Air Pollutant Transformation of Indoor Allergens

About This Grant

SUMMARY According to the World Health Organization, air pollution leads to 7 million premature deaths annually, ac- counting for 11% of global mortality. In the United States, 400-1,100 disability-adjusted life-years (DALY) per 100,000 people are lost due to indoor air pollutant exposure. Given that humans spend about 90% of their time inside, our primary chemical exposures occur indoors, whether from indoor activities or outdoor pollutants infil- trating buildings. Indoor dust is a well-studied chemical reservoir containing house dust mites (HDM), skin cells, pollen, soil, clothing fibers, hair, pet dander, and absorbed chemicals, making it a complex entity. HDM and their proteins are known allergens within house dust that can trigger allergic inflammatory responses in humans. However, there is limited understanding of how chemical alterations from reactive indoor pollutants affect HDM and HDM-sorbed chemicals, and subsequently, human health. Our recent research has indicated that exposure of HDM to ozone (a common indoor reactive gas and outdoor air pollutant) and diesel fuel chem- icals (found in homes near roadways where diesel exhaust is present) leads to increased oxidative potential of HDM. Using a mouse model of allergic airway inflammation (AAI), akin to human asthma, we demonstrated that chemically altered HDM exacerbates inflammation, correlating with increased production of allergic cyto- kines. Our central hypothesis is that chemical modifications to HDM from environmental pollutant ex- posure enhance their oxidative potential, resulting in more severe inflammation in an HDM model of AAI. To test this hypothesis, we propose two specific aims. In Aim 1, we will assess the chemical transfor- mations of Der p 1 (the major HDM allergen), HDM, and genuine house dust via chromatography-mass spec- trometry, and associated changes to each mixture’s oxidative potential via an acellular assay. We hypothesize that diesel fuel components will sorb to HDM and, when the mixture is exposed to ozone, it will undergo oxida- tion, altering both HDM-sorbed diesel hydrocarbons and HDM’s protein composition, thus increasing the mix- ture's oxidative potential. In Aim 2, we will evaluate the impact of chemically contaminated HDM on a mouse model of AAI. We hypothesize that HDM chemically transformed by diesel fuel components and ozone will worsen AAI and be associated with increased oxidative stress markers. Our approach includes comparing standard AAI measures, such as bronchoalveolar lavage cell counts, cytokine expression, and airway hyperre- sponsiveness in mice exposed to chemically-treated HDM versus HDM alone. We will define and validate key cell types and pathways involved by performing single-cell RNA-seq on lung tissues post-exposure. This study advances our understanding of indoor transformation chemistry of dust-sorbed chemicals and HDM, address- ing the health impacts of these chemically processed species at cellular and systemic levels.