ABCA3-related interstitial lung disease beyond infancy

Li, Yang; Seidl, Elias ; Knoflach, Katrin; Gothe, Florian; Forstner, Maria Elisabeth; Michel, Katarzyna; Pawlita, Ingo; Gesenhues, Florian; Sattler, Franziska; Yang, Xiaohua; Kroener, Carolin; Reu-Hofer, Simone; Ley-Zaporozhan, Julia; Kammer, Birgit; Krüger-Stollfuß, Ingrid; Dinkel, Julien; Carlens, Julia; Wetzke, Martin; Moreno-Galdó, Antonio ; Torrent-Vernetta, Alba ; Lange, Joanna; Krenke, Katarzyna; Rumman, Nisreen; Mayell, Sarah; Sismanlar, Tugba; Aslan, Ayse; Regamey, Nicolas; Proesmans, Marijke; Stehling, Florian; Naehrlich, Lutz; Ayse, Kilinc; Becker, Sebastian; Koerner-Rettberg, Cordula; Plattner, Erika; Manali, Effrosyni D; Papiris, Spyridon A; Campo, Ilaria; Kappler, Matthias; Schwerk, Nicolaus und Griese, Matthias (2023): ABCA3-related interstitial lung disease beyond infancy. In: Thorax, Bd. 78, Nr. 6: S. 587-595

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Klinikum der LMU München > Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0040-6376
• Sprache: Englisch