Ambient Pollution Related Reprogramming of the Human Small Airway Epithelial Transcriptome

Epidemiological studies have demonstrated that exposure to particulate matter (PM) ambient pollution has adverse effects on lung health, exacerbated by cigarette smoking. Fine airborne particles <2.5 µm (PM2.5) are the most harmful of the urban pollutants, and the most closely linked to respiratory disease. Based on the knowledge that the small airway epithelium (SAE) plays a central role in pathogenesis of smoking-related lung disease, we hypothesized that elevated PM2.5 levels are associated with dysregulation of SAE gene expression. From 2009-2012, healthy nonsmoker (n=29) and smoker (n=129), residents of New York City (NYC) underwent serial bronchoscopy with SAE brushing (2.6 ± 1.3 procedures/subject, total of 405 samples) over 12 months. PM2.5 levels varied from 6.2-18 μg/m3. SAE gene expression was assessed by Affymetrix HG-U133_Plus_2 microarray. SAE gene expression was modeled as a linear function of 30-day mean NYC PM2.5 levels over the same time period. Significance was calculated by two-sided Wald test, reflecting the probability that the regression coefficient for the pollution variable was non-zero. PM2.5-related gene dysregulation was quantified using Benjamini-Hochberg correction. In non-smokers, there was no dysregulation associated with ambient PM2.5 levels. In marked contrast, n=180 genes were significantly dysregulated in association with PM2.5 levels in smokers.