靶向二代测序技术对无痰肺结核患者的诊断效能评估

doi:10.19982/j.issn.1000-6621.20250127

中国防痨杂志 ›› 2025, Vol. 47 ›› Issue (7): 878-883.doi: 10.19982/j.issn.1000-6621.20250127

靶向二代测序技术对无痰肺结核患者的诊断效能评估

杨泽亮¹, 马子淳¹, 尚媛媛¹, 石金², 荆玮³, 逄宇¹(), 秦林⁴()

¹ 首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所细菌免疫学实验室/耐药结核病研究北京市重点实验室,北京 101149
² 首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所结核二科,北京 101149
³ 首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所结核一科,北京 101149
⁴ 首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所内镜诊疗中心,北京 101149

收稿日期:2025-04-01 出版日期:2025-07-10 发布日期:2025-07-03
通信作者: 秦林,Email:phqinlin@126.com; 逄宇,Email:pangyupound@163.com
基金资助:
北京市高层次公共卫生技术人才建设项目（学科带头人-02-26）

The diagnostic value of targeted next generation sequencing in sputum-free pulmonary tuberculosis patients

Yang Zeliang¹, Ma Zichun¹, Shang Yuanyuan¹, Shi Jin², Jing Wei³, Pang Yu¹(), Qin Lin⁴()

¹ Beijing Key Laboratory on Drug-resistant Tuberculosis Research, Bacterial Immunology Laboratory, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Institute, Beijing 101149, China
² Department Ⅱ of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Institute, Beijing 101149, China
³ Department Ⅰ of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Institute, Beijing 101149, China
⁴ Department of Endoscopic Diagnosis and Treatment, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Institute, Beijing 101149, China

Received:2025-04-01 Online:2025-07-10 Published:2025-07-03
Contact: Qin Lin, Email: phqinlin@126.com; Pang Yu, Email: pangyupound@163.com
Supported by:
Beijing High Level Public Health Technical Personnel Construction Project (Discipline Leader-02-26)

摘要/Abstract

摘要：

目的:评估靶向二代测序(targeted next generation sequencing,tNGS)技术对无痰肺结核患者的诊断效能。方法:收集2023年12月至2024年3月在首都医科大学附属北京胸科医院就诊的149例无痰肺结核患者的支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)标本,分别进行BECTEC MGIT 960液体培养(简称“培养”)、GeneXpert MTB/RIF(简称“Xpert”)和tNGS检测。分别以微生物学参考标准(microbiological reference standard,MRS)和临床参考标准(clinical reference standard,CRS)为标准,对比3种检测方法的肺结核诊断效能。结果:培养、Xpert和tNGS技术的阳性检出率分别为47.0%(70/149)、53.0%(79/149)和89.3%(133/149)。以MRS作为诊断标准,tNGS的敏感度为100.0%(81/81),与Xpert的97.5%(79/81)相比,差异无统计学意义(χ²=2.025,P=0.155),高于培养的86.4%(70/81),差异有统计学意义(χ²=11.801,P=0.001)。将CRS作为诊断标准后,tNGS的敏感度和特异度分别为96.3%(131/136)和84.6%(11/13),敏感度高于Xpert的59.6%(81/136)和培养的51.5%(70/136),差异均有统计学意义(χ²=53.459,P<0.001;χ²=70.921,P<0.001)。结论:tNGS技术对无痰肺结核患者的BALF标本具有良好的诊断效能,可以用于疑似肺结核患者的早期诊断。

关键词: 结核, 肺, 痰, 支气管肺泡灌洗液, 诊断技术和方法, 靶向二代测序

Abstract:

