Article(id=1324044780266730302, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324044701648695723, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202510185, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1760630400000, receivedDateStr=2025-10-17, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793606475177, onlineDateStr=2026-11-02, pubDate=1779638400000, pubDateStr=2026-05-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793606475177, onlineIssueDateStr=2026-11-02, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793606475177, creator=13701087609, updateTime=1793606475177, updator=13701087609, issue=Issue{id=1324044701648695723, tenantId=1146029695717560320, journalId=1227665162245664772, year='2026', volume='53', issue='10', pageStart='1729', pageEnd='1920', issueExtLink='null', onlineDate='null', pubDate='1779638400000', pubDateStr='2026-05-25', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793606456434, creator='13701087609', updateTime=1793670074552, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1324311535425815306, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324044701648695723, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1324311535425815307, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324044701648695723, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=1914, endPage=1920, ext={EN=ArticleExt(id=1324044780468056895, articleId=1324044780266730302, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Consistency of TB-LAMP and T-SPOT.TB in the diagnosis of tuberculosis and influencing factors of the accuracy of their combined diagnosis, columnId=1228016569138213037, journalTitle=Modern Preventive Medicine, columnName=Clinical Medicine and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective

To analyze the consistency between the Mycobacterium tuberculosis loop-mediated isothermal amplification (Mycobacterium tuberculosis loop-mediated isothermal amplification, TB-LAMP) and the tuberculosis T-cell spot test (tuberculous infection of T cells spot test, T-SPOT.TB) in the diagnosis of tuberculosis (tuberculosis, TB), as well as the influencing factors of the accuracy of combined diagnosis.

Methods

A total of 556 suspected TB patients hospitalized in our hospital from January 2022 to December 2024 were selected. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic values of the two methods used alone and in combination. The Kappa test was employed to assess the consistency between the two methods and Mycobacterium tuberculosis (MTB). Univariate and multivariate Logistic regression analyses were conducted to identify the factors influencing the combined diagnostic accuracy of the two methods.

Results

The positive rates of TB-LAMP in the three groups were 87.32%, 75.00%, and 12.23% respectively, those of T-SPOT.TB were 92.39%, 71.74%, and 23.40% respectively, and those of the combined detection were 93.48%, 85.87%, and 18.09% respectively, with significant differences among the groups (P<0.001). There was a high consistency between T-SPOT.TB, TB-LAMP, and their combined detection and MTB culture (Kappa=0.747, 0.733, 0.751). The sensitivities of TB-LAMP, T-SPOT.TB, and the combined detection were 84.24%, 87.23%, and 91.58% respectively, the specificities were 92.63%, 90.43%, and 83.51% respectively, the diagnostic accuracies were 87.41%, 88.31%, and 88.85% respectively, and the AUCs were 0.840, 0.910, and 0.930 respectively. Age≥60 years, CD4+ T lymphocyte count<350 cells/μL, albumin<35 g/L, diabetes, number of specimen submissions<3 times, time from collection to processing>2 h, and failed microscopic examination were independent risk factors affecting the combined diagnostic accuracy (P<0.05). Genderstratified analysis showed that except for age which was not significant in the female subgroup, all other risk factors remained independently significant in both male and female subgroups. Gender did not substantially interfere with the effects of these risk factors.

Conclusion

The combined detection of TB-LAMP and T-SPOT.TB can significantly improve the diagnostic accuracy. Age≥60 years old, CD4+ T lymphocyte count<350 cells/μL, albumin<35 g/L, diabetes, number of tests sent for examination<3 times, collection-to-processing time>2 hours, and insufficiently qualified for microscopic examination are all independent risk factors affecting the accuracy of the combined diagnosis.

, authors=Xiao-ying AN1, Mei LIU1, Jia-qi CHEN3, Yun-ting ZHANG2, Di-jing JIA2, authorsList=Xiao-ying AN, Mei LIU, Jia-qi CHEN, Yun-ting ZHANG, Di-jing JIA, authorCompany=null, correspAuthors=Di-jing JIA, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1324044783576036178, articleId=1324044780266730302, tenantId=1146029695717560320, journalId=1227665162245664772, language=CN, title=TB-LAMP与T-SPOT. TB诊断结核病的一致性及联合诊断准确率影响因素, columnId=1228016570119680182, journalTitle=现代预防医学, columnName=临床与预防, runingTitle=null, highlight=null, articleAbstract=
目的

分析结核分枝杆菌环介导等温扩增技术(Mycobacterium tuberculosis loop-mediated isothermal amplification,TB-LAMP)与结核感染T细胞斑点试验(tuberculous infection of T cells spot test,T-SPOT.TB)在结核病(tuberculosis,TB)诊断中的一致性及联合诊断准确率的影响因素。

方法

选取2022年1月至2024年12月于我院住院治疗556例的疑似TB患者。采用受试者工作特征(receiver operating characteristic,ROC)曲线衡量两种方法单独及联合检测的诊断价值;Kappa检验评估两种方法与MTB的一致性;单因素及多因素logistic回归分析影响两种方法联合检测准确率的因素。

