在症状未控制的持续哮喘患者中吸入性糖皮质激素联合长效毒蕈碱受体拮抗剂与哮喘控制的关系：一项系统性回顾 Meta 分析
2018/06/04
摘要
重要性：长效毒蕈碱受体拮抗剂（LAMAs）可作为吸入性糖皮质激素（Inhaled Corticosteroids, ICS）的潜在辅助疗法，来治疗持续性哮喘。
目的：搜集关于在症状未控制的持续哮喘患者中应用LAMA作为ICS附加用药，与安慰剂或其他对照药物的疗效对比的研究，以及ICS+LAMA+LABA vs. ICS+LAMA的疗效对比研究，并将相关依据汇总成系统回顾和荟萃分析。
数据源：MEDLINE，EMBASE，Cochrane数据库和临床试验注册表（从建库至2017年11月28日）。
研究选择：两名研究者选择关于比较ICS联合LAMA与ICS 联合安慰剂或其他方法，以及三联与单纯ICS联合LABA对症状未控制持续哮喘患者的疗效的随机临床试验或观察性研究。
数据提取和合成：使用随机效应模型进行Meta分析以计算风险比（RR），风险差异（RD）和平均差异（MDs）以及相应的95％置信区间。纳入研究的筛选，数据的提取，风险的评估和证据强度的分级均由2位研究者独立完成。
主要终点：哮喘急性加重。
结果：共搜索到1326篇研究，最终纳入15项随机临床试验（共 7122例患者）。大多数试验比较了ICS联合LAMA与ICS联合安慰剂或ICS联合LAMA与ICS联合LABA对哮喘患者的疗效。其中，ICS联合LAMA与联合安慰剂相比，急性加重的风险（需要系统性应用糖皮质激素）显着降低（RR=0.67, 95％CI[0.48-0.92]; RD=-0.02, 95％CI[-0.04-0.00]）。与ICS联合LABA相比，ICS联合LAMA治疗并没有显著改善哮喘患者急性加重的风险（RR=0.87, 95％CI[0.53-1.42]; RD=0.00, 95％CI[-0.02- 0.02]），对其他感兴趣的指标比较也未发现差异。三联疗法与单纯ICS联合LABA相比也未显著改善患者急性加重风险（RR=0.84, 95％CI[0.57-1.22]; RD=-0.01, 95％CI[-0.08-0.07]）。
结论和相关性：在本系统回顾和荟萃分析中，与联合安慰剂相比，ICS联合LAMA与哮喘急性加重的风险减低相关；但联合LAMA治疗的相关获益并不比联合LABA更高。此外，三联疗法与急性加重风险减低无关。
Association of Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists With Asthma Control in Patients With Uncontrolled, Persistent Asthma: A Systematic Review and Meta-analysis.
Abstract
Importance:Long-acting muscarinic antagonists (LAMAs) are a potential adjunct therapy to inhaled corticosteroids in the management of persistent asthma.
Objective:To conduct a systematic review and meta-analysis of the effects associated with LAMA vs placebo or vs other controllers as an add-on therapy to inhaled corticosteroids and the use of a LAMA as add-on therapy to inhaled corticosteroids and long-acting β-agonists (LABAs; hereafter referred to as triple therapy) vs inhaled corticosteroids and LABA in patients with uncontrolled, persistent asthma.
Data Sources:MEDLINE, EMBASE, Cochrane databases, and clinical trial registries (earliest date through November 28, 2017).
Study Selection:Two reviewers selected randomized clinical trials or observational studies evaluating a LAMA vs placebo or vs another controller as an add-on therapy to inhaled corticosteroids or triple therapy vs inhaled corticosteroids and LABA in patients with uncontrolled, persistent asthma reporting on an outcome of interest.
Data Extraction and Synthesis:Meta-analyses using a random-effects model was conducted to calculate risk ratios (RRs), risk differences (RDs), and mean differences (MDs) with corresponding 95% CIs. Citation screening, data abstraction, risk assessment, and strength-of-evidence grading were completed by 2 independent reviewers.
Main Outcomes and Measures: Asthma exacerbations.
Results:Of 1326 records identified, 15 randomized clinical trials (N = 7122 patients) were included. Most trials assessed adding LAMA vs placebo or LAMA vs LABA to inhaled corticosteroids. Adding LAMA vs placebo to inhaled corticosteroids was associated with a significantly reduced risk of exacerbation requiring systemic corticosteroids (RR, 0.67 [95% CI, 0.48 to 0.92]; RD, -0.02 [95% CI, -0.04 to 0.00]). Compared with adding LABA, adding LAMA to inhaled corticosteroids was not associated with significant improvements in exacerbation risk (RR, 0.87 [95% CI, 0.53 to 1.42]; RD, 0.00 [95% CI, -0.02 to 0.02]), or any other outcomes of interest. Triple therapy was not significantly associated with improved exacerbation risk vs inhaled corticosteroids and LABA (RR, 0.84 [95% CI, 0.57 to 1.22]; RD, -0.01 [95% CI, -0.08 to 0.07]).
Conclusions and Relevance:In this systematic review and meta-analysis, the use of LAMA compared with placebo as add-on therapy to inhaled corticosteroids was associated with a lower risk of asthma exacerbations; however, the association of LAMA with benefit may not be greater than that with LABA. Triple therapy was not associated with a lower risk of exacerbations.
