Host gene expression classifiers diagnose acute respiratory illness etiology.
Host gene expression classifiers diagnose acute respiratory illness etiology.
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DOI：
10.1126/scitranslmed.aad6873
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发表时间：
2016-01-20
影响因子：
17.1
通讯作者：
Woods CW
中科院分区：
文献类型：
--
作者：
Tsalik EL;Henao R;Nichols M;Burke T;Ko ER;McClain MT;Hudson LL;Mazur A;Freeman DH;Veldman T;Langley RJ;Quackenbush EB;Glickman SW;Cairns CB;Jaehne AK;Rivers EP;Otero RM;Zaas AK;Kingsmore SF;Lucas J;Fowler VG Jr;Carin L;Ginsburg GS;Woods CW
由细菌或病毒病原体引起的急性呼吸道感染是寻求医疗保健的最常见原因之一。尽管基于病原体的诊断有所改善，但大多数患者接受了不适当的抗生素。宿主反应生物标志物为直接使用抗菌药物提供了另一种诊断方法。这项观察性队列研究确定了宿主基因表达模式是否区分非感染性疾病和感染性疾病，以及急性呼吸道感染的细菌和病毒原因。采用微阵列技术检测了273例社区发病急性呼吸道感染（ARI）或非传染性疾病患者以及44例健康对照者外周血全血基因表达。稀疏逻辑回归用于开发细菌性ARI（71个探针）、病毒性ARI（33个探针）或非感染性疾病原因（26个探针）的分类器。总体准确率为87%（238/273与临床判定相符），高于降钙素原（78%,p<0.03）和三种已发表的细菌与病毒感染分类（78-83%）。这里开发的分类器在五个公开可用的数据集中进行了外部验证（AUC为0.90-0.99）。第六个公开可用的数据集包括25例细菌和病毒病原体共同鉴定的患者。应用ARI分类器定义了四个不同的组：宿主对细菌性ARI的反应；病毒阿里;合并感染;既没有细菌也没有病毒反应。这些发现为开发和利用宿主基因表达分类器作为诊断平台来对抗不适当的抗生素使用和新出现的抗生素耐药性创造了机会。
Acute respiratory infections caused by bacterial or viral pathogens are among the most common reasons for seeking medical care. Despite improvements in pathogen-based diagnostics, most patients receive inappropriate antibiotics. Host response biomarkers offer an alternative diagnostic approach to direct antimicrobial use. This observational, cohort study determined whether host gene expression patterns discriminate non-infectious from infectious illness, and bacterial from viral causes of acute respiratory infection in the acute care setting. Peripheral whole blood gene expression from 273 subjects with community-onset acute respiratory infection (ARI) or non-infectious illness as well as 44 healthy controls was measured using microarrays. Sparse logistic regression was used to develop classifiers for bacterial ARI (71 probes), viral ARI (33 probes), or a non-infectious cause of illness (26 probes). Overall accuracy was 87% (238/273 concordant with clinical adjudication), which was more accurate than procalcitonin (78%, p<0.03) and three published classifiers of bacterial vs. viral infection (78-83%). The classifiers developed here externally validated in five publicly available datasets (AUC 0.90-0.99). A sixth publically available dataset included twenty-five patients with co-identification of bacterial and viral pathogens. Applying the ARI classifiers defined four distinct groups: a host response to bacterial ARI; viral ARI; co-infection; and neither a bacterial nor viral response. These findings create an opportunity to develop and utilize host gene expression classifiers as diagnostic platforms to combat inappropriate antibiotic use and emerging antibiotic resistance.