结果

三组的TB-LAMP阳性率分别为87.32%、75.00%、12.23%,T-SPOT.TB阳性率分别为92.39%、71.74%、23.40%,联合检测阳性率分别为93.48%、85.87%、18.09%,组间均有差异(P<0.001)。T-SPOT.TB、TB-LAMP及二者联合检测均与MTB培养有较高一致性(Kappa=0.747、0.733、0.751)。TB-LAMP、T-SPOT.TB与联合检测的敏感度分别为84.24%、87.23%、91.58%,特异度分别为92.63%、90.43%、83.51%,诊断准确率分别为87.41%、88.31%、88.85%,AUC分别为0.840、0.910和0.930。年龄≥60岁、CD4+T淋巴细胞计数<350 cells/μL、白蛋白<35 g/L、糖尿病、送检次数<3次、采集至处理时间>2 h、镜检不合格是影响联合诊断准确率的独立危险因素(P<0.05)。按性别分层分析显示,除年龄在女性亚组无统计学意义外,其余危险因素在男、女亚组中均保持一致的独立效应,区间重叠明显,性别未对危险因素效应产生实质性干扰。

结论

TB-LAMP与T-SPOT.TB联合检测可明显提高诊断准确率;年龄≥60岁、CD4+T淋巴细胞计数<350 cells/μL、白蛋白<35 g/L、糖尿病、送检次数<3次、采集至处理时间>2 h、镜检不合格均为影响联合诊断准确率的独立危险因素。

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安晓颖(1982—),女,硕士,副主任医师,研究方向:分子病理

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贾涤静,E-mail:
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J Immunol Res, 2022, 2022: 6837745., articleTitle=Cellular immunity of patients with tuberculosis combined with diabetes, refAbstract=null)], funds=[Fund(id=1324045060018418103, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, awardId=20242154, language=CN, fundingSource=河北省2024年度医学科学研究课题计划(20242154), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1324045053747933565, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, xref=1., ext=[AuthorCompanyExt(id=1324045053756322174, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, companyId=1324045053747933565, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Pathology, Hebei Chest Hospital, Hebei Key Laboratory of Pulmonary Diseases, Shijiazhuang, Hebei 050000, China), AuthorCompanyExt(id=1324045053789876607, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, companyId=1324045053747933565, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.河北省胸科医院病理科,河北省肺病重点实验室,河北 石家庄 050000)]), AuthorCompany(id=1324045053877956992, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, xref=2., ext=[AuthorCompanyExt(id=1324045053894734209, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, companyId=1324045053877956992, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.河北省胸科医院感染性疾病实验诊断中心,河北省肺病重点实验室)]), AuthorCompany(id=1324045053961843074, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, xref=3., ext=[AuthorCompanyExt(id=1324045053970231683, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, companyId=1324045053961843074, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.河北省胸科医院检验科,河北省肺病重点实验室)])], figs=[ArticleFig(id=1324045056314847655, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=EN, label=Fig.1, caption=Comparison of ROC curves for the three detection strategies, figureFileSmall=Z0DmIVrLSHOCaBAehK6nBw==, figureFileBig=SK4kU1IwqtK5o+aE7IeAnw==, tableContent=null), ArticleFig(id=1324045056587477416, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=CN, label=图1, caption=三种检测策略的ROC曲线比较, figureFileSmall=Z0DmIVrLSHOCaBAehK6nBw==, figureFileBig=SK4kU1IwqtK5o+aE7IeAnw==, tableContent=null), ArticleFig(id=1324045058122592681, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=EN, label=Table 1, caption=

Comparison of basic information of the three groups of patients[,n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
指标TB组
(n=276)
EPTB组
(n=92)
非TB组
(n=188)
χ2/F值P值
性别2.9110.233
男178(64.49)52(56.52)109(57.98)
女98(35.51)40(43.48)79(42.02)
年龄(岁)52.34±16.7149.87±16.2840.56±18.25ab26.981<0.001
BMI(kg/m2)51.724<0.001
<18.5171(61.96)30(32.61)a60(31.91)a
18.5~24.099(35.87)59(64.13)a116(61.70)a
>24.06(2.17)3(3.26)12(6.39)a
吸烟(是)166(60.14)48(52.17)61(32.45)ab34.646<0.001
糖尿病(是)72(26.09)37(40.22)a52(27.66)b6.9300.031
贫血(是)99(35.87)35(38.04)63(33.51)0.6010.741
CD4+ T细胞计数(cells/μL)473.22±131.63496.36±129.68569.36±156.07ab26.832<0.001
WBC(×109/L)6.92±2.036.75±1.995.13±1.78ab50.642<0.001
中性粒细胞绝对值(×109/L)3.02±0.982.98±0.742.63±1.05ab9.614<0.001
CRP(mg/L)8.23±2.448.02±1.954.51±3.80ab89.997<0.001
白蛋白(g/L)32.65±10.0835.67±10.1243.76±9.89ab69.536<0.001
总蛋白(g/L)56.36±10.2959.74±10.3363.22±11.34a23.264<0.001
痰样本性状66.183<0.001
脓性痰196(71.01)47(51.09)a68(36.16)ab
黏液脓性痰70(25.36)28(30.43)85(45.21)ab
唾液样痰10(3.63)17(18.48)a35(18.62)a
镜检合格率(合格)239(86.59)71(77.17)a119(63.30)ab34.436<0.001
送检次数(≥3次)90(32.61)35(38.04)100(53.19)ab19.934<0.001
采集至处理时间(≤2 h)50(18.12)32(34.78)a65(34.57)a19.522<0.001
培养时长(≥14 d)40(14.49)42(45.65)a120(63.83)ab121.817<0.001
), ArticleFig(id=1324045058231644586, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=CN, label=表1, caption=

