PDF(Pubmed)
Abstract：
BACKGROUND: An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF). Azithromycin plus inhaled terbutaline has been used in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children with impaired pulmonary function, but previous randomized controlled trials (RCTs) showed inconsistent efficacy and safety. This study is aimed to firstly provide a systematic review of the combined therapy.
METHODS: This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42023452139). A PRISMA-compliant systematic review and meta-analysis was performed. Six English and four Chinese databases were comprehensively searched up to June, 2023. RCTs of azithromycin sequential therapy plus inhaled terbutaline were selected. The revised Cochrane risk of bias tool for randomized trials (RoB2) was used to evaluate the methodological quality of all studies, and meta-analysis was performed using Stata 15.0 with planned subgroup and sensitivity analyses. Publication bias was evaluated by a funnel plot and the Harbord\' test. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation recommendations.
RESULTS: A total of 1,938 pediatric patients from 20 RCTs were eventually included. The results of meta-analysis showed that combined therapy was able to significantly increase total effectiveness rate (RR = 1.20, 95%CI 1.15 to 1.25), forced expiratory volume in one second (SMD = 1.14, 95%CIs, 0.98 to 1.29), the ratio of forced expiratory volume in one second/forced vital capacity (SMD = 2.16, 95%CIs, 1.46 to 2.86), peak expiratory flow (SMD = 1.17, 95%CIs, 0.91 to 1.43). The combined therapy was associated with a 23% increased risk of adverse reactions compared to azithromycin therapy alone, but no significant differences were found. Harbord regression showed no publication bias (P = 0.148). The overall quality of the evidence ranged from moderate to very low.
CONCLUSIONS: This first systematic review and meta-analysis suggested that azithromycin sequential therapy plus inhaled terbutaline was safe and beneficial for children with MPP. In addition, the combined therapy represented significant improvement of PVF. Due to lack of high-quality evidence, our results should be confirmed by adequately powered RCTs in the future.
METHODS: This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42023452139). A PRISMA-compliant systematic review and meta-analysis was performed. Six English and four Chinese databases were comprehensively searched up to June, 2023. RCTs of azithromycin sequential therapy plus inhaled terbutaline were selected. The revised Cochrane risk of bias tool for randomized trials (RoB2) was used to evaluate the methodological quality of all studies, and meta-analysis was performed using Stata 15.0 with planned subgroup and sensitivity analyses. Publication bias was evaluated by a funnel plot and the Harbord\' test. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation recommendations.
RESULTS: A total of 1,938 pediatric patients from 20 RCTs were eventually included. The results of meta-analysis showed that combined therapy was able to significantly increase total effectiveness rate (RR = 1.20, 95%CI 1.15 to 1.25), forced expiratory volume in one second (SMD = 1.14, 95%CIs, 0.98 to 1.29), the ratio of forced expiratory volume in one second/forced vital capacity (SMD = 2.16, 95%CIs, 1.46 to 2.86), peak expiratory flow (SMD = 1.17, 95%CIs, 0.91 to 1.43). The combined therapy was associated with a 23% increased risk of adverse reactions compared to azithromycin therapy alone, but no significant differences were found. Harbord regression showed no publication bias (P = 0.148). The overall quality of the evidence ranged from moderate to very low.
CONCLUSIONS: This first systematic review and meta-analysis suggested that azithromycin sequential therapy plus inhaled terbutaline was safe and beneficial for children with MPP. In addition, the combined therapy represented significant improvement of PVF. Due to lack of high-quality evidence, our results should be confirmed by adequately powered RCTs in the future.
摘要：
背景：宿主对肺炎支原体的不当免疫反应会产生过度的炎症，导致肺通气功能（PVF）受损。阿奇霉素加吸入特布他林已用于治疗肺功能受损儿童的肺炎支原体肺炎（MPP），但之前的随机对照试验(RCTs)显示疗效和安全性不一致.本研究旨在首先对该综合疗法进行系统评价。
方法：本研究在国际前瞻性系统评价注册中心（PROSPEROCRD42023452139）注册。进行了符合PRISMA的系统评价和荟萃分析。截至6月,全面检索了6个英文数据库和4个中文数据库,2023年。选择阿奇霉素序贯疗法加吸入特布他林的RCTs。修订后的Cochrane风险偏倚工具（RoB2）用于评估所有研究的方法学质量，使用Stata15.0进行meta分析,并进行计划亚组和敏感性分析.通过漏斗图和Harbord检验评估出版偏倚。使用建议分级评估证据的确定性，评估,发展和评价建议。
结果：最终纳入20个随机对照试验中的1,938名儿科患者。荟萃分析结果显示,联合治疗能够显著提高总有效率(RR=1.20,95CI1.15~1.25),一秒用力呼气量(SMD=1.14,95CIs,0.98至1.29），一秒用力呼气量/用力肺活量之比(SMD=2.16，95CIs，1.46to2.86),最大呼气流量（SMD=1.17，95CIs，0.91至1.43）。与阿奇霉素单独治疗相比，联合治疗的不良反应风险增加了23%。但没有发现显著差异。Harbord回归分析显示无发表偏倚(P=0.148)。证据的总体质量从中等到非常低。
结论：首次系统评价和荟萃分析提示阿奇霉素序贯疗法联合吸入特布他林对MPP患儿是安全且有益的。此外,联合治疗代表PVF的显著改善。由于缺乏高质量的证据,我们的结果应该在未来得到足够有力的随机对照试验的证实.
方法：本研究在国际前瞻性系统评价注册中心（PROSPEROCRD42023452139）注册。进行了符合PRISMA的系统评价和荟萃分析。截至6月,全面检索了6个英文数据库和4个中文数据库,2023年。选择阿奇霉素序贯疗法加吸入特布他林的RCTs。修订后的Cochrane风险偏倚工具（RoB2）用于评估所有研究的方法学质量，使用Stata15.0进行meta分析,并进行计划亚组和敏感性分析.通过漏斗图和Harbord检验评估出版偏倚。使用建议分级评估证据的确定性，评估,发展和评价建议。
结果：最终纳入20个随机对照试验中的1,938名儿科患者。荟萃分析结果显示,联合治疗能够显著提高总有效率(RR=1.20,95CI1.15~1.25),一秒用力呼气量(SMD=1.14,95CIs,0.98至1.29），一秒用力呼气量/用力肺活量之比(SMD=2.16，95CIs，1.46to2.86),最大呼气流量（SMD=1.17，95CIs，0.91至1.43）。与阿奇霉素单独治疗相比，联合治疗的不良反应风险增加了23%。但没有发现显著差异。Harbord回归分析显示无发表偏倚(P=0.148)。证据的总体质量从中等到非常低。
结论：首次系统评价和荟萃分析提示阿奇霉素序贯疗法联合吸入特布他林对MPP患儿是安全且有益的。此外,联合治疗代表PVF的显著改善。由于缺乏高质量的证据,我们的结果应该在未来得到足够有力的随机对照试验的证实.
