Does Diesel Exhaust Exposure Alter Epigenetic Signatures in Individuals with Specific Allergies? A Translational Study to Understand the Role of Particulate Matter.

Asthma is a chronic lung disease affecting more than 2.8 million Canadians. It is estimated that numbers may rise to 400 million globally by 2025, substantially increasing both human and financial costs.

One possible explanation is that environmental exposures, including diesel exhaust (DE) air pollution (which usually increases as countries develop), may synergize with inhaled allergens in both the development and worsening of asthma, often leading to “lung attacks.” Exposure to air pollution may affect healthy gene expression in the lungs through “epigenetic modifications,” which change how cells “read” DNA. In preliminary studies, we confirmed that DE exposure caused numerous epigenetic changes, but we still need to understand how this causes the worsening of asthma symptoms. Moreover, we do not understand which components of DE (gases or particles) are driving these changes and which are more harmful. Therefore, I will leverage a state-of-the-art human exposure chamber and an ongoing clinical study to determine whether exposure to DE (with or without particles) and specific allergens affects epigenetics and gene expression.

Healthy and mild asthmatic volunteers will be recruited; over the course of four randomly-ordered visits (each separated by a month), they will be exposed for two hours to filtered air, DE, or particle-depleted DE, followed by inhalation of volunteer specific allergen or salt water. After 48 hours, cells lining the lungs will be collected and genetic material will be analysed.

Parallel to this clinical study, I will perform basic research experiments exposing lung cells to DE, and investigate the mechanisms through which these changes may occur. In addition, these experiments will examine how DE alters responses to asthma therapies and thereby the risk of “lung attacks.”

These studies may contribute biological plausibility and deepen our mechanistic understanding of emerging epidemiology, suggesting a role for air pollution in “lung attacks,” asthma development, and clinical outcomes.