三组患者基本情况比较[,n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
指标TB组
(n=276)
EPTB组
(n=92)
非TB组
(n=188)
χ2/F值P值
性别2.9110.233
男178(64.49)52(56.52)109(57.98)
女98(35.51)40(43.48)79(42.02)
年龄(岁)52.34±16.7149.87±16.2840.56±18.25ab26.981<0.001
BMI(kg/m2)51.724<0.001
<18.5171(61.96)30(32.61)a60(31.91)a
18.5~24.099(35.87)59(64.13)a116(61.70)a
>24.06(2.17)3(3.26)12(6.39)a
吸烟(是)166(60.14)48(52.17)61(32.45)ab34.646<0.001
糖尿病(是)72(26.09)37(40.22)a52(27.66)b6.9300.031
贫血(是)99(35.87)35(38.04)63(33.51)0.6010.741
CD4+ T细胞计数(cells/μL)473.22±131.63496.36±129.68569.36±156.07ab26.832<0.001
WBC(×109/L)6.92±2.036.75±1.995.13±1.78ab50.642<0.001
中性粒细胞绝对值(×109/L)3.02±0.982.98±0.742.63±1.05ab9.614<0.001
CRP(mg/L)8.23±2.448.02±1.954.51±3.80ab89.997<0.001
白蛋白(g/L)32.65±10.0835.67±10.1243.76±9.89ab69.536<0.001
总蛋白(g/L)56.36±10.2959.74±10.3363.22±11.34a23.264<0.001
痰样本性状66.183<0.001
脓性痰196(71.01)47(51.09)a68(36.16)ab
黏液脓性痰70(25.36)28(30.43)85(45.21)ab
唾液样痰10(3.63)17(18.48)a35(18.62)a
镜检合格率(合格)239(86.59)71(77.17)a119(63.30)ab34.436<0.001
送检次数(≥3次)90(32.61)35(38.04)100(53.19)ab19.934<0.001
采集至处理时间(≤2 h)50(18.12)32(34.78)a65(34.57)a19.522<0.001
培养时长(≥14 d)40(14.49)42(45.65)a120(63.83)ab121.817<0.001
), ArticleFig(id=1324045058332307883, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=EN, label=Table 2, caption=

Diagnostic results of TB-LAMP and T-SPOT.TB[n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
检测方法例数(n)阴性数(n)阳性数(n)阳性率(%)χ2值P值
TB-LAMP272.929<0.001
TB组2763524187.32
EPTB组92236975.00
非TB组1881652312.23
T-SPOT.TB304.493<0.001
TB组2762125592.39
EPTB组92266671.74
非TB组1881444423.40
联合检测237.812<0.001
TB组2761825893.48
EPTB组92137985.87
非TB组1881543418.09
), ArticleFig(id=1324045058458137004, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=CN, label=表2, caption=

TB-LAMP与T-SPOT.TB的诊断结果[n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
检测方法例数(n)阴性数(n)阳性数(n)阳性率(%)χ2值P值
TB-LAMP272.929<0.001
TB组2763524187.32
EPTB组92236975.00
非TB组1881652312.23
T-SPOT.TB304.493<0.001
TB组2762125592.39
EPTB组92266671.74
非TB组1881444423.40
联合检测237.812<0.001
TB组2761825893.48
EPTB组92137985.87
非TB组1881543418.09
), ArticleFig(id=1324045058676240813, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=EN, label=Table 3, caption=

Consistency analysis of diagnostic results of the two detection methods

, figureFileSmall=null, figureFileBig=null, tableContent=
检测方法诊断结果MTB培养阳性MTB培养阴性Kappa值P值
TB-LAMP阳性310120.733<0.001
阴性58176
T-SPOT.TB阳性321180.747<0.001
阴性47170
联合检测阳性337310.751<0.001
阴性31157
), ArticleFig(id=1324045058760126894, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=CN, label=表3, caption=

两种检测方法诊断结果的一致性分析

, figureFileSmall=null, figureFileBig=null, tableContent=
检测方法诊断结果MTB培养阳性MTB培养阴性Kappa值P值
TB-LAMP阳性310120.733<0.001
阴性58176
T-SPOT.TB阳性321180.747<0.001
阴性47170
联合检测阳性337310.751<0.001
阴性31157
), ArticleFig(id=1324045058856595887, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=EN, label=Table 4, caption=

Comparison of diagnostic evaluation indicators for single use and combined detection of TB-LAMP and T-SPOT.TB methods

, figureFileSmall=null, figureFileBig=null, tableContent=
诊断方法敏感度
(%)
特异度
(%)
阳性预测值
(%)
阴性预测值
(%)
阳性似然比阴性似然比准确率
(%)
TB-LAMP84.2492.6396.2775.2111.4300.17087.41
T-SPOT.TB87.2390.4394.6978.349.1150.14188.31
联合检测91.5883.5191.5883.515.5500.10188.85
), ArticleFig(id=1324045059158585776, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=CN, label=表4, caption=

TB-LAMP和T-SPOT.TB两种方法单用及联合检测的诊断评价指标比较

, figureFileSmall=null, figureFileBig=null, tableContent=
诊断方法敏感度
(%)
特异度
(%)
阳性预测值
(%)
阴性预测值
(%)
阳性似然比阴性似然比准确率
(%)
TB-LAMP84.2492.6396.2775.2111.4300.17087.41
T-SPOT.TB87.2390.4394.6978.349.1150.14188.31
联合检测91.5883.5191.5883.515.5500.10188.85
), ArticleFig(id=1324045059238277553, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=EN, label=Table 5, caption=

