title: Biologic phenotyping of the human small airway epithelial response to cigarette smoking.
abstract: BACKGROUND
  The first changes associated with smoking are in the small airway epithelium (SAE). Given that smoking alters SAE gene expression, but only a fraction of smokers develop chronic obstructive pulmonary disease (COPD), we hypothesized that assessment of SAE genome-wide gene expression would permit biologic phenotyping of the smoking response, and that a subset of healthy smokers would have a "COPD-like" SAE transcriptome.
  
  
  RESULTS
  SAE (10th-12th generation) was obtained via bronchoscopy of healthy nonsmokers, healthy smokers and COPD smokers and microarray analysis was used to identify differentially expressed genes. Individual responsiveness to smoking was quantified with an index representing the % of smoking-responsive genes abnormally expressed (I(SAE)), with healthy smokers grouped into "high" and "low" responders based on the proportion of smoking-responsive genes up- or down-regulated in each smoker. Smokers demonstrated significant variability in SAE transcriptome with I(SAE) ranging from 2.9 to 51.5%. While the SAE transcriptome of "low" responder healthy smokers differed from both "high" responders and smokers with COPD, the transcriptome of the "high" responder healthy smokers was indistinguishable from COPD smokers.
  
  
  CONCLUSIONS
  The SAE transcriptome can be used to classify clinically healthy smokers into subgroups with lesser and greater responses to cigarette smoking, even though these subgroups are indistinguishable by clinical criteria. This identifies a group of smokers with a "COPD-like" SAE transcriptome.
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Tilley
authors.forename: Timothy P
authors.initials: TP
authors.lastname: O'Connor
authors.forename: Neil R
authors.initials: NR
authors.lastname: Hackett
authors.forename: Yael
authors.initials: Y
authors.lastname: Strulovici-Barel
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Salit
authors.forename: Nancy
authors.initials: N
authors.lastname: Amoroso
authors.forename: Xi Kathy
authors.initials: XK
authors.lastname: Zhou
authors.forename: Tina
authors.initials: T
authors.lastname: Raman
authors.forename: Larsson
authors.initials: L
authors.lastname: Omberg
authors.forename: Andrew
authors.initials: A
authors.lastname: Clark
authors.forename: Jason
authors.initials: J
authors.lastname: Mezey
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D004848:Epithelium / Q000187:drug effects*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology* / Q000473:pathology; D020545:Respiratory Mucosa / Q000187:drug effects*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D015415:Biomarkers