Polycyclic aromatic hydrocarbon internal dose, oxidative stress, inflammation and asthma exacerbation in asthmatic adults and children in Baltimore City
Peters, Kamau O.
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Background: Asthma is a common chronic inflammatory respiratory disease that disproportionately affects children and African Americans residing in urban, low socioeconomic status communities. Polycyclic aromatic hydrocarbons (PAH) are products of incomplete combustion of organic materials and are found in gas phase, and on fine and ultrafine particulate matter (PM). In vitro, animal and human studies have shown PAHs to be associated with increased oxidative stress, allergen-mediated inflammatory responses and asthma exacerbation. Methods: In this study, we examined whether internal dose of PAHs (urinary 1-OHPG) was associated with early effect biomarkers of oxidative stress, inflammation, and asthma-related symptoms in the DISCOVER/Asthma-Diet study (children with asthma in Baltimore) and the Nasal Challenge to Indoor Particulate Matter study (adults with atopic asthma in Baltimore). Results: We found that children spending time in homes with low air nicotine concentrations showed inverse associations between time spent indoors and urinary 1-OHPG concentrations. In addition, time spent outdoors was independently associated with increased 1-OHPG in boys. Atopy modulated the associations between urinary 1-OHPG and peripheral blood eosinophils and neutrophils, with significantly stronger positive associations among atopic asthmatic children compared to non-atopic asthmatic children. Children with high urinary 1-OHPG concentrations were also at an increased risk for nighttime waking due to asthma symptoms and nighttime rescue medication use. We also found that GSTM1 genotype modified the associations between 1-OHPG and urinary isoprostane and serum and peripheral blood inflammatory biomarkers in adult atopic asthmatics, with significantly stronger positive associations among GSTM1-null participants compared to GSTM1-present participants. Conclusion: Our results suggest that exposures to second hand smoke, and combustion products in outdoor ambient air are major contributors to internal dose of PAHs in inner city children. In addition, PAH exposures may contribute to allergen-mediated systemic inflammatory responses (with possible adjuvant effects by PAHs in atopic asthmatics), and to asthma exacerbation in inner city children with asthma. Our results also suggest that PAH exposures contribute to increased local and systemic inflammation in adults with atopic asthma in Baltimore, and that individuals with the GSTM1-null polymorphism may be more susceptible to inflammatory responses associated with PAH exposures, due to reduced antioxidant capacity.