ABCA3-related interstitial lung disease beyond infancy

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.

• Li, Y.
• Seidl, E.
• Knoflach, K.
• Gothe, F.
• Forstner, M. E.
• Michel, K.
• Pawlita, I.
• Gesenhues, F.
• Sattler, F.
• Yang, X.
• Kroener, C.
• Reu-Hofer, S.
• Ley-Zaporozhan, J.
• Kammer, B.
• Krüger-Stollfuß, I.
• Dinkel, J.
• Carlens, J.
• Wetzke, M.
• Moreno-Galdó, 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, E. D.
• Papiris, S. A.
• Campo, I.
• Kappler, M.
• Schwerk, N.
• Griese, M.