结核γ干扰素释放试验酶联免疫试管法和结核菌素皮试试验对行维持性血液透析合并结核患者的诊断和预后判断价值研究
|
摘要
目的探讨结核γ干扰素释放试验酶联免疫试管法(QFT)和结核菌素皮试试验(TST)对结核高流行地区(海南地区)行维持性血液透析(MHD)合并结核[包括隐性结核(LTBI)和结核病]患者的诊断、预后判断价值。方法选择2013—2015年在海南省人民医院血液净化中心行MHD时间>3个月的患者198例,收集患者的一般资料,进行QFT和TST,评估其对MHD合并结核的诊断和预后判断价值。采用多因素Logistic回归分析分析QFT阳性和TST阳性的影响因素。观察患者3年的预后情况,绘制生存曲线,采用Cox比例风险模型分析其预后影响因素。结果最终156例患者完成研究,其中男109例、女47例,平均年龄(54.4±16.6)岁,平均透析龄(1.9±0.4)年。MHD患者QFT阳性率为34.6%(54/156),TST阳性率为67.9%(106/156),TST与QFT结果无一致性(Kappa值=0.053,P=0.405)。多因素Logistic回归分析显示,在校正其他因素的情况下,性别[OR=0.345,95%CI(0.144,0.828),P=0.017]、有无卡介苗接种瘢痕[OR=0.345,95%CI(0.144,0.828),P=0.017]是QFT阳性的影响因素;性别[OR=2.836,95%CI(1.120,7.177),P=0.028]、淋巴细胞分数[OR=3.573,95%CI(1.410,12.295),P=0.043]是TST阳性的影响因素。37例LTBI患者中11例转为肺结核(29.7%)。本组患者3年结核患病率为42 948.7/10万。MHD患者1、2、3年生存率分别为89.7%、77.6%、69.9%,粗死亡率(CDR)为301.3/1 000人。Cox比例风险模型分析发现QFT阳性、C反应蛋白升高是生存的不利因素;抗结核治疗、前清蛋白升高是生存的有利因素(P<0.05)。结论在海南地区,男性MHD患者QFT阳性率较高;TST与QFT对MHD合并结核的诊断无一致性。QFT阳性、C反应蛋白升高是生存的不利因素,抗结核治疗、前清蛋白升高是生存的有利因素。在结核高流行地区MHD患者合并LTBI、结核病的诊断依然需要结合流行病学、病史、结核易感因素、肺部影像学,排除其他感染,行试验性抗结核治疗,需大力推进组织病理、肺支气管肺泡灌洗液的诊断措施。
Objective To study the diagnostic and prognostic values of quantification ELISA interferon-γ release test(QFT) and tuberculosis skin test(TST) for patients with tuberculosis[including both latent tuberculosis infection(LTBI) and tuberculosis(TB)] undergoing maintenance hemodialysis(MHD) in areas with high prevalence of tuberculosis.Methods Totaled 198 patients who underwent MHD in Blood Purification Center,Hainan General Hospital,for more than 3 months during 2013—2015 were enrolled.All of them were given a 3-year follow-up.Baseline clinical data were collected.The results of QFT and TST were also obtained and their values in the diagnosis and prediction of the prognosis of these patients were evaluated.Multivariate Logistic regression analysis was performed to investigate the influencing factors for positive results of QFT and TST.The prognosis of patients in 3 years was observed,and survival curves were drawn.Cox proportional hazards regression analysis was carried out to explore the factors associated with the prognosis.Results 156 cases who completed the study were included in the final analysis,including 109 males and 47 females,with an average age of(54.4±16.6)years and an average hemodialysis duration of(1.9±0.4) years.The prevalences of positive QFT,positive TST were 34.6%(54/156),67.9%(106/156),respectively.The results of TST and QFT in identifying TB showed no consistency(Kappa=0.053,P=0.405).Multivariate Logistic regression analysis revealed that,after adjusting for other factors,sex[OR=0.345,95%CI(0.144,0.828),P=0.017]and no BCG vaccine scar[OR=0.345,95%CI(0.144,0.828),P=0.017]were risk factors for having a positive QFT result,the sex [OR=2.836,95%CI(1.120,7.177),P=0.028]and the total lymphocyte count[OR=3.573,95%CI(1.410,12.295),P=0.043]were risk factors for having a positive TST result.Of the 37 patients identified with LTBI,11(29.7%) developed TB.The 3-year prevalence of TB in these patients was 42 948.7/100 000.The 1-,2-,3-year survival rates were 89.7%,77.6%,and 69.9%,respectively.Crud death rate was(CDR)301.3/1 000.Multivariate Cox proportional hazard regression analysis found that positive QFT results and elevated C-reactive protein(CRP) were unfavorable prognostic factors for the overall survival,while anti-TB treatment and elevated prealbumin were favorable prognostic factors for the overall survival(P<0.05).Conclusion In areas with high prevalence of tuberculosis in Hainan Province,among the CKD patients undergoing MHD,males were more likely to have a positive QFT result.The results of TST and QFT in diagnosing TB demonstrated no consistency.Positive QFT results and elevated CRP were unfavorable factors whereas anti-TB treatment and elevated prealbumin were favorable prognostic factors for the overall survival.In this population,the diagnosis of LTBI or TB should be based on epidemiologic data,past medical history,predisposing factors of TB,lung imaging data,exclusion of other infections and results of experimental anti-TB treatment.In addition,diagnostic measures such as histopathological examination and determination of bronchoalveolar lavage fluid concentration should be promoted vigorously.
