This proposal seeks to examine the hypothesis that pre-existing oxidant burden is a risk factor in the exacerbation of allergic asthma by ozone. The investigators propose that varying the level of oxidant stress present in asthma can alter an individual's susceptibility to oxidant- induce lung injury. The investigator's suggested that an individual with asthma will be closer to a critical threshold that oxidant exposure can then exceed. The hypothesis predicts that persons with allergic asthma vary in their susceptibility to the exacerbating effects of ozone and those subjects with the greatest susceptibility will have decreased antioxidant capacity and increased levels of cellular oxidative activity. To test this hypothesis two specific aims are presented. The first specific aim is to determine the relationship between measures of oxidant stress and the ozone-enhanced allergen responsiveness and/or non-specific airway reactivity. Resting and phorbol ester-stimulated oxidative activity will be determined in sputum-derived airway cells and in peripheral leukocytes using a luminol chemiluminescence assay. This will be accompanied by measurement of Trolox equivalent antioxidant capacity of plasma. Asthmatic subjects (n=24) will be exposed to ozone (2h X 0.25 ppm) with intermediate exercise or air (control). Airway function by bronchoprovocation followed by bronchial challenge with allergen will be assessed 18-21 hours later. The allergen dose to produce a 20% decrease in FEV1 and lung function (FEV and FVC) during the next 6-8 hours will be determined. The extent to which ozone exposure increases the response to allergen will be evaluated by comparison between the responses with and without ozone. Non-specific bronchial reactivity to methacholine will also be assessed. The second specific aim is to determine whether vitamin C can attenuate the ability of ozone to enhance responsiveness to allergen challenge after ozone. Subjects (n=10) will be given vitamin C (500mg X 4/d) or placebo for 3 days before ozone exposure. The level of cellular chemiluminescence and plasma Trolox equivalent antioxidant capacity will be determined before and after ingestion of vitamin C. Allergen challenge will again be conducted 18 hours following ozone exposure. This study's overall goal is to determine whether baseline oxidative state is a useful marker of risk for asthma exacerbation by oxidant pollutants, such as ozone.
