TY -的T1 Anti-alarmins哮喘: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,一个重要的疾病负担。可用的生物治疗方法,包括anti-immunoglobulin (Ig) E, anti-interleukin (IL) 5、anti-IL-5Rαanti-IL-4Rα,减少恶化率研究人口仅约50%。此外,目前没有有效的治疗方法对患者严重,2型(T2)低哮喘。现有生物目标免疫通路下游的T2炎症级联,这或许可以解释为什么发作只是部分废除。例如,T2气道炎症的结果从几个除了IL-5炎症信号。临床上,这可以观察到部分呼出一氧化氮(FeNO),这是由IL-13,可能保持不变anti-IL-5治疗期间尽管减少嗜酸性粒细胞,嗜酸性粒细胞如何可能在治疗anti-IL-4Rα尽管减少FeNO维持不变。广泛的炎症反应涉及细胞因子il - 4、IL-5 IL-13,最终导致发作的典型特征(嗜酸性炎症,粘液生产和支气管痉挛)是由释放“alarmins”胸腺基质淋巴细胞生成素(TSLP) IL-33和IL-25反应气道上皮的触发器。中央,上游这些上皮细胞因子已经确定他们的角色作为强大的潜在的治疗靶点,以防止恶化和改善T2-high和T2-low哮喘患者的肺功能。本文描述的影响alarmins并讨论anti-alarmins的潜在作用的背景下,现有的生物制剂。 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 -