title: The impact of allergic rhinitis and asthma on human nasal and bronchial epithelial gene expression.
abstract: BACKGROUND
  The link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium.
  
  
  OBJECTIVE
  Defining gene expression profiles of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles.
  
  
  METHODS
  This cross-sectional study included 18 subjects (6 allergic asthma and allergic rhinitis; 6 allergic rhinitis; 6 healthy controls). The estimated false discovery rate comparing 6 subjects per group was approximately 5%. RNA was extracted from isolated and cultured epithelial cells from bronchial brushings and nasal biopsies, and analyzed by microarray (Affymetrix U133+ PM Genechip Array). Data were analysed using R and Bioconductor Limma package. For gene ontology GeneSpring GX12 was used.
  
  
  RESULTS
  The study was successfully completed by 17 subjects (6 allergic asthma and allergic rhinitis; 5 allergic rhinitis; 6 healthy controls). Using correction for multiple testing, 1988 genes were differentially expressed between healthy lower and upper airway epithelium, whereas in allergic rhinitis with or without asthma this was only 40 and 301 genes, respectively. Genes influenced by allergic rhinitis with or without asthma were linked to lung development, remodeling, regulation of peptidases and normal epithelial barrier functions.
  
  
  CONCLUSIONS
  Differences in epithelial gene expression between the upper and lower airway epithelium, as observed in healthy subjects, largely disappear in patients with allergic rhinitis with or without asthma, whilst new differences emerge. The present data identify several pathways and genes that might be potential targets for future drug development.
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Ariane H
authors.initials: AH
authors.lastname: Wagener
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Silvia
authors.initials: S
authors.lastname: Luiten
authors.forename: Wytske J
authors.initials: WJ
authors.lastname: Fokkens
authors.forename: Elisabeth H
authors.initials: EH
authors.lastname: Bel
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
authors.forename: Cornelis M
authors.initials: CM
authors.lastname: van Drunen
mesh_terms: D000328:Adult; D001249:Asthma / Q000235:genetics*; D001980:Bronchi / Q000378:metabolism*; D003430:Cross-Sectional Studies; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D009297:Nasal Mucosa / Q000378:metabolism*; D065631:Rhinitis, Allergic / Q000235:genetics*