侵袭性曲霉菌病--ICU患者的高危因素
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侵袭性曲霉菌病(Invasive Aspergillosis , IA)是曲霉菌感染人体致病最严重的一种形式。对于ICU的危重患者，有报道的IA的发病率高达10%，1 这个数字要高于以往其他疾病人群所报道的数字0.33-6.9%。2 事实上， 在ICU患者中，IA的危险因素有很多，不仅仅限于由EORTC/MSG指南中提到的单一的宿主因素。比如，长期糖皮质激素治疗的患者，慢性阻塞性肺病(Chronic Obstructive Pulmonary Disease, COPD)，肝硬化，实体器官肿瘤，HIV感染，肺移植，以及较长时间的ICU住院(大于21天)等。3
两项针对COPD患者伴发IA研究分析发现，这类患者的临床结局都非常差，死亡率均达到了100%。4,5 在2014年另一项研究中，COPD伴发IA的死亡率为66%。1 在欧洲癌症研究和治疗组织和真菌病研究组(European Organization for Research and Treatment Cancer and Mycoses Study Group, EORTC/MSG)的标准中，类固醇使用超过三周以上被认为是IA的危险因素。对于严重的和/或持续的败血性休克患者，使用低剂量的类固醇(盐皮质激素)可以改善临床结局。6 但它们也对 巨噬细胞 杀伤曲霉菌孢子和单核细胞杀伤曲霉菌菌丝的作用存在损害。7对于有肺部疾病的患者，即使使用低剂量的类固醇，其伴发IA的风险也会更高。8 对于肝硬化患者，由于其细胞吞噬作用和趋化作用受损，被认为是导致IA发病的可能因素。9
由于ICU患者伴发IA有较高的发病率和死亡率，建立可以实现早期诊断的检测方法或诊断标准就非常有意义。 血清 曲霉菌抗或半乳甘露聚糖(galactomannan, GM)是有报道的血液肿瘤患者中IA检测的可靠手段。10GM检测比较于其他方法，可以帮助临床提早8天诊断IA。11 血清GM抗原是曲霉菌细胞壁的多糖成分，在曲霉菌菌丝侵袭机体组织时释放。这个成分可通过一步夹心酶联免疫法进行检测。近年的一些研究证实，在血液肿瘤患者中，由于GM水平升高与较差的临床结局呈强相关，因此认为GM抗原检测也可作为IA临床结局的衡量工具。12,13
GM抗原检测所使用的试剂为 Bio-Rad 公司的曲霉菌抗原检测试剂盒(PlateliaTMAspergillusAg)，该试剂为一步夹心酶联免疫法，利用单克隆抗体(EBA-2)对血液循环中的GM抗原。推荐首次检测时间点一般为当临床怀疑患者发生IA时，或者需要对免疫妥协患者进行常规筛查时。1另外，对于开始进行抗真菌治疗的患者，推荐进行每周两次的GM水平监测，以帮助判断临床疗效及患者预后。14
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