Clinical trial NCT03869515: Genetic Causes and Clinical Features of Childhood Interstitial Lung Diseases in China
Official title: Genetic Causes and Clinical Features of Childhood Interstitial Lung Diseases in China
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Interstitial Lung Diseases of Childhood
Genetic Testing
Keywords: chILD
clinic features
genetic backgrounds
outcomes
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
First posted: 2019-03-11
Enrollment: 271
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: all children under 18 years old, hospitalized in Children's Hospital of Fudan University during Mar.1, 2019 and Dec.30, 2025, diagnosed with chILD , accepting empirical treatments

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Diagnosed with specific cause for chILD
timeFrame: 6 years
Secondary outcomes:
measure: Having pathogenic gene mutations
timeFrame: 6 years
measure: Hypoxemia
timeFrame: 6 years
measure: Deterioration of pulmonary imaging
timeFrame: 6 years
measure: Change from baseline in lung function on the spirometry forced expiratory
timeFrame: 6 years
measure: Abnormal autoantibody at baseline when diagnosed with chILD
timeFrame: 6 years
measure: Pathological change of lung biopsy
timeFrame: 6 years
measure: Deterioration of pulmonary arterial hypertension
timeFrame: 6 years
measure: Change of BALF(bronchoalveolar lavage fluid)
timeFrame: 6 years
measure: Survival
timeFrame: 1 years
measure: Survival
timeFrame: 2 years
measure: Survival
timeFrame: 5 years
measure: Abnormal thyroid hormone at baseline when diagnosed with chILD
timeFrame: 6 years
measure: Abnormal myocardial zymogram at baseline when diagnosed with chILD
timeFrame: 6 years
measure: Abnormal serum immunoglobulin at baseline when diagnosed with chILD
timeFrame: 6 years
measure: Abnormal serum creatinine at baseline when diagnosed with chILD
timeFrame: 6 years
measure: Abnormal blood urea nitrogen at baseline when diagnosed with chILD
timeFrame: 6 years
measure: Abnormal alanine transferase at baseline when diagnosed with chILD
timeFrame: 6 years
measure: Abnormal allergen at baseline when diagnosed with chILD
timeFrame: 6 years
measure: Recurrent hospitalization
timeFrame: 1 year after diagnosis
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Children's hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Children's Hospital of Fudan University
name: Liling Qian, MD
role: STUDY_CHAIR
References:
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.
citation: 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.
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.
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.
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. An official American Thoracic Society clinical practice guideline: classification, evaluation, and management of childhood interstitial lung disease in infancy. Am J Respir Crit Care Med. 2013 Aug 1;188(3):376-94. doi: 10.1164/rccm.201305-0923ST.