ICS 和 LABA 作为控制及快速缓解治疗与持续性哮喘患者急性发作及症状控制之间的关系:一项系统性回顾 Meta 分析
2018/06/04
摘要
重要性：吸入性糖皮质激素（inhaled corticosteroids, ICS）联合长效β受体激动剂（LABAs）作为哮喘控制和快速缓解用药被称为维持缓解治疗（SMART），是持续性哮喘的潜在治疗策略。
目的：针对SMART在持续性哮喘患者中的疗效进行系统评价和meta分析。
数据来源和研究选择：通过OVID检索的MEDLINE数据库，EMBASE，Cochrane对照试验注册中心和Cochrane系统评价数据库中从2016年8月建库开始至2017年11月28日的研究。由两位研究者选择关于比较SMART与ICS联合或不联合LABA作为控制治疗及短效β受体激动剂（SABA）作为缓解治疗方案在5岁以上的持续哮喘患者中的疗效的随机临床试验或观察性研究。
数据提取和合成：采用随机效应模型进行Meta分析，计算风险比（RR），风险差异（RD），平均差异以及与之相应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。
主要结局：哮喘急性加重。
结果：本分析包括16项随机临床试验（共22748例患者），其中15项评估了SMART策略联合布地奈德/福莫特罗干粉吸入剂的治疗效果。在12岁及以上的患者中（n=22 524，平均年龄42岁，女性14634人（65％）），与相同剂量的ICS联合LABA作为控制性治疗（RR=0.68，95％CI[0.58-0.80]; RD=-6.4％，95％CI[-10.2％--2.6％]）或高剂量的ICS联合LABA作为控制性治疗（RR=0.77，95％CI[0.60-0.98]; RD=-2.8％，95％CI[-5.2％--0.3％]）相比，SMART与哮喘急性加重的风险降低相关。当与单独应用ICS作为控制性治疗相比时，也得到相似结果。在4至11岁的患者中（n = 341，年龄中位数=8，女性69人（31％）），与高剂量的ICS联合LABA作为控制性治疗（RR=0.55，95％CI[0.32-0.94]; RD=-12.0％，95％CI[-22.5％--1.5％]）或相同剂量的ICS联合LABA作为控制性治疗（RR=0.38，95％CI[0.23-0.63]; RD=-23.2％，95％CI[-33.6％--12.1％]），SMART方案与急性加重风险减低相关。
结论和相关性：在对持续性哮喘患者的荟萃分析中，与吸入皮质类固醇作为控制性治疗（有或无长效β受体激动剂）和短效β受体激动剂作为缓解治疗相比， 维持和缓解治疗应用单一药物与哮喘急性加重的风险降低有关。但4至11岁患者的证据有限。
Association of Inhaled Corticosteroids and Long-Acting β-Agonists as Controller and Quick Relief Therapy With Exacerbations and Symptom Control in Persistent Asthma: A Systematic Review and Meta-analysis.
Abstract
Importance:Combined use of inhaled corticosteroids and long-acting β-agonists (LABAs) as the controller and the quick relief therapy termed single maintenance and reliever therapy (SMART) is a potential therapeutic regimen for the management of persistent asthma.
Objective:To conduct a systematic review and meta-analysis of the effects of SMART in patients with persistent asthma.
Data Sources and Study Selection:The databases of MEDLINE via OVID, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched from database inception through August 2016 and updated through November 28, 2017. Two reviewers selected randomized clinical trials or observational studies evaluating SMART vs inhaled corticosteroids with or without a LABA used as the controller therapy and short-acting β-agonists as the relief therapy for patients aged 5 years or older with persistent asthma and reporting on an outcome of interest.
Data Extraction and Synthesis:Meta-analyses were conducted using a random-effects model to calculate risk ratios (RRs), risk differences (RDs), and mean differences 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:The analyses included 16 randomized clinical trials (N = 22 748 patients), 15 of which evaluated SMART as a combination therapy with budesonide and formoterol in a dry-powder inhaler. Among patients aged 12 years or older (n = 22 524; mean age, 42 years; 14 634 [65%] were female), SMART was associated with a reduced risk of asthma exacerbations compared with the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.68 [95% CI, 0.58 to 0.80]; RD, −6.4% [95% CI, −10.2% to −2.6%]) and a higher dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.77 [95% CI, 0.60 to 0.98]; RD, −2.8% [95% CI, −5.2% to −0.3%]). Similar results were seen when SMART was compared with inhaled corticosteroids alone as the controller therapy. Among patients aged 4 to 11 years (n = 341; median age, 8 [range, 4-11] years; 69 [31%] were female), SMART was associated with a reduced risk of asthma exacerbations compared with a higher dose of inhaled corticosteroids as the controller therapy (RR, 0.55 [95% CI, 0.32 to 0.94]; RD, −12.0% [95% CI, −22.5% to −1.5%]) or the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.38 [95% CI, 0.23 to 0.63]; RD, −23.2% [95% CI, −33.6% to −12.1%]).
Conclusions and Relevance:In this meta-analysis of patients with persistent asthma, the use of single maintenance and reliever therapy compared with inhaled corticosteroids as the controller therapy (with or without a long-acting β-agonist) and short-acting β-agonists as the relief therapy was associated with a lower risk of asthma exacerbations. Evidence for patients aged 4 to 11 years was limited.
