支气管肺泡灌洗液血清半乳甘露聚糖检测在非粒缺侵袭性肺曲霉病中的诊断价值评估

Value of galactomannan detection in bronchoalveolar lavage fluid and serum in diagnosis of invasive pulmonary aspergillosis among nonneutropenic patients

目的评价支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)及血清中半乳甘露聚糖(galactomannan,GM)抗原检测对非粒缺侵袭性肺曲霉病(invasive pulmonary aspergillosis,IPA)患者的诊断价值。方法材料来源于2017年11月-2018年10月天津市第三中心医院ICU和呼吸科收治的可疑IPA(228例)患者,分为IPA组104例,非IPA组124例。采用双抗体夹心酶联免疫吸附实验(enzyme linked immunosorbent assay,ELISA)方法和竞争法检测支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)样本半乳甘露聚糖(galactomannan,GM)浓度及双抗体夹心ELISA法检测血清样本GM浓度;当界值分别为0.5、1.0、1.5、2.0时,比较三种方法的敏感度、特异度、阳性预测值(Positive Prediction Value,PPV)、阴性预测值(Negative Prediction Value,NPV)、约登指数,及对非粒缺IPA的诊断价值;通过ROC曲线面积的比较,确定早期诊断IPA的最佳方法及其最佳界值。结果IPA组夹心法和竞争法BALF-GM及血清GM测定的吸光度(optical delnsity,OD)值分别为0.837(0.553,1.124)、0.806(0.441,1.113)、0.440(0.190,0.680),比非IPA组血清GM和BALF-GM均提高(P<0.05)。夹心法BALF-GM ROC检测曲线下面积与竞争法BALF-GM及血清GM比较,差异均有统计学意义(P<0.05)。夹心法BALF-GM对IPA的诊断效能最高,其最佳的界值为0.81。结论夹心法BALF-GM试验在诊断非粒缺侵袭性肺曲霉病患者时敏感性、特异度均高于竞争法BALF-GM和血清GM试验,可以用于非粒缺IPA患者的早期辅助诊断,其最佳cut off值为0.81。

OBJECTIVE To evaluate the diagnostic value of galactomannan(GM)antigen in bronchoalveolar lavage fluid(BALF)and serum in patients with non-invasive pulmonary aspergillosis(IPA).METHODS Total of 228 suspected IPA patients were divided into IPA group(104 cases)and non-IPA group(124 cases).The GM concentration in BALF was detected by double antibody sandwich ELISA method and competitive method,and the GM concentration in serum was detected by double antibody sandwich ELISA method.When the cut off values were 0.5,1.0,1.5 and 2.0,the sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),Yoden index and diagnostic value of the three methods were compared.And the area ratio of ROC curve was used to determine the most suitable method for early diagnosis of IPA and the cut off value.RESULTS The median absorbance(optical delnsity,OD)values of sandwich method and competitive method BALF-GM and serum GM in the IPA group were 0.837(0.553,1.124),0.806(0.441,1.113),0.440(0.190,0.680),which were significantly higher than that in the non-IPA group(P<0.05).The area under the curve of the sandwich BALF-GM ROC was significantly higher than that of the competition BALF-GM(P<0.05).Sandwich BALF-GM has the highest diagnostic efficiency for IPA,which has the cut off value of 0.81.CONCLUSION The sensitivity and specificity of sandwich BALF-GM test were significantly higher than that of competitive BALF-GM test and serum GM test.The sandwich BALF-GM test can be used for early auxiliary diagnosis of invasive pulmonary aspergillosis among nonneutropenic patients.The optimal cut off value is 0.81.