目的 評(píng)估不同隨訪時(shí)間下細(xì)菌溶解產(chǎn)物膠囊預(yù)防兒童反復(fù)呼吸道感染（RRTIs），力求還原該藥在RRTIs中的真實(shí)循證證據(jù)。方法 檢索PubMed、the Cochrane Library、中國(guó)學(xué)術(shù)期刊全文數(shù)據(jù)庫（CNKI）、萬方數(shù)據(jù)庫（Wanfang Data）、中國(guó)生物醫(yī)學(xué)數(shù)據(jù)庫（CBM）、維普全文數(shù)據(jù)庫（VIP）等數(shù)據(jù)庫，搜索細(xì)菌溶解產(chǎn)物膠囊預(yù)防兒童RRTIs的臨床隨機(jī)對(duì)照試驗(yàn)（RCT），檢索時(shí)間為各數(shù)據(jù)庫建庫起至2021年8月。采用Cochrane協(xié)作網(wǎng)研發(fā)的偏倚風(fēng)險(xiǎn)評(píng)估工具評(píng)價(jià)文獻(xiàn)質(zhì)量，采用RevMan 5.3軟件進(jìn)行Meta分析。將研究中的呼吸道感染次數(shù)納入主要結(jié)局指標(biāo)，包括血清免疫球蛋白水平、抗菌藥物使用時(shí)間、不良反應(yīng)發(fā)生率等9項(xiàng)作為次要結(jié)局指標(biāo)。結(jié)果 共納入22項(xiàng)RCTs、包括2 421例患兒，其中實(shí)驗(yàn)組1 177例、對(duì)照組1 244例，均為服用1個(gè)療程細(xì)菌溶解產(chǎn)物。結(jié)果表明，細(xì)菌溶解產(chǎn)物膠囊的使用與呼吸道感染的頻率降低顯著相關(guān)［SMD=-1.76，95% CI（-2.00，-1.52），P＜0.000 1］，但組間異質(zhì)性明顯，其中觀察時(shí)間窗為3個(gè)月時(shí)［SMD=-2.35，95% CI（-2.72，-1.98），P＜0.000 1］，6個(gè)月時(shí)［SMD=-1.42，95% CI（-1.66，-1.18），P＜0.000 1］，12個(gè)月時(shí)［SMD=-2.39，95% CI（-2.74，-2.03），P＜0.000 1］；與抗菌藥物使用天數(shù)、發(fā)熱天數(shù)、咳嗽天數(shù)、喘息天數(shù)的減少呈正相關(guān)；與IgG、IgA水平的增加呈正相關(guān)，有統(tǒng)計(jì)學(xué)意義；與IgM水平的升高相關(guān)性不明顯；不良反應(yīng)發(fā)生率無明顯差異。結(jié)論 細(xì)菌溶解產(chǎn)物膠囊的使用能夠使患兒呼吸道感染次數(shù)降低，其差異主要來源于不同觀察時(shí)間窗；且每個(gè)時(shí)間窗內(nèi)獲益可能不同，3個(gè)月時(shí)效果較為明顯；遠(yuǎn)期來看，該藥物對(duì)癥狀的控制有效，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 August 2021. 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.

R985;R974

應(yīng)急管理部應(yīng)急總醫(yī)院科研立項(xiàng)（K202015）