Impact of the specificity of the exposure metric on exposure-response relationships

Background: Exposure misclassification. may occur when nonspecific exposure indicators are used. Developing estimates of more specific measures may be difficult due to sampling limitations or a paucity of historical measurements and, thus, often requires substantial effort. We examine the impact on exposure-response relationships of moving from 2 measures of exposure mixtures (dust, chlorophenols) to more specific exposure indicators (wood dust, pentachlorophenol,.tetrachlorophenol) in a retrospective cohort. Methods: The study population consisted of 26,847 male sawmill workers (>= 1 year employment between 1950 and 1995) with linkage to national cancer registries. A subcohort (n = 11,273 employed more than 1 day between 1985 and 1995) was linked to hospital discharge records. We evaluated the shape (log-linear vs log-log models), goodness of fit, precision, and expected versus observed attenuation of the exposure-response relationships. Results: The correlation between the cumulative exposure indices was moderately high (dust/wood dust, r = 0.68; total chlorophenol/ pentachlorophenol, r = 0.88; total chlorophenol/tetrachlorophenol, r = 0.78). An increase in chronic obstructive pulmonary disease hospitalizations was found with wood dust but not with total dust. Stronger associations for non-Hodgkin lymphoma and kidney cancer incidence were observed with pentachlorophenol than with total chlorophenol; no association was observed with tetrachlorophenol. We observed greater attenuation than expected using total dust, but less than expected using total chlorophenol. Conclusions: The relationships between health outcomes were substantially attenuated when nonspecific exposure indicators were used. This study demonstrates the importance of developing exposure metrics as specific to the disease-causing agent as possible, particularly when the composition of mixed exposures varies by work areas.