Etiologic spectrum of interstitial lung diseases in Chinese children older than 2 years of age

Abstract

Background: Childhood interstitial lung diseases (ILD) (chILD) refer to a rare heterogeneous group of disorders. Global collaborations have been working on the etiologies and classification scheme of chILD. With the development of medical technologies, some new diseases were identified to be associated with chILD and its etiologic spectrum is expanding. The aim of this study is to describe the etiologic spectrum of chILD in children older than 2 years of age and summarize the approaches to diagnosis of chILD. Methods: We made a retrospective analysis of children older than 2 years of age with chILD who referred to Beijing Children's Hospital from 21 provinces all over China from 2013 to 2018. After excluding pulmonary infection, congenital heart disease, bronchopulmonary dysplasia, bronchiolitis obliterans and bronchiectasis, 133 patients were included and categorized by etiology. Clinical manifestations, high-resolution computed tomography, laboratory data, genetic data and pathologic findings were all collected and reviewed. Results: Systemic disease associated ILD were the most common causes, accounting for 49.6% of the patients, followed by alveolar structure disorder-associated ILD (27%), exposure related ILD (13.5%), and disorders masquerading as ILD (3.8%). In systemic disease associated ILD, in addition to common etiologies such as vasculitis (10.5%) and connective tissue diseases (9.0%), primary immunodeficiency diseases (PID) associated ILD (9.8%), interstitial pneumonia with autoimmune features (6.8%), and metabolic diseases (6.8%) were not rarely found. Some newly reported etiologies such as STING-associated vasculopathy with onset in infancy, COPA syndrome and STAT3 mutation were included in PID associated ILD. Genetic tests contributed to 15% of the diagnoses which mainly distributed in PID associated ILD, metabolic diseases and surfactant dysfunction disorders, and contributed to the final diagnoses more than lung biopsies (13.5%) and biopsies of rashes or other tissues (12%). Conclusions: This study first demonstrated an etiologic spectrum of chILD in Chinese children older than 2 years of age and summarized the approaches to diagnosis. The etiologic spectrum of chILD is expanding with more genetic etiologies being recognized.

Etiologic Profile of Older Children With Diffuse Radiological Changes in Eastern China

“…Furthermore, among systemic disease associated ILD, most of etiologies was connective tissue disease. This result was similar to the previous report by Tang et al ( 5 ) presenting with the common causes of systemic disease associated ILD, alveolar structure disorder associated ILD and exposure related ILD. These studies also indicated that HRCT may also reflect the presence of ILD and disease composition of ChILD.…”

Genetic testing in interstitial lung disease: An international survey

“…A study in children with ILD (age > 2 years) showed that genetic tests contributed to 15% of the diagnoses, which was slightly better than the contribution of lung biopsies (13.5%) to the diagnosis, without having the risk associated with the surgical procedure. 23 In a pilot study for multidisciplinary team discussion on inherited pulmonary fibrosis in 95 subjects, discussion of the combined clinical, familial and genetic findings of patients resulted in a modification of the diagnosis in 10% of cases. While histology was only available in 23% of patients, performing an additional surgical lung biopsy was only proposed for four patients.…”

Genetics in Idiopathic Pulmonary Fibrosis: A Clinical Perspective

“…ABCA3 mutations-related ILDs have been described in cases of chILD surviving into adulthood and in adults [ 79 , 80 , 105 , 106 , 107 ]. The radiological imaging patterns conform more often to unclassifiable ILD with reticular abnormalities, ground glass opacities and scattered cystic lesions and may lead to the decision for lung biopsy, often disclosing a UIP pattern and in some association with non-specific or desquamative interstitial pneumonitis pattern or even pulmonary alveolar proteinosis (PAP)-like histology [ 108 , 109 , 110 ]. The major clinical implication so far described in SRG mutations relates to the high frequency (37%) of lung carcinoma (mostly of the adenocarcinoma type) alone (12%) or in combination with pulmonary fibrosis (25%) in SFTPA1/SFTPA2 adult carriers.…”