PT  - JOURNAL ARTICLE
AU  - Li, Yang
AU  - Seidl, Elias
AU  - Knoflach, Katrin
AU  - Gothe, Florian
AU  - Forstner, Maria Elisabeth
AU  - Michel, Katarzyna
AU  - Pawlita, Ingo
AU  - Gesenhues, Florian
AU  - Sattler, Franziska
AU  - Yang, Xiaohua
AU  - Kroener, Carolin
AU  - Reu-Hofer, Simone
AU  - Ley-Zaporozhan, Julia
AU  - Kammer, Birgit
AU  - Krüger-Stollfuß, Ingrid
AU  - Dinkel, Julien
AU  - Carlens, Julia
AU  - Wetzke, Martin
AU  - Moreno-Galdó, Antonio
AU  - Torrent-Vernetta, Alba
AU  - Lange, Joanna
AU  - Krenke, Katarzyna
AU  - Rumman, Nisreen
AU  - Mayell, Sarah
AU  - Sismanlar, Tugba
AU  - Aslan, Ayse
AU  - Regamey, Nicolas
AU  - Proesmans, Marijke
AU  - Stehling, Florian
AU  - Naehrlich, Lutz
AU  - Ayse, Kilinc
AU  - Becker, Sebastian
AU  - Koerner-Rettberg, Cordula
AU  - Plattner, Erika
AU  - Manali, Effrosyni D
AU  - Papiris, Spyridon A
AU  - Campo, Ilaria
AU  - Kappler, Matthias
AU  - Schwerk, Nicolaus
AU  - Griese, Matthias
TI  - ABCA3-related interstitial lung disease beyond infancy
AID  - 10.1136/thorax-2022-219434
DP  - 2023 Jun 01
TA  - Thorax
PG  - 587--595
VI  - 78
IP  - 6
4099  - http://thorax.bmj.com/content/78/6/587.short
4100  - http://thorax.bmj.com/content/78/6/587.full
SO  - Thorax2023 Jun 01; 78
AB  - Background The 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.Method Over 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.Results At 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.Conclusion The natural history of ABCA3-related interstitial lung disease progresses during childhood and adolescence. Disease-modifying treatments are desirable to delay such disease course.Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information.