【作者】 张群；

【导师】 肖伟；

【作者基本信息】 山东大学 ， 内科学（呼吸系病）（专业学位）， 2016， 硕士

【摘要】 研究目的：探讨T-SPOT对结核病诊断的敏感性及其影响因素。研究方法：采用回顾性病例对照研究的方法,选择符合中华人民共和国卫生部2008年版的《肺结核诊断标准》确诊的肺结核患者以及符合《协和呼吸病学》结核性胸膜炎诊断标准确诊结核性胸膜炎患者；记录入组患者的基本资料、病史、实验室检查指标及外周血T-SPOT.TB检查结果；对上述确诊的结核病患者的T-SPOT.TB结果进行分析,比较T-SPOT.TB阳性患者及阴性患者的临床症状及各项实验室检查指标；应用SPSS18.0软件进行统计学分析。研究结果：1.肺结核患者36例,年龄21-80岁,平均55.4±17.7岁,男18例,女18例；结核性胸膜炎患者35例,年龄23-83岁,平均50.3+15.9岁,男26例,女9例。2.肺结核组T-SPOT.TB阳性32/36例,阳性率88.9%；结核性胸膜炎组T-SPOT.TB阳性24/35例,阳性率68.6%；肺结核患者组T-SPOT.TB阳性率显著高于结核性胸膜炎患者组T-SPOT.TB的阳性率(P=0.036)。3.对肺结核组和结核性胸膜炎组中T-SPOT.TB阳性和阴性患者的特征及指标进行单因素分析显示：相比于T-SPOT.TB阳性患者,T-SPOT.TB阴性患者有如下特征：年龄偏大(59.6±11.8 vs.51.1±17.1,P=0.035)、男性患者所占比例高(86.7% vs.55.4%,P=0.027)、检测前症状持续时间较长(>1月,60% vs.23.2%,P=0.005)、血清GGT/ALB(γ-谷丙酰基转肽酶／白蛋白)比值偏高(1.59±1.94 U/Lvs.0.72±0.86 U/L, P=0.009)以及结核性胸膜炎的患者所占比例高(73.3%vs.42.9%,P=0.036)：多因素分析显示：年龄偏大(OR=0.94,95% CI:0.89-0.995).检测前症状持续时间较长(>1月,OR=48.47,95% CI:3.64-646.41)和结核性胸膜炎(OR=5.79,95% CI:1.03-32.38)是导致结核病患者中T-SPOT.TB结果阴性的独立危险因素。4.结核病患者T-SPOT.TB勺敏感性随年龄增高而降低：20-40岁、40-60岁和大于60岁的患者T-SPOT的敏感性分别为94.7%、77.3%和69.0%；同时,T-SPOT.TB的敏感性随检测前症状持续时间而变化：检测前症状持续时间小于0.5月的结核病患者T-SPOT.TB检查的敏感性为76.2%,持续时间为0.5-1月患者敏感性为96.4%,而持续时间大于1月患者的T-SPOT.TB敏感性则降至59.1%。5.不同因素对γ-干扰素释放的影响：(以每25万个外周血单个核细胞经抗原刺激后形成的斑点数SFCs数量/2.5*10^5PBMCs为γ-干扰素的释放水平的标准)大于60岁患者γ干扰素释放量显著高于60岁以下患者(70.0±99.0 vs 41.5±73.3 P=0.045)；症状持续时间大于1个月患者的γ-干扰素释放量显著低于症状持续时间小于1个月的患者(14.5±70.0 vs 80.0±60.8 P=0.002)；结核性胸膜炎患者的γ-干扰素释放量显著低于肺结核的患者(30.0±80.0 vs 70±75P=0.012)。但是,γ-干扰素释放量与性别和血清GGT/ALB比值未发现有显著的相关性,P值分别为0.082和0.097。结论：1.本研究人群样本显示,肺结核患者T-SPOT.TB敏感性为88.9%,结核性胸膜炎患者T-SPOT.TB敏感性为68.6%；肺结核患者的T-SPOT.TB敏感性显著高于结核性胸膜炎患者。2.高龄、检测前症状持续时间大于1个月和结核性胸膜炎是引起结核病患者T-SPOT.TB结果阴性的独立危险因素,易降低结核病患者T-SPOT.TB的敏感性。更多还原

