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《中华肺部疾病杂志》[ISSN:1006-6977/CN:61-1281/TN]

卷:

期数:

2025年01期

页码:

74-79

栏目:

论著

出版日期:

2025-02-25

文章信息/Info

Title:

Clinical analysis of sputum lipoarabinomannan in predicting the effectiveness of pulmonary tuberculosis treatment

作者:

贾 斐¹; 张权武²; 高 瑜³; 辛 超¹

710100 西安,陕西省结核病防治院内七科¹
710100 西安,陕西省结核病防治院内一科²
710100 西安,陕西省结核病防治院内五科³

Author(s):

Jia Fei¹;  Zhang Quanwu²;  Gao Yu³;  Xin Chao¹.

¹Internal Medicine Department 7, Tuberculosis Prevention Hospital in Shaanxi Province, Xi'an 710100, China; ²Internal Medicine Department 1, Tuberculosis Prevention Hospital in Shaanxi Province, Xi'an 710100, China; ³Inter

关键词:

肺结核;  脂阿拉伯甘露聚糖;  细菌负荷;  治疗反应

Keywords:

Pulmonary tuberculosis;  Lipoarabinomannan;  Bacterial load;  Therapeutic response

分类号:

R562

DOI:

10.3877/cma.j.issn.1674-6902.2025.01.012

摘要:

目的 分析痰脂阿拉伯甘露聚糖(lipoarabinomannan, LAM)与肺结核(pulmonary tuberculosis, PTB)细菌负荷及疗效的相关性。方法 选择2020年5月至2022年6月我院收治的77例PTB患者为对象,痰涂片阳性+痰培养阳性45例为PTB涂阳组和痰涂片阴性+痰培养阳性32例为PTB涂阴组。PTB涂阳患者接受标准治疗,采用夹心酶联免疫吸附试验法检测治疗前及治疗第7、14、28和56天痰LAM(痰LAM>15 pg/ml为阳性)。根据液体分枝杆菌培养管(Mycobacteria growth indicator tube, MGIT)阳性检出时间(time-to-detection,TTD)分析14 d早期杀菌活性(early bactericidal activity, EBA)。结果 痰LAM识别PTB涂阳的敏感度和特异度分别为98.67%和47.27%,阳性和阴性预测值分别为71.84%和96.30%,约登指数为0.46。治疗第14天痰LAM(2.88±1.00)log₁₀ pg/ml低于治疗前痰LAM(3.74±0.96)log₁₀ pg/ml(P<0.001); 治疗第14天MGIT TTD(308.69±108.67)h较治疗前MGIT TTD(133.56±34.63)h延长(P<0.001)。治疗第14天 EBA增加(202.42±84.94)h,痰LAM浓度下降(1.54±0.93)log₁₀ pg/ml。治疗前和治疗期间45例LAM-ELISA与MGIT培养的检测一致。Pearson相关性分析显示,患者log10转化的LAM浓度与MGIT TTD治疗前(r=-0.680,P<0.001)及治疗第7天(r=-0.541,P<0.001)、第14天(r=-0.420,P=0.008)、第28天(r=-0.415,P=0.015)呈负相关。强化治疗后PTB涂阳组6例(13.33%)痰未转阴,痰未转阴者治疗前痰LAM(4.46±1.05)log₁₀ pg/ml高于痰转阴者治疗前痰LAM(3.58±0.93)log₁₀ pg/ml(P=0.040)。治疗前LAM预测强化治疗后痰未转阴的受试者操作特征(receiver operating characteristic curve,ROC)曲线下面积为0.872(95%CI:0.753～0.991),敏感度和特异度分别为83.33%和84.62%,截断值为4.61 log₁₀ pg/ml。结论 痰LAM是治疗前结核分枝杆菌(Mycobacterium tuberculosis, MTB)负荷的生物标志物及治疗期间细菌负荷变化的药效学生物标志物,可实时监测细菌负荷及疗效。

Abstract:

Objective To analyze the correlation between the concentration of lipoarabinomannan(LAM)in sputum and bacterial load and treatment response of pulmonary tuberculosis(PTB). Methods All of 77 patients with PTB treated in our hospital from May 2020 to June 2022 were selected as subjects, 45 patients with smear and culture positive PTB smear positive group and 32 patients with smear negative but sputum culture positive PTB smear negative group. Patients with PTB smear positive received standard treatment, and sputum LAM was detected by sandwich enzyme-linked immunosorbent assay before treatment and at 7, 14, 28, and 56 days after treatment. Sputum LAM>15 pg/ml was positive. The outcome of the study was 14-day early bactericidal activity(EBA), which was assessed based on mycobacteria growth indicator tube(MGIT)positive detection time(TTD). Results The sensitivity and specificity of sputum LAM were 98.67% and 47.27%, respectively, the positive predictive value and negative predictive value were 71.84% and 96.30%, respectively, the Yodon index was 0.46. Compared with before treatment, sputum LAM decreased on the 14th day of treatment [(3.74±0.96)log₁₀ pg/ml vs.(2.88±1.00)log₁₀ pg/ml, P<0.001]. MGIT TTD was significantly prolonged on the 14th day of treatment compared with before treatment [(133.56±34.63)h vs.(308.69±108.67)h, P<0.001]. At 14 days of EBA, the EBA represented by MGIT TTD increased(202.42±84.94)h, and the sputum LAM concentration decreased(1.54±0.93)log₁₀ pg/ml. There was high consistency between LAM-ELISA and MGIT in 45 cases before and during treatment.By Pearson correlation analysis, the LAM concentration of log₁₀ transformation in all patients was correlated with MGIT TTD before treatment(r=-0.680, P<0.001), on day 7(r=-0.541, P<0.001), and on day 14(r=-0.420, P=0.008)and the 28th day(r=-0.415, P=0.015)showed a significant negative correlation. 6 cases(13.33%)phlegm did not turn negative after intensive treatment. Sputum LAM before treatment was higher in patients without sputum conversion than in patients with sputum conversion [(4.46±1.05)log₁₀ pg/ml vs.(3.58±0.93)log₁₀ pg/ml, P=0.040]. The area under the receiver operating characteristic(ROC)curve of LAM before treatment for predicting sputum not turning negative after intensive treatment was 0.872(95%CI: 0.753-0.991), the sensitivity and specificity were 83.33% and 84.62%, respectively, and the cut-off value was 4.61 log₁₀ pg/ml. Conclusion Sputum LAM may be a biomarker of Mycobacterium tuberculosis(MTB)load before treatment and a pharmacodynamic biomarker of bacterial load change during treatment. Sputum LAM may be a useful tool for real-time monitoring of bacterial load and therapeutic response.

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备注/Memo

备注/Memo:

基金项目: 陕西省重点研发计划项目(2020SF-105)
通信作者: 张权武, Email: 415899249@qq.com

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更新日期/Last Update: 2025-02-20