雾化吸入两性霉素B对侵袭性肺曲霉病预防效果的Meta分析

目的采用Meta分析方法对现已发表的关于雾化吸入两性霉素B（AmB）预防侵袭性肺曲霉病（IPA）的文献进行综合分析,从动物实验和临床研究两个方面分别评价雾化吸入AmB对IPA的预防作用。方法检索MEDLINE生物医学数据库、科学引文索引（ISI）、医学文摘资料库（EMBASE）及万方数据库,检索发表于2011年3月以前关于雾化吸入AmB预防IPA的文献,由2名评价员分别筛选符合标准的文献,进行质量评价和数据提取。采用RevMan 4.22软件进行异质性分析,合并效应量的检验采用优势比（OR）及95%可信区间（95%CI）。结果共纳入符合标准的动物实验文献5篇,包括实验动物626只;临床研究文献6篇,包括1354例真菌感染高危病人。Meta分析结果显示感染前雾化吸入AmB的实验动物存活率高于安慰剂对照组（38.3%比9.7%,OR=13.93,95%CI 7.46～26.01,P〈0.000 01）。真菌感染高危人群中,预防性雾化吸入AmB的患者IPA发生率较安慰剂或空白对照组为低（2.6%比9.2%,OR=0.27,95%CI 0.16～0.46,P〈0.000 01）;雾化预防组与对照组患者IPA相关病死率及总死亡率差异无统计学意义（RR=0.65,95%CI 0.33～1.30,P=0.23;OR=1.17,95%CI 0.73～1.89,P=0.51）;雾化吸入AmB绝大部分不良反应程度轻微。结论预防性雾化吸入AmB能有效降低实验动物肺曲霉感染死亡率,对粒细胞缺乏等高危人群预防性雾化吸入AmB能有效降低IPA发生率,不良反应轻微,但未降低曲霉感染相关病死率及总死亡率。需要更多高质量大型临床研究进一步提供循证医学证据。

Efficacy and Safety of Inhaled Amphotericin B in Prophylaxis of Invasive Pulmonary Aspergillosis:A Meta-analysis

Objective To evaluate the efficacy and safety of inhaled amphotericin B(AmB)in prophylaxis of invasive pulmonary aspergillosis(IPA) in both animal studies and clinical researches.Methods MEDLINE,ISI,EMBASE and Wanfang Periodical Databases were searched until march 2011 for case-control study on the efficacy and safety of inhaled AmB in prophylaxis of IPA.The articles were evaluated according to inclusion criteria.Poor-quality studies were excluded,and RevMan 4.22 sofeware was applied for investigating the heterogeneity among individual studies and calculating the pooled odds ratio(OR) and 95% confidence interval(CI).Results Five animal studies with a total of 626 animals were included.The overall survival rate of the immunosuppressed animals with pulmonary aspergillosis treated with nebulized AmB was increased(38.3% vs.9.7%,OR=13.93,95%CI 7.46~26.01,P<0.000 01).Six clinical trials including 1354 patients were considered.Our meta-analysis showed that inhaled AmB could significantly reduce the incidence rate of IPA(2.6% vs.9.2%,OR=0.27,95%CI 0.16~0.46,P<0.000 01),but had no definite benefit on mortality.Four studies evaluated the potential side effects of nebulized AmB and showed that there were no significant adverse events.Conclusions Empirical inhaled AmB is associated with a lower rate of IPA but no significant difference in overall mortality.Further high quality clinical trials are needed to provide more evidences.