【Abstract】 Objectives:To investigate the sensitivity of T-SPOT.TB assay for detection of tuberculosis and the risk factors for negative T-SPOT. TB results in patients with tuberculosis.Methods:The research was conducted by a method of retrospective case-control analysis study. We collected 36 cases of pulmonary tuberculosis (PTB) and 35 cases of tuberculous pleural effusion (TPE) from Qilu Hospital, Shandong University during December 2014 to February 2016. The diagnosis was made according to the Diagnostic Criteria for Pulmonary Tuberculosis (2008) and PUMC Respirology, respectively. The individual information, disease history and laboratory examination of the patients were investigated, all patients underwent valid T-SPOT.TB tests. Basic clinical characteristics and laboratory findings were compared and analyzed between the positive and negative T-SPOT.TB groups of tuberculosis patients. All the data was analyzed by SPSS 18.0 statistic software.Results:1、 There were 36 patients with PTB in our research. The range of their age was 21 to 80 years old,18 of them were males, with the mean age (55.4±17.7).35 cases were included in TPE group. The range of their age was 23 to 83 years old,26 of them were males, with the mean age (50.3±1 5.9).2、36 cases were included in PTB group. Among the PTB patients, the T-SPOT.TB test of 32 patients were identified as postive results, with the sensitivity of 88.9%.35 patients were diagnosed with TPE,24 cases (68.6%) among the TPE patients were with negative T-SPOT.TB test results. Compared with the percentage of PTB patients with positive results, the rate of patients with positive results in TPE group was significantly higher (P=0.036).3、Comparisons of basal characteristics and clinical laboratory findings for patients with false-negative and true-positive T-SPOT.TB results were performed. Univariate analysis showed that older age (P=0.035), male cases (P=0.027), longer duration of symptoms before hospitalization (>one month, P=0.005) and higher serum y-Glutamyl transpeptidase/albumin (GGT/ALB) level (P=0.009) were significantly correlated with the negative T-SPOT.TB results in tuberculosis patients. Multivariate analysis showed that increased age (odds radio (OR) 0.94,95% confidence interval (CI) 0.89-0.995), a longer period of illness before hospitalization (>one month, OR 48.47,95% CI 3.64-646.41), and TPE (OR 5.79,95% CI 1.03-32.38) were independent risk factors for false-negative T-SPOT.TB results in TB patients.4、The sensitivity of T-SPOT.TB assay in tuberculosis patients was negative related with age:the sensitivity of T-SPOT.TB assay of 20-40 years old、40-60 years old and more than 60 years old were 94.7%、77.3% and 69.0% respectively. The relationship between sensitivity of T-SPOT.TB assay and periods of illness before hospitalization was showed that the sensitivity of T-SPOT.TB assay was 76.2% in periods of illness before hospitalization less than 0.5 month group,96.4% in periods of illness before hospitalization more than 0.5 and less than one month group, and 59.1% in more than one month.5、We further investigated the relationship between IFN-y production (the number of SFCs/2.5*10^5 PBMCs) in the T-SPOT. TB test and the affected factors identified. Patients with age over 60 years old had significantly lower level of IFN-y production than those with age less than 60 years old (P=0.045). Significantly lower level of IFN-y production was also detected in patients with longer periods of illness before hospitalization (>one month), compared to the patients who had been ill for more than 0.5 month but less than one month (P=0.002). Patients with TPE had significantly lower level of IFN-y production than those with PTB (P=0.012). There were no significantly relationship between IFN-γ production and the gender (P=0.082) or serum GGT/ALB level (P=0.097).Conclusion:1、The sensitivity of T-SPOT.TB assay in patients with PTB was 88.9%. The sensitivity of T-SPOT.TB assay in patients with TPE was 68.6%. The sensitivity of T-SPOT.TB assay in patients with PTB was prominently higher than that in the TPE group.2、Older age, longer duration of symptoms before hospital admission, and TPE were the independent risk factors of the negative T-SPOT.TB results in tuberculosis patients, which decreased the sensitivity of T-SPOT.TB test.更多还原