1. ABCA3-related interstitial lung disease beyond infancy
- Author
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Yang Li, Elias Seidl, Katrin Knoflach, Florian Gothe, Maria Elisabeth Forstner, Katarzyna Michel, Ingo Pawlita, Florian Gesenhues, Franziska Sattler, Xiaohua Yang, Carolin Kroener, Simone Reu-Hofer, Julia Ley-Zaporozhan, Birgit Kammer, Ingrid Krüger-Stollfuß, Julien Dinkel, Julia Carlens, Martin Wetzke, Antonio Moreno-Galdó, Alba Torrent-Vernetta, Joanna Lange, Katarzyna Krenke, Nisreen Rumman, Sarah Mayell, Tugba Sismanlar, Ayse Aslan, Nicolas Regamey, Marijke Proesmans, Florian Stehling, Lutz Naehrlich, Kilinc Ayse, Sebastian Becker, Cordula Koerner-Rettberg, Erika Plattner, Effrosyni D Manali, Spyridon A Papiris, Ilaria Campo, Matthias Kappler, Nicolaus Schwerk, and Matthias Griese
- Subjects
Pulmonary and Respiratory Medicine ,Medizin ,ddc:610 - 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, theABCA3sequence 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.
- Published
- 2023