Ozone is an air pollutant formed in at ground level by the chemical reaction between oxygen
and automobile emissions in the presence of sunlight. The objective of this research is to
determine how lung size, chemical composition, and normal functioning of the respiratory
system affect the amount of inhaled ozone that reaches internal sites of tissue irritation
and damage. To infer the distribution of inhaled ozone within the respiratory system,
measurements of ozone concentration and air flow are made just outside the nose and mouth of
healthy subjects who breathe laboratory-generated, ozonated air for about one hour.
Biochemical composition of respiratory mucus is then inferred from nasal washings made with
salt water. The amount of ozone that a subject retains in one of these experiments is less
than the daily exposure in a large city such as New York or Los Angeles.
Ozone is a ground-level air pollutant generated primarily by the photochemical reaction of
automobile emissions. The primary objective of this research is to determine the mechanism
by which anatomical, physiological, and biochemical factors influence the longitudinal
distribution of respiratory ozone dose that is delivered to respiratory tissue during a
particular exposure condition. The specific aims are: 1) test the hypothesis that an
increase in respiratory flow increases the sensitivity of ozone dose to antioxidant levels
in the epithelial lining fluid. Ozone absorption will be measured in the nose of healthy
nonsmokers at different nasal flows while antioxidant levels are measured in nasal liquid;
2) test the hypothesis that the continuous inhalation of ozone and co-pollutant gases
affects antioxidant levels in the epithelial lining fluid, thereby modulating the ozone
dose. Ozone absorption and antioxidant levels in nasal lavage will be intermittently
measured in the nose of healthy nonsmokers while these subjects are continuously exposed to
clean air, ozone, nitrogen dioxide or sulfur dioxide during quiet nasal breathing for two
hours; 3) test the hypothesis that antioxidant concentrations in epithelial lining fluid are
directly related to plasma concentrations so that ozone absorption are modulated by the
appropriate pharmacological or dietary interventions. The longitudinal distribution of ozone
absorption will be measured throughout the conducting airways of healthy nonsmokers during
quiet nasal breathing. Measurements will be repeated at baseline conditions, after using
probenecid to pharmacologically reduce systemic urate, and after vitamin C supplementation
to increase systemic ascorbate; 4) quantify the reaction kinetics between ozone and
antioxidants in epithelial lining fluid. Samples of nasal liquid will be reacted with a
controlled flow of ozone in a miniature bioreactor to determine the reaction rate constant
and reaction order of ozone consumption; and 5) further develop a single-path diffusion
model. Respiratory absorption as well as in vitro reaction kinetics data will be used to
validate a mathematical ozone dosimetry model that can predict the longitudinal distribution
of ozone dose to airway tissue.
A subject will be enrolled in the study only if he or she: has not smoked within the past
3 years; and does not have hay fever, asthma, allergic rhinitis, nasal breathing disorders
or anatomical abnormalities, chronic respiratory disease, or any other chronic diseases.
Women will not be included in the study if they are pregnant. Subjects who regularly take
mediation will be excluded from the study.