Modelling of individual subject ozone exposure response kinetics.
BACKGROUND
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 (FEV(1)) induced by the acute inhalation of O(3) lasting up to 8 h.


METHODS
FEV(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.


RESULTS
Overall 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).


CONCLUSIONS
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.
Department of Anatomy, Physiology and Cell Biology, University of California, School of Veterinary Medicine, Davis, CA 95616, USA. esschelegle@ucdavis.edu
Edward S
ES
Schelegle
William C
WC
Adams
William F
WF
Walby
M Susan
MS
Marion
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects*; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D010126:Ozone / Q000633:toxicity*; D055815:Young Adult
D000393:Air Pollutants; D010126:Ozone