胸腔积液游离核酸检测在结核性胸膜炎早期诊断中的价值

doi:10.19982/j.issn.1000-6621.20220064

中国防痨杂志 ›› 2022, Vol. 44 ›› Issue (8): 835-843.doi: 10.19982/j.issn.1000-6621.20220064

胸腔积液游离核酸检测在结核性胸膜炎早期诊断中的价值

张芸¹, 李琨², 梁清涛¹, 刘子臣², 段鸿飞¹, 李雪莲¹, 郭茹¹, 车南颖²(), 杨新婷¹()

¹首都医科大学附属北京胸科医院结核三科,北京 101149
²北京市结核病胸部肿瘤研究所病理科,北京 101149

收稿日期:2022-03-07 出版日期:2022-08-10 发布日期:2022-08-03
通信作者: 车南颖,杨新婷 E-mail:cheny0448@163.com;2320652139@qq.com
基金资助:
北京市医院管理局“登峰”计划专项经费资助(DFL20151501);北京市医院管理局“登峰”计划专项经费资助(DFL20181601);北京市科学技术委员会重点项目(D181100000418003);北京市科学技术委员会重点项目(Z191100006619078);北京市卫生和计划生育委员会北京市卫生与健康科技成果和适宜技术推广项目(2018-TG-43)

The diagnostic value of cell-free Mycobacterium tuberculosis DNA test on pleural effusion in early diagnosis of tuberculous pleurisy

Zhang Yun¹, Li Kun², Liang Qingtao¹, Liu Zichen², Duan Hongfei¹, Li Xuelian¹, Guo Ru¹, Che Nanying²(), Yang Xinting¹()

¹Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China
²Department of Pathology, Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China

Received:2022-03-07 Online:2022-08-10 Published:2022-08-03
Contact: Che Nanying,Yang Xinting E-mail:cheny0448@163.com;2320652139@qq.com
Supported by:
Special Fund for the “Peak Climbing” Program of Beijing Municipal Hospital Administration(DFL20151501);Special Fund for the “Peak Climbing” Program of Beijing Municipal Hospital Administration(DFL20181601);Beijing Municipal Science and Technology Project(D181100000418003);Beijing Municipal Science and Technology Project(Z191100006619078);Beijing Municipal Health Commission New Achievement and Technology Popularization Project(2018-TG-43)

摘要/Abstract

摘要：

目的: 评价胸腔积液结核分枝杆菌游离核酸检测技术(cell-free Mycobacterium tuberculosis DNA test,CF.TB)在结核性胸膜炎中的诊断价值。方法: 选取2016年7月至2018年12月收住于首都医科大学附属北京胸科医院初诊不明原因胸腔积液患者216例。所有患者均在B超引导下进行胸腔穿刺术或置管术留取胸腔积液,并同时进行胸腔积液CF.TB、SAT-PCR、GeneXpert MTB/RIF及腺苷脱氨酶(adenosine deaminase,ADA)检测和血结核感染T细胞斑点试验(T-SPOT.TB)检测。以临床复合标准(composite reference standard,CRS)为参考标准,评价胸腔积液CF.TB、SAT-PCR、GeneXpert MTB/RIF、ADA及血T-SPOT.TB检测诊断结核性胸膜炎的敏感度、特异度、阳性预测值、阴性预测值。评价胸腔积液CF.TB方法单独或与ADA联合检测对结核性胸膜炎早期诊断的价值。结果: 216例患者中,165例患者临床确诊为结核性胸膜炎,51例患者确诊为其他病因胸腔积液。以CRS为参考标准,CF.TB、SAT-PCR、GeneXpert MTB/RIF、ADA及T-SPOT.TB方法对结核性胸膜炎诊断的敏感度分别为70.30%(116/165)、7.88%(13/165)、12.12%(20/165)、67.27%(111/165)和87.27%(144/165),特异度分别为100.00%(51/51)、100.00%(51/51)、100.00%(51/51)、92.16%(47/51)和62.75%(32/51),阳性预测值分别为100.00%(116/116)、100.00%(13/13)、100.00%(20/20)、96.52%(111/115)和88.34%(144/163),阴性预测值分别为51.00%(51/100)、25.12%(51/203)、26.02%(51/196)、46.53%(47/101)和60.38%(32/53)。CF.TB检测胸腔积液MTB的敏感度(70.30%)明显高于SAT-PCR(7.88%)、 GeneXpert MTB/RIF(12.12%)和ADA(67.27%)(χ²=1.350、1.153、1.025,P值均=0.000),差异均有统计学意义;而且CF.TB与ADA联合检测(88.48%, 146/165)可明显提高CF.TB(70.30%, 116/165)诊断结核性胸膜炎患者的敏感度,差异有统计学意义(χ²=16.670,P=0.000)。结论: 胸腔积液CF.TB检测技术对结核性胸膜炎诊断的敏感度优于SAT-PCR及GeneXpert MTB/RIF技术,特异度优于ADA及T-SPOT.TB方法,而且CF.TB与ADA联合检测可明显提高其在结核性胸膜炎中的诊断价值,建议CF.TB技术可作为结核性胸膜炎的辅助诊断。

