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。

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.