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Modelling of individual subject ozone exposure response kinetics.
CONTEXTA 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.
OBJECTIVETo develop a simple two compartment exposure-response model that describes individual subject decrements in forced expiratory volume in one second (FEV(1)) induced by the acute inhalation of O(3) lasting up to 8 h.
METHODSFEV(1) 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 FEV(1) of the 220 subjects were used for validation of the model. Further validation was provided by comparing the observed O(3)-induced FEV(1) decrements in an additional eight studies with predicted values obtained using model coefficients estimated from the 220 subjects used in cross validation.
RESULTSOverall the individual subject measured and modeled FEV(1) 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 FEV(1).
CONCLUSIONThis 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.
Inhalation toxicology 24:7 2012 Jun pg 401-15
Clinical Trials as Topic
Dose-Response Relationship, Drug
Forced Expiratory Volume
Pub Type(s)Journal Article
Research Support, Non-U.S. Gov't