Objective To study the diagnostic and prognostic values of quantification ELISA interferon-γ release test(QFT) and tuberculosis skin test(TST) for patients with tuberculosis[including both latent tuberculosis infection(LTBI) and tuberculosis(TB)] undergoing maintenance hemodialysis(MHD) in areas with high prevalence of tuberculosis.Methods Totaled 198 patients who underwent MHD in Blood Purification Center,Hainan General Hospital,for more than 3 months during 2013—2015 were enrolled.All of them were given a 3-year follow-up.Baseline clinical data were collected.The results of QFT and TST were also obtained and their values in the diagnosis and prediction of the prognosis of these patients were evaluated.Multivariate Logistic regression analysis was performed to investigate the influencing factors for positive results of QFT and TST.The prognosis of patients in 3 years was observed,and survival curves were drawn.Cox proportional hazards regression analysis was carried out to explore the factors associated with the prognosis.Results 156 cases who completed the study were included in the final analysis,including 109 males and 47 females,with an average age of(54.4±16.6)years and an average hemodialysis duration of(1.9±0.4) years.The prevalences of positive QFT,positive TST were 34.6%(54/156),67.9%(106/156),respectively.The results of TST and QFT in identifying TB showed no consistency(Kappa=0.053,P=0.405).Multivariate Logistic regression analysis revealed that,after adjusting for other factors,sex[OR=0.345,95%CI(0.144,0.828),P=0.017]and no BCG vaccine scar[OR=0.345,95%CI(0.144,0.828),P=0.017]were risk factors for having a positive QFT result,the sex [OR=2.836,95%CI(1.120,7.177),P=0.028]and the total lymphocyte count[OR=3.573,95%CI(1.410,12.295),P=0.043]were risk factors for having a positive TST result.Of the 37 patients identified with LTBI,11(29.7%) developed TB.The 3-year prevalence of TB in these patients was 42 948.7/100 000.The 1-,2-,3-year survival rates were 89.7%,77.6%,and 69.9%,respectively.Crud death rate was(CDR)301.3/1 000.Multivariate Cox proportional hazard regression analysis found that positive QFT results and elevated C-reactive protein(CRP) were unfavorable prognostic factors for the overall survival,while anti-TB treatment and elevated prealbumin were favorable prognostic factors for the overall survival(P<0.05).Conclusion In areas with high prevalence of tuberculosis in Hainan Province,among the CKD patients undergoing MHD,males were more likely to have a positive QFT result.The results of TST and QFT in diagnosing TB demonstrated no consistency.Positive QFT results and elevated CRP were unfavorable factors whereas anti-TB treatment and elevated prealbumin were favorable prognostic factors for the overall survival.In this population,the diagnosis of LTBI or TB should be based on epidemiologic data,past medical history,predisposing factors of TB,lung imaging data,exclusion of other infections and results of experimental anti-TB treatment.In addition,diagnostic measures such as histopathological examination and determination of bronchoalveolar lavage fluid concentration should be promoted vigorously.
