Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
BMC Infect Dis. 2024 Jun 28;24(1):653. doi: 10.1186/s12879-024-09564-x.
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.
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.
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.
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.
肺炎支原体（Mycoplasma pneumoniae）引起的宿主免疫反应不当会导致过度炎症，从而损害肺通气功能（PVF）。阿奇霉素联合吸入特布他林已用于治疗肺功能受损的儿童肺炎支原体肺炎（MPP），但先前的随机对照试验（RCT）显示疗效和安全性不一致。本研究旨在首次对联合治疗进行系统评价。
本研究在国际前瞻性系统评价注册库（PROSPERO CRD42023452139）进行登记。采用 PRISMA 指南进行系统评价和荟萃分析。全面检索了截至 2023 年 6 月的 6 个英文数据库和 4 个中文数据库。纳入阿奇霉素序贯治疗联合吸入特布他林的 RCT。使用修订后的 Cochrane 随机对照试验偏倚风险工具（RoB2）评估所有研究的方法学质量，并使用 Stata 15.0 进行荟萃分析，并计划进行亚组和敏感性分析。通过漏斗图和 Harbord 检验评估发表偏倚。使用推荐、评估、开发和评估建议（GRADE）评估证据确定性。
最终纳入了 20 项 RCT 的 1938 名儿科患者。荟萃分析结果表明，联合治疗可显著提高总有效率（RR=1.20，95%CI 1.15-1.25）、用力呼气量（SMD=1.14，95%CI 0.98-1.29）、用力呼气量/用力肺活量比值（SMD=2.16，95%CI 1.46-2.86）、呼气峰流速（SMD=1.17，95%CI 0.91-1.43）。与阿奇霉素治疗相比，联合治疗不良反应风险增加 23%，但无统计学差异。Harbord 回归显示无发表偏倚（P=0.148）。证据的总体质量从中等到极低不等。
这是首次对阿奇霉素序贯治疗联合吸入特布他林治疗 MPP 的系统评价和荟萃分析，提示该联合治疗安全且有益，可改善 MPP 患儿的 PVF。由于缺乏高质量证据，我们的结果需要未来通过足够大样本的 RCT 进一步证实。
