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.

中文翻译：

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婴儿期以后与 ABCA3 相关的间质性肺疾病

背景 大多数由 ATP 结合盒亚家族 A 成员 3 (ABCA3) 致病性变异引起的儿童间质性肺疾病 (chILD) 患者在出生后第一年内出现严重呼吸功能不全，如果不进行肺移植，就会死于疾病。这项基于登记的队列研究回顾了存活超过 1 岁的 ABCA3 肺病患者。方法 在 21 年的时间里，从儿童肺登记数据库中识别出因 ABCA3 缺乏症而被诊断为儿童的患者。44 名患者存活超过一年，并对他们的长期临床病程、供氧情况和肺功能进行了回顾。胸部CT和组织病理学进行盲法评分。结果 观察期结束时，中位年龄为 6.3 岁（IQR：2.8-11）。7) 和 36/44 (82%) 在没有移植的情况下仍然存活。从未接受过吸氧治疗的患者比持续需要吸氧的患者存活时间更长（9.7 年（95% CI 6.7 至 27.7） vs 3.0 年（95% CI 1.5 至 5.0），p = 0.0126）。根据肺功能（用力肺活量％预测绝对损失-1.1％/年）和胸部CT（重复成像的囊性病变增加），间质性肺疾病随着时间的推移明显进展。肺组织学模式各不相同（婴儿慢性肺炎、非特异性间质性肺炎和脱屑性间质性肺炎）。在 37/44 的受试者中，ABCA3 序列变异是错义变异、小插入或缺失，用计算机工具预测一些残留的 ABCA3 转运蛋白功能。结论 ABCA3 相关间质性肺疾病的自然病程在儿童期和青春期进展。需要缓解疾病的治疗来延缓这种病程。可根据合理要求提供数据。与研究相关的所有数据都包含在文章中或作为在线补充信息上传。