Objective: To evaluate the diagnostic value of targeted next generation sequencing (tNGS) for sputum-free pulmonary tuberculosis (TB) patients. Methods: We enrolled 149 sputum-free pulmonary TB patients derived from Beijing Chest Hospital, Capital Medical University from December, 2023 to March, 2024 for the collection of bronchoalveolar lavage fluids (BALFs), followed by culture, Xpert test, and tNGS. Based on microbiological reference standard (MRS) and clinical reference standard (CRS), the diagnostic capacity of these detection methods was compared. Results: The positive detection rates of culture, Xpert, and tNGS were 47.0% (70/149), 53.0% (79/149), and 89.3% (133/149), accordingly. Compared with MRS, the sensitivity of tNGS was 100.0% (81/81), which was similar to Xpert with 97.5% (79/81, χ²=2.025, P=0.155) and higher than culture with 86.4% (70/81, χ²=11.801, P=0.001). Based on CRS, tNGS exhibited the sensitivity of 96.3% (131/136) and the specificity of 84.6% (11/13). The sensitivity of tNGS was significantly higher than Xpert with 59.6% (81/136; χ²=53.459, P<0.001) and culture with 51.5% (70/136; χ²=70.921, P<0.001). Conclusion: tNGS showed an excellent diagnostic potential for sputum-free pulmonary TB patients, thus providing an alternative method for early TB diagnosis.

Key words: Tuberculosis, pulmonary, Sputum, Bronchoalveolar lavage fluid, Diagnostic techniques and procedures, Targeted next generation sequencing

中图分类号:

R521
R446

杨泽亮, 马子淳, 尚媛媛, 石金, 荆玮, 逄宇, 秦林. 靶向二代测序技术对无痰肺结核患者的诊断效能评估[J]. 中国防痨杂志, 2025, 47(7): 878-883. doi: 10.19982/j.issn.1000-6621.20250127

Yang Zeliang, Ma Zichun, Shang Yuanyuan, Shi Jin, Jing Wei, Pang Yu, Qin Lin. The diagnostic value of targeted next generation sequencing in sputum-free pulmonary tuberculosis patients[J]. Chinese Journal of Antituberculosis, 2025, 47(7): 878-883. doi: 10.19982/j.issn.1000-6621.20250127

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方法	微生物学参考标准		敏感度 (%,95%CI)	特异度 (%,95%CI)	阳性预测值 (%,95%CI)	阴性预测值 (%,95%CI)	符合率 (%,95%CI)
方法	阳性(例)	阴性(例)	敏感度 (%,95%CI)	特异度 (%,95%CI)	阳性预测值 (%,95%CI)	阴性预测值 (%,95%CI)	符合率 (%,95%CI)
tNGS技术			100.0 (94.4~100.0)	23.5 (14.4~43.4)	60.9 (52.0~69.1)	100.0 (75.9~100.0)	65.1 (57.2~72.3)
阳性	81	52
阴性	0	16
Xpert			97.5 (90.5~99.6)	100.0 (93.3~100.0)	100.0 (94.2~100.0)	97.1 (89.1~99.5)	98.7 (95.2~99.6)
阳性	79	0
阴性	2	68
培养			86.4 (76.6~92.7)	100.0 (93.3~100.0)	100.0 (93.5~100.0)	86.1 (76.0~92.5)	92.6 (87.3~95.8)
阳性	70	0
阴性	11	68

方法	临床参考标准		敏感度 (%,95%CI)	特异度 (%,95%CI)	阳性预测值 (%,95%CI)	阴性预测值 (%,95%CI)	符合率 (%)
方法	阳性(例)	阴性(例)	敏感度 (%,95%CI)	特异度 (%,95%CI)	阳性预测值 (%,95%CI)	阴性预测值 (%,95%CI)	符合率 (%)
tNGS技术			96.3 (91.2~98.6)	84.6 (53.7~97.3)	98.5 (94.1~99.7)	68.8 (41.5~87.9)	95.3 (90.6~97.7)
阳性	131	2
阴性	5	11
Xpert			59.6 (50.8~67.8)	100.0 (71.7~100.0)	100.0 (94.4~100.0)	19.1 (11.0~30.8)	63.1 (55.1~70.4)
阳性	81	0
阴性	55	13
培养			51.5 (42.8~60.1)	100.0 (71.7~100.0)	100.0 (93.5~100.0)	16.5 (9.4~26.9)	55.7 (47.7~63.4)
阳性	70	0
阴性	66	13

靶向二代测序技术对无痰肺结核患者的诊断效能评估

The diagnostic value of targeted next generation sequencing in sputum-free pulmonary tuberculosis patients

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