Background Airway obstruction and wheezing in preschool children with recurrent viral infections are a major clinical problem, and are recognised as a risk factor for the development of chronic asthma. We aimed to analyse whether gene expression profiling provides evidence for pathways that delineate distinct groups of children with wheeze, and in combination with clinical information could contribute to diagnosis and prognosis of disease development. Methods We analysed leukocyte transcriptomes from preschool children (6 months–3 years) at acute wheeze (n=107), and at a revisit 2–3 months later, comparing them to age-matched healthy controls (n=66). RNA-sequencing applying GlobinLock was used. The cases were followed clinically until age 7 years. Differential expression tests, weighted correlation network analysis and logistic regression were applied and correlations to 76 clinical traits evaluated. Findings Significant enrichment of genes involved in the innate immune responses was observed in children with wheeze. We identified a unique acute wheeze-specific gene-module, which was associated with vitamin D levels (p<0.005) in infancy, and asthma medication and FEV1%/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio several years later, at age 7 years (p<0.005). A model that predicts leukotriene receptor antagonist medication at 7 years of age with high accuracy was developed (area under the curve 0.815, 95% CI 0.668–0.962). Interpretation Gene expression profiles in blood from preschool wheezers predict asthma symptoms at school age, and therefore serve as biomarkers. The acute wheeze-specific gene module suggests that molecular phenotyping in combination with clinical information already at an early episode of wheeze may help to distinguish children who will outgrow their wheeze from those who will develop chronic asthma. Gene expression profiles at acute preschool wheeze correlate with vitamin D, and asthma medication and lung function several years later. These profiles provide candidate prognostic biomarkers and support the role of immune response in preschool wheeze. http://bit.ly/318Ilde

中文翻译：

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急性喘息特异性基因模块显示与维生素 D 和哮喘药物的相关性

背景 反复病毒感染的学龄前儿童气道阻塞和喘息是一个主要的临床问题，被认为是慢性哮喘发展的危险因素。我们旨在分析基因表达谱是否为描绘不同喘息儿童群体的途径提供证据，并结合临床信息可能有助于疾病发展的诊断和预后。方法 我们分析了学龄前儿童（6 个月至 3 岁）在急性喘息时（n=107）和 2-3 个月后复诊时的白细胞转录组，并将它们与年龄匹配的健康对照（n=66）进行比较。使用了应用 GlobinLock 的 RNA 测序。对病例进行临床随访直至 7 岁。差异表达测试，应用加权相关网络分析和逻辑回归并评估与 76 项临床特征的相关性。结果 在患有喘息的儿童中观察到参与先天免疫反应的基因显着富集。我们确定了一个独特的急性喘息特异性基因模块，它与婴儿期维生素 D 水平（p<0.005）、哮喘药物治疗和 FEV1%/FVC（1 秒用力呼气量/用力肺活量）比值相关后来，在 7 岁时（p<0.005）。开发了一个模型，可以高精度预测 7 岁时白三烯受体拮抗剂的用药情况（曲线下面积 0.815，95% CI 0.668–0.962）。解释学龄前喘息者血液中的基因表达谱可预测学龄期哮喘症状，因此可作为生物标志物。急性喘息特异基因模块表明，分子表型结合早在喘息发作时的临床信息可能有助于区分将不再出现喘息的儿童与将发展为慢性哮喘的儿童。几年后急性学龄前喘息的基因表达谱与维生素 D、哮喘药物和肺功能相关。这些特征提供了候选的预后生物标志物，并支持免疫反应在学龄前喘息中的作用。http://bit.ly/318Ilde 几年后哮喘药物和肺功能。这些特征提供了候选的预后生物标志物，并支持免疫反应在学龄前喘息中的作用。http://bit.ly/318Ilde 几年后哮喘药物和肺功能。这些特征提供了候选的预后生物标志物，并支持免疫反应在学龄前喘息中的作用。http://bit.ly/318Ilde