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Emerging therapies in adult and paediatric bronchiectasis

机译:在成人和小儿支气管扩张中的新出现的疗法

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ABSTRACT Bronchiectasis is a chronic respiratory disorder characterized by persistent productive cough and recurrent chest infections secondary to permanent structural airway damage. The current treatment strategies for this debilitating disorder are limited to prompt antibiotic treatment of infective exacerbations and regular airway clearance techniques. Despite its high morbidity and associated mortality across all age groups, it has been a neglected area of research in respiratory medicine and there remain no licensed disease‐modifying therapies. In this review, we have explored the numerous potential therapeutic targets to break the vicious cycle of infection and inflammation seen in these patients and the novel therapeutic agents that have been developed to target them. We have reviewed the role of novel anti‐inflammatory agents designed to target the persistent neutrophilic inflammatory infiltrate seen in bronchiectatic airways, including neutrophil elastase inhibitors, CXCR2 (CXC chemokine receptor 2) antagonists, DPP‐1 (dipeptidyl peptidase 1) inhibitors, PDE4 (phosphodiesterase 4) inhibitors and statins. Furthermore, we have explored novel targets to improve mucociliary clearance, namely ENaC (epithelial sodium channel) inhibitors, and discussed the potential of alternative antimicrobial strategies such as inhaled phages. Our review highlights the importance of a multi‐faceted approach to bronchiectasis management, which aims not only to eradicate or suppress bronchial infection but also to break the cycle of persistent airway inflammation that results in progressive lung damage in these patients.
机译:摘要支气管扩张是一种慢性呼吸系统障碍,其特征在于持续的生产性咳嗽和继发性胸部感染,继发于永久结构气道损坏。这种衰弱障碍的目前的治疗策略仅限于促进感染性加剧和常规气道清除技术的抗生素治疗。尽管所有年龄群体的发病率高和相关的死亡率高,但它已被忽视的呼吸系统研究领域,并且仍然没有许可的疾病改性疗法。在这篇综述中,我们探讨了众多潜在的治疗目标来破坏这些患者中所见的感染和炎症的恶性循环和已开发为靶向它们的新型治疗剂。我们已经审查了新型抗炎剂的作用,该抗炎剂设计用于靶向支气管血管中的持续性嗜中性炎症浸润,包括中性粒细胞弹性蛋白酶抑制剂,CXCR2(CXC趋化因子受体2)拮抗剂,DPP-1(二肽基肽酶1)抑制剂,PDE4(磷酸二酯酶4)抑制剂和他汀类药物。此外,我们已经探索了新的靶标以改善粘蛋白清除,即enac(上皮钠通道)抑制剂,并讨论了吸入噬菌体等替代抗微生物策略的潜力。我们的评论强调了多方面方法对支气管扩张管理的重要性,这不仅旨在消除或抑制支气管感染,还旨在破坏持续的气道炎症的循环,导致这些患者的进步肺部损伤。

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