血清半乳甘露聚糖检测对血液肿瘤患者侵袭性曲霉病诊断价值的评估

Cinical value of serum galactomannan detection for invasive aspergillosis patients with hematologic disease/cancer

目的:探讨血清半乳甘露聚糖(GM)抗原检测对于血液肿瘤患者侵袭性曲霉病(invasive aspergillo-sis,IA)的早期诊断和疗效评判的临床意义。方法:选取127例血液肿瘤并发中性粒细胞减少伴发热、广谱抗生素治疗无效的患者治疗前后的402份血清标本。采用ELISA法进行血清GM浓度测定,同时收集患者的临床资料。评价GM测定对于血液肿瘤患者IA的诊断价值和抗真菌治疗前后GM浓度变化的意义,并进行统计学分析。结果:拟将本观察组血液肿瘤患者并发IA的血清GM检测结果的单次I≥0.7,或连续2次I≥0.5做为阳性界值时,本试验的敏感性、特异性、阳性预测值和阴性预测值分别为92.3%、82.4%、57.1%和97.7%,与试剂盒提供的血清GM试验结果的I≥1.5的阳性界值相比灵敏度提高,而特异性无明显降低,因此能够有效区分临床诊断和拟诊两个IA级别。在其他实验室检测和影像学结果基础上加入GM试验后,临床诊断病例组的人数明显增加。根据我们确定的阳性界值标准,GM实验阳性早于痰培养或涂片平均(6.1±4.5)d(1～11d);也早于CT影像学证据平均(7.2±5.5)d(1～15d)。抗真菌治疗有效患者的GM水平随着治疗呈波动性下降,无效患者GM水平无变化。GM浓度与本观察组患者疾病的治疗及预后具有相关性。结论:血清GM抗原检测是早期诊断IA的一种有效方法。将单次I≥0.7或连续2次I≥0.5作为阳性界值比单用一种界值敏感性提高,特异性理想。在高危血液肿瘤伴粒细胞缺乏患者中以GM实验阳性为起点抢先抗曲霉菌治疗,可降低IA病死率,监测血清GM浓度的动态变化具有评判疗效的重要价值。

Objective：To assess the value of serum galactomannan（GM） detection for early diagnosis and therapeutic effect of invasive aspergillosis（IA） in patients with hematologic disease/cancer.Method：Four Hundred and two serum samples of 127 inpatients with high IA risk were selected according to the domestic diagnosis standard of invasive fungus infection in patients with hematologic disease/cancer.The serum GM concentration was detected by platelia Aspergillus double-sandwich enzyme linked immunosorbent assay（PADSELISA）.According to the diagnostic criteria of invasive fungal infections in China,the changes of GM concentration before and after antifungal treatment and its value for diagnosis were evaluated by statistical analyse.Result：The sensitivity,specificity,positive predictive value and negative predictive value of the PADSELISA were 92.3%,82.4%,57.1%,and 97.7% respectively by using the serum GM cut-off value of single index≥0.7 and（or） 2 consecutive index≥0.5.Comparing with the provided reagent serum GM cut-off index≥1.5,it had an increased sensitivity without obviously decreasing specificity,which effectively distinguished the two IA levels between probable and possible patients.The probable IA cases were increased from 10 to 19 after adding the GM detection.GM test was positive（6.1±4.5） d（1-11 d）ahead of sputum culture,and（7.2±5.5） d（1-15 d） ahead of CT scan.A fluctuant reduction of GM level was found in patients sensitive to antifungal treatment,and an increased or constant GM level was seen in insensitive patients.The GM false positive rate could become obviously high in control group patients with intravenous injection of piperacillin-Tazobactam.The GM level of IA patients after using echinocandin increased in early stage and showed a decreased trend during the whole course.The concentration of GM had a relation with the prognosis of the disease.Conclusion：Serum GM antigen detection is an effective method for early diagnosis of IA.Comparing with other diagnostic accessory examination,such as typical CT imaging and direct microbiological test,GM test has an obvious advantage on the positive rate and time.Comparing with single value,single index≥0.7 and（or） 2 consecutive index≥0.5 can increase the sensitivity without obviously decreasing specificity.Among patients with high risk of hematologic disease/cancer,using GM test positive as a starting point to preemption of the anti-Aspergillus treatment can reduce mortality of IA patients.We can estimate the anti-fungal effect by dynamic detection of serum GM.