Although it is well known that exposure to ambient 03 induces respiratory irritation and decrements in pulmonary function, there is little information available as to the mechanism(s) of these responses in humans. There is some evidence from animal studies (primarily dogs) that cholinergic pathways are involved, although it is clear that more than one mechanism is involved. Other possible mechanisms include alpha-adrenergic and H-1 histamine receptors, and prostaglandin release. This study is designed to investigate which receptors/pathways/ neurotransmitters are involved. The information obtained will not only clarify the mechanisms involved in the responses to 03 exposure, but will also help to explain why there is such a wide range of individual responses to 03, and why older adults seem to be less responsive to On than young adults. The subjects will be non-smoking young adults, 18-30 years of age (N=40), and nonsmoking older adults, over 60 years of age (N=20), They will participate in 8 experiments. Experiments will be conducted in an environmental chamber, where subjects will be exposed to 0.35 PPM 03 7 times, and to filtered air once for two hours. All subjects will follow an intermittent exercise protocol at a minute ventilation of 35 L/min. Subjects will be pre-treated with one of five pharmacological agents used in treating asthma (which has been considered a model of 03-induced airway hyperresponsiveness) prior to 5 of the exposures: (1) albuterol, (2) ipratropium bromide, (3) beclomethasone, (4) cromolyn sodium, and (5) terfenadine. The subjects will also be exposed to 0.35 ppm 03 once with no pre-treatment, and once pretreated with inhaled physiological saline, as baseline and placebo conditions.
