Prediction of lung function response for populations exposed to a wide range of ozone conditions.
BACKGROUND
A human exposure-response (E-R) model previously 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.


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 version of the model that contains a threshold below which no response occurs 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 threshold model, however, provided a better fit to the data than the original, particularly at the lowest levels of exposure.


CONCLUSIONS
The models identified in this manuscript predict population FEV₁ response characteristics for 18-35-year-old individuals exposed to ozone over a wide range of conditions and represent a substantial improvement over earlier E-R models. Because of its better fit to the data, particularly at low levels of exposure, the threshold model is likely to provide more accurate estimates of risk in future risk assessments of ozone-induced FEV₁ effects.
William F McDonnell Consulting, Chapel Hill, NC, USA. McDonnell.William@Earthlink.Net
William F
WF
McDonnell
Paul W
PW
Stewart
Marjo V
MV
Smith
Chong S
CS
Kim
Edward S
ES
Schelegle
D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology*; D008171:Lung Diseases / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008954:Models, Biological; D017711:Nonlinear Dynamics; D010083:Oxidants, Photochemical / Q000008:administration & dosage / Q000633:toxicity*; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D018570:Risk Assessment / Q000379:methods; D013997:Time Factors; D014481:United States; D055815:Young Adult
D010083:Oxidants, Photochemical; D010126:Ozone