不同随访时间下细菌溶解产物胶囊预防儿童反复呼吸道感染的系统评价

Systematic evaluation of Bacterial Lysate Capsules in prevention of RRTIs in children at different follow-up times

目的 评估不同随访时间下细菌溶解产物胶囊预防儿童反复呼吸道感染(RRTIs),力求还原该药在RRTIs中的真实循证证据。方法 检索PubMed、the Cochrane Library、中国学术期刊全文数据库(CNKI)、万方数据库(Wanfang Data)、中国生物医学数据库(CBM)、维普全文数据库(VIP)等数据库,搜索细菌溶解产物胶囊预防儿童RRTIs的临床随机对照试验(RCT),检索时间为各数据库建库起至2021年8月。采用Cochrane协作网研发的偏倚风险评估工具评价文献质量,采用RevMan 5.3软件进行Meta分析。将研究中的呼吸道感染次数纳入主要结局指标,包括血清免疫球蛋白水平、抗菌药物使用时间、不良反应发生率等9项作为次要结局指标。结果 共纳入22项RCTs、包括2 421例患儿,其中实验组1 177例、对照组1 244例,均为服用1个疗程细菌溶解产物。结果表明,细菌溶解产物胶囊的使用与呼吸道感染的频率降低显著相关[SMD=-1.76,95%CI(-2.00,-1.52),P<0.000 1],但组间异质性明显,其中观察时间窗为3个月时[SMD=-2.35,95%CI(-2.72,-1.98),P<0.000 1],6个月时[SMD=-1.42,95%CI(-1.66,-1.18),P<0.000 1],12个月时[SMD=-2.39,95%CI(-2.74,-2.03),P<0.000 1];与抗菌药物使用天数、发热天数、咳嗽天数、喘息天数的减少呈正相关;与IgG、IgA水平的增加呈正相关,有统计学意义;与IgM水平的升高相关性不明显;不良反应发生率无明显差异。结论 细菌溶解产物胶囊的使用能够使患儿呼吸道感染次数降低,其差异主要来源于不同观察时间窗;且每个时间窗内获益可能不同,3个月时效果较为明显;远期来看,该药物对症状的控制有效,且安全性好。

Objective To more comprehensively evaluate the relationship between studies on Bacterial Lysate Capsules prevention of recurrent respiratory tract infections(RRTIs) at different follow-up times, and strive to restore the true evidence-based evidence of this drug in RRTIs. Methods PubMed, the Cochrane Library, CNKI, Wanfang Data, CBM, VIP database were searched for RCTs of Bacterial Lysate Capsules to prevent RRTIs in children. The retrieval time was from the establishment of each database to August2021. The bias risk assessment tool developed by the Cochrane Collaboration Network was used to evaluate the quality of the literature. Finally, the RevMan 5.3 software was used for Meta-analysis. The "number of respiratory tract infections" in the study was included in the primary outcome indicators, including "serum immunoglobulin level" "time of use of antimicrobial drugs" and "incidence of adverse reactions" as secondary outcome indicators. Results A total of 2 421 children were included in 22 RCTs,including 1 177 cases in the experimental group and 1 244 cases in the control group. All of them took Bacterial Lysate Capsules for one course of treatment. The results showed that the use of Bacterial Lysate Capsules was significantly correlated with the decrease of the frequency of respiratory tract infection [SMD =-1.76, 95%CI(-2.02,-1.51), P < 0.000 1], there was significant heterogeneity between two groups, at three months [SMD =-2.35, 95%CI(-2.72,-1.98), P < 0.000 1], at six months [SMD =-1.42,95%CI(-1.66,-1.18), P < 0.000 1], at 12 months [SMD =-2.39, 95%CI(-2.74,-2.03), P < 0.000 1]. It was positively correlated with the decrease of antibacterial use days, fever days, cough days and wheezing days;It was positively correlated with the increase of IgG and IgA levels, which was statistically significant. There was no significant correlation with the increase of IgM level. There was no significant difference in the incidence of adverse reactions. Conclusions The use of Bacterial Lysate Capsules can reduce the number of respiratory tract infections in children. The difference mainly due to different observation time windows;the benefits may be different in each time window. Three months follow-up may shows the best benefit, in the long run, the drug is effective in the control of symptoms, and has good safety.