Univariate analysis of factors affecting the accuracy of combined diagnosis[,n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
因素准确诊断组(n=497)错误诊断组(n=59)χ2/t值P值
年龄(岁)47.82±15.3661.74±12.587.635<0.001
性别6.3120.012
男312(62.78)27(45.76)
女185(37.22)32(54.24)
BMI(kg/m2)15.724<0.001
<18.5141(28.37)30(50.85)
18.5~24.0321(64.59)26(44.07)
>24.035(7.04)3(5.08)
吸烟(是)205(41.25)22(37.29)0.3520.553
糖尿病(是)98(19.72)26(44.07)19.864<0.001
贫血(是)125(25.15)37(62.71)35.692<0.001
CD4+T淋巴细胞计数(cells/μL)529.47±142.35348.62±121.839.842<0.001
WBC(×109/L)6.18±2.116.87±2.352.3170.021
中性粒细胞绝对值(×109/L)2.85±1.023.24±1.172.6720.008
CRP(mg/L)5.89±3.4212.37±4.8511.274<0.001
白蛋白(g/L)39.75±8.6229.83±7.948.935<0.001
总蛋白(g/L)61.34±10.8754.28±9.765.129<0.001
痰样本性状12.705<0.001
脓性痰318(63.98)18(30.51)
黏液脓性痰142(28.57)25(42.37)
唾液样痰37(7.45)16(27.12)
镜检合格率(合格)401(80.68)28(47.46)18.326<0.001
送检次数(≥3次)388(78.07)32(54.24)15.207<0.001
采集至处理时间(≤2 h)452(90.95)42(71.19)21.112<0.001
培养时长(≥14 d)475(95.57)48(81.36)18.594<0.001
疾病类型61.995<0.001
TB267(53.72)9(15.25)
EPTB89(17.91)3(5.08)
非TB141(28.37)47(79.66)
), ArticleFig(id=1324045059305386418, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=CN, label=表5, caption=

影响联合诊断准确率的单因素分析[,n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
因素准确诊断组(n=497)错误诊断组(n=59)χ2/t值P值
年龄(岁)47.82±15.3661.74±12.587.635<0.001
性别6.3120.012
男312(62.78)27(45.76)
女185(37.22)32(54.24)
BMI(kg/m2)15.724<0.001
<18.5141(28.37)30(50.85)
18.5~24.0321(64.59)26(44.07)
>24.035(7.04)3(5.08)
吸烟(是)205(41.25)22(37.29)0.3520.553
糖尿病(是)98(19.72)26(44.07)19.864<0.001
贫血(是)125(25.15)37(62.71)35.692<0.001
CD4+T淋巴细胞计数(cells/μL)529.47±142.35348.62±121.839.842<0.001
WBC(×109/L)6.18±2.116.87±2.352.3170.021
中性粒细胞绝对值(×109/L)2.85±1.023.24±1.172.6720.008
CRP(mg/L)5.89±3.4212.37±4.8511.274<0.001
白蛋白(g/L)39.75±8.6229.83±7.948.935<0.001
总蛋白(g/L)61.34±10.8754.28±9.765.129<0.001
痰样本性状12.705<0.001
脓性痰318(63.98)18(30.51)
黏液脓性痰142(28.57)25(42.37)
唾液样痰37(7.45)16(27.12)
镜检合格率(合格)401(80.68)28(47.46)18.326<0.001
送检次数(≥3次)388(78.07)32(54.24)15.207<0.001
采集至处理时间(≤2 h)452(90.95)42(71.19)21.112<0.001
培养时长(≥14 d)475(95.57)48(81.36)18.594<0.001
疾病类型61.995<0.001
TB267(53.72)9(15.25)
EPTB89(17.91)3(5.08)
非TB141(28.37)47(79.66)
), ArticleFig(id=1324045059477352883, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=EN, label=Table 6, caption=

Multivariate logistic analysis of influencing factors on the combined diagnostic accuracy of the two methods

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因素βSEwald χ2OR值(95%CI)P值
常数-2.4170.53820.161-<0.001
年龄0.8310.2858.5071.574(1.066~2.436)0.021
CD4+T淋巴细胞计数1.1420.30214.323.133(1.736~5.657)<0.001
白蛋白1.0520.30711.7242.862(1.569~5.224)<0.001
糖尿病0.4630.1896.0012.295(1.312~4.017)0.004
送检次数0.8930.3277.4592.442(1.288~4.631)0.006
采集至处理时间1.1180.3659.3873.058(1.496~6.252)0.002
镜检合格率1.1840.34112.0923.268(1.677~6.370)<0.001
), ArticleFig(id=1324045059552850356, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=CN, label=表6, caption=

两种方法联合诊断准确率的影响因素的多因素logistic分析

, figureFileSmall=null, figureFileBig=null, tableContent=
因素βSEwald χ2OR值(95%CI)P值
常数-2.4170.53820.161-<0.001
年龄0.8310.2858.5071.574(1.066~2.436)0.021
CD4+T淋巴细胞计数1.1420.30214.323.133(1.736~5.657)<0.001
白蛋白1.0520.30711.7242.862(1.569~5.224)<0.001
糖尿病0.4630.1896.0012.295(1.312~4.017)0.004
送检次数0.8930.3277.4592.442(1.288~4.631)0.006
采集至处理时间1.1180.3659.3873.058(1.496~6.252)0.002
镜检合格率1.1840.34112.0923.268(1.677~6.370)<0.001
), ArticleFig(id=1324045059624153525, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=EN, label=Table 7, caption=

