ABCA3-related interstitial lung disease beyond infancy

Li Y, Seidl E, Knoflach K, Gothe F, Forstner ME, Michel K, Pawlita I, Gesenhues F, Sattler F, Yang X, Kroener C, Reu-Hofer S, Ley-Zaporozhan J, Kammer B, Krueger-Stollfuss I, Dinkel J, Carlens J, Wetzke M, Moreno-Galdo A, Torrent-Vernetta A, Lange J, Krenke K, Rumman N, Mayell S, Sismanlar T, Aslan A, Regamey N, Proesmans M, Stehling F, Naehrlich L, Ayse K, Becker S, Koerner-Rettberg C, Plattner E, Manali ED, Papiris SA, Campo I, Kappler M, Schwerk N, Griese M (2023)

Publication Type: Journal article

Publication year: 2023

Journal

DOI: 10.1136/thorax-2022-219434

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.

Involved external institutions

Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu Poland (PL) Ludwig-Maximilians-Universität (LMU) Germany (DE) Autonomous University of Barcelona (UAB) / Universitat Autònoma de Barcelona Spain (ES) National and Kapodistrian University of Athens Greece (GR) Universitätsklinikum Essen Germany (DE) Policlinico San Matteo Pavia Fondazione IRCCS Italy (IT) Luzerner Kantonsspital (LUKS) Switzerland (CH) Marien-Hospital Germany (DE) Deutsches Zentrum für Lungenforschung e.V. (DZL) Germany (DE) Julius-Maximilians-Universität Würzburg Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Gazi University Turkey (TR) Justus-Liebig-Universität Gießen Germany (DE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Istanbul University Cerrahpaşa / İstanbul Üniversitesi Cerrahpaşa (IUC) Turkey (TR) Darmstädter Kinderkliniken Prinzessin Margaret Germany (DE) Makassed Islamic Charitable Society Palestinian Territory, Occupied (PS) Alder Hey Children's Hospital United Kingdom (GB)

How to cite

APA:

Li, Y., Seidl, E., Knoflach, K., Gothe, F., Forstner, M.E., Michel, K.,... Griese, M. (2023). ABCA3-related interstitial lung disease beyond infancy. Thorax. https://dx.doi.org/10.1136/thorax-2022-219434

MLA:

Li, Yang, et al. "ABCA3-related interstitial lung disease beyond infancy." Thorax (2023).

BibTeX: Download