引文
[1]KAY N E,RAIJ L R.Immune abnormalities in renal failure and hemodialysis[J].Blood Purif,1986,4(1/3):120-129.DOI:10.1159/000169435.
[2]GIBBONS A S,MARTINEZ O M,GAROVOY M R.Altered monocyte function in uremia[J].Clin Iromunol Immunopathol,1990,56(1):66-80.
[3]MASHAIRAS G S,SABO P J,HICKEY M J,et al.Molecular analysis of genetic differences between Mtcobacterium bovis BCGand virulent M.bovis[J].J Bacteriol,1996,178(5):1274-1282.DOI:10.1128/jb.178.5.1274-1282.1996.
[4]LEE S S,CHOU K J,DOU H Y,et al.High prevalence of latent tuberculosis infection in dialysis patients using the interferon-γrelease assay and tuberculin skin test[J].Clin J Am Soc Nephrol,2010,5(8):1451-1457.DOI:10.2215/CJN.01790210.
[5]SHU C C,WU V C,YANG F J,et al.Predictors and prevalence of latent tuberculosis infection in patients receiving long-term hemodialysis and peritoneal dialysis[J].PLoS One,2012,7(8):e42592.DOI:10.1371/journal.pone.0042592.
[6]INOUE T,NAKAMURA T,KATSUMA A,et al.The value of QuantiFERONR-TB-Gold in the diagnosis of tuberculosis among dialysis patients[J].Nephrol Dial Transplant,2009,24(7):2252-2257.DOI:10.1093/ndt/gfp030.
[7]WHO.Guidelines on the management of latent tuberculosis infection[EB/OL].[2018-01-10].http://www.who.int/tb/publications/latent-tuberculosis-infection/en/.
[8]中华医学会结核病分会.肺结核诊断与治疗指南[J].中华结核和呼吸杂志,2001,2(24):70-74.
[9]中华医学会结核病分会.中国结核病分类法[J].中华结核和呼吸杂志,1998,12:716-717.
[10]European Best Practice Guidelines for Haemodialysis(Part 1)[J].Nephrol Dial Transplant,2002,17(suppl 7):77-78.DOI:10.1093/NDT/17.
[11]California Tuberculosis Controllers Association.Guidelines for tuberculosis(TB)screening and treatment of patients with chronic kidney disease(CKD),patients receiving hemodialysis(HD),patients receiving peritoneal dialysis(PD),patients undergoing renal transplantation and employees of dialysis facilities[EB/OL].[2018-01-10].http://www.ctca.org.
[12]Guidelines for the prevention and management of Mycobacterium tuberculosis infection and disease in adult patients with chronic kidney disease[J].Thorax,2010,65:559-570.DOI:10.1136/thx.2009.133173.
[13]全国结核病流行病学抽样调查技术指导组,全国结核病流行病学抽样调查办公室.2010年全国肺结核患病率现况调查[J].中华结核和呼吸杂志,2012,35(9):665-668.
[14]杜建伟,王春雷,张广恩,等.海南省2010年结核病流行病学抽样调查[J].中国热带医学,2012,1(11):1323-1326.DU J W,WANG C L,ZHANG G E,et al.Epidemiological sampling survey of tuberculosis in Hainan province in 2010[J].China Tropical Medicine,2012,1(11):1323-1326.
[15]张广恩,陈成江.海南省2010-2014年肺结核疫情特征分析[J].中国热带医学,2015,15(8):1004-1006.ZHANG G E,CHEN C J.Analysis of epidemic feature of pulmonary tuberculosis in Hainan province during 2010-2014[J].China Tropical Medicine,2015,15(8):1004-1006.
[16]袁发焕,赵生家.1069例慢性肾衰患者合并结核病的临床研究[J].西部医学,2003,1(3):199-201.
[17]张训,侯凡凡,魏冬梅,等.慢性肾功能衰竭接受肾替代治疗病人并发结核病[J].中华内科学杂志,1995,34(10):666-669.
