ABCA3-related interstitial lung disease beyond infancy

Language
en
Document Type
Article
Issue Date
2023-05-22
First published
2023-06-01
Issue Year
2023
Authors
Li, Yang
Seidl, Elias
Knoflach, Katrin
Gothe, Florian
Forstner, Maria Elisabeth
Michel, Katarzyna
Pawlita, Ingo
Gesenhues, Florian
Sattler, Franziska
Yang, Xiaohua
Editor
Publisher
BMJ Publishing Group Ltd and British Thoracic Society
Abstract

BackgroundThe majority of patients with childhood interstitial lung disease (chILD) caused by pathogenic variants in ATP binding cassette subfamily A member 3 (ABCA3) develop severe respiratory insufficiency within their first year of life and succumb to disease if not lung transplanted. This register-based cohort study reviews patients with ABCA3 lung disease who survived beyond the age of 1 year.MethodOver a 21-year period, patients diagnosed as chILD due to ABCA3 deficiency were identified from the Kids Lung Register database. 44 patients survived beyond the first year of life and their long-term clinical course, oxygen supplementation and pulmonary function were reviewed. Chest CT and histopathology were scored blindly.ResultsAt the end of the observation period, median age was 6.3 years (IQR: 2.8–11.7) and 36/44 (82%) were still alive without transplantation. Patients who had never received supplemental oxygen therapy survived longer than those persistently required oxygen supplementation (9.7 (95% CI 6.7 to 27.7) vs 3.0 years (95% CI 1.5 to 5.0), p=0.0126). Interstitial lung disease was clearly progressive over time based on lung function (forced vital capacity % predicted absolute loss −1.1% /year) and on chest CT (increasing cystic lesions in those with repetitive imaging). Lung histology pattern were variable (chronic pneumonitis of infancy, non-specific interstitial pneumonia, and desquamative interstitial pneumonia). In 37/44 subjects, the ABCA3 sequence variants were missense variants, small insertions or deletions with in-silico tools predicting some residual ABCA3 transporter function.ConclusionThe natural history of ABCA3-related interstitial lung disease progresses during childhood and adolescence. Disease-modifying treatments are desirable to delay such disease course.

Journal Title
Thorax
Volume
78
Issue
6
Citation

Thorax 78.6 (2023): S. 587-595. https://thorax.bmj.com/content/78/6/587