Rare lung diseases in children: phenotyping, genetics, course and disease burden

儿童间质性肺病（chILD）包括许多罕见的慢性疾病，通常由强烈的遗传因素引起，其病程在很大程度上尚未查明。儿童肺生物库注册（chILD-EU）是一个收集、同行评审和监测这些疾病的开放平台。在之前的资助期内，我们实施并成功应用了基于数据的途径，分子遗传学，儿童的功能和临床特征，并产生了新的，可测试的假设。现在，通过应用适当的、技术先进的分子方法，这些问题将在具有所需生物材料的仔细表型的患者群体中得到解答。第一个工作包将调查是否可以通过有针对性地使用先进的基因组和转录组分析，将病因解决的儿童病例的比例至少提高10%。第二个工作包将使用大量的婴儿持续性呼吸急促（NEHI）家庭队列来研究病原学相关基因是否位于我们在1号染色体上确定的候选区域的假设。在第3个工作包中，我们将研究儿童肺纤维化是否会对长期预后产生不良影响，继发性肺动脉高压是否没有影响，以及伴有chILD和肺外器官表现的婴儿是否会增加发病率和降低生活质量。我们期望从分子上阐明新的疾病实体，改善其遗传学诊断，并阐明儿童肺纤维化、肺动脉高压的影响，以及合并症对儿童间质性肺疾病患者长期病程的影响。

Childhood interstitial lung diseases (chILD) comprises many, rare chronic diseases, often caused by strong genetic factors, whose disease course is largely unexplored. The Children's Lung Registry with Biobank (chILD-EU) is an open platform for the collection, peer-review, and monitoring of these diseases. In the previous funding period, we implemented and successfully applied pathways for data-based, molecular genetics, functional and clinical characterization of chILD, and also generated new, testable hypotheses. These will now be answered in carefully phenotyped patient populations with the required biomaterials, by applying appropriate, technically advanced molecular methods. The 1st work package will investigate whether the proportion of etiologically resolved cases of chILD can be increased by at least 10% by targeted use of advanced genomic and transcriptome analyses. The 2nd work package will use a large cohort of families with persistent tachypnea of infancy (NEHI) to investigate the hypothesis of whether etiologically relevant genes are located in the candidate regions we have identified on chromosome 1. In the 3rd work package, we will investigate whether pulmonary fibrosis in children adversely affects long-term outcome, whether secondary pulmonary hypertension has no effect, and whether infants with chILD and extrapulmonary organ manifestations have increased morbidity and poorer quality of life.We expect to molecularly elucidate new disease entities, improve their genetic diagnosis, and clarify the impact of childhood pulmonary fibrosis, pulmonary hypertension, and the influence of co-morbidities on the long-term course of patients with childhood interstitial lung diseases.