Cystic fibrosis (CF) is a monogenic disorder cause by mutations in the CF Transmembrane Regulator (CFTR) gene. The prognosis of cystic fibrosis has been transformed by the discovery of highly effective modulator therapies (HEMT). Treatment has changed from reactive therapy dealing with complications of the disease to pro-active correction of the underlying molecular functional abnormality. This has come about by discovering the detailed biology of the different CF molecular sub-endotypes; the development of biomarkers to assess response even in mild disease or young children; the performance of definitive large randomised controlled trials in patients with a common mutation and the development of in vitro testing systems to test efficacy in those patients with rare CFTR mutations. As a result, CF is now an umbrella term, rather than a specific diagnostic label; we have moved from clinical phenotypes to molecular subendotypes. Children’s Interstitial Lung Diseases (chILDs) comprise more than 200 entities, and are a diverse group of diseases, for an increasing number of which an underlying gene mutation has been discovered. Many of these entities are umbrella terms, such as pulmonary alveolar proteinosis or hypersensitivity pneumonitis, for each of which there are multiple and very different endotypes. Even those chILDs for which a specific gene mutation has been discovered comprise, as with CF, different molecular subendotypes likely mandating different therapies. For most chILDs, current treatment is non-specific (corticosteroids, azithromycin, hydroxychloroquine). The variability of the different entities means that there is little evidence for the efficacy of any treatment. This review considers how some of the lessons of the success story of CF are being applied to chILD, thus opening the opportunities for truly personalised medicine in these conditions. Advances in knowledge in the molecular biology of surfactant protein C and Adenosine triphosphate binding cassette subfamily A member 3 (ABCA3), and the possibilities of discovering novel therapies by in vitro studies will especially be highlighted.

囊性纤维化 (CF) 是一种单基因疾病，由 CF 跨膜调节因子 ( CFTR ) 基因突变引起。高效调节剂疗法 (HEMT) 的发现改变了囊性纤维化的预后。治疗已从处理疾病并发症的反应性治疗转变为主动纠正潜在的分子功能异常。这是通过发现不同 CF 分子亚型的详细生物学而实现的；开发生物标志物来评估即使是轻度疾病或幼儿的反应；在具有常见突变的患者中进行明确的大型随机对照试验，并开发体外测试系统来测试具有罕见 CFTR 突变的患者的疗效。因此，CF 现在是一个总括术语，而不是一个特定的诊断标签；我们已经从临床表型转向分子亚内型。儿童间质性肺疾病 (chILD) 包括 200 多种疾病，是一组不同的疾病，其中越来越多的疾病已被发现存在潜在的基因突变。其中许多实体都是总括术语，例如肺泡蛋白沉积症或过敏性肺炎，每种实体都有多种且截然不同的内型。即使是那些已发现特定基因突变的儿童，与 CF 一样，也包含不同的分子亚内型，可能需要不同的治疗。对于大多数儿童，目前的治疗是非特异性的（皮质类固醇、阿奇霉素、羟氯喹）。不同实体的可变性意味着几乎没有证据表明任何治疗方法有效。这篇综述考虑了如何将 CF 成功故事的一些经验教训应用于儿童，从而为这些情况下真正的个性化医疗提供机会。表面活性剂蛋白 C 和三磷酸腺苷结合盒亚家族 A 成员 3 (ABCA3) 分子生物学知识的进步，以及通过体外研究发现新疗法的可能性将得到特别强调。