UBC Theses and Dissertations
Sensitivity of exposure-response relationships to exposure assessment strategies in retrospective cohort studies Friesen, Melissa Charmaine
Introduction: Exposure misclassification in epidemiologic studies results in attenuated exposure-response relationships. Using quantitative exposure estimates helps reduce exposure misclassification in retrospective studies, but it does not eliminate it. This study focused on two areas that impact the degree of exposure misclassification inherent in quantitative exposure estimates: (1) the choice of exposure indicator where the exposure of interest is a component of a mixture; (2) the choice between expert judgment and measurement-based exposure assessment strategies. Methods: These themes were examined empirically using data from two Canadian retrospective occupational cohort studies: the BC Aluminum Smelter Cohort (n=6423) and the BC Sawmill Cohort (n=26,847). In the smelter cohort exposure to polycyclic aromatic hydrocarbons (PAH), measured as benzene soluble materials (BSM) and benzo(a)pyrene (BaP), was examined in relation to mortality and cancer incidence. In the sawmill cohort three exposures classes were evaluated: (1) nonspecific dust and wood dust in relation to chronic obstructive pulmonary disease hospitalizations; (2) total chlorophenols, pentachlorophenols (PCP), and tetrachlorophenol (TCP) in relation to cancer incidence; and (3) noise estimated using expert-based and measurement-based approaches in relation to heart disease mortality. The shape, goodness of fit, and precision of the exposure-response relationships were evaluated using Poisson regression. Results: Using a more specific exposure measure that was more proximal to the causal agent(s) improved the precision of the exposure-response relationship by between 1--14% for BaP over BSM, by 10--30% for PCP over total chlorophenols, and by 218% for wood dust over nonspecific dust. Measurement-based noise estimates improved the precision by 12--108% over the use of expert ratings. Accounting for hearing protection use in the measurement-based noise estimates improved the precision by 58% over the unadjusted estimates. The observed attenuation was not correlated with predicted attenuation from theoretical equations. Conclusions: Examining the precision of exposure-response relationships provided a quantifiable measure for evaluating different exposure assessment approaches. Refining the quantitative exposure estimates, through the use of more proximal exposure measures and the use of exposure measurements, resulted in stronger, more precise exposure-response relationships. With the exception of the expert-based noise estimates, the more common, less specific exposure measures resulted in inconclusive exposure-disease associations.
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