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Prediction of lung function response for populations exposed to a wide range of ozone conditions
Citation:
McDonnell, W., P. Stewart, M. Smith, C. Kim, AND E. Schelegle. Prediction of lung function response for populations exposed to a wide range of ozone conditions. INHALATION TOXICOLOGY. Informa Healthcare USA, New York, NY, 24(10):619-633, (2012).
Impact/Purpose:
The purposes of this study were to 1) merge the individual exposure and response measures from the three datasets into a single analysis dataset; 2) develop several models that are related to our original model form and that incorporate a threshold; 3) fit the original model form as well as threshold models to the combined dataset; 4) evaluate the agreement between mean observed responses and mean population predicted responses for the original model form as well as threshold models; and 5) evaluate the agreement between the observed and predicted proportions of individuals experiencing a 10%, 15%, and 20% FEV1 decrement and the observed proportions.
Description:
Abstract Context: A human exposure-response (E-R) model that has previously been demonstrated to accurately predict population mean FEV1 response to ozone exposure has been proposed as the foundation for future risk assessments for ambient ozone. Objective: Fit the original and related models to a larger data set with a wider range of exposure conditions and assess agreement between observed and population mean predicted values. Materials and Methods: Existing individual E-R data for 23 human controlled ozone exposure studies with a wide range of concentrations, activity levels, and exposure patterns have been obtained. The data were fit to the original model and to a modified version of the model using a statistical program for fitting nonlinear mixed models. Results: Mean predicted FEV1 responses and the predicted proportions of individuals experiencing FEV1 responses greater than 10%, 15%, and 20% were found to be in agreement with observed responses across a wide range of exposure conditions for both models. The modified model that contains a threshold exposure below which no response was observed appeared to fit the data better than the original. Conclusion: The models identified in this manuscript predict population FEV1 response characteristics for 18-35 year olds exposed to ozone over a wide range of conditions. Use of either of these models in future risk assessments of ozone-induced FEV1 effects would represent a substantial improvement over previously used models.