Ambient Pollution Related Reprogramming of the Human Small Airway Epithelial Transcriptome.

RATIONALE: Epidemiological studies have demonstrated that exposure to particulate matter ambient pollution has adverse effects on lung health, exacerbated by cigarette smoking. Fine air-borne particles <2.5 μm (PM2.5) are among the most harmful urban pollutants, and are closely linked to respiratory disease.

OBJECTIVES: Based on the knowledge that the small airway epithelium (SAE) plays a central role in the pathogenesis of smoking-related lung disease, we hypothesized that elevated PM2.5 levels are associated with dysregulation of SAE gene expression.

METHODS: From 2009-2012, healthy nonsmoker (n=29) and smoker (n=129) residents of New York City (NYC) underwent bronchoscopy with SAE brushing (2.6 ± 1.3 samples/subject, total of 405 samples). SAE gene expression was assessed by Affymetrix HG-U133 Plus 2.0 microarray. NYC PM2.5 levels (Environmental Protection Agency data) were averaged for the 30 days prior to bronchoscopy. A linear mixed model was used to assess PM2.5-related gene dysregulation accounting for multiple clinical and methodologic variables with multiple test correction to assess significance.

MEASUREMENTS AND MAIN RESULTS: Thirty-day mean PM2.5 levels varied from 6.2-18 µg/m3. In nonsmokers, there was no dysregulation of SAE gene expression associated with ambient PM2.5 levels. In marked contrast, n=219 genes were significantly dysregulated in association with PM2.5 levels in the SAE of smokers. Many of these genes relate to cell growth and transcription regulation. Interestingly, 11% of genes were mitochondria-associated.

CONCLUSIONS: PM2.5 exposure contributes to significant dysregulation of the SAE transcriptome of smokers, linking pollution and airway epithelial biology in the risk of development of respiratory disease in susceptible individuals.