纳米孔测序技术对涂阴肺结核患者诊断价值的多中心临床研究

doi:10.19982/j.issn.1000-6621.20240481

中国防痨杂志 ›› 2025, Vol. 47 ›› Issue (2): 169-174.doi: 10.19982/j.issn.1000-6621.20240481

纳米孔测序技术对涂阴肺结核患者诊断价值的多中心临床研究

闫晓婧¹, 王宇津¹, 王隽¹, 荆玮¹, 李雪莲¹, 程洁², 杨国立³, 王玉清⁴, 初乃惠¹, 聂文娟¹(), 矫晓克¹()

¹首都医科大学附属北京胸科医院结核一科,北京 101149
²安徽省胸科医院结核科,合肥 230022
³吉林省结核病医院结核科,长春 130500
⁴青海省第四人民医院呼吸科,西宁 810000

收稿日期:2024-11-04 出版日期:2025-02-10 发布日期:2025-02-08
通信作者: 聂文娟,Email:xiaobingxiaomei@sina.cn;矫晓克,Email:kekejiao83@vip.sina.com
基金资助:
高层次公共卫生技术人才建设项目和首都医科大学临床专科开放课题(CCMU2022ZKYXZ003);临床医学发展专项“扬帆3.0”计划项目(ZLRK202331)

A multicenter clinical study on the diagnostic value of nanopore sequencing technology in patients with smear-negative tuberculosis

Yan Xiaojing¹, Wang Yujin¹, Wang Jun¹, Jing Wei¹, Li Xuelian¹, Cheng Jie², Yang Guoli³, Wang Yuqing⁴, Chu Naihui¹, Nie Wenjuan¹(), Jiao Xiaoke¹()

¹Department Ⅰ of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China
²Department of Tuberculosis, Anhui Provincial Chest Hospital, Hefei 230022, China
³Department of Tuberculosis, Tuberculosis Hospital of Jilin Province, Changchun 130500, China
⁴Department of Respiratory,The Fourth People’s Hospital of Qinghai Province, Xining 810000, China

Received:2024-11-04 Online:2025-02-10 Published:2025-02-08
Contact: Nie Wenjuan, Email: xiaobingxiaomei@sina.cn;Jiao Xiaoke, Email:kekejiao83@vip.sina.com
Supported by:
High Level Public Health Technical Personnel Construction Project and Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University(CCMU2022ZKYXZ003);Clinical Medicine Development Special Project “Sailing” Plan Project(ZLRK202331)

摘要/Abstract

摘要：

目的: 分析纳米孔测序技术用于涂阴肺结核患者的诊断价值。方法: 本研究采集了来自北京、安徽、青海和吉林4个不同省份传染病专科医院2021年9月至2022年4月收治的107例疑似涂片阴性肺结核患者的支气管肺泡灌洗液(BALF)作为研究样本,对其进行BACTEC MGIT 960液体培养 (简称“MGIT 960培养”)和 GeneXpert MTB/RIF(简称“Xpert”)检测和纳米孔测序。以临床最终诊断结果为参照标准,比较3种方法对肺结核的检测效能。结果: 107例疑似肺结核患者中,最终诊断为肺结核70例(65.42%),非结核分枝杆菌病15例(14.02%),非结核病22例(20.56%)。以临床最终诊断结果为参照标准,纳米孔测序技术、MGIT 960培养和Xpert 检测的敏感度分别为84.29%(59/70)、37.14%(26/70)和41.43%(29/70),特异度分别为86.49%(32/37)、75.68%(28/37)和97.30%(36/37),约登指数分别为0.71、0.13和0.39。纳米孔测序的曲线下面积(AUC值)为0.854(95%CI:0.773~0.935),Xpert 检测的AUC值为0.694(95%CI:0.596~0.792),MGIT 960培养的AUC值为0.564(95%CI:0.451~0.677)。结论: 纳米孔测序技术在检测涂阴肺结核方面具有较 Xpert和MGIT 960培养更好的诊断效能。

关键词: 结核,肺, 支气管肺泡灌洗液, 纳米技术, 多中心研究

Abstract:

Objective: To analyze the diagnostic value of nanopore sequencing technology in patients with smear-negative pulmonary tuberculosis (PTB). Methods: In this study, 107 smear-negative patients with suspected PTB admitted to infectious disease hospitals from Beijing, Anhui, Qinghai and Jilin Provinces from September 2021 to April 2022 were enrolled as research subjects. Samples of these cases were subjected to BACTEC MGIT 960 liquid culture (MGIT 960 culture), GeneXpert MTB/RIF (Xpert) assay and nanopore sequencing. The final clinical diagnosis was used as reference standard to evaluate diagnostic accuracy of the three methods for detecting PTB. Results: Among the 107 patients with suspected PTB, 70 cases (65.42%) were finally diagnosed as PTB,15 cases (14.02%) were nontuberculous mycobacteria and 22 cases (20.56%) were non-TB. The sensitivities of nanopore sequencing technology, MGIT 960 culture and Xpert detection were 84.29% (59/70), 37.14% (26/70) and 41.43% (29/70), respectively, and their specificities were 86.49% (32/37), 75.68% (28/37) and 97.30% (36/37), respectively. Their Youden index were 0.71, 0.13, and 0.39, respectively. Their AUC values were 0.854 (95%CI: 0.773-0.935), 0.694 (95%CI: 0.596-0.792) and 0.564 (95%CI: 0.451-0.677), respectively. Conclusion: Nanopore sequencing technology has better diagnostic performance than Xpert and MGIT 960 culture in the detection of smear-negative PTB.

Key words: Tuberculosis, pulmonary, Bronchoalveolar lavage fluids, Nanotechnology, Multicenter study

中图分类号:

R521
R446

闫晓婧, 王宇津, 王隽, 荆玮, 李雪莲, 程洁, 杨国立, 王玉清, 初乃惠, 聂文娟, 矫晓克. 纳米孔测序技术对涂阴肺结核患者诊断价值的多中心临床研究[J]. 中国防痨杂志, 2025, 47(2): 169-174. doi: 10.19982/j.issn.1000-6621.20240481

Yan Xiaojing, Wang Yujin, Wang Jun, Jing Wei, Li Xuelian, Cheng Jie, Yang Guoli, Wang Yuqing, Chu Naihui, Nie Wenjuan, Jiao Xiaoke. A multicenter clinical study on the diagnostic value of nanopore sequencing technology in patients with smear-negative tuberculosis[J]. Chinese Journal of Antituberculosis, 2025, 47(2): 169-174. doi: 10.19982/j.issn.1000-6621.20240481

图/表 3

表1

表2

图1

参考文献 13

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特征	患者例数	构成比(%)
性别
男性	69	64.49
女性	38	35.51
年龄组(岁)
≤30	22	20.56
31~40	11	10.28
41~50	17	15.89
51~60	26	24.30
>60	31	28.97
疾病诊断
肺结核	70	65.42
非肺结核	37	34.58
纳米孔测序
阳性	64	59.81
阴性	43	40.19
MGIT 960培养
阳性	35	32.71
阴性	72	67.29
Xpert
阳性	30	28.04
阴性	77	71.96
临床最终诊断结果阳性
纳米孔测序阴性;Xpert 阴性;MGIT 960培养阴性	11	10.28
纳米孔测序阳性;Xpert 阴性;MGIT 960培养阴性	25	23.36
纳米孔测序阳性;Xpert 阴性;MGIT 960培养阳性	5	4.67
纳米孔测序阳性;Xpert 阳性;MGIT 960培养阴性	8	7.48
纳米孔测序阳性;Xpert阳性;MGIT 960培养阳性	21	19.63
临床最终诊断结果阴性
纳米孔测序阴性;Xpert阴性;MGIT 960培养阴性	25	23.36
纳米孔测序阴性;Xpert阴性;MGIT 960培养阳性	6	5.61
纳米孔测序阴性;Xpert阳性;MGIT 960培养阴性	1	0.93
纳米孔测序阳性;Xpert阴性;MGIT 960培养阴性	2	1.87
纳米孔测序阳性;Xpert阴性;MGIT 960培养阳性	3	2.80

检验方法	临床诊断		敏感度 (%)	特异度 (%)	阳性预测值(%)	阴性预测值(%)	约登指数	符合率 (%)
检验方法	阳性(例)	阴性(例)	敏感度 (%)	特异度 (%)	阳性预测值(%)	阴性预测值(%)	约登指数	符合率 (%)
MGIT 960培养			37.14	75.68	74.29	38.89	0.13	50.47
阳性	26	9
阴性	44	28
Xpert			41.43	97.30	96.67	46.75	0.39	60.75
阳性	29	1
阴性	41	36
纳米孔测序			84.29	86.49	92.19	74.42	0.71	85.05
阳性	59	5
阴性	11	32

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纳米孔测序技术对涂阴肺结核患者诊断价值的多中心临床研究

A multicenter clinical study on the diagnostic value of nanopore sequencing technology in patients with smear-negative tuberculosis

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