Dataset Information

Ambient Pollution-related Reprogramming of the Human Small Airway Epithelial Transcriptome.

ABSTRACT:

Rationale

Epidemiologic 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 (PM_2.5) is among the most harmful urban pollutants and is 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 PM_2.5 levels are associated with dysregulation of SAE gene expression, which may contribute to the development of respiratory disease.

Methods

From 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 PM_2.5 levels (Environmental Protection Agency data) were averaged for the 30 days before bronchoscopy. A linear mixed model was used to assess PM_2.5-related gene dysregulation accounting for multiple clinical and methodologic variables.

Measurements and main results

Thirty-day mean PM_2.5 levels varied from 6.2 to 18 μg/m³. In nonsmokers, there was no dysregulation of SAE gene expression associated with ambient PM_2.5 levels. In marked contrast, n = 219 genes were significantly dysregulated in association with PM_2.5 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

PM_2.5 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.

SUBMITTER: O'Beirne SL

PROVIDER: S-EPMC6290954 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ambient Pollution-related Reprogramming of the Human Small Airway Epithelial Transcriptome.

O'Beirne Sarah L SL Shenoy Sushila A SA Salit Jacqueline J Strulovici-Barel Yael Y Kaner Robert J RJ Visvanathan Sudha S Fine Jay S JS Mezey Jason G JG Crystal Ronald G RG

American journal of respiratory and critical care medicine 20181201 11

<h4>Rationale</h4>Epidemiologic 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 (PM<sub>2.5</sub>) is among the most harmful urban pollutants and is closely linked to respiratory disease.<h4>Objectives</h4>Based on the knowledge that the small airway epithelium (SAE) plays a central role in the pathogenesis of smoking-relate ...[more]

PMID: 29897792

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Project description:BackgroundAlthough ambient air pollution has been linked to reduced lung function in healthy children, longitudinal analyses of pollution effects in asthmatic patients are lacking.ObjectiveWe sought to investigate pollution effects in a longitudinal asthma study and effect modification by controller medications.MethodsWe examined associations of lung function and methacholine responsiveness (PC20) with ozone, carbon monoxide (CO), nitrogen dioxide, and sulfur dioxide concentrations in 1003 asthmatic children participating in a 4-year clinical trial. We further investigated whether budesonide and nedocromil modified pollution effects. Daily pollutant concentrations were linked to ZIP/postal code of residence. Linear mixed models tested associations of within-subject pollutant concentrations with FEV1 and forced vital capacity (FVC) percent predicted, FEV1/FVC ratio, and PC20, adjusting for seasonality and confounders.ResultsSame-day and 1-week average CO concentrations were negatively associated with postbronchodilator percent predicted FEV1 (change per interquartile range, -0.33 [95% CI, -0.49 to -0.16] and -0.41 [95% CI, -0.62 to -0.21], respectively) and FVC (-0.19 [95% CI, -0.25 to -0.07] and -0.25 [95% CI, -0.43 to -0.07], respectively). Longer-term 4-month CO averages were negatively associated with prebronchodilator percent predicted FEV1 and FVC (-0.36 [95% CI, -0.62 to -0.10] and -0.21 [95% CI, -0.42 to -0.01], respectively). Four-month averaged CO and ozone concentrations were negatively associated with FEV1/FVC ratio (P < .05). Increased 4-month average nitrogen dioxide concentrations were associated with reduced postbronchodilator FEV1 and FVC percent predicted. Long-term exposures to sulfur dioxide were associated with reduced PC20 (percent change per interquartile range, -6% [95% CI, -11% to -1.5%]). Treatment augmented the negative short-term CO effect on PC20.ConclusionsAir pollution adversely influences lung function and PC20 in asthmatic children. Treatment with controller medications might not protect but rather worsens the effects of CO on PC20. This clinical trial design evaluates modification of pollution effects by treatment without confounding by indication.

Dataset Information

Ambient Pollution-related Reprogramming of the Human Small Airway Epithelial Transcriptome.

Rationale

Objectives

Methods

Measurements and main results

Conclusions

Publications

Ambient Pollution-related Reprogramming of the Human Small Airway Epithelial Transcriptome.

Similar Datasets

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