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Organic pollutants factor in Asthma risk
Changes in immune cell gene regulation brought on by exposure to organic chemical pollutants appear to be a factor in childhood asthma risk.
In a cohort of children and teens living in Fresno, Calif., which is a city with an unusually high asthma prevalence, high levels of exposure to polycyclic aromatic hydrocarbons (PAHs) correlated significantly with methylation of the FoxP3 gene in regulatory T cells, and also with increased levels of total serum IgE and risk of an asthma diagnosis, said Arunima Kohli of Stanford University in Stanford, Calif.
Speaking at the American Academy of Allergy, Asthma, and Immunology’s annual meeting, Kohli told attendees that the study was important in tying together three elements previously known to affect asthma risk: environmental exposures, epigenetics in regulatory T cells, and excessive immune activity as reflected in high levels of IgE.
The study involved 153 youths, ages 10 to 18, residing in Fresno. The region is notorious for heavy air pollution as it is criss-crossed with major highways and sits in a deep valley that is a major center of industrial agriculture. Kohli cited statistics showing Fresno in the top five U.S. cities for particulate and ground-level ozone concentrations.
At a press conference held prior to Kohli’s presentation, senior investigator Kari Nadeau, MD, also at Stanford, explained that the research team focused on Fresno for precisely those reasons, as well as its high rate of asthma prevalence — about 22% compared with a California statewide average of 12%.
Fresno residents also show very high rates of allergy as well, she said, with up to 70% of the population reporting an allergy at some point in their lives, more than twice the state average.
The researchers hypothesized that levels of exposure to PAH compounds, such as benzopyrene and coronene, would correlate significantly with methylation of the FoxP3 gene in peripheral blood immune cells and with decreased regulatory T cell activity.
Both were borne out in the study.
The authors estimated PAH exposures over time for individual study participants, based on where they lived, using data from monitoring stations in the Fresno area and a published air pollution dispersion model.
Participants also underwent spirometry and provided blood samples for the FoxP3 methylation and serum IgE assays.
Mean age of the participants was 14. About 45% were boys, 7% had allergic rhinitis, and 25% had asthma. The mean level of total IgE was 109 kU/L.
A plot of cumulative 3-month PAH exposure against an index of FoxP3 methylation showed a significant positive correlation, with a slope of 0.09 (95% CI 0.07 to 0.11) and an R2 value of 0.3829, Kohli reported.
PAH exposure also correlated negatively with regulatory T cell function in a standard assay, with a slope of -0.14 (95% CI -0.16 to -0.11) and an R2 value of 0.5051.
The relationship between PAH exposure and serum IgE was even stronger: slope 0.78 (95% CI 0.69 to 0.87) and R2 of 0.6772.
Kohli said that analysis using estimated 6- and 12-month PAH exposures showed similar results.
Finally, the analysis showed a significant association (P<0.05) between 3-month PAH exposure and the probability of an asthma diagnosis. Individuals with exposures of 600 ng/m3 had a risk of asthma diagnosis approaching 60%, compared with a risk less than 25% for those with cumulative exposures of 200 ng/m3. Total IgE also correlated positively with asthma risk.
The study was funded by the Environmental Protection Agency and the National Institute of Environmental Health Sciences.
Kohli and Nadeau declared they had no relevant financial interests.
