Human exposure to airborne particulate matter (PM) increases the risk of negative health outcomes; however, substantial uncertainty remains in quantifying these exposure‐response relationships. In particular, relating increased risk of mortality to exposure to PM with diameters smaller than 2.5 μm (PM2.5) neglects variability in the underlying size distribution of PM2.5 exposure and size‐resolved deposition in human airways. In this study, we combine a size‐resolved respiratory particle‐deposition model with a global size‐resolved aerosol model to estimate the variability in particle deposition along the respiratory tract due to variability in ambient PM size distributions. We find that the ratio of deposited PM mass in the tracheobronchial and alveolar regions per unit ambient PM2.5 exposure (deposition ratio and DRTB + AV) varies by 20–30% between populated regions due to variability in ambient PM size distributions. Furthermore, DRTB + AV can vary by as high as a factor of 4 between the fossil‐fuel‐dominated region of the Eastern United States and the desert‐dust‐dominated region of North Africa. When considering individual PM species, such as sulfate or organic matter, we still find variability in the DRTB + AV on the order of 30% due to regional variability in the size distribution. Finally, the spatial distribution of DRTB + AV based on number or surface area is substantially different than the DRTB + AV based on mass. These results suggest that regional variability in ambient aerosol size distributions drive variability in PM deposition in the body, which may lead to variability in the health response from exposure to PM2.5.
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