重要性：长效毒蕈碱受体拮抗剂（LAMAs）可作为吸入性糖皮质激素（Inhaled Corticosteroids, ICS）的潜在辅助疗法，来治疗持续性哮喘。
目的：搜集关于在症状未控制的持续哮喘患者中应用LAMA作为ICS附加用药，与安慰剂或其他对照药物的疗效对比的研究，以及ICS+LAMA+LABA vs. ICS+LAMA的疗效对比研究，并将相关依据汇总成系统回顾和荟萃分析。
数据源：MEDLINE，EMBASE，Cochrane数据库和临床试验注册表（从建库至2017年11月28日）。
研究选择：两名研究者选择关于比较ICS联合LAMA与ICS 联合安慰剂或其他方法，以及三联与单纯ICS联合LABA对症状未控制持续哮喘患者的疗效的随机临床试验或观察性研究。
数据提取和合成：使用随机效应模型进行Meta分析以计算风险比（RR），风险差异（RD）和平均差异（MDs）以及相应的95％置信区间。纳入研究的筛选，数据的提取，风险的评估和证据强度的分级均由2位研究者独立完成。
主要终点：哮喘急性加重。
结果：共搜索到1326篇研究，最终纳入15项随机临床试验（共 7122例患者）。大多数试验比较了ICS联合LAMA与ICS联合安慰剂或ICS联合LAMA与ICS联合LABA对哮喘患者的疗效。其中，ICS联合LAMA与联合安慰剂相比，急性加重的风险（需要系统性应用糖皮质激素）显着降低（RR=0.67, 95％CI[0.48-0.92]; RD=-0.02, 95％CI[-0.04-0.00]）。与ICS联合LABA相比，ICS联合LAMA治疗并没有显著改善哮喘患者急性加重的风险（RR=0.87, 95％CI[0.53-1.42]; RD=0.00, 95％CI[-0.02- 0.02]），对其他感兴趣的指标比较也未发现差异。三联疗法与单纯ICS联合LABA相比也未显著改善患者急性加重风险（RR=0.84, 95％CI[0.57-1.22]; RD=-0.01, 95％CI[-0.08-0.07]）。
结论和相关性：在本系统回顾和荟萃分析中，与联合安慰剂相比，ICS联合LAMA与哮喘急性加重的风险减低相关；但联合LAMA治疗的相关获益并不比联合LABA更高。此外，三联疗法与急性加重风险减低无关。
(中国医科大学附属第一医院呼吸与危重症医学科 李文扬 摘译 杨冬 审校)
(Sobieraj DM et al. JAMA. 2018 Mar 19. )
(Sobieraj DM et al. JAMA. 2018 Mar 19. )
Association of Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists With Asthma Control in Patients With Uncontrolled, Persistent Asthma: A Systematic Review and Meta-analysis.
Abstract
Importance:Long-acting muscarinic antagonists (LAMAs) are a potential adjunct therapy to inhaled corticosteroids in the management of persistent asthma.
Objective:To conduct a systematic review and meta-analysis of the effects associated with LAMA vs placebo or vs other controllers as an add-on therapy to inhaled corticosteroids and the use of a LAMA as add-on therapy to inhaled corticosteroids and long-acting β-agonists (LABAs; hereafter referred to as triple therapy) vs inhaled corticosteroids and LABA in patients with uncontrolled, persistent asthma.
Data Sources:MEDLINE, EMBASE, Cochrane databases, and clinical trial registries (earliest date through November 28, 2017).
Study Selection:Two reviewers selected randomized clinical trials or observational studies evaluating a LAMA vs placebo or vs another controller as an add-on therapy to inhaled corticosteroids or triple therapy vs inhaled corticosteroids and LABA in patients with uncontrolled, persistent asthma reporting on an outcome of interest.
Data Extraction and Synthesis:Meta-analyses using a random-effects model was conducted to calculate risk ratios (RRs), risk differences (RDs), and mean differences (MDs) with corresponding 95% CIs. Citation screening, data abstraction, risk assessment, and strength-of-evidence grading were completed by 2 independent reviewers.
Main Outcomes and Measures: Asthma exacerbations.
Results:Of 1326 records identified, 15 randomized clinical trials (N = 7122 patients) were included. Most trials assessed adding LAMA vs placebo or LAMA vs LABA to inhaled corticosteroids. Adding LAMA vs placebo to inhaled corticosteroids was associated with a significantly reduced risk of exacerbation requiring systemic corticosteroids (RR, 0.67 [95% CI, 0.48 to 0.92]; RD, -0.02 [95% CI, -0.04 to 0.00]). Compared with adding LABA, adding LAMA to inhaled corticosteroids was not associated with significant improvements in exacerbation risk (RR, 0.87 [95% CI, 0.53 to 1.42]; RD, 0.00 [95% CI, -0.02 to 0.02]), or any other outcomes of interest. Triple therapy was not significantly associated with improved exacerbation risk vs inhaled corticosteroids and LABA (RR, 0.84 [95% CI, 0.57 to 1.22]; RD, -0.01 [95% CI, -0.08 to 0.07]).
Conclusions and Relevance:In this systematic review and meta-analysis, the use of LAMA compared with placebo as add-on therapy to inhaled corticosteroids was associated with a lower risk of asthma exacerbations; however, the association of LAMA with benefit may not be greater than that with LABA. Triple therapy was not associated with a lower risk of exacerbations.
