• Sarah L O'Beirne, Sushila A Shenoy, Jacqueline Salit, Yael Strulovici-Barel, Robert J Kaner, Sudha Visvanathan, Jay S Fine, Jason G Mezey, and Ronald G Crystal.
• 1 Department of Genetic Medicine and.
• Am. J. Respir. Crit. Care Med. 2018 Dec 1; 198 (11): 141314221413-1422.

RationaleEpidemiologic studies have demonstrated that exposure to particulate matter ambient pollution has adverse effects on lung health, exacerbated by cigarette smoking. Particulate matter less than or equal to 2.5 μm in aerodynamic diameter (PM2.5) is among the most harmful urban pollutants and is closely linked to respiratory disease.ObjectivesBased 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, which may contribute to the development of respiratory disease.MethodsFrom 2009 to 2012, healthy nonsmoker (n = 29) and smoker (n = 129) residents of New York City 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. New York City PM2.5 levels (Environmental Protection Agency data) were averaged for the 30 days before bronchoscopy. A linear mixed model was used to assess PM2.5-related gene dysregulation accounting for multiple clinical and methodologic variables.Measurements And Main ResultsThirty-day mean PM2.5 levels varied from 6.2 to 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.ConclusionsPM2.5 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.

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