重度哮喘的抗上皮来源细胞因子：系统评价和荟萃分析
2023/07/25
摘要
背景：针对上皮来源的细胞因子(通常称为警报素)的疗法已在大型随机试验中进行过研究，有报告提示对非2型和2型重度哮喘可能有益。
方法：我们对Medline、Embase、Cochrane Central Register of Controlled Trials、Medline In-Process和Web of Science数据库进行了一项系统综述，时间从建库至2022年3月。我们对抗警报素治疗重度哮喘的随机对照试验进行了随机效应配对荟萃分析。结果采用相对危险度(RR)值和95%可信区间(CIs)。对于连续结局，我们报告了平均差(MD)值和95% CI。我们将高嗜酸性粒细胞定义为300个/muL，而将低嗜酸性粒细胞定义为300个/muL。采用RoB 2.0软件评估纳入研究的偏倚风险，采用推荐的分级、评估、制定与评价（GRADE）框架评估证据质量。
结果：我们确定了12项随机试验，包括2,391例患者。抗警报素可能降低高嗜酸性粒细胞患者的年加重率(RR 0.33 [95% CI 0.28～0.38];中等质量)。在嗜酸性粒细胞低的患者中，抗警报素可能降低这一发生率(RR 0.59 [95% CI 0.38～0.90];低质量)。抗警报素改善高嗜酸性粒细胞患者的FEV(1)(MD 218.5 mL [95% CI 160.2～276.7];高质量)。抗警报素治疗可能不能改善低嗜酸性粒细胞患者的FEV(1)(MD 68.8 mL [95% CI 22.4～115.2];中等质量)。抗警报素可降低研究对象的血嗜酸性粒细胞、总IgE和一氧化氮排泄分数。
结论：对于血嗜酸性粒细胞=300个/muL的严重哮喘患者，抗警报素可有效改善肺功能，并可能减少发作。对嗜酸性粒细胞较低的患者产生的影响不太确定。
Anti-epithelial-derived cytokines for severe asthma: Systematic review and meta-analysis
J. Su, T. Pitre, K. Desai, J. Mah, P. Nair, T. Ho, et al.
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.
METHOD: 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/muL and low eosinophils as <300 cells/muL. 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.
RESULT: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 FEV(1) in patients with high eosinophils (MD 218.5 mL [95% CI 160.2 to 276.7]; high certainty). Antialarmin therapy probably does not improve FEV(1) 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.
CONCLUSION: Antialarmins are effective at improving lung function and probably reduce exacerbations in patients with severe asthma and blood eosinophils >/=300 cells/muL. The effect on patients with lower eosinophils is less certain.
背景：针对上皮来源的细胞因子(通常称为警报素)的疗法已在大型随机试验中进行过研究，有报告提示对非2型和2型重度哮喘可能有益。
方法：我们对Medline、Embase、Cochrane Central Register of Controlled Trials、Medline In-Process和Web of Science数据库进行了一项系统综述，时间从建库至2022年3月。我们对抗警报素治疗重度哮喘的随机对照试验进行了随机效应配对荟萃分析。结果采用相对危险度(RR)值和95%可信区间(CIs)。对于连续结局，我们报告了平均差(MD)值和95% CI。我们将高嗜酸性粒细胞定义为300个/muL，而将低嗜酸性粒细胞定义为300个/muL。采用RoB 2.0软件评估纳入研究的偏倚风险，采用推荐的分级、评估、制定与评价（GRADE）框架评估证据质量。
结果：我们确定了12项随机试验，包括2,391例患者。抗警报素可能降低高嗜酸性粒细胞患者的年加重率(RR 0.33 [95% CI 0.28～0.38];中等质量)。在嗜酸性粒细胞低的患者中，抗警报素可能降低这一发生率(RR 0.59 [95% CI 0.38～0.90];低质量)。抗警报素改善高嗜酸性粒细胞患者的FEV(1)(MD 218.5 mL [95% CI 160.2～276.7];高质量)。抗警报素治疗可能不能改善低嗜酸性粒细胞患者的FEV(1)(MD 68.8 mL [95% CI 22.4～115.2];中等质量)。抗警报素可降低研究对象的血嗜酸性粒细胞、总IgE和一氧化氮排泄分数。
结论：对于血嗜酸性粒细胞=300个/muL的严重哮喘患者，抗警报素可有效改善肺功能，并可能减少发作。对嗜酸性粒细胞较低的患者产生的影响不太确定。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（J Allergy Clin Immunol 2023 Vol. 151 Issue 6 Pages 1566-1576 DOI: 10.1016/j.jaci.2023.02.021）
Anti-epithelial-derived cytokines for severe asthma: Systematic review and meta-analysis
J. Su, T. Pitre, K. Desai, J. Mah, P. Nair, T. Ho, et al.
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.
METHOD: 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/muL and low eosinophils as <300 cells/muL. 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.
RESULT: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 FEV(1) in patients with high eosinophils (MD 218.5 mL [95% CI 160.2 to 276.7]; high certainty). Antialarmin therapy probably does not improve FEV(1) 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.
CONCLUSION: Antialarmins are effective at improving lung function and probably reduce exacerbations in patients with severe asthma and blood eosinophils >/=300 cells/muL. The effect on patients with lower eosinophils is less certain.
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