

Bromley S, Vizcaya D. Pulmonary hypertension in childhood interstitial lung disease: A systematic review of the literature. Pediatr Pulmonol. 2017 May;52(5):689-698. doi: 10.1002/ppul.23632. Epub 2016 Oct 23. — View Citation

Eldridge WB, Zhang Q, Faro A, Sweet SC, Eghtesady P, Hamvas A, Cole FS, Wambach JA. Outcomes of Lung Transplantation for Infants and Children with Genetic Disorders of Surfactant Metabolism. J Pediatr. 2017 May;184:157-164.e2. doi: 10.1016/j.jpeds.2017.01.017. Epub 2017 Feb 16. — View Citation

Hime NJ, Zurynski Y, Fitzgerald D, Selvadurai H, Phu A, Deverell M, Elliott EJ, Jaffe A. Childhood interstitial lung disease: A systematic review. Pediatr Pulmonol. 2015 Dec;50(12):1383-92. doi: 10.1002/ppul.23183. Epub 2015 Apr 30. — View Citation

Kurland G, Deterding RR, Hagood JS, Young LR, Brody AS, Castile RG, Dell S, Fan LL, Hamvas A, Hilman BC, Langston C, Nogee LM, Redding GJ; American Thoracic Society Committee on Childhood Interstitial Lung Disease (chILD) and the chILD Research Network. A — View Citation

Thacker PG, Vargas SO, Fishman MP, Casey AM, Lee EY. Current Update on Interstitial Lung Disease of Infancy: New Classification System, Diagnostic Evaluation, Imaging Algorithms, Imaging Findings, and Prognosis. Radiol Clin North Am. 2016 Nov;54(6):1065-1076. doi: 10.1016/j.rcl.2016.05.012. Epub 2016 Aug 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diagnosed with specific cause for chILD	(yes/no) Specific causes for chILD based on the 2013 Official American Thoracic Society Clinical Practice Guideline: classification, evaluation, and management of childhood interstitial lung disease in infancy	6 years
Secondary	Having pathogenic gene mutations	(yes/no) Genetic variations have been mainly described in genes encoding (or interacting with) the surfactant proteins (SP): SP-C (SFTPC) and the ATP-binding cassette-family A-member 3 (ABCA3) (ABCA3), and less frequently in the genes encoding NKX homeobox 2 (NKX2)-1 (NKX2-1), SP-B (SFTPB), SP-A (SFTPA) ,MARS and other genes.	6 years
Secondary	Hypoxemia	(yes/no) Change of PO2 in arterial blood gases from baseline when diagnosed with chILD	6 years
Secondary	Deterioration of pulmonary imaging	(yes/no) Change of clinical judgment on pulmonary imaging from baseline if X-ray or CT were done	6 years
Secondary	Change from baseline in lung function on the spirometry forced expiratory	Volume at one second (FEV1) in Liter	6 years
Secondary	Abnormal autoantibody at baseline when diagnosed with chILD	(yes/ no)	6 years
Secondary	Pathological change of lung biopsy	(yes/no) Clinical judgment on histopathological categorization of lung biopsy when diagnosed with chILD	6 years
Secondary	Deterioration of pulmonary arterial hypertension	(yes/no) Change of pulmonary artery pressure from baseline in echocardiagraphy	6 years
Secondary	Change of BALF(bronchoalveolar lavage fluid)	(yes/no) Cytology analysis on BALF at the baseline when diagnosed with chILD	6 years
Secondary	Survival	(yes/no)	1 years
Secondary	Survival	(yes/no)	2 years
Secondary	Survival	Five-year	5 years
Secondary	Abnormal thyroid hormone at baseline when diagnosed with chILD	(yes/no)	6 years
Secondary	Abnormal myocardial zymogram at baseline when diagnosed with chILD	(yes/no)	6 years
Secondary	Abnormal serum immunoglobulin at baseline when diagnosed with chILD	(yes/no)	6 years
Secondary	Abnormal serum creatinine at baseline when diagnosed with chILD	(yes/no)	6 years
Secondary	Abnormal blood urea nitrogen at baseline when diagnosed with chILD	(yes/no)	6 years
Secondary	Abnormal alanine transferase at baseline when diagnosed with chILD	(yes/no)	6 years
Secondary	Abnormal allergen at baseline when diagnosed with chILD	(yes/no)	6 years
Secondary	Recurrent hospitalization	yes:Hospitalization more than twice per year after diagnosed with chILD; no:Hospitalization less than three times per year after diagnosed with chILD;	1 year after diagnosis