Modelling of individual subject ozone exposure response kinetics

Context: A better understanding of individual subject ozone (O-3) exposure response kinetics will provide insight into how to improve models used in the risk assessment of ambient ozone exposure. Objective: To develop a simple two compartment exposure-response model that describes individual subject decrements in forced expiratory volume in one second (FEV1) induced by the acute inhalation of O-3 lasting up to 8 h. Methods: FEV1 measurements of 220 subjects who participated in 14 previously completed studies were fit to the model using both particle swarm and nonlinear least squares optimization techniques to identify three subject-specific coefficients producing minimum global and local errors, respectively. Observed and predicted decrements in FEV1 of the 220 subjects were used for validation of the model. Further validation was provided by comparing the observed O-3-induced FEV1 decrements in an additional eight studies with predicted values obtained using model coefficients estimated from the 220 subjects used in cross validation. Results: Overall the individual subject measured and modeled FEV1 decrements were highly correlated (mean R-2 of 0.69 +/- 0.24). In addition, it was shown that a matrix of individual subject model coefficients can be used to predict the mean and variance of group decrements in FEV1. Conclusion: This modeling approach provides insight into individual subject O-3 exposure response kinetics and provides a potential starting point for improving the risk assessment of environmental O-3 exposure.