背景:大多数由ATP结合盒亚家族A成员3(ABCA3)的致病变体引起的儿童间质性肺病(chILD)患者在其生命的第一年内出现严重的呼吸功能不全,如果不进行肺移植,则会死于疾病。这项基于注册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KidsLungRegister数据库中确定了因ABCA3缺乏而被诊断为chILD的患者.44例患者存活超过生命的第一年和他们的长期临床过程,对氧补充和肺功能进行了回顾。对胸部CT和组织病理学进行盲目评分。
结果:在观察期结束时,中位年龄为6.3岁(IQR:2.8~11.7),36/44(82%)在没有移植的情况下仍然存活.从未接受过补充氧气治疗的患者比持续需要补充氧气的患者存活时间更长(9.7(95%CI6.7至27.7)vs3.0年(95%CI1.5至5.0),p=0.0126)。根据肺功能(强制肺活量百分比预测绝对损失-1.1%/年)和胸部CT(重复成像的囊性病变增加),间质性肺病明显随时间进展。肺组织学模式是可变的(婴儿期慢性肺炎,非特异性间质性肺炎,和脱屑性间质性肺炎)。在37/44科目中,ABCA3序列变异是错义变异,使用计算机工具进行小的插入或缺失,可以预测一些残留的ABCA3转运蛋白功能。
结论:ABCA3相关间质性肺病的自然史在儿童期和青春期发展。改善疾病的治疗是期望的,以延迟这样的疾病进程。
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.
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.
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.
The natural history of ABCA3-related interstitial lung disease progresses during childhood and adolescence. Disease-modifying treatments are desirable to delay such disease course.