Alcohol Use Disorders Are Associated With a Unique Impact on Airways Epithelial Cell Gene Expression

Background Alcohol use disorders (AUDs) and cigarette smoking both increase risk for development of community-acquired pneumonia (CAP), likely through adverse effects on proximal airway mucociliary clearance and pathogen recognition. Smoking-related alterations on airways gene expression are well-described, but little is known about the impact of AUDs. We measured gene expression in human airways epithelial cells (AECs), hypothesizing that AUDs would be associated with novel differences in gene expression that could alter risk for CAP. Methods Bronchoscopy with airway brushings were performed in participants with AUDs and controls to obtain AECs. An Alcohol Use Disorders Identification Test was used to define AUD. RNA was extracted from AECs, and mRNA expression data were collected on an Agilent micro-array. Differential expression analyses were performed on the filtered and normalized data with correction for multiple testing. Enrichment analyses were performed using clusterProfiler. Results Expression data from 19 control and 18 AUD participants were evaluated. After adjustment for smoking, AUDs were associated with significant differential expression of 520 AEC genes, including genes for ribosomal proteins and genes involved in protein folding. Enrichment analyses indicated significant differential expression of 24 pathways in AUDs, including those implicated in protein targeting to membrane and viral gene expression. Smoking-associated AEC gene expression differences mirrored previous reports, but differed from those associated with AUDs. Conclusions AUDs have a distinct impact on AEC gene expression that may influence proximal airway function independent of smoking. Alcohol-associated alterations may influence risk for CAP through modifying key mechanisms important in protecting proximal airways integrity.