Serial Sampling of the Small Airway Epithelium to Identify Persistent Smoking-dysregulated Genes.
Academic Article
Overview
abstract
INTRODUCTION: The small airway epithelium (>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 small airway epithelium transcriptome is dynamic, fluctuating not only among smokers, but also within each smoker. OBJECTIVES: Accurate assessment of the smoking-related dysregulation of the human small airway epithelium despite the variation of smoking within the same individual, and of the effects of smoking cessation on the dysregulated transcriptome. METHODS: Serial sampling of the same smokers and nonsmoker controls over time to identify persistent smoking-dysregulation of the biology of the small airway epithelium over 1 yr. Serial sampling of smokers who quit smoking, before and after smoking cessation, to assess the effect of smoking cessation on the smoking-deregulated genes. MEASUREMENTS AND MAIN RESULTS: Repeated measures ANOVA of the small airway epithelium transcriptome sampled 4 times in the same individuals over 1 year enabled the identification of 475 persistent smoking-dysregulated genes. Most genes were normalized following 12 months of smoking cessation, however, 53 (11%) genes, including CYP1B1, PIR, ME1 and TRIM16 remained persistently abnormally expressed. Dysregulated pathways enriched with the non-reversible genes included xenobiotic metabolism signaling, bupropion degradation and nicotine degradation. CONCLUSIONS: Analysis of repetitive sampling of the same individuals identified persistent smoking-induced dysregulation of the small airway epithelium transcriptome and the effect of smoking cessation. These results help identify targets for the development of therapies that can be applicable to smoking-related airway diseases.
