Introduction Previous epidemiologic studies have reported associations between respiratory symptoms, lung function, and biomarkers of lung disease and indices of cumulative exposure and plasma indium in indium-exposed workers. Indices of exposure at a location more proximal to the dose at target tissue might provide more precise and accurate estimates of dose-response relationships. The objective of this study was to compare exposure-response relationships for respiratory health outcomes with indices of cumulative exposure, alveolar indium, and plasma indium.

Methods In a study of 110 indium-tin oxide manufacturing workers, indium exposures, plasma indium, respiratory symptoms, lung function, and serum biomarkers of lung disease were measured during two surveys. Cumulative exposure was calculated by multiplying current exposures with time spent in jobs and summed across all jobs. The International Commission on Radiological Protection’s Human Respiratory Tract Model was used to calculate the mass of indium remaining in the alveolar compartment after accounting for initial deposition, particle characteristics, and mechanical and dissolution clearances. Relationships between exposure indices and health outcomes were evaluated using generalized linear mixed models with subject as a random factor and adjusted for smoking status and age. Models were compared using a ratio of the regression coefficient to its standard error, a measure of precision, and the Akaike Information Criterion (AIC), a relative measure of model fit.

Results The alveolar dose metric correlated well with cumulative exposure (rsp = 0.876) and plasma indium (rsp = 0.726). All three exposure indices were associated with respiratory symptoms, lung function, and serum biomarkers, but alveolar dose identified additional significant or borderline significant associations not present for cumulative or plasma indium. Alveolar dose often had the highest precision for the effect estimate and lowest AIC.

Conclusion The alveolar dose metric performed better than cumulative exposure and plasma indium despite the high correlation, demonstrating that dose-based metrics can improve exposure-response modeling.