TY - JOUR T1 -哮喘抗警报:针对下一代生物制剂的气道上皮JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.00260 -2020欧元SP - 2000260 AU Porsbjerg Celeste m . AU - Sverrild asg AU -劳埃德,克莱尔m . AU - Menzies-Gow安德鲁·n . AU -贝尔,伊丽莎白h . Y1 - 2020/01/01 UR - //www.qdcxjkg.com/content/early/2020/06/11/13993003.00260 - 2020. -抽象N2 -单克隆抗体治疗明显改善严重哮喘患者的治疗结果;然而，严重的疾病负担仍然存在。现有的生物治疗，包括抗免疫球蛋白(Ig) E、抗白介素(IL)-5、抗IL- 5r α和抗IL- 4r α，仅可将研究人群的恶化率降低约50%。此外，目前还没有有效的治疗重度2型(T2)低型哮喘的方法。现有的生物制剂靶向T2炎症级联下游的免疫通路，这可能解释了为什么加重只被部分消除。例如，T2气道炎症是由除IL-5外的其他炎症信号引起的。在临床上，可以观察到IL-13驱动的部分呼出一氧化氮(FeNO)如何在抗il -5治疗中保持不变，尽管嗜酸性粒细胞减少，以及抗il - 4r α治疗中嗜酸性粒细胞如何保持不变，尽管FeNO减少。广泛的炎症反应包括包括IL-4、IL-5和IL-13在内的细胞因子，最终导致典型的加重特征(嗜酸性粒细胞性炎症、粘液产生和支气管痉挛)，是由“警报”胸腺基质淋巴生成素(TSLP)、IL-33和IL-25从气道上皮中释放，以应对触发因素。这些上皮细胞因子的中心和上游作用已被确定为强大的潜在治疗靶点，以防止病情加重和改善t2 -高和t2 -低哮喘患者的肺功能。 This article describes the effects of alarmins and discusses the potential role of anti-alarmins in the context of existing biologics. Clinical phenotypes of patients who may benefit from these treatments are also discussed, including how biomarkers may help identify potential responders.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. Porsbjerg reports grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, grants and personal fees from GlaxoSmithKline, grants and personal fees from Icepharma, grants and personal fees from Janssen, grants and personal fees from Nigaard, grants and personal fees from Nopharma, grants and personal fees from Novartis, grants and personal fees from Pharmaxis, grants and personal fees from Roche, grants and personal fees from Sandoz, grants and personal fees from Sanofi, grants and personal fees from Teva, outside the submitted work.Conflict of interest: Dr. Sverrild reports personal fees from AstraZeneca, from Sanofi Genzyme, personal fees from Novartis, outside the submitted work.Conflict of interest: Dr. Lloyd reports and Clare M Lloyd is a Wellcome Senior Fellow in Basic Biomedical Science (107059/15/Z).Conflict of interest: Dr. Menzies-Gow reports grants and personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from GlaxoSmithKline, personal fees from Novartis, personal fees from Sanofi, personal fees from Teva, personal fees from Roche, personal fees from Vectura, outside the submitted work.Conflict of interest: Dr. Bel reports personal fees from AstraZeneca, personal fees from Chiesi, personal fees from GlaxoSmithKline, personal fees from Novartis, personal fees from Sanofi, personal fees from Sterna, personal fees from Teva, outside the submitted work. ER -