急性喘息特异性基因模块显示维生素D和哮喘药物治疗相关
2020/02/11
摘要
背景：学龄前儿童由于反复病毒感染所致的呼吸道阻塞和喘息是一个主要的临床问题，并被认为是发展为慢性哮喘的危险因素。我们的目的是分析基因表达谱能否为描述不同类型的喘息儿童提供依据，并结合临床信息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-3岁)急性喘息期(n=107)和2-3个月后再访时的白细胞转录组(n=66)，并将其与年龄匹配的健康对照组(n=66)进行比较。使用了GlobinLock进行RNA测序。临床随访至7岁。应用差异表达检验、加权相关网络分析和logistic回归对76个临床性状进行相关性评价。
结果：在喘息儿童中观察到与先天免疫反应有关的基因显著富集。我们确定了一个独特的急性喘息的特异性基因模块，它与婴儿时期的维生素D水平(p<0.005)，以及几年后7岁时的哮喘药物和FEV%/FVC (1 s用力肺活量/用力呼气量)的比例相关(p<0.005)。建立了预测7岁时白三烯受体拮抗剂用药的高精度模型(曲线下面积0.815,95% CI 0.668-0.962)。
解释：学龄前喘息的儿童血液中的基因表达谱可以预测学龄期的哮喘症状，因此可以作为生物标志物。急性喘息特异性基因模块提示，结合早期喘息临床信息和分子表型可能有助于区分哪些儿童将不再喘息，哪些儿童将发展为慢性哮喘。
Acute wheeze-specific gene module shows correlation with vitamin D and asthma medication.
Katayama S, Stenberg Hammar K, Krjutškov K, Einarsdottir E, Hedlin G, Kere J,
Söderhäll C,
Eur. Respir. J. 2020 Jan;55(1)
Abstract
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 Dlevels (p<0.005) in infancy, and asthma medication and FEV%/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.
背景：学龄前儿童由于反复病毒感染所致的呼吸道阻塞和喘息是一个主要的临床问题，并被认为是发展为慢性哮喘的危险因素。我们的目的是分析基因表达谱能否为描述不同类型的喘息儿童提供依据，并结合临床信息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-3岁)急性喘息期(n=107)和2-3个月后再访时的白细胞转录组(n=66)，并将其与年龄匹配的健康对照组(n=66)进行比较。使用了GlobinLock进行RNA测序。临床随访至7岁。应用差异表达检验、加权相关网络分析和logistic回归对76个临床性状进行相关性评价。
结果：在喘息儿童中观察到与先天免疫反应有关的基因显著富集。我们确定了一个独特的急性喘息的特异性基因模块，它与婴儿时期的维生素D水平(p<0.005)，以及几年后7岁时的哮喘药物和FEV%/FVC (1 s用力肺活量/用力呼气量)的比例相关(p<0.005)。建立了预测7岁时白三烯受体拮抗剂用药的高精度模型(曲线下面积0.815,95% CI 0.668-0.962)。
解释：学龄前喘息的儿童血液中的基因表达谱可以预测学龄期的哮喘症状，因此可以作为生物标志物。急性喘息特异性基因模块提示，结合早期喘息临床信息和分子表型可能有助于区分哪些儿童将不再喘息，哪些儿童将发展为慢性哮喘。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(Eur. Respir. J. 2020 Jan;55(1))
(Eur. Respir. J. 2020 Jan;55(1))
Acute wheeze-specific gene module shows correlation with vitamin D and asthma medication.
Katayama S, Stenberg Hammar K, Krjutškov K, Einarsdottir E, Hedlin G, Kere J,
Söderhäll C,
Eur. Respir. J. 2020 Jan;55(1)
Abstract
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 Dlevels (p<0.005) in infancy, and asthma medication and FEV%/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.
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