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

Active, not recruiting
Conditions
Genetic Testing
Interstitial Lung Diseases of Childhood
Interventions
Other: No intervention
Registration Number
NCT03869515
Lead Sponsor
Children's Hospital of Fudan University
Brief 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.

Detailed 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 & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
271
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.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
chILDNo interventionThe 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.
Primary Outcome Measures
NameTimeMethod
Diagnosed with specific cause for chILD6 years

(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

Secondary Outcome Measures
NameTimeMethod
Change of BALF(bronchoalveolar lavage fluid)6 years

(yes/no) Cytology analysis on BALF at the baseline when diagnosed with chILD

Abnormal autoantibody at baseline when diagnosed with chILD6 years

(yes/ no)

Pathological change of lung biopsy6 years

(yes/no) Clinical judgment on histopathological categorization of lung biopsy when diagnosed with chILD

Abnormal serum immunoglobulin at baseline when diagnosed with chILD6 years

(yes/no)

Abnormal blood urea nitrogen at baseline when diagnosed with chILD6 years

(yes/no)

Having pathogenic gene mutations6 years

(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.

Deterioration of pulmonary imaging6 years

(yes/no) Change of clinical judgment on pulmonary imaging from baseline if X-ray or CT were done

Change from baseline in lung function on the spirometry forced expiratory6 years

Volume at one second (FEV1) in Liter

Abnormal serum creatinine at baseline when diagnosed with chILD6 years

(yes/no)

Deterioration of pulmonary arterial hypertension6 years

(yes/no) Change of pulmonary artery pressure from baseline in echocardiagraphy

Hypoxemia6 years

(yes/no) Change of PO2 in arterial blood gases from baseline when diagnosed with chILD

Survival5 years

Five-year

Abnormal thyroid hormone at baseline when diagnosed with chILD6 years

(yes/no)

Abnormal myocardial zymogram at baseline when diagnosed with chILD6 years

(yes/no)

Abnormal alanine transferase at baseline when diagnosed with chILD6 years

(yes/no)

Recurrent hospitalization1 year after diagnosis

yes:Hospitalization more than twice per year after diagnosed with chILD; no:Hospitalization less than three times per year after diagnosed with chILD;

Abnormal allergen at baseline when diagnosed with chILD6 years

(yes/no)

Trial Locations

Locations (1)

Children's hospital of Fudan University

🇨🇳

Shanghai, Shanghai, China

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