Carrasco-Hernández Laura, Quintana-Gallego Esther, Calero Carmen, Reinoso-Arija Rocío, Ruiz-Duque Borja, López-Campos José Luis
Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, 41013 Sevilla, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Biomedicines. 2021 Oct 10;9(10):1437. doi: 10.3390/biomedicines9101437.
In recent years, numerous pathways were explored in the pathogenesis of COPD in the quest for new potential therapeutic targets for more personalised medical care. In this context, the study of the cystic fibrosis transmembrane conductance regulator (CFTR) began to gain importance, especially since the advent of the new CFTR modulators which had the potential to correct this protein's dysfunction in COPD. The CFTR is an ion transporter that regulates the hydration and viscosity of mucous secretions in the airway. Therefore, its abnormal function favours the accumulation of thicker and more viscous secretions, reduces the periciliary layer and mucociliary clearance, and produces inflammation in the airway, as a consequence of a bronchial infection by both bacteria and viruses. Identifying CFTR dysfunction in the context of COPD pathogenesis is key to fully understanding its role in the complex pathophysiology of COPD and the potential of the different therapeutic approaches proposed to overcome this dysfunction. In particular, the potential of the rehydration of mucus and the role of antioxidants and phosphodiesterase inhibitors should be discussed. Additionally, the modulatory drugs which enhance or restore decreased levels of the protein CFTR were recently described. In particular, two CFTR potentiators, ivacaftor and icenticaftor, were explored in COPD. The present review updated the pathophysiology of the complex role of CFTR in COPD and the therapeutic options which could be explored.
近年来,为了寻求更具个性化医疗护理的新潜在治疗靶点,人们在慢性阻塞性肺疾病(COPD)的发病机制中探索了众多途径。在此背景下,囊性纤维化跨膜传导调节因子(CFTR)的研究开始变得重要起来,尤其是自新型CFTR调节剂问世以来,这些调节剂有可能纠正COPD中该蛋白的功能障碍。CFTR是一种离子转运体,可调节气道黏液分泌物的水合作用和黏稠度。因此,其功能异常有利于更黏稠分泌物的积聚,减少纤毛周围层和黏液纤毛清除功能,并由于细菌和病毒引起的支气管感染而导致气道炎症。在COPD发病机制的背景下识别CFTR功能障碍,对于全面理解其在COPD复杂病理生理学中的作用以及为克服这种功能障碍而提出的不同治疗方法的潜力至关重要。特别是,应讨论黏液再水化的潜力以及抗氧化剂和磷酸二酯酶抑制剂的作用。此外,最近还描述了增强或恢复CFTR蛋白降低水平的调节药物。特别是,在COPD中探索了两种CFTR增强剂,依伐卡托和艾替卡托。本综述更新了CFTR在COPD中复杂作用的病理生理学以及可探索的治疗选择。