加拿大麦克马斯特大学医学中心Derek K. Chu团队研究了三联与二联吸入疗法治疗中重度哮喘患者对预后的影响。2021年5月19日，该研究发表在《美国医学会杂志》上。

将长效毒蕈碱拮抗剂（LAMAs）添加到吸入糖皮质激素（ICS）和长效β2-激动剂（LABAs）中来治疗中重度哮喘的利弊尚不清楚。

为了系统综合分析三联疗法（ICS+LABA+LAMA）与二联疗法（ICS+LABA）治疗持续性哮喘失控的儿童和成人的疗效和不良事件，研究组在MEDLINE、Embase、CENTRAL等大型数据库中检索2017年11月至2020年12月的文献，由两名研究人员独立选择随机临床试验（RCT），比较三联疗法和二联疗法对中重度哮喘患者的疗效。

两名评审员独立提取数据并评估偏倚风险，使用随机效应荟萃分析。主要观察指标为严重恶化、哮喘控制（哮喘控制问卷[ACQ-7]，0-6分，分数越高越严重）、生活质量（哮喘相关生活质量[AQLQ]评分，1-7分，分数越低质量越差）、死亡率和不良事件。

采用三联LAMA类型的20个随机对照试验共包括11894名儿童和成人，平均年龄为52岁，57.7%为女性。高度确定性的证据表明，三联疗法组严重恶化的风险为22.7%，显著低于二联疗法组（27.4%），且哮喘控制改善程度显著优于二联疗法组。

三联疗法组与二联疗法组中与哮喘相关的生活质量和死亡率无显著差异。三联疗法组中口干和发音困难的发生率为3.0%，显著高于二联疗法组（1.8%），但两组间治疗相关和严重不良事件没有显著差异（中等确定性证据）。

研究结果表明，在儿童（6-18岁）和成人中重度哮喘患者中，三联疗法与二联疗法相比，严重哮喘发作较少，哮喘控制有轻微改善，但生活质量和死亡率均无显著差异。

附：英文原文

Title: Triple vs Dual Inhaler Therapy and Asthma Outcomes in Moderate to Severe Asthma: A Systematic Review and Meta-analysis

Author: Lisa H. Y. Kim, Carol Saleh, Anna Whalen-Browne, Paul M. O’Byrne, Derek K. Chu

Issue&Volume: 2021-05-19

Abstract:

Importance  The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) for moderate to severe asthma remain unclear.

Objective  To systematically synthesize the outcomes and adverse events associated with triple therapy (ICS, LABA, and LAMA) vs dual therapy (ICS plus LABA) in children and adults with persistent uncontrolled asthma.

Data Sources  MEDLINE, Embase, CENTRAL, ICTRP, FDA, and EMA databases from November 2017, to December 8, 2020, without language restriction.

Study Selection  Two investigators independently selected randomized clinical trials (RCTs) comparing triple vs dual therapy in patients with moderate to severe asthma.

Data Extraction and Synthesis  Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses, including individual patient-level exacerbation data, were used. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence.

Main Outcomes and Measures  Severe exacerbations, asthma control (measured using the Asthma Control Questionnaire [ACQ-7], a 7-item list with each item ranging from 0 [totally controlled] to 6 [severely uncontrolled]; minimal important difference, 0.5), quality of life (measured using the Asthma-related Quality of Life [AQLQ] tool; score range, 1 [severely impaired] to 7 [no impairment]; minimal important difference, 0.5), mortality, and adverse events.

Results  Twenty RCTs using 3 LAMA types that enrolled 11894 children and adults (mean age, 52 years [range, 9-71 years]; 57.7% female) were included. High-certainty evidence showed that triple therapy vs dual therapy was significantly associated with a reduction in severe exacerbation risk (9 trials [9932 patients]; 22.7% vs 27.4%; risk ratio, 0.83 [95% CI, 0.77 to 0.90]) and an improvement in asthma control (14 trials [11230 patients]; standardized mean difference [SMD], 0.06 [95% CI, 0.10 to 0.02]; mean difference in ACQ-7 scale, 0.04 [95% CI, 0.07 to 0.01]). There were no significant differences in asthma-related quality of life (7 trials [5247 patients]; SMD, 0.05 [95% CI, 0.03 to 0.13]; mean difference in AQLQ score, 0.05 [95% CI, 0.03 to 0.13]; moderate-certainty evidence) or mortality (17 trials [11595 patients]; 0.12% vs 0.12%; risk ratio, 0.96 [95% CI, 0.33 to 2.75]; high-certainty evidence) between dual and triple therapy. Triple therapy was significantly associated with increased dry mouth and dysphonia (10 trials [7395 patients]; 3.0% vs 1.8%; risk ratio, 1.65 [95% CI, 1.14 to 2.38]; high-certainty evidence), but treatment-related and serious adverse events were not significantly different between groups (moderate-certainty evidence).

Conclusions and Relevance  Among children (aged 6 to 18 years) and adults with moderate to severe asthma, triple therapy, compared with dual therapy, was significantly associated with fewer severe asthma exacerbations and modest improvements in asthma control without significant differences in quality of life or mortality.

DOI: 10.1001/jama.2021.7872

Source: https://jamanetwork.com/journals/jama/fullarticle/2780374