Environmentally Persistent Free Radicals Alter Pulmonary Immunologic Homeostasis

Dr. Stephania Cormier

 

Asthma affects 300 million people worldwide, and its prevalence has been steadily increasing. Epidemiological data demonstrate associated increases in particulate matter (PM) with increases in acute asthma exacerbations and the risk of developing asthma; however, the reasons for these increases are poorly understood. Dr. Cormier's research group seeks to establish the mechanism by which exposure to PM from Superfund sites modulates pulmonary immune homeostasis and results in the development of asthma. The presence of a newly realized class of pollutants, environmentally persistent free radicals (EPFRs), in contaminated soils at Superfund sites and PM from combustion and thermal treatment of hazardous substances suggests a potentially unrecognized risk factor for the development and/or exacerbation of asthma.

 

The major goals of the project are to:

  1. Define the immunological and pathophysiological impact of acute and chronic inhalation exposures to environmentally persistent free radicals (EPFRs) on normal and diseased lungs.
  2. Characterize the impact of exposure to EPFRs on pulmonary DC responses.
  3. Illustrate the role of the Th17 T lymphocyte subset in EPFR-induced asthma.

We have made a number of important discoveries in the past few years.  First, we continue to demonstrate that EPFRs associated with PM from thermal remediation sources or other combustion processes elicit the adverse health effects and not the particle. Traditional methods of analyzing PM (i.e. solvent extraction) results in the conversion of EPFRs to their molecular species suggesting that they are being misidentified as molecular pollutants or worse, not being detected at all.  We have identified EPFRs in PM from combustion of electronic wastes, in situ burning of oil from the Gulf Oil Spill, and even in electronic cigarette vapor.  Thus, we believe that EPFRs represent a new paradigm for the human health impacts of environmental PM.  Second, we have demonstrated that EPFRs induced the recruitment and activation of cells to the lungs, which in humans correlates with a severe form of asthma that is resistant to steroid therapy.  We continue to explore the mechanisms responsible for this type of asthma to identify therapeutics and provide data demonstrating a need to reduce exposures to EPFRs.