TY - JOUR T1 - Neutrophil dysfunction in bronchiectasis: an emerging role for immunometabolism JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.03157-2020 SP - 2003157 AU - Giam, Yan Hui AU - Shoemark, Amelia AU - Chalmers,James D Y1-2021/01/01 UR -http：//www.qdcxjkg.com/content/early/2021/01/01/21/13993003.03157-2020.Abstract N2-支气管疾病 - 支气管疾病是多种下层疾病的异常疾病。病理生理学知之甚少，但嗜中性炎症和病原体功能失调被认为是关键。但是，没有直接靶向嗜中性炎症的支气管扩张的许可疗法。在这篇综述中，我们讨论了我们目前对支气管扩张中嗜中性粒细胞功能障碍和治疗靶向的理解。免疫代谢重编程是在多种炎症性和自身免疫性疾病中越来越多地识别出炎症通过改变细胞内代谢途径来改变炎症细胞行为的过程。在这里，我们显示的证据表明，支气管扩张中观察到的许多中性粒细胞功能障碍与免疫代谢重编程一致。先前试图开发靶向嗜中性粒细胞的疗法的尝试已重点是减少中性粒细胞数量，从而增加感染。需要新的方法，我们建议靶向代谢理论上可以反向中性粒细胞功能障碍和失调的炎症。作为一个典范，AMPK激活已被证明可以逆转肺部疾病模型中的吞噬性功能障碍和中性粒细胞外陷阱。 AMPK modulates multiple metabolic pathways including glycolysis which is critical for energy generation in neutrophils. AMPK activators can reverse metabolic reprogramming and are already in clinical use and/or development. We propose the need for a new immunomodulatory, rather than anti-inflammatory, approach to enhance bacterial clearance and reduce bronchiectasis disease severity.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Giam has nothing to disclose.Conflict of interest: Dr. Shoemark has nothing to disclose.Conflict of interest: Dr. Chalmers reports grants and personal fees from Astrazeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Chiesi, grants and personal fees from Glaxosmithkline, grants from Gilead Sciences, grants and personal fees from Insmed, personal fees from Novartis, personal fees from Zambon, outside the submitted work;. ER -