[18]叶文玲,李学旺,李航.慢性肾功能衰竭血液透析患者合并结核感染的诊治[J].中国医学院学报,2001,23(5):535-536.
[19]The National Collaborating Center for Chronic Conditions.Tuberculosis:clinical diagnosis and management of tuberculosis and measures for its prevention and control[M].London:Royal College of Physicians,2006.
[20]WHO. Weekly epidemiological record[EB/OL].[2018-01-10].http://www.who.int/wer.
[21]PASSALENT L K K,RICHARDSON R,WANG J,et al.Detecting latent tuberculosis infection in hemodialysis patients:a head-to-head comparison of the T-SPOT.TB Test,Tuberculin Skin Test,and an expert physician panel[J].Clin J Am Soc Nephrol,2007,2:68-73.DOI:10.2215/CJN.01280406.
[22]ROGERSON T E,CHEN S,KOK J,et al.Tests for latent tuberculosis in people with ESRD:a systematic review[J].Am J Kidney Dis,2013,61(1):33-43.DOI:10.1053/j.ajkd.2012.07.019.
[23]REDELMAN-SIDI G,SEPKOWITZ K A.IFN-γrelease assays in the diagnosis of latent tuberculosis infection among immunocompromised adults[J].Am J Respir Crit Care Med,2013,188(4):422-431.DOI:10.1164/rccm.201209-1621CI.
[24]LIANG L,SHI R,LIU X,et al.Interferon-gamma response to the treatment of active pulmonary and extra-pulmonary tuberculosis[J].Int J Tuberc Lung Dis,2017,21(10):1145-1149.DOI:10.5588/ijtld.16.0880.
[25]O'SHEA M K,FLETCHER T E,BEECHING N J,et al.Tuberculin skin testing and treatment modulates interferon-gamma release assay results for latent tuberculosis in migrants[J].PLoS One,2014,9(5):e97366.DOI:10.1371/journal.pone.0097366.
[26]中国医院协会血液净化中心管理分会专家组.中国成人慢性肾脏病合并结核病管理专家共识[J].中国血液净化,2016,15(11):577-586.The Blood Purification Center Management Branch of China Hospital Association.The management consensus of China chronic kidney disease combine with tuberculosis[J].Chin J Blood Purif,2016,15(11):577-586.
[2]GIBBONS A S,MARTINEZ O M,GAROVOY M R.Altered monocyte function in uremia[J].Clin Iromunol Immunopathol,1990,56(1):66-80.
[3]MASHAIRAS G S,SABO P J,HICKEY M J,et al.Molecular analysis of genetic differences between Mtcobacterium bovis BCGand virulent M.bovis[J].J Bacteriol,1996,178(5):1274-1282.DOI:10.1128/jb.178.5.1274-1282.1996.
[4]LEE S S,CHOU K J,DOU H Y,et al.High prevalence of latent tuberculosis infection in dialysis patients using the interferon-γrelease assay and tuberculin skin test[J].Clin J Am Soc Nephrol,2010,5(8):1451-1457.DOI:10.2215/CJN.01790210.
[5]SHU C C,WU V C,YANG F J,et al.Predictors and prevalence of latent tuberculosis infection in patients receiving long-term hemodialysis and peritoneal dialysis[J].PLoS One,2012,7(8):e42592.DOI:10.1371/journal.pone.0042592.
[6]INOUE T,NAKAMURA T,KATSUMA A,et al.The value of QuantiFERONR-TB-Gold in the diagnosis of tuberculosis among dialysis patients[J].Nephrol Dial Transplant,2009,24(7):2252-2257.DOI:10.1093/ndt/gfp030.
[7]WHO.Guidelines on the management of latent tuberculosis infection[EB/OL].[2018-01-10].http://www.who.int/tb/publications/latent-tuberculosis-infection/en/.
[8]中华医学会结核病分会.肺结核诊断与治疗指南[J].中华结核和呼吸杂志,2001,2(24):70-74.
[9]中华医学会结核病分会.中国结核病分类法[J].中华结核和呼吸杂志,1998,12:716-717.
