title: Asthmatics with exacerbation during acute respiratory illness exhibit unique transcriptional signatures within the nasal mucosa.
abstract: BACKGROUND
  Acute 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.
  
  
  METHODS
  Transcriptional 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Findings from our study represent a significant contribution towards clarifying the complex molecular interactions that typify acute respiratory illness-induced asthma exacerbations.
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: McErlean
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Sergejs
authors.initials: S
authors.lastname: Berdnikovs
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Silvio
authors.initials: S
authors.lastname: Favoreto
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Junqing
authors.initials: J
authors.lastname: Shen
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Assel
authors.initials: A
authors.lastname: Biyasheva
authors.affiliation: Sandler Asthma Basic Research (SABRE) Center Functional Genomics Core Facility, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Barbeau
authors.affiliation: Sandler Asthma Basic Research (SABRE) Center Functional Genomics Core Facility, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Eisley
authors.affiliation: Sandler Asthma Basic Research (SABRE) Center Functional Genomics Core Facility, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Barczak
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: Ward
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Schleimer
authors.affiliation: Sandler Asthma Basic Research (SABRE) Center Functional Genomics Core Facility, University of California San Francisco, San Francisco, CA, USA ; Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Erle
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Homer A
authors.initials: HA
authors.lastname: Boushey
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila