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Asthmatics with exacerbation during acute respiratory illness exhibit unique transcriptional signatures within the nasal mucosa - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Genome Medicine

, 6:1

1. Genomics and epigenomics of disease


BackgroundAcute respiratory illness is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular events characterizing acute respiratory illness-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of acute respiratory illness amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease.

MethodsTranscriptional profiling experiments were performed using the Agilent Whole Human Genome 4X44K array platform. Time point-based microarray and principal component analyses were conducted to identify and distinguish acute respiratory illness-associated transcriptional profiles over the course of our study. Gene enrichment analysis was conducted to identify biological processes over-represented within each acute respiratory illness-associated profile, and gene expression was subsequently confirmed by quantitative polymerase chain reaction.

ResultsWe found that acute respiratory illness is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during acute respiratory illness. Most strikingly, we report that people with asthma who experience acute respiratory illness-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair, and the expression of a newly described exacerbation-specific transcriptional signature.

ConclusionFindings from our study represent a significant contribution towards clarifying the complex molecular interactions that typify acute respiratory illness-induced asthma exacerbations.

AbbreviationsAllrg Rhinpatients with allergic rhinitis

ARIacute respiratory illness

Asm Expatients with asthma and exacerbation

Asm NoExpatients with asthma without exacerbation


CCLChemokine C-C motif ligand

CXCLChemokine C-X-C motif ligand

D2day 2

D6day 6

eNOexhaled nitric oxide

FEV1forced expiratory flow in 1 second

GEAgene enrichment analysis

ICSinhaled corticosteroids

NSnasal steroids

PC1principal component 1

PCAprincipal component analysis

PCRpolymerase chain reaction

PEFpeak expiratory flow rate

TMEMtransmembrane protein.

Electronic supplementary materialThe online version of this article doi:10.1186-gm520 contains supplementary material, which is available to authorized users.

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Autor: Peter McErlean - Sergejs Berdnikovs - Silvio FavoretoJr - Junqing Shen - Assel Biyasheva - Rebecca Barbeau - Chris Eisley -


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