Multivariate logistic regression analysis of factors affecting the accuracy of combined diagnosis under gender stratification

, figureFileSmall=null, figureFileBig=null, tableContent=
危险因素男性(n=339)女性(n=217)
OR值(95%CI)POR值(95%CI)P
年龄1.612(1.015~2.558)0.0421.528(0.903~2.585)0.117
CD4+T淋巴细胞计数3.089(1.621~5.885)<0.0013.207(1.543~6.665)0.002
白蛋白2.795(1.453~5.376)0.0022.941(1.408~6.142)0.004
糖尿病2.351(1.268~4.361)0.0072.218(1.056~4.656)0.036
送检次数2.397(1.182~4.863)0.0152.512(1.124~5.611)0.025
采集至处理时间3.112(1.433~6.751)0.0042.985(1.278~6.987)0.012
镜检合格率3.315(1.632~6.733)0.0013.201(1.489~6.887)0.003
), ArticleFig(id=1324045059695456694, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324044780266730302, language=CN, label=表7, caption=

性别分层下联合诊断准确率影响因素的多因素logistic回归分析

, figureFileSmall=null, figureFileBig=null, tableContent=
危险因素男性(n=339)女性(n=217)
OR值(95%CI)POR值(95%CI)P
年龄1.612(1.015~2.558)0.0421.528(0.903~2.585)0.117
CD4+T淋巴细胞计数3.089(1.621~5.885)<0.0013.207(1.543~6.665)0.002
白蛋白2.795(1.453~5.376)0.0022.941(1.408~6.142)0.004
糖尿病2.351(1.268~4.361)0.0072.218(1.056~4.656)0.036
送检次数2.397(1.182~4.863)0.0152.512(1.124~5.611)0.025
采集至处理时间3.112(1.433~6.751)0.0042.985(1.278~6.987)0.012
镜检合格率3.315(1.632~6.733)0.0013.201(1.489~6.887)0.003
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TB-LAMP与T-SPOT. TB诊断结核病的一致性及联合诊断准确率影响因素
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安晓颖 1 , 刘美 1 , 陈佳琪 3 , 张云婷 2 , 贾涤静 2
现代预防医学 | 临床与预防 2026,53(10): 1914-1920
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现代预防医学 |临床与预防 2026 , 53 (10) : 1914 -1920
TB-LAMP与T-SPOT. TB诊断结核病的一致性及联合诊断准确率影响因素
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安晓颖1, 刘美1, 陈佳琪3, 张云婷2, 贾涤静2
作者信息
  • 1.河北省胸科医院病理科,河北省肺病重点实验室,河北 石家庄 050000
  • 2.河北省胸科医院感染性疾病实验诊断中心,河北省肺病重点实验室
  • 3.河北省胸科医院检验科,河北省肺病重点实验室
通讯作者:
贾涤静,E-mail:
作者简介:

安晓颖(1982—),女,硕士,副主任医师,研究方向:分子病理

Consistency of TB-LAMP and T-SPOT.TB in the diagnosis of tuberculosis and influencing factors of the accuracy of their combined diagnosis
Xiao-ying AN1, Mei LIU1, Jia-qi CHEN3, Yun-ting ZHANG2, Di-jing JIA2
Affiliations
  • Department of Pathology, Hebei Chest Hospital, Hebei Key Laboratory of Pulmonary Diseases, Shijiazhuang, Hebei 050000, China
出版时间: 2026-05-25 doi: 10.20043/j.cnki.MPM.202510185
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目的

分析结核分枝杆菌环介导等温扩增技术(Mycobacterium tuberculosis loop-mediated isothermal amplification,TB-LAMP)与结核感染T细胞斑点试验(tuberculous infection of T cells spot test,T-SPOT.TB)在结核病(tuberculosis,TB)诊断中的一致性及联合诊断准确率的影响因素。

方法

选取2022年1月至2024年12月于我院住院治疗556例的疑似TB患者。采用受试者工作特征(receiver operating characteristic,ROC)曲线衡量两种方法单独及联合检测的诊断价值;Kappa检验评估两种方法与MTB的一致性;单因素及多因素logistic回归分析影响两种方法联合检测准确率的因素。

结果

三组的TB-LAMP阳性率分别为87.32%、75.00%、12.23%,T-SPOT.TB阳性率分别为92.39%、71.74%、23.40%,联合检测阳性率分别为93.48%、85.87%、18.09%,组间均有差异(P<0.001)。T-SPOT.TB、TB-LAMP及二者联合检测均与MTB培养有较高一致性(Kappa=0.747、0.733、0.751)。TB-LAMP、T-SPOT.TB与联合检测的敏感度分别为84.24%、87.23%、91.58%,特异度分别为92.63%、90.43%、83.51%,诊断准确率分别为87.41%、88.31%、88.85%,AUC分别为0.840、0.910和0.930。年龄≥60岁、CD4+T淋巴细胞计数<350 cells/μL、白蛋白<35 g/L、糖尿病、送检次数<3次、采集至处理时间>2 h、镜检不合格是影响联合诊断准确率的独立危险因素(P<0.05)。按性别分层分析显示,除年龄在女性亚组无统计学意义外,其余危险因素在男、女亚组中均保持一致的独立效应,区间重叠明显,性别未对危险因素效应产生实质性干扰。

结论

TB-LAMP与T-SPOT.TB联合检测可明显提高诊断准确率;年龄≥60岁、CD4+T淋巴细胞计数<350 cells/μL、白蛋白<35 g/L、糖尿病、送检次数<3次、采集至处理时间>2 h、镜检不合格均为影响联合诊断准确率的独立危险因素。

结核分枝杆菌环介导等温扩增技术  /  结核感染T细胞斑点试验  /  结核病诊断  /  一致性分析  /  联合诊断
Objective

To analyze the consistency between the Mycobacterium tuberculosis loop-mediated isothermal amplification (Mycobacterium tuberculosis loop-mediated isothermal amplification, TB-LAMP) and the tuberculosis T-cell spot test (tuberculous infection of T cells spot test, T-SPOT.TB) in the diagnosis of tuberculosis (tuberculosis, TB), as well as the influencing factors of the accuracy of combined diagnosis.