[10]European Best Practice Guidelines for Haemodialysis(Part 1)[J].Nephrol Dial Transplant,2002,17(suppl 7):77-78.DOI:10.1093/NDT/17.
[11]California Tuberculosis Controllers Association.Guidelines for tuberculosis(TB)screening and treatment of patients with chronic kidney disease(CKD),patients receiving hemodialysis(HD),patients receiving peritoneal dialysis(PD),patients undergoing renal transplantation and employees of dialysis facilities[EB/OL].[2018-01-10].http://www.ctca.org.
[12]Guidelines for the prevention and management of Mycobacterium tuberculosis infection and disease in adult patients with chronic kidney disease[J].Thorax,2010,65:559-570.DOI:10.1136/thx.2009.133173.
[13]全国结核病流行病学抽样调查技术指导组,全国结核病流行病学抽样调查办公室.2010年全国肺结核患病率现况调查[J].中华结核和呼吸杂志,2012,35(9):665-668.
[14]杜建伟,王春雷,张广恩,等.海南省2010年结核病流行病学抽样调查[J].中国热带医学,2012,1(11):1323-1326.DU J W,WANG C L,ZHANG G E,et al.Epidemiological sampling survey of tuberculosis in Hainan province in 2010[J].China Tropical Medicine,2012,1(11):1323-1326.
[15]张广恩,陈成江.海南省2010-2014年肺结核疫情特征分析[J].中国热带医学,2015,15(8):1004-1006.ZHANG G E,CHEN C J.Analysis of epidemic feature of pulmonary tuberculosis in Hainan province during 2010-2014[J].China Tropical Medicine,2015,15(8):1004-1006.
[16]袁发焕,赵生家.1069例慢性肾衰患者合并结核病的临床研究[J].西部医学,2003,1(3):199-201.
[17]张训,侯凡凡,魏冬梅,等.慢性肾功能衰竭接受肾替代治疗病人并发结核病[J].中华内科学杂志,1995,34(10):666-669.
[18]叶文玲,李学旺,李航.慢性肾功能衰竭血液透析患者合并结核感染的诊治[J].中国医学院学报,2001,23(5):535-536.
[19]The National Collaborating Center for Chronic Conditions.Tuberculosis:clinical diagnosis and management of tuberculosis and measures for its prevention and control[M].London:Royal College of Physicians,2006.
[20]WHO. Weekly epidemiological record[EB/OL].[2018-01-10].http://www.who.int/wer.
[21]PASSALENT L K K,RICHARDSON R,WANG J,et al.Detecting latent tuberculosis infection in hemodialysis patients:a head-to-head comparison of the T-SPOT.TB Test,Tuberculin Skin Test,and an expert physician panel[J].Clin J Am Soc Nephrol,2007,2:68-73.DOI:10.2215/CJN.01280406.
[22]ROGERSON T E,CHEN S,KOK J,et al.Tests for latent tuberculosis in people with ESRD:a systematic review[J].Am J Kidney Dis,2013,61(1):33-43.DOI:10.1053/j.ajkd.2012.07.019.
[23]REDELMAN-SIDI G,SEPKOWITZ K A.IFN-γrelease assays in the diagnosis of latent tuberculosis infection among immunocompromised adults[J].Am J Respir Crit Care Med,2013,188(4):422-431.DOI:10.1164/rccm.201209-1621CI.
[24]LIANG L,SHI R,LIU X,et al.Interferon-gamma response to the treatment of active pulmonary and extra-pulmonary tuberculosis[J].Int J Tuberc Lung Dis,2017,21(10):1145-1149.DOI:10.5588/ijtld.16.0880.
[25]O'SHEA M K,FLETCHER T E,BEECHING N J,et al.Tuberculin skin testing and treatment modulates interferon-gamma release assay results for latent tuberculosis in migrants[J].PLoS One,2014,9(5):e97366.DOI:10.1371/journal.pone.0097366.
[26]中国医院协会血液净化中心管理分会专家组.中国成人慢性肾脏病合并结核病管理专家共识[J].中国血液净化,2016,15(11):577-586.The Blood Purification Center Management Branch of China Hospital Association.The management consensus of China chronic kidney disease combine with tuberculosis[J].Chin J Blood Purif,2016,15(11):577-586.