title: Transcriptional phenotypes of asthma defined by gene expression profiling of induced sputum samples.
abstract: BACKGROUND
  Previous studies have identified clinical or inflammatory phenotypes of asthma on the basis of clinical and demographic parameters or sputum cell counts; however, few studies have defined transcriptional phenotypes of asthma.
  
  
  OBJECTIVE
  To investigate asthma phenotypes at a transcriptional level by using gene expression profiling of induced sputum.
  
  
  METHODS
  Induced sputum samples were collected from 59 people with asthma with a mean age of 58 years and an FEV(1)% predicted of 76%, and 69% were taking inhaled corticosteroids. Thirteen healthy controls without asthma were also assessed. Inflammatory cell counts were performed, and RNA was extracted from selected sputum. Transcriptional profiles were generated (Illumina Humanref-8 V2) and analyzed by using GeneSpring GX11.
  
  
  RESULTS
  Unsupervised hierarchical clustering of gene expression profiles in asthma revealed 3 distinct groups. The first transcriptional phenotype (n = 21) had lower FEV(1)% predicted and higher asthma control questionnaire scores, exhaled nitric oxide, and sputum eosinophils. The second transcriptional phenotype (n = 14) had lower FEV(1)% predicted and forced vital capacity % predicted and higher sputum neutrophils compared with a third transcriptional phenotype (n = 24) that had higher sputum macrophages and resembled healthy controls. Differentially expressed genes between transcriptional asthma phenotypes were related to inflammatory and immune responses. Genes in the IL-1 and TNF-α/nuclear factor-κB pathways were overexpressed and correlated with clinical parameters and neutrophilic airway inflammation.
  
  
  CONCLUSIONS
  Gene expression profiling provides a novel means to investigate the molecular mechanisms and classifications of asthma phenotypes. There are 3 distinct transcriptional phenotypes of asthma that relate to both clinical and inflammatory parameters.
authors.affiliation: Centre for Asthma and Respiratory Diseases, Hunter Medical Research Institute, University of Newcastle, Callaghan, Australia. katherine.baines@newcastle.edu.au
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Baines
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Simpson
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Wood
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gibson
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000096:biosynthesis / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012129:Respiratory Function Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013183:Sputum / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D007375:Interleukin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha