Modelling of individual subject ozone exposure response kinetics

Context: A better understanding of individual subject ozone (O₃) 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 O₃ 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 O₃-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 R² 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 O₃ exposure response kinetics and provides a potential starting point for improving the risk assessment of environmental O₃ exposure.