Methods

A total of 556 suspected TB patients hospitalized in our hospital from January 2022 to December 2024 were selected. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic values of the two methods used alone and in combination. The Kappa test was employed to assess the consistency between the two methods and Mycobacterium tuberculosis (MTB). Univariate and multivariate Logistic regression analyses were conducted to identify the factors influencing the combined diagnostic accuracy of the two methods.

Results

The positive rates of TB-LAMP in the three groups were 87.32%, 75.00%, and 12.23% respectively, those of T-SPOT.TB were 92.39%, 71.74%, and 23.40% respectively, and those of the combined detection were 93.48%, 85.87%, and 18.09% respectively, with significant differences among the groups (P<0.001). There was a high consistency between T-SPOT.TB, TB-LAMP, and their combined detection and MTB culture (Kappa=0.747, 0.733, 0.751). The sensitivities of TB-LAMP, T-SPOT.TB, and the combined detection were 84.24%, 87.23%, and 91.58% respectively, the specificities were 92.63%, 90.43%, and 83.51% respectively, the diagnostic accuracies were 87.41%, 88.31%, and 88.85% respectively, and the AUCs were 0.840, 0.910, and 0.930 respectively. Age≥60 years, CD4+ T lymphocyte count<350 cells/μL, albumin<35 g/L, diabetes, number of specimen submissions<3 times, time from collection to processing>2 h, and failed microscopic examination were independent risk factors affecting the combined diagnostic accuracy (P<0.05). Genderstratified analysis showed that except for age which was not significant in the female subgroup, all other risk factors remained independently significant in both male and female subgroups. Gender did not substantially interfere with the effects of these risk factors.

Conclusion

The combined detection of TB-LAMP and T-SPOT.TB can significantly improve the diagnostic accuracy. Age≥60 years old, CD4+ T lymphocyte count<350 cells/μL, albumin<35 g/L, diabetes, number of tests sent for examination<3 times, collection-to-processing time>2 hours, and insufficiently qualified for microscopic examination are all independent risk factors affecting the accuracy of the combined diagnosis.

