The Dose-Response of Inhaled Corticosteroids in Combination Inhaled Corticosteroid/Long Acting Beta2-Agonist Maintenance Therapy for Asthma: A Systematic Review and Meta-Analysis.

The ICS dose-response relationship when administered as maintenance combination ICS/long-acting beta2-agonist (LABA) therapy is uncertain.

当ICS作为维持性联合ICS/长效β2受体激动剂（LABA）治疗时，其剂量反应关系尚不确定。

research_question

What is the ICS dose-response of maintenance ICS/LABA therapy?

维持ICS/LABA治疗的ICS剂量反应是什么？

study_design_and_methods

A systematic reviewwas conducted using MEDLINE, Embase, the Cochrane Register of Controlled Trials, and ClinicalTrials.gov databases to identify randomized controlled trials that allocated participants to > 1 ICS dose category, per Global Initiative for Asthma categorization, administered in combination with ICS/LABA inhalers.

使用MEDLINE、Embase、Cochrane对照试验注册处和ClinicalTrials.gov数据库进行了一项系统评价，以确定随机对照试验，这些试验将参与者分配到>1 ICS剂量类别，按照全球哮喘倡议的分类，与ICS/LABA吸入器联合使用。

Meta-analysiscompared outcomes of high-dose (HD) and medium-dose (MD), HD and low-dose (LD), and MD and LD ICS/LABA.

荟萃分析比较了高剂量(HD)与中剂量(MD)、HD与低剂量(LD)以及MD与LD吸入性皮质类固醇/长效β2受体激动剂(ICS/LABA)的治疗结果。

The primary outcome was the proportion of participants with ≥ 1 severe asthma exacerbation; secondary outcomes were patient-reported outcome measures of asthma control, spirometry, and serious adverse events.

主要结果是参与者中≥1次严重哮喘发作的比例；次要结果包括患者报告的哮喘控制结果、肺功能测试和严重不良事件。

Certainty of evidence was assessed by using the Grading of Recommendations, Assessment, Development and Evaluations domains.

证据的确定性是通过使用 GRADE 域进行评估的。

Results

Twelve randomized controlled trials (6,373 participants) were identified: 7 comparing HD vs MD ICS/LABA, 1 HD vs LD ICS/LABA, and 4 MD vs LD ICS/LABA.

确定了12项随机对照试验（6,373名参与者）：7项比较高剂量与中等剂量ICS/LABA，1项高剂量与低剂量ICS/LABA，以及4项中等剂量与低剂量ICS/LABA。

HD vs MD ICS/LABA reduced the odds of a severe asthma exacerbation (Peto's OR, 0.81; 95% CI, 0.67-0.98) with high certainty.

HD与MD ICS/LABA相比，降低了严重哮喘发作的几率（Peto's OR, 0.81; 95% 置信区间, 0.67-0.98），具有很高的确定性。

There were no other clinically important differences in efficacy or safety outcomes of HD vs MD ICS/LABA.

在疗效或安全性结果方面，HD与MD ICS/LABA之间没有其他临床上重要的差异。

There was no difference in all outcomes comparing HD with LD or MD with LD ICS/LABA.

在比较高剂量（HD）与低剂量（LD）或中剂量（MD）吸入皮质类固醇/长效β2受体激动剂（ICS/LABA）时，所有结果均无差异。

interpretation

Our results showed that maintenance HD ICS/LABA reduced the odds of a severe exacerbation by about 20% compared with MD ICS/LABA.

我们的结果显示，维持高剂量ICS/LABA与中剂量ICS/LABA相比，严重发作的几率降低了大约20%。

The absolute reduction in severe exacerbation risk with HD ICS/LABA is determined by patients' exacerbation risk, and this effect size may be clinically relevant for patients if this risk is high.

HD ICS/LABA 对严重加重风险的绝对降低取决于患者的加重风险，如果这种风险很高，这种效应大小可能对患者具有临床相关性。

Comparisons of other doses of ICS/LABA were limited by the number of identified studies, although no large difference in effect sizes were observed.

尽管观察到的效应大小没有大的差异，但其他剂量的ICS/LABA比较受到已识别研究数量的限制。