Biologic phenotyping of the human small airway epithelial response to cigarette smoking

Ann E. Tilley, Timothy P. O'Connor, Neil R. Hackett, Yael Strulovici-Barel, Jacqueline Salit, Nancy Amoroso, Xi Kathy Zhou, Tina Raman, Larsson Omberg, Andrew Clark, Jason Mezey, Ronald Crystal

Research output: Contribution to journalArticle

43 Citations (Scopus)

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. Methodology/Principal Findings: 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. Conclusion/Significance: 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.

Original languageEnglish
Article numbere22798
JournalPLoS One
Volume6
Issue number7
DOIs
Publication statusPublished - 2 Aug 2011
Externally publishedYes

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smoking (habit)
Tobacco Products
epithelium
Epithelium
Smoking
Pulmonary diseases
phenotype
Transcriptome
transcriptome
respiratory tract diseases
Chronic Obstructive Pulmonary Disease
Genes
Gene expression
bronchoscopy
Gene Expression
gene expression
genes
Bronchoscopy
Microarray Analysis
Microarrays

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Tilley, A. E., O'Connor, T. P., Hackett, N. R., Strulovici-Barel, Y., Salit, J., Amoroso, N., ... Crystal, R. (2011). Biologic phenotyping of the human small airway epithelial response to cigarette smoking. PLoS One, 6(7), [e22798]. https://doi.org/10.1371/journal.pone.0022798

Biologic phenotyping of the human small airway epithelial response to cigarette smoking. / Tilley, Ann E.; O'Connor, Timothy P.; Hackett, Neil R.; Strulovici-Barel, Yael; Salit, Jacqueline; Amoroso, Nancy; Zhou, Xi Kathy; Raman, Tina; Omberg, Larsson; Clark, Andrew; Mezey, Jason; Crystal, Ronald.

In: PLoS One, Vol. 6, No. 7, e22798, 02.08.2011.

Research output: Contribution to journalArticle

Tilley, AE, O'Connor, TP, Hackett, NR, Strulovici-Barel, Y, Salit, J, Amoroso, N, Zhou, XK, Raman, T, Omberg, L, Clark, A, Mezey, J & Crystal, R 2011, 'Biologic phenotyping of the human small airway epithelial response to cigarette smoking', PLoS One, vol. 6, no. 7, e22798. https://doi.org/10.1371/journal.pone.0022798
Tilley AE, O'Connor TP, Hackett NR, Strulovici-Barel Y, Salit J, Amoroso N et al. Biologic phenotyping of the human small airway epithelial response to cigarette smoking. PLoS One. 2011 Aug 2;6(7). e22798. https://doi.org/10.1371/journal.pone.0022798
Tilley, Ann E. ; O'Connor, Timothy P. ; Hackett, Neil R. ; Strulovici-Barel, Yael ; Salit, Jacqueline ; Amoroso, Nancy ; Zhou, Xi Kathy ; Raman, Tina ; Omberg, Larsson ; Clark, Andrew ; Mezey, Jason ; Crystal, Ronald. / Biologic phenotyping of the human small airway epithelial response to cigarette smoking. In: PLoS One. 2011 ; Vol. 6, No. 7.
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