Mycobacterium tuberculosis loop-mediated isothermal amplification  /  Tuberculous infection of T cells spot test  /  Tuberculosis diagnosis  /  Consistency analysis  /  Combined diagnosis
安晓颖, 刘美, 陈佳琪, 张云婷, 贾涤静. TB-LAMP与T-SPOT. TB诊断结核病的一致性及联合诊断准确率影响因素. 现代预防医学, 2026 , 53 (10) : 1914 -1920 . DOI: 10.20043/j.cnki.MPM.202510185
Xiao-ying AN, Mei LIU, Jia-qi CHEN, Yun-ting ZHANG, Di-jing JIA. Consistency of TB-LAMP and T-SPOT.TB in the diagnosis of tuberculosis and influencing factors of the accuracy of their combined diagnosis[J]. Modern Preventive Medicine, 2026 , 53 (10) : 1914 -1920 . DOI: 10.20043/j.cnki.MPM.202510185
结核病(tuberculosis, TB)是以呼吸道传播为主的慢性传染病,具有较强传染性,早期精准诊断至关重要。结核分枝杆菌(Mycobacterium tuberculosis, MTB)培养作为临床诊断的金标准,耗时长,培养阳性率偏低;抗酸染色涂片镜检的敏感度较低;分子检测如结核分枝杆菌及利福平耐药基因检测受设备、成本及操作环境的限制[1-2]。结核分枝杆菌环介导等温扩增技术(Mycobacterium tuberculosis loop-mediated isothermal amplification, TB-LAMP)操作简便、快速、设备依赖性低[3]。结核感染T细胞斑点试验(tuberculous infection of T cells spot test, T-SPOT.TB)基于细胞免疫应答,敏感度和特异度较高[4],可有效区分结核感染与环境分枝杆菌,不受卡介苗接种干扰[2]。目前二者联合应用的诊断效能影响因素的研究较少,本研究通过系统评估TB-LAMP与T-SPOT.TB的诊断一致性以及联合诊断效果,分析影响诊断效能的关键因素,为优化TB诊断路径提供循证依据。
基于诊断试验样本量公式:计算,参考前期研究[2],设定容许误差(δ)为5%,置信水平(1-α)为95%,考虑10%脱落率及多因素logistic回归要求(事件数≥自变量数×10),结合本院年均病例量,最终纳入556例。
选取2022年1月至2024年12月本院收治的556例疑似TB患者,年龄范围22~69岁,平均年龄46.45±17.23岁;男性339名,女性217名。纳入标准:(1)无TB史;(2)影像学或临床疑似为TB(3)无支气管检查禁忌证;(4)资料完整;排除标准:(1)HIV或其他活动性感染;(2)长期使用免疫抑制剂者;(3)标本不合格者。以MTB培养结果为金标准,参考《肺结核诊断标准(WS288-2017)》[5]和《结核病分类(WS196-2017)》[6]中的标准,将患者分为TB组(n=276)、EPTB组(n=92)和非TB组(n=188)。研究经河北省胸科医院伦理委员会审核批准(审批号:2023066),豁免患者知情同意。所有疑似TB患者均根据临床采样规范进行痰/支气管肺泡灌洗液采样,单次采样后均同步完成TB-LAMP、T-SPOT.TB及MTB培养三种检测操作,无时间间隔;患者送检次数为临床根据病情及标本质量进行的多次采样次数,不同采样间隔时间为24~48 h,所有检测均在患者入院后1周内完成,且均在MTB培养结果出具前开展。
主要试剂与仪器包括:TB-LAMP检测试剂盒(日本荣研化学,LoopampTM MTBC Detection Kit)、T-SPOT.TB检测试剂盒(英国牛津Immunotec公司,T-SPOT.TB Kit)、二级生物安全柜(新加坡Esco集团,Class II Type A2)、恒温培养箱(美国Thermo Scientific,Heracell 150i)、离心机(德国Eppendorf,Centrifuge 5424 R)、光学显微镜(日本Olympus,CX23正置显微镜)。
收集年龄、性别、体质量指数(body mass index, BMI)、吸烟、合并症、CD4+ T淋巴细胞、白细胞计数(white blood cell count, WBC)、中性粒细胞绝对值、C反应蛋白(C reactive protein, CRP)、总蛋白、白蛋白、痰样本性状、镜检合格率、送检次数、采集至处理时间、培养时长等资料。根据中国体质指数标准[7]将患者BMI分为3组。不合格标本存在杂质污染等问题,可能降低核酸提取效率,影响检测结果准确性,故纳入镜检合格率;本研究将痰/支气管肺泡灌洗液标本镜检下鳞状上皮细胞<10个/低倍视野、白细胞>25个/低倍视野为合格,反之为不合格。送检次数与标本采集的一次性合格性相关,会影响联合诊断的准确性,故纳入送检次数;本研究送检次数指患者入院后,为实现结核病诊断检测目的所进行的标本采集总次数,以实验室实际接收的标本数量累计计算。标本离体后,核酸易降解、外周血单个核细胞活性会随时间下降,直接影响检测结果,故纳入采集至处理时间;本研究的采集至处理时间指标本从临床采集完成到实验室开始检测操作的时间间隔。MTB培养时长与菌株活性、标本中菌量相关,可间接关联联合诊断的参照标准可靠性,故纳入培养时长;本研究的培养时长指标本接种至MTB培养培养基后,至培养结果判读的培养时间。
采集患者支气管肺泡灌洗液或病变部位标本。严格按试剂盒说明操作。取样本进行热裂解,提取核酸后加入反应管,67 ℃恒温扩增40 min,紫外线下观察荧光,绿色荧光判为阳性,无荧光判为阴性。
采用肝素钠抗凝真空管采集患者外周静脉全血4 mL,采血过程严格遵循无菌操作,避免溶血、凝血与泡沫产生。采血后立即轻柔颠倒混匀8~10次,确保抗凝充分,禁止剧烈震荡。标本全程避光、室温(18~25℃)保存,并在4 h内送达实验室并启动检测,严禁冷藏或冷冻,以保障外周血单个核细胞活性与检测准确性。分离外周血单个核细胞,调整浓度后加入含有抗原的孔板,37 ℃、5% CO2培养18-20 h。经洗涤、酶标抗体孵育及显色后,于显微镜下计数斑点。检测孔斑点数符合试剂盒阳性标准判为阳性,否则为阴性。
TB-LAMP检测阳性或T-SPOT.TB检测阳性,判定为联合检测阳性;仅当TB-LAMP检测阴性且T-SPOT.TB检测阴性时,判定为联合检测阴性。
