People with preexisting airway disease (e.g., asthma, bronchitis, chronic obstructive pulmonary disease), have increased susceptibility to the adverse health effects of air pollution exposure. Human clinical studies demonstrate enhanced inflammatory and allergic responses in asthmatics exposed to ozone, a common pollutant of ambient air during summer months, and airborne endotoxin, a bacterial product present in bioaerosols in agricultural, offices, and household settings. The mechansims of air pollutant exacerbation of allergic airways is unknown, and commonly prescribed pharmaceuticals provide limited benefits. The goal of this research is to test the safety and efficacy of novel complementary alternative medicines (CAMs; e.g., vitamins E, C, polyphenols) that possess antioxidant properties, using allergic rodents exposed to ozone and endotoxin.
Our specific aims are to 1) to test the safety and pharmacokinetics of CAM compounds, 2) to test the hypothesis that CAM therapies inhibit allergic airway responses (inflammation, increased mucus storage and secretion) in allergic Brown Norway rats, 3) to test efficacy of CAMs in endotoxin-induced exacerbation of allergic airway responses, with and without co-treatment of commonly prescribed allergy medications, and 4) to test the efficacy of CAMs against ozone-induced augmentation of allergic responses, given alone in combination with traditional therapeutics. These studies are consistent with the goals of NCCAM to provide high quality data with regard to the safety, efficacy, and mechanism of action of CAM therapies that address an important environmental health problem which affects millions of Americans. This project provides an important scientific bridge between the discovery of potential CAM therapies from in vitro and cell culture systems, to the recommendations of effective CAM candidates for potential use human clinical studies. Furthermore, results from these animal studies may suggest other applications for antioxidant CAM therapies for airway diseases characterized by inflammation and oxidative stress.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Program Projects (P01)
Project #
5P01AT002620-03
Application #
7279761
Study Section
Special Emphasis Panel (ZAT1)
Project Start
Project End
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
3
Fiscal Year
2006
Total Cost
$286,900
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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Wang, Yun; Moreland, Michelle; Wagner, James G et al. (2012) Vitamin E forms inhibit IL-13/STAT6-induced eotaxin-3 secretion by up-regulation of PAR4, an endogenous inhibitor of atypical PKC in human lung epithelial cells. J Nutr Biochem 23:602-8
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Dillon, Madeline A; Harris, Bradford; Hernandez, Michelle L et al. (2011) Enhancement of systemic and sputum granulocyte response to inhaled endotoxin in people with the GSTM1 null genotype. Occup Environ Med 68:783-5

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