Noninvasive Analysis of the Sputum TranScriptome Discriminates Clinical Phenotypes of Asthma
Noninvasive Analysis of the Sputum TranScriptome Discriminates Clinical Phenotypes of Asthma
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DOI：
10.1164/rccm.201408-1440oc
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发表时间：
2015-05-15
影响因子：
24.7
通讯作者：
Chupp, Geoffrey L.
中科院分区：
文献类型：
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作者：
Yan, Xiting;Chu, Jen-Hwa;Chupp, Geoffrey L.
基本原理：气道转录组包括基因的病理生理异质性，在个体哮喘objectives.Objectives：我们分析了痰基因表达的转录组内型哮喘（TEA），基因的签名，区分疾病的表型。使用基于来自京都基因和基因组百科全书的途径的无监督聚类分析来鉴定TEA簇。Logistic回归分析匹配的血液样本定义的表达谱在循环中，以确定TEA集群分配在一个队列的儿童哮喘复制临床phenotypes. Measures和主要结果：三个TEA集群被确定。与其他TEA组相比，TEA组1的大多数受试者有插管史（P = 0.05）、较低的支气管扩张剂前FEV 1（P = 0.006）、较高的支气管扩张剂反应（P = 0.03）和较高的呼出气一氧化氮水平（P = 0.04）。TEA聚类2是最小的聚类，有最多的受试者因哮喘住院（P = 0.04）。TEA集群3是最大的集群，肺功能正常，呼出的一氧化氮水平较低，吸入的类固醇需求较低。对儿童TEA簇的评估证实TEA簇1和2分别与插管史（P = 5.58 × 10（-6））和住院史（P = 0.01）相关。结论：儿童和成人的痰和血液中存在与几乎致命、严重和轻度哮喘相关的共同基因表达模式。
Rationale: The airway transcriptome includes genes that contribute to the pathophysiologic heterogeneity seen in individuals with asthma.Objectives: We analyzed sputum gene expression for transcriptomic endotypes of asthma (TEA), gene signatures that discriminate phenotypes of disease.Methods: Gene expression in the sputum and blood of patients with asthma was measured using Affymetrix microarrays. Unsupervised clustering analysis based on pathways from the Kyoto Encyclopedia of Genes and Genomes was used to identify TEA clusters. Logistic regression analysis of matched blood samples defined an expression profile in the circulation to determine the TEA cluster assignment in a cohort of children with asthma to replicate clinical phenotypes.Measurements and Main Results: Three TEA clusters were identified. TEA cluster 1 had the most subjects with a history of intubation (P = 0.05), a lower prebronchodilator FEV1 (P = 0.006), a higher bronchodilator response (P = 0.03), and higher exhaled nitric oxide levels (P = 0.04) compared with the other TEA clusters. TEA cluster 2, the smallest cluster, had the most subjects that were hospitalized for asthma (P = 0.04). TEA cluster 3, the largest cluster, had normal lung function, low exhaled nitric oxide levels, and lower inhaled steroid requirements. Evaluation of TEA clusters in children confirmed that TEA clusters 1 and 2 are associated with a history of intubation (P = 5.58 X 10(-6)) and hospitalization (P = 0.01), respectively.Conclusions: There are common patterns of gene expression in the sputum and blood of children and adults that are associated with near-fatal, severe, and milder asthma.