哮喘联盟

   摘要
   背景：气道转录组学包括一系列有助于哮喘患者出现个体病理生理异质性的基因。
   目的：研究旨在分析哮喘转录亚型（TEA）的痰液基因的表达情况，并通过基因标签区分哮喘患者的临床表型。
   方法：研究采用Affymetrix基因表达芯片分析哮喘患者痰液和血液中的基因表达谱。基于京都基因与基因组百科全书，采用无监督聚类分析确定哮喘患者的基因转录情况。通过对配对血液标本中的基因转录谱（可以定义外周血循环的基因表达谱）进行Logistic回归分析，以确定TEA集群在儿童哮喘患者中的分布情况并进行验证。
评估和主要检测结果：本研究总共确定了3种TEA集群。TEA集群1与另外两种集群相比，伴有气管插管史患者更多（P = 0.05），支气管扩张剂使用前FEV1更低（P = 0.006），支气管扩张剂反应性更高（P = 0.03），呼出气体中一氧化氮浓度更高（P = 0.04）。TEA集群2患者所占的比例最小，但该类患者因哮喘的住院率最高（P = 0.04）。TEA集群3患者所占的比例最高，患者肺功能正常，呼出气体中一氧化氮浓度低，对吸入性皮质类激素的需求更少。儿童哮喘患者TEA集群分析结果显示，TEA集群1和2分别与气管插管史（P = 5.58 x 10-06）与住院史相关（P = 0.01）。
   结论：儿童或成年患者的痰液与外周血循环中的基因表达情况类似，并与轻型、重型和近乎致命型哮喘相关。
 

（杨冬 审校）
Am J Respir Crit Care Med. 2015 Mar 12. [Epub ahead of print]
 

Non-invasive Analysis of the Sputum Transcriptome Discriminates Clinical Phenotypes of Asthma.
 

Yan X1, Chu JH, Gomez J, Koenigs M, Holm C, He X, Perez MF, Zhao H, Mane S, Martinez FD, Ober C, Nicolae DL, Barnes KC, London SJ, Gilliland F, Weiss ST, Raby BA, Cohn L, Chupp GL.

Author information
 

ABSTRACT
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 sputum and blood of asthma patients was measured using Affymetrix gene expression 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 for validation.
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 pre-bronchodilator FEV1 (P = 0.006), a higher bronchodilator response (P = 0.03), and higher exhaled nitric oxide levels (P = 0.04), compared to 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 10-06) 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.
 

Am J Respir Crit Care Med. 2015 Mar 12. [Epub ahead of print]