Gamma tocopherol chemoprevention of wood smoke PM2.5-induced airway inflammation

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 DESCRIPTION (provided by applicant): Wood smoke particles (WSP) derived from wildland and other fires produce a significant fraction of ambient air particulate matter. Health effects associated with WSP include acute bronchitis, asthma exacerbation, pneumonia, cough and systemic inflammation in in healthy persons and those with asthma. Cardiovascular effects have also been reported with WSP exposure. WSP from wildland fires can cause abrupt increases in ambient air PM 2.5 levels, and avoidance of rapidly increasing PM air pollution is not feasible as many residents cannot leave the burn region, and wildland firefighters move into wildland fire sites, often for several consecutive days. As avoidance of PM is not feasible in these settings, there is a clear unmet need for interventions to reduce adverse health effects caused by acute WSP exposure. Our team has developed gamma tocopherol (gT), an isoform of vitamin E with robust anti-inflammatory actions, as a chemopreventive intervention for inflammation caused by environmental contaminants. Our animal studies show that gT inhibits allergen, ozone and endotoxin-induced airway inflammation. Our human phase I studies show that gT decreases inflammatory response of circulating monocytes, decreases nitrosative stress, and inhibits neutrophil (PMN) influx to the airway in vivo after endotoxin challenge. Thus, gT supplementation is an attractive nutritional/nutraceutical approach to decreasing the adverse health effects of inhaled WSP. We have also developed a 500µg/m3 WSP exposure protocol which induces both airway and systemic increases in PMNs in human volunteers. Using this challenge protocol, we will undertake a randomized, placebo-controlled study to determine if of supplementation with 1200 mg of on WSP-induced airway and systemic PMN increases in healthy and asthmatic volunteers. Exploratory endpoints will include non-specific bronchial reactivity (NSBR), and cardiovascular responses reported to be impacted by PM exposure. These studies will also allow us to compare responses of allergic asthmatic (AA) and healthy volunteers (HV) to determine if atopy or other facets of asthma modify risk for inflammatory response to WSP. This study will be the first to test a specific nutritional supplement as a chemopreventive intervention for WSP-induced inflammation in either AAs or NVs, and to specifically compare the response of these groups to WSP-induced inflammation.