关键词: 结核,胸膜, 胸腔积液, 核酸扩增技术, 对比研究

Abstract:

Objective: To evaluate the diagnostic value of cell-free Mycobacterium tuberculosis DNA test (CF.TB) on pleural effusion in detecting tuberculous pleurisy. Methods: A total of 216 patients with unexplained pleural effusion in Beijing Chest Hospital Affiliated with Capital Medical University from July 2016 to December 2018 were enrolled. All patients were given thoracentesis or thoracic catheterization to collect pleural effusion. The CF.TB, SAT-PCR, GeneXpert MTB/RIF and adenosine deaminase (ADA) assay were performed on pleural effusion samples and T-SPOT.TB test was used on blood sample. With a composite reference standard (CRS) as the reference standard, the sensitivity, specificity, positive prediction value and negative prediction value of CF.TB, SAT-PCR, GeneXpert MTB/RIF assay, ADA and T-SPOT.TB were evaluated. Moreover, the diagnostic value of CF.TB alone and CF.TB plus ADA test were assessed. Results: Among those 216 patients, 165 cases were confirmed as tuberculous pleurisy clinically,51 cases were non-tuberculosis pleural effusion. With CRS as the reference standard, the sensitivity of CF.TB, SAT-PCR and GeneXpert MTB/RIF assay, ADA and T-SPOT.TB were 70.30% (116/165), 7.88% (13/165), 12.12% (20/165), 67.27% (111/165) and 87.27% (144/165) respectively. The specificity of five tests were 100.00% (51/51), 100.00% (51/51), 100.00% (51/51), 92.16% (47/51), and 62.75% (32/51) respectively. The positive prediction value were 100.00% (116/116), 100.00% (13/13), 100.00% (20/20), 96.52% (111/115) and 88.34% (144/163) respectively. The negative prediction value were 51.00% (51/100), 25.12% (51/203), 26.02% (51/196), 46.53% (47/101) and 60.38% (32/53) respectively. The sensitivity of CF.TB test was significantly higher than that of SAT-PCR (70.30% vs. 7.88%), GeneXpert MTB/RIF (12.12%) and ADA test (67.27%), the differences were statistically significant (χ² values were 1.350, 1.153 and 1.025, respectively, all P values=0.000). Furthermore, comparing with CF.TB test alone, performing CF.TB plus ADA could significantly improve the sensitivity of detecting tuberculous pleurisy (88.48%, 146/165 vs 70.30%, 116/165), the difference was statistically significant (χ² value was 16.670, P value=0.000). Conclusion: CF.TB test has higher sensitivity than SAT-PCR and GeneXpert MTB/RIF, and higher specificity than ADA and T-SPOT.TB in diagnosing tuberculous pleurisy. Moreover, jointly using CF.TB and ADA can significantly improve its sensitivity. We suggest it should be adopted as an important assisting diagnostic method for detecting tuberculous pleurisy.

