Serial Sampling of the Small Airway Epithelium Over 1 Year in the Same Individuals to Identify “Public” Genes Commonly Dysregulated by Smoking [array]

Background: The small airway epithelium (SAE, >6th generations), the initiation site of smoking-induced airway disorders, is highly sensitive to the stress of smoking. Due to variations over time in smoking habits, the SAE transcriptome fluctuates not only among smokers, but within each smoker. Averaging the HG-U133 Plus 2.0 transcriptome sampled 4 times in the same individuals over 1 yr enabled the identification of “public” smoking-dysregulated genes, i.e., genes consistently dysregulated within each smoker and shared by most smokers. Using an independent cohort of smokers assessed before and after quitting smoking, it was possible to assess the effect of smoking cessation on the “public” genes over time and identify a subset of genes that remain persistently abnormally expressed despite 12 months of smoking cessation. These nonsmoker and smoker samples processed on Affymetrix HG-U133 Plus 2.0 mcroarrays were used as the "replication cohort 1" for the consensus genes that were identified in a study of HG-U133 Plus 2.0 expression from small airway epithelium sampled 4 times in the same individuals over 1 yr to identify genes consistently dysregulated within each smoker and shared by most smokers.