Abstract：
BACKGROUND: Therapies directed against epithelial-derived cytokines, often referred to as alarmins, have been studied in large randomized trials, and reports suggest possible benefit for non-type 2 as well as type 2 severe asthma.
METHODS: We performed a systematic review of Medline, Embase, Cochrane Central Register of Controlled Trials, Medline In-Process, and Web of Science databases from inception to March 2022. We performed a random-effects pairwise meta-analysis of randomized controlled trials addressing antialarmin therapy in severe asthma. Results use relative risk (RR) values and 95% confidence intervals (CIs). For continuous outcomes, we report mean difference (MD) values and 95% CIs. We define high eosinophils as ≥300 cells/μL and low eosinophils as <300 cells/μL. We used Cochrane-endorsed RoB 2.0 software to assess the risk of bias of trials, and we used the Grades of Recommendation Assessment, Development, and Evaluation (aka GRADE) framework to assess the certainty of the evidence.
RESULTS: We identified 12 randomized trials including 2391 patients. Antialarmins probably reduce annualized exacerbation rates in patients with high eosinophils (RR 0.33 [95% CI 0.28 to 0.38]; moderate certainty). Antialarmins may reduce this rate in patients with low eosinophils (RR 0.59 [95% CI 0.38 to 0.90]; low certainty). Antialarmins improve FEV1 in patients with high eosinophils (MD 218.5 mL [95% CI 160.2 to 276.7]; high certainty). Antialarmin therapy probably does not improve FEV1 in patients with low eosinophils (MD 68.8 mL [95% CI 22.4 to 115.2]; moderate certainty). Antialarmins reduce blood eosinophils, total IgE, and fractional excretion of nitric oxide across studied subjects.
CONCLUSIONS: Antialarmins are effective at improving lung function and probably reduce exacerbations in patients with severe asthma and blood eosinophils ≥300 cells/μL. The effect on patients with lower eosinophils is less certain.
METHODS: We performed a systematic review of Medline, Embase, Cochrane Central Register of Controlled Trials, Medline In-Process, and Web of Science databases from inception to March 2022. We performed a random-effects pairwise meta-analysis of randomized controlled trials addressing antialarmin therapy in severe asthma. Results use relative risk (RR) values and 95% confidence intervals (CIs). For continuous outcomes, we report mean difference (MD) values and 95% CIs. We define high eosinophils as ≥300 cells/μL and low eosinophils as <300 cells/μL. We used Cochrane-endorsed RoB 2.0 software to assess the risk of bias of trials, and we used the Grades of Recommendation Assessment, Development, and Evaluation (aka GRADE) framework to assess the certainty of the evidence.
RESULTS: We identified 12 randomized trials including 2391 patients. Antialarmins probably reduce annualized exacerbation rates in patients with high eosinophils (RR 0.33 [95% CI 0.28 to 0.38]; moderate certainty). Antialarmins may reduce this rate in patients with low eosinophils (RR 0.59 [95% CI 0.38 to 0.90]; low certainty). Antialarmins improve FEV1 in patients with high eosinophils (MD 218.5 mL [95% CI 160.2 to 276.7]; high certainty). Antialarmin therapy probably does not improve FEV1 in patients with low eosinophils (MD 68.8 mL [95% CI 22.4 to 115.2]; moderate certainty). Antialarmins reduce blood eosinophils, total IgE, and fractional excretion of nitric oxide across studied subjects.
CONCLUSIONS: Antialarmins are effective at improving lung function and probably reduce exacerbations in patients with severe asthma and blood eosinophils ≥300 cells/μL. The effect on patients with lower eosinophils is less certain.
摘要：
背景：上皮衍生细胞因子（EDC），通常被称为“警报”，疗法已经被大量研究，随机试验和报告提示非T2和T2重度哮喘可能获益.
方法：我们对MEDLINE进行了系统评价，Embase,Cochrane中央控制试验登记册,MedlineIn-Process和WebofScience从成立到2022年3月。我们对针对重度哮喘患者的抗alarmin治疗的随机对照试验进行了随机效应成对荟萃分析。我们使用相对风险（RR）和95％置信区间（CI）呈现我们的发现结果。对于连续的结果，我们报告平均差异(MD)和95%CI。我们将高嗜酸性粒细胞定义为大于300个细胞/uL，低嗜酸性粒细胞定义为小于300个细胞/uL。我们使用Cochrane认可的RoB2.0来评估试验偏倚的风险，并使用GRADE框架来评估证据的确定性。
结果：我们确定了12项随机试验，包括2391名患者。在高嗜酸性粒细胞患者中，抗警报因子可能会降低AER（RR0.33[95％CI0.28至0.38]；中度确定性）。抗alarmin可降低低嗜酸性粒细胞患者的AER（RR0.59[95％CI0.38至0.90]；低确定性）。在高嗜酸性粒细胞（MD218.5mL[95％CI160.2至276.7mL]；高确定性）的患者中，抗警报因子可改善FEV1。抗alarmin治疗可能不会改善低嗜酸性粒细胞患者的FEV1（MD68.8mL[95％CI22.4至115.2mL]；中等确定性）。抗警报因子减少血液嗜酸性粒细胞，研究对象的总IgE和FeNO。
结论：在重度哮喘和血液嗜酸性粒细胞大于300个细胞/uL的患者中，抗警报素可有效改善肺功能，并可能减少恶化。对嗜酸性粒细胞较低的患者的影响不太确定。
方法：我们对MEDLINE进行了系统评价，Embase,Cochrane中央控制试验登记册,MedlineIn-Process和WebofScience从成立到2022年3月。我们对针对重度哮喘患者的抗alarmin治疗的随机对照试验进行了随机效应成对荟萃分析。我们使用相对风险（RR）和95％置信区间（CI）呈现我们的发现结果。对于连续的结果，我们报告平均差异(MD)和95%CI。我们将高嗜酸性粒细胞定义为大于300个细胞/uL，低嗜酸性粒细胞定义为小于300个细胞/uL。我们使用Cochrane认可的RoB2.0来评估试验偏倚的风险，并使用GRADE框架来评估证据的确定性。
结果：我们确定了12项随机试验，包括2391名患者。在高嗜酸性粒细胞患者中，抗警报因子可能会降低AER（RR0.33[95％CI0.28至0.38]；中度确定性）。抗alarmin可降低低嗜酸性粒细胞患者的AER（RR0.59[95％CI0.38至0.90]；低确定性）。在高嗜酸性粒细胞（MD218.5mL[95％CI160.2至276.7mL]；高确定性）的患者中，抗警报因子可改善FEV1。抗alarmin治疗可能不会改善低嗜酸性粒细胞患者的FEV1（MD68.8mL[95％CI22.4至115.2mL]；中等确定性）。抗警报因子减少血液嗜酸性粒细胞，研究对象的总IgE和FeNO。
结论：在重度哮喘和血液嗜酸性粒细胞大于300个细胞/uL的患者中，抗警报素可有效改善肺功能，并可能减少恶化。对嗜酸性粒细胞较低的患者的影响不太确定。
