Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy.
Cystic Fibrosis Support Center, Ospedale "G. Tatarella", 71042 Cerignola, Italy.
Genes (Basel). 2023 Oct 20;14(10):1966. doi: 10.3390/genes14101966.
Cystic fibrosis (CF) is a monogenic syndrome determined by over 2000 mutations in the () gene harbored on chromosome 7. In people with CF (PWCF), lung disease is the major determinant of morbidity and mortality and is characterized by a clinical phenotype which differs in the presence of equal mutational assets, indicating that genetic and environmental modifiers play an important role in this variability. Airway inflammation determines the pathophysiology of CF lung disease (CFLD) both at its onset and progression. In this narrative review, we aim to depict the inflammatory process in CF lung, with a particular emphasis on those genetic polymorphisms that could modify the clinical outcome of the respiratory disease in PWCF. The natural history of CF has been changed since the introduction of CFTR modulator therapies in the clinical arena. However, also in this case, there is a patient-to-patient variable response. We provide an overview on inflammatory/immunity gene variants that affect CFLD severity and an appraisal of the effects of CFTR modulator therapies on the inflammatory process in lung disease and how this knowledge may advance the optimization of the management of PWCF.
囊性纤维化 (CF) 是一种由位于 7 号染色体上的 () 基因中超过 2000 种突变引起的单基因综合征。在患有 CF (PWCF) 的人中，肺部疾病是发病率和死亡率的主要决定因素，其临床表型特征为在具有相同突变资产的情况下存在差异，表明遗传和环境修饰因子在这种变异性中起着重要作用。气道炎症决定了 CF 肺部疾病 (CFLD) 的发病机制及其进展。在这篇叙述性综述中，我们旨在描述 CF 肺部的炎症过程，特别强调那些可能改变 PWCF 呼吸道疾病临床结果的遗传多态性。自从 CFTR 调节剂治疗在临床领域问世以来，CF 的自然史已经发生了变化。然而，即使在这种情况下，也存在患者间的可变反应。我们概述了影响 CFLD 严重程度的炎症/免疫基因变异，并评估了 CFTR 调节剂治疗对肺部疾病炎症过程的影响，以及这些知识如何有助于优化 PWCF 的管理。
