Journal Article

Biologic Phenotyping of the Human Small Airway Epithelial Response to Cigarette Smoking

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

2011

Overview

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. 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Airway management / Analysis / Biology / Biomarkers - metabolism / Bronchoscopy / Case-Control Studies / Cell cycle / Chronic obstructive lung disease / Chronic obstructive pulmonary disease / Cigarette smoking / Cigarettes / Critical care / Development and progression / DNA microarrays / Epithelium / Epithelium - drug effects / Female / Gene expression / Gene Expression Profiling / Gene Expression Regulation / Genes / Genomes / Genomics / Health care / Human behavior / Humans / Lung cancer / Lung diseases / Male / Medicine / Middle Aged / Obstructive lung disease / Oligonucleotide Array Sequence Analysis / Pathogenesis / Phenotype / Phenotyping / Pulmonary Disease, Chronic Obstructive - etiology / Pulmonary Disease, Chronic Obstructive - pathology / Respiratory Mucosa - drug effects / Respiratory tract / Smokers / Smoking / Smoking - adverse effects / Smoking cessation / Subgroups