支气管肺泡灌洗液送检mNGS对影像学不典型疑似肺结核的诊断及鉴别诊断的临床应用价值  

Diagnostic and differential diagnostic value of metagenomic next-generation sequencing of bronchoalveolar lavage fluid in atypical imaging cases suspected with pulmonary tuberculosis

作　　者：杭天星 孙素越 方刚 张浩[1] 胡春梅 Hang Tianxing;Sun Suyue;Fang Gang;Zhang Hao;Hu Chunmei(Department of Tuberculosis,Nanjing Hospital Affiliated to Nanjing University of Traditional Chinese Medicine(the Second Hospital of Nanjing),Nanjing 210037,China)

机构地区：[1]南京中医药大学附属南京医院(南京市第二医院)结核科,南京210037

出　　处：《国际呼吸杂志》2023年第4期390-394,共5页International Journal of Respiration

基　　金：江苏省"六大人才高峰"高层次人才选拔培养资助项目(WSN-160)。

摘　　要：目的探究支气管肺泡灌洗液(BALF)送检宏基因组二代测序(mNGS)对影像学不典型疑似肺结核的诊断及鉴别诊断的临床应用价值。方法本研究为横断面研究。采用单纯随机抽样方法,收集2020年5月至12月在南京市第二医院行气管镜检查,影像学不典型且痰结核菌涂片阴性的疑似肺结核患者合计86例的临床资料,统计分析BALF并行送检mNGS、分枝杆菌培养+鉴定、GeneXpert MTB/RIF分析(Xpert)的结果。结果86例疑似肺结核患者中,因数据不完整去除22例,最终纳入分析64例,其中诊断活动性肺结核患者44例,排除肺结核诊断患者20例。在诊断活动性肺结核方面,mNGS的敏感度与Xpert相当(36.36%比34.09%),高于分枝杆菌培养检测(36.36%比18.18%);并行分枝杆菌培养+Xpert+mNGS的联合诊断可有效提高肺结核病原检测的敏感度(54.55%);同时mNGS还以非靶向方法检测到3例活动性肺结核合并其他病原体的混合感染。对于抗酸杆菌涂片阴性影像学不典型的20例疑似肺结核患者鉴别诊断方面,mNGS检测到13例结核分枝杆菌以外的病原体(13/20,65.00%),其中7例通过mNGS直接鉴定出非结核分枝杆菌菌种,1例人葡萄球菌感染,5例均仅由mNGS鉴定为真菌。结论BALF送检mNGS对结核分枝杆菌检测的敏感度优于培养,并行分枝杆菌培养+Xpert+mNGS联合使用可提高结核分枝杆菌的检出率,有助于早期对影像学不典型肺结核患者作出明确诊断。更有意义的是,对于痰涂片阴性影像学不典型的疑似肺结核患者,mNGS可快速鉴别诊断出非结核分枝杆菌和其他病原体(比如真菌)的感染,从而为临床提供更多的病原学依据,提高鉴别诊断的能力,降低漏诊率和误诊率。Objective To investigate the diagnostic and differential diagnostic value of metagenomic next-generation sequencing(mNGS)of bronchoalveolar lavage fluid(BALF)in atypical imaging cases suspected with pulmonary tuberculosis.Methods This was a cross-sectional study.The clinical data of 86 suspected pulmonary tuberculosis patients who underwent tracheoscopy in Nanjing Second Hospital from May to December 2020 with atypical imaging and negative sputum and tuberculosis smear were collected by simple random sampling method.The results of BALF mNGS,Mycobacterium culture+identification,and GeneXpert MTB/RIF(Xpert)were statistically analyzed.Results Of 86 suspected tuberculosis patients,22 were excluded due to incomplete data,and finally 44 cases were diagnosed as active pulmonary tuberculosis and 20 cases were excluded from tuberculosis.Compared to the final clinical diagnosis,the sensitivity of mNGS in diagnosing active pulmonary tuberculosis was similar to that of Xpert(36.36%vs 34.09%),but higher than that of culture(36.36%vs 18.18%).Moreover,the combined diagnosis of culture+Xpert+mNGS can effectively improve the sensitivity of tuberculosis detection(54.55%).At the same time,3 cases infected by Mycobacterium tuberculosis(MTB)mixed with other pathogens were identified by non-targeted methods mNGS.In 20 cases of non-tuberculosis infection,13 cases infected other than MTB were detected by mNGS(13/20,65.00%),of which 7 cases were directly identified as Nontuberculosis mycobacteria strains by mNGS,1 case was identified as Staphylococcus hominis,and 5 cases were identified as fungi,only by mNGS.Conclusions The sensitivity of mNGS from BALF samples is superior to that of culture in detecting active pulmonary tuberculosis.The combined use of culture+Xpert+mNGS can increase the detection rate of MTB,which can help diagnose pulmonary tuberculosis with atypical imaging early.More meaningfully,mNGS can rapidly differentiate the infections of Nontuberculosis mycobacteria and other pathogens(such as fungi),thereby providing more et

关 键 词：结核 肺 诊断 支气管肺泡灌洗液 宏基因组二代测序 

分 类 号：R521[医药卫生—内科学]