支气管肺泡灌洗液高通量测序技术在成人肺部感染中的应用价值  

Application value of high-throughput sequencing technology for bronchoalveolar lavage fluid in adult pulmonary infection

作　　者：朱常军 杜兴冉[1] 吕敏捷 张长文 翁哲琪 金霄 邵明玥 陈思锡 冯旰珠[1] Zhu Changjun;Du Xingran;Lyu Minjie;Zhang Changwen;Weng Zheqi;Jin Xiao;Shao Mingyue;Chen Sixi;Feng Ganzhu(Department of Pulmonary and Critical Care Medicine,the Second Affiliated Hospital of Nanjing Medical University,Nanjing 210000,China)

机构地区：[1]南京医科大学第二附属医院呼吸与危重症医学科,南京210000

出　　处：《国际呼吸杂志》2022年第15期1148-1157,共10页International Journal of Respiration

基　　金：国家自然科学基金(81870009)。

摘　　要：目的评估支气管肺泡灌洗液(BALF)高通量测序技术在肺部感染病原学诊断中的价值及对患者预后的影响。方法计算机检索PubMed、Embase、Cochrane Library、Web of science、clinical trials.gov.cn、中国知网、万方数据库和中国生物医学文献数据库,检索时间为自建库时间至2021年12月8日。比较BALF宏基因组测序与传统病原学检测方法对肺部感染检测的阳性率、敏感度及特异度;根据病原学检测结果调整治疗方案,比较2组患者的抗生素使用强度、住院时长、28/30 d及90 d病死率。采用Review Manager 5.4.1软件对上述指标分别进行meta分析。结果最终纳入35篇文献,共2624例患者,其中高通量测序组2248例,传统病原学检测组2493例。meta分析结果显示,高通量测序组阳性率为79.8%(1793/2248),高于传统病原学检测组41.7%(1039/2493)(OR=6.84,95%CI:4.84~9.67,Z=10.88,P<0.001);敏感度、特异度及汇总受试者工作特征曲线下面积均高于传统病原学检测组。9篇论文纳入的患者为重症肺炎患者,亚组分析结果示,重症肺炎患者BALF高通量测序阳性率为85.8%(495/577),高于传统病原学检测组42.9%(282/657)(OR=6.52,95%CI:4.04~10.52,Z=7.69,P<0.001)。根据病原检测结果调整治疗方案,与传统病原学检测组相比,高通量测序组患者抗生素使用强度降低(SMD=-40.04,95%CI:-47.05~-33.03,Z=11.19,P<0.001);平均住院时长缩短(SMD=-4.68,95%CI:-6.12~-3.25,Z=6.40,P<0.001)。高通量测序组28/30 d及90 d病死率分别为9.09%和12.82%,均低于传统检测组26.44%(OR=0.26,95%CI:0.13~0.51,Z=3.89,P<0.001)和38.30%(OR=0.21,95%CI:0.07~0.66,Z=2.67,P=0.008)。结论与传统病原学诊断方法相比,BALF高通量测序对肺部感染具有更高的诊断价值。根据BALF高通量测序结果调整治疗方案,可降低患者的抗生素使用强度,缩短住院时间,降低病死率,改善患者预后。Objective To evaluate the value of high-throughput sequencing(HTS)technology for bronchoalveolar lavage fluid(BALF)in diagnosing pulmonary infection pathogen and corresponding effects on the prognosis of patients.Methods A computer retrieval was performed in Pubmed,Embase,Cochrane Library,Wanfang database,Web of Science,clinical trials.gov,CNKI,Wanfang database,and China biology medicine dise(CBM)from the setup date of the database to December 8,2021.The positive rate,sensitivity and specificity of BALF metagenomic sequencing and traditional pathogen detection method on pulmonary infection detection were compared.The intensity of antibiotics used,length of hospital stay,28/30 day mortality,and 90-day mortality were compared by adjusting the therapeutic regimen according to pathogenic test results.Review Manager 5.4.1 software was used for meta-analysis on the abovementioned indexes.Results A total of 35 papers with 2624 patients were included,involving 2248 cases in the HTS group and 2493 cases in the traditional pathogen detection group.The results of the meta-analysis showed that the positive rate of the HTS group was 79.8%(1793/2248),being significantly higher than that of the traditional pathogen detection group at 41.7%(1039/2493)(OR=6.84,95%CI:4.84~9.67,Z=10.88,P<0.001).The sensitivity,specificity,and the area under the curve of receiver operating characteristic curves by BALF metagenomic sequencing was higher than those by traditional pathogen detection method.The patients enrolled in nine papers were patients with severe pneumonia,and the subgroup analysis showed that the positive rate of BALF high-throughput sequencing in patients with severe pneumonia was 85.8%(495/577),being significantly higher than that in the traditional pathogen detection group at 42.9%(282/657)(OR=6.52,95%CI:4.04~10.52,Z=7.69,P<0.001).According to the results of pathogen detection,the intensity of antibiotic use in the high-throughput sequencing group was significantly lower than that in the traditional detection group(SMD=-40.04,

关 键 词：感染 高通量测序 支气管肺泡灌洗液 META分析 

分 类 号：R563.1[医药卫生—呼吸系统]