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A DYNAMIC NONLINEAR MODEL OF OZONE-INDUCED FEV1 RESPONSE UNDER CHANGING EXPOSURE CONDITIONS
Citation:
McDonnell, W. F., P. W. Stewart, AND M. V. Smith. A DYNAMIC NONLINEAR MODEL OF OZONE-INDUCED FEV1 RESPONSE UNDER CHANGING EXPOSURE CONDITIONS. Presented at American Thoracic Society Meeting, Seattle, WA, May 16-21, 2003.
Description:
A Dynamic Nonlinear Model of Ozone-induced FEV1 Response under Changing Exposure Conditions. 1WF McDonnell, 2PW Stewart, 3MV Smith. 1Human Studies Division, NHEERL, U.S. EPA, RTP, NC. 2University of North Carolina, Chapel Hill, NC. 3ASI, Durham, NC.
Ozone exposure results in FEV1 decrements which are a function of ozone concentration (C), minute ventilation, time, and age. We have previously identified a two-compartment dynamic exposure-response model which accurately predicted mean FEV1 change as a function of these variables for two-hour controlled ozone exposures. The purpose of the present analysis was to determine whether a similar, but improved, model could accurately describe FEV1 responses from an expanded group of 15 existing studies including some of longer duration, some with changing activity patterns, and some which include measures made during recovery in clean air. Participants were healthy, white males, ages 18-35 yrs., exposed under various conditions (C=0.0 to 0.4 ppm, activity level = rest to heavy exercise, exposure = 1 to 7 hrs, recovery = 0.5 to 3.3 hrs). A total of 3502 observations were provided by 547 participants. The data were successfully fit to the nonlinear mixed effects model using SAS proc NLMIXED with all coefficients observed to be statistically significant. Response decreased by 3.9% (95% CI = 1.8 to 6.1%) per year of increased age, and the time constant of the first compartment was 4.1 hr (95% CI = 3.6 to 4.6 hr). The model described the 3502 responses accurately with the exception of some underprediction at the highest dose rates. We concluded that this model was capable of accurately describing response to ozone across the range of conditions of these studies, and we hypothesize that it is capable of predicting FEV1 response over time as a result of the dynamic ozone exposure conditions experienced in the environment. This is an abstract of a proposed presentation and does not necessarily represent EPA policy.