采用SPSS 26.0软件和Mplus 7.4软件。符合正态分布的计量资料用()表示,两组间比较采用两独立样本t检验;三组间比较采用单因素方差分析,若存在差异,进一步通过LSD法进行两两比较。计数资料用[n(%)]表示,组间比较采用χ2检验。检验水准α=0.05。采用Kappa检验评估两种方法与MTB的一致性。受试者工作特征(receiver operating characteristic, ROC)曲线分析两种方法单独及联合检测的诊断价值。单因素及多因素logistic回归分析影响两种方法联合诊断准确率的因素。
三组患者年龄、BMI、吸烟、糖尿病、CD4+T细胞计数、WBC、中性粒细胞绝对值、CRP、白蛋白、总蛋白、痰样本性状、镜检合格率、送检次数、采集至处理时间、培养时长均有差异(P<0.05),见表1。
三组TB-LAMP、T-SPOT.TB以及联合检测阳性率组间差异明显(P<0.001),见表2。
T-SPOT.TB、TB-LAMP及联合检测与MTB培养的一致性较高(Kappa=0.747、0.733、0.751,P<0.001),见表3。
TB-LAMP与T-SPOT.TB联合诊断的准确率、敏感度、阴性预测值、均高于二者单一诊断;特异度、阳性预测值均低于二者单一诊断,见表4。
T-SPOT.TB的AUC高于TB-LAMP;联合检测的AUC最高,见图1。
性别、年龄、BMI、合并糖尿病、贫血、CD4+T淋巴细胞计数、WBC、中性粒细胞绝对值、CRP、白蛋白、总蛋白、痰样本性状、镜检合格率、送检次数、采集至处理时间、培养时长、疾病类型可能会影响联合诊断的准确率(P<0.05),见表5。
以单因素分析中差异有统计学意义的变量为自变量,其中BMI分组与前文保持一致,年龄、CD4+T淋巴细胞计数、白蛋白均根据中位数切点进行二分类分组,自变量具体赋值如下:年龄(≥60岁=1,<60岁=0)、CD4+T淋巴细胞计数(<350 cells/μL=1,≥350 cells/μL=0)、白蛋白(<35 g/L=1,≥35 g/L=0)、糖尿病(是=1,否=0)、送检次数(<3次=1,≥3次=0)、采集至处理时间(>2 h=1,≤2 h=0)、镜检合格率(不合格=1,合格=0);以诊断准确性(准确诊断=0,错误诊断=1)为因变量,结果显示,年龄≥60岁、CD4+T淋巴细胞计数<350 cells/μL、白蛋白<35 g/L、合并糖尿病、送检次数<3次、采集至处理时间>2 h、镜检不合格是影响联合诊断准确率的独立危险因素(P<0.05),见表6。
除年龄外,其余各危险因素均在两亚组中达到统计学水平(P<0.05),OR值与95%CI接近、置信区间重叠明显,性别并未对上述影响因素产生实质性干扰,见表7。
TB-LAMP和T-SPOT.TB检测因其简便、快捷、敏感度高的优势受到高度关注。TB-LAMP检测是一种恒温核酸扩增技术,可通过特异性引物靶向MTB DNA进行扩增,并在1 h内通过目测荧光判读结果,并采用封闭系统以最大限度地降低污染的风险[8-10]。T-SPOT.TB则基于MTB特异性抗原刺激T细胞释放γ-干扰素的原理,利用酶联免疫斑点技术进行检测,通常在24 h内获得结果,不易受非MTB的影响[11-12]。本研究显示TB-LAMP与T-SPOT.TB均具有较高诊断效能:诊断准确率与相关文献报道的基本接近[13-14],T-SPOT.TB的敏感度更高,可能源于其检测MTB特异性T细胞免疫应答的特性,可有效识别活动性TB及潜伏感染[15];TB-LAMP特异度更优,可直接扩增MTB特异性DNA序列,但在EPTB或低菌量样本中敏感度可能受限[14]。两种方法分别从病原体直接检测和宿主免疫应答切入,其差异反映了TB诊断中病原与宿主相互作用的复杂性。本研究发现两种方法联合检测可以明显提升诊断效能:敏感度为91.58%,阴性预测值83.51%,AUC为0.930,明显降低漏诊率,体现了联合诊断的增效作用,适用于高危人群筛查,可最大限度减少漏诊。
多因素分析发现,CD4+T淋巴细胞<350 cells/μL、白蛋白<35 g/L、年龄≥60岁、糖尿病、送检次数<3次、采集至处理时间>2 h、镜检不合格是影响联合诊断准确率的独立危险因素。其病理机制可能源于:CD4+T淋巴细胞减少可削弱T-SPOT.TB的细胞免疫应答,导致假阴性[16];而低白蛋白和低BMI会降低机体炎症反应能力,影响检测敏感性[17];高血糖环境抑制巨噬细胞吞噬功能[18];镜检不合格的标本可能导致核酸提取效率降低,并影响外周血单个核细胞纯度,增加假阴性率;采集至处理时间>2 h会导致核酸降解及T细胞活性下降,均降低诊断准确性。性别分层分析显示,除年龄因素在女性亚组未达统计学意义外,CD4+T 淋巴细胞计数降低、低白蛋白血症、糖尿病、送检次数不足、标本采集至处理时间过长、镜检不合格等危险因素在男性与女性亚组中均为联合诊断不准确的独立影响因素,且各因素OR值与95%CI高度接近、置信区间明显重叠,提示性别并未对核心危险因素的效应方向与强度产生实质性干扰,联合诊断准确率的影响因素在不同性别间具有良好的稳定性与普适性。
本研究为单中心回顾性设计,患者来源局限,EPTB组样本量较小,样本性别比例失衡;未来需开展多中心前瞻性研究以验证结论的普适性,扩大EPTB样本量,采用分层分析或Bootstrap法进一步提升亚组结果的可靠性。
综上,TB-LAMP与T-SPOT.TB联合诊断TB具有互补价值,能提高诊断敏感度。年龄≥60岁、白蛋白<35 g/L、CD4+T<350 cells/μL、糖尿病、送检次数<3次、采集至处理时间>2 h、镜检不合格是联合诊断准确性的独立影响因素。对于存在多重危险因素的患者,建议结合其他检测方法综合判断以优化诊断。
  • 河北省2024年度医学科学研究课题计划(20242154)
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doi: 10.20043/j.cnki.MPM.202510185
  • 接收时间:2025-10-17
  • 首发时间:2026-11-02
  • 出版时间:2026-05-25
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  • 收稿日期:2025-10-17
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河北省2024年度医学科学研究课题计划(20242154)
作者信息
    1.河北省胸科医院病理科,河北省肺病重点实验室,河北 石家庄 050000
    2.河北省胸科医院感染性疾病实验诊断中心,河北省肺病重点实验室
    3.河北省胸科医院检验科,河北省肺病重点实验室

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2种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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