Key words: Tuberculosis, pleurisy, Pleural effusion, Nucleic acid amplification techniques, Comparative study

中图分类号:

R521

张芸, 李琨, 梁清涛, 刘子臣, 段鸿飞, 李雪莲, 郭茹, 车南颖, 杨新婷. 胸腔积液游离核酸检测在结核性胸膜炎早期诊断中的价值[J]. 中国防痨杂志, 2022, 44(8): 835-843. doi: 10.19982/j.issn.1000-6621.20220064

Zhang Yun, Li Kun, Liang Qingtao, Liu Zichen, Duan Hongfei, Li Xuelian, Guo Ru, Che Nanying, Yang Xinting. The diagnostic value of cell-free Mycobacterium tuberculosis DNA test on pleural effusion in early diagnosis of tuberculous pleurisy[J]. Chinese Journal of Antituberculosis, 2022, 44(8): 835-843. doi: 10.19982/j.issn.1000-6621.20220064

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临床资料	结核组(165例)	非结核组(51例)	统计检验值	P值
年龄[岁, M(Q₁,Q₃)]	40(26,57)	58(48,66)	Z=4.818	0.001
性别[男性例数,构成比(%)]	126(76.36)	27(52.94)	χ²=10.345	0.001
渗出液[例数,发生率(%)]	160(96.97)	51(100.00)	χ²=1.567	0.594
单侧胸腔积液[例数,发生率(%)]	147(89.09)	49(96.08)	χ²=1.692	0.172
T-SPOT.TB阳性[例数,阳性率(%)]	144(87.27)	19(37.25)	χ²=11.858	0.001

组别	CF.TB					SAT-PCR			GeneXpert MTB/RIF
组别	检测例数		阳性例数	阳性率(%)	检测例数		阳性例数	阳性率(%)	检测例数	阳性例数	阳性率(%)
合并肺结核
有	106		80	75.47	105		9	8.57	106	17	16.04
无	59		36	61.02	57		4	7.02	59	3	5.08
χ²值		3.793				0.002			4.269
P值		0.051				0.964			0.039
呼吸道病原学
阳性	49		36	73.47	48		4	8.33	49	6	12.24
无痰/阴性	116		80	68.97	114		9	7.89	116	14	12.07
χ²值		3.352				0.001			0.001
P值		0.563				0.999			0.975
ADA
≥40U/L	111		81	72.97	108		11	10.19	111	15	13.51
<40U/L	54		35	64.81	54		2	3.70	54	5	9.26
χ²值		1.158				1.265			0.617
P值		0.282				0.261			0.432
年龄(岁)
15~39	81		60	74.07	78		6	7.69	81	8	9.88
40~59	48		34	70.83	48		5	10.42	48	7	14.58
≥60	36		22	61.11	36		2	5.56	36	5	13.89
χ²值		2.015				0.671			0.930
P值		0.365				0.806			0.705
组别	CF.TB					SAT-PCR			GeneXpert MTB/RIF
组别	检测例数		阳性例数	阳性率(%)	检测例数		阳性例数	阳性率(%)	检测例数	阳性例数	阳性率(%)
性别
男性	126		90	71.43	123		11	8.94	126	16	12.70
女性	39		26	66.67	39		2	5.13	39	4	10.26
χ²值		0.323				0.181			0.016
P值		0.571				0.672			0.888

胸腔积液游离核酸检测在结核性胸膜炎早期诊断中的价值

The diagnostic value of cell-free Mycobacterium tuberculosis DNA test on pleural effusion in early diagnosis of tuberculous pleurisy

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参考文献 27

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检测方法	临床确诊(例)		敏感度 (%)	特异度 (%)	阳性预测值 (%)	阴性预测值 (%)	符合率 (%)
检测方法	结核 (165例)	非结核 (51例)	敏感度 (%)	特异度 (%)	阳性预测值 (%)	阴性预测值 (%)	符合率 (%)
SAT-PCR			7.88	100.00	100.00	25.12	29.63
阳性	13	0
阴性	152	51
GeneXpert MTB/RIF			12.12	100.00	100.00	26.02	32.87
阳性	20	0
阴性	145	51
CF.TB			70.30	100.00	100.00	51.00	77.31
阳性	116	0
阴性	49	51
分枝杆菌培养			15.15	100.00	100.00	26.70	35.19
阳性	25	0
阴性	140	51

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