重要性：吸入性糖皮质激素（inhaled corticosteroids, ICS）联合长效β受体激动剂（LABAs）作为哮喘控制和快速缓解用药被称为维持缓解治疗（SMART），是持续性哮喘的潜在治疗策略。
目的：针对SMART在持续性哮喘患者中的疗效进行系统评价和meta分析。
数据来源和研究选择：通过OVID检索的MEDLINE数据库，EMBASE，Cochrane对照试验注册中心和Cochrane系统评价数据库中从2016年8月建库开始至2017年11月28日的研究。由两位研究者选择关于比较SMART与ICS联合或不联合LABA作为控制治疗及短效β受体激动剂（SABA）作为缓解治疗方案在5岁以上的持续哮喘患者中的疗效的随机临床试验或观察性研究。
数据提取和合成：采用随机效应模型进行Meta分析，计算风险比（RR），风险差异（RD），平均差异以及与之相应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。
主要结局：哮喘急性加重。
结果：本分析包括16项随机临床试验（共22748例患者），其中15项评估了SMART策略联合布地奈德/福莫特罗干粉吸入剂的治疗效果。在12岁及以上的患者中（n=22 524，平均年龄42岁，女性14634人（65％）），与相同剂量的ICS联合LABA作为控制性治疗（RR=0.68，95％CI[0.58-0.80]; RD=-6.4％，95％CI[-10.2％--2.6％]）或高剂量的ICS联合LABA作为控制性治疗（RR=0.77，95％CI[0.60-0.98]; RD=-2.8％，95％CI[-5.2％--0.3％]）相比，SMART与哮喘急性加重的风险降低相关。当与单独应用ICS作为控制性治疗相比时，也得到相似结果。在4至11岁的患者中（n = 341，年龄中位数=8，女性69人（31％）），与高剂量的ICS联合LABA作为控制性治疗（RR=0.55，95％CI[0.32-0.94]; RD=-12.0％，95％CI[-22.5％--1.5％]）或相同剂量的ICS联合LABA作为控制性治疗（RR=0.38，95％CI[0.23-0.63]; RD=-23.2％，95％CI[-33.6％--12.1％]），SMART方案与急性加重风险减低相关。
结论和相关性：在对持续性哮喘患者的荟萃分析中，与吸入皮质类固醇作为控制性治疗（有或无长效β受体激动剂）和短效β受体激动剂作为缓解治疗相比， 维持和缓解治疗应用单一药物与哮喘急性加重的风险降低有关。但4至11岁患者的证据有限。
(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. Abstract )
(Sobieraj DM et al. JAMA. 2018 Mar 19. Abstract )
Association of Inhaled Corticosteroids and Long-Acting β-Agonists as Controller and Quick Relief Therapy With Exacerbations and Symptom Control in Persistent Asthma: A Systematic Review and Meta-analysis.
Abstract
Importance:Combined use of inhaled corticosteroids and long-acting β-agonists (LABAs) as the controller and the quick relief therapy termed single maintenance and reliever therapy (SMART) is a potential therapeutic regimen for the management of persistent asthma.
Objective:To conduct a systematic review and meta-analysis of the effects of SMART in patients with persistent asthma.
Data Sources and Study Selection:The databases of MEDLINE via OVID, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched from database inception through August 2016 and updated through November 28, 2017. Two reviewers selected randomized clinical trials or observational studies evaluating SMART vs inhaled corticosteroids with or without a LABA used as the controller therapy and short-acting β-agonists as the relief therapy for patients aged 5 years or older with persistent asthma and reporting on an outcome of interest.
Data Extraction and Synthesis:Meta-analyses were conducted using a random-effects model to calculate risk ratios (RRs), risk differences (RDs), and mean differences 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:The analyses included 16 randomized clinical trials (N = 22 748 patients), 15 of which evaluated SMART as a combination therapy with budesonide and formoterol in a dry-powder inhaler. Among patients aged 12 years or older (n = 22 524; mean age, 42 years; 14 634 [65%] were female), SMART was associated with a reduced risk of asthma exacerbations compared with the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.68 [95% CI, 0.58 to 0.80]; RD, −6.4% [95% CI, −10.2% to −2.6%]) and a higher dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.77 [95% CI, 0.60 to 0.98]; RD, −2.8% [95% CI, −5.2% to −0.3%]). Similar results were seen when SMART was compared with inhaled corticosteroids alone as the controller therapy. Among patients aged 4 to 11 years (n = 341; median age, 8 [range, 4-11] years; 69 [31%] were female), SMART was associated with a reduced risk of asthma exacerbations compared with a higher dose of inhaled corticosteroids as the controller therapy (RR, 0.55 [95% CI, 0.32 to 0.94]; RD, −12.0% [95% CI, −22.5% to −1.5%]) or the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.38 [95% CI, 0.23 to 0.63]; RD, −23.2% [95% CI, −33.6% to −12.1%]).
Conclusions and Relevance:In this meta-analysis of patients with persistent asthma, the use of single maintenance and reliever therapy compared with inhaled corticosteroids as the controller therapy (with or without a long-acting β-agonist) and short-acting β-agonists as the relief therapy was associated with a lower risk of asthma exacerbations. Evidence for patients aged 4 to 11 years was limited.
