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OZONE-INDUCED RESPIRATORY SYMPTOMS AND LUNG FUNCTION DECREMENTS IN HUMANS: EXPOSURE-RESPONSE MODELS
Citation:
McDonnell, W F., P. W. Stewart, AND M. Smith. OZONE-INDUCED RESPIRATORY SYMPTOMS AND LUNG FUNCTION DECREMENTS IN HUMANS: EXPOSURE-RESPONSE MODELS. Presented at NHEERL Symposium, Research Triangle Park, NC, June 6-8, 2000.
Description:
Short duration exposure to ozone (<8 hr) is known to result in lung function decrements and respiratory symptoms in humans. The magnitudes of these responses are functions of ozone concentration (C), activity level measured by minute ventilation (Ve), duration of exposure (T), and age. Considerable variability in response among individuals with similar exposures is evident and reproducible suggesting a large range in ozone responsiveness among the population. In order to conduct quantitative risk assessment with minimal uncertainty for short-term exposure to ozone and other respiratory irritants, one must identify an exposure-response (E-R) model which accurately predicts the distribution of the magnitudes of response (or the proportion of individuals experiencing a given response) across the range of ambient exposure scenarios and personal characteristics of interest. The purpose of this presentation is to describe such a model for ozone which may also be applicable to other respiratory irritants. Data were available for four hundred and eight-five healthy male volunteers (ages 18-35 yrs) who had previously been exposed for 2 hr to one of six ozone concentrations at one of three activity levels. Symptoms and forced expiratory volume in one second (FEV1) had been evaluated before and after 1 and 2 hr of exposure. A two compartment model which is consistent with known ozone E-R characteristics was identified. That is, the overall E-R curve was sigmoid-shaped, age was allowed to modify the E-R relationship, the sensitivity in response to changes in C, Ve, and T was allowed to differ, and the model allowed for recovery following exposure. This model can also provide predictions of response when C and Ve vary over time which is the case for most ambient exposures. The model was found to accurately describe the mean change in FEV1, the proportions of individuals reporting cough, shortness of breath, and pain on deep inspiration, and the proportions of individuals with an FEV1 decrement larger than 15% over the entire range of exposures (C=0.12-0.40 ppm, Ve=10-37 L/min, T=1-2 hr, and age = 18-35 yr). All responses were found to be significantly negatively related to age. We did not find that response was more sensitive to changes in C than in Ve. In summary, we have identified an E-R model which accurately predicts symptom and lung function changes as a function of concentration, minute ventilation, duration of exposure, and age for young adult males exposed to ozone. Such a model should be useful in conducting risk assessment for short-term exposures to ozone, and this modeling approach may be applicable to describing E-R characteristics for other respiratory irritants. This abstract does not necessarily reflect EPA policy.