Regional deposition of gases and particles in the lung: implications for mixtures

Considerations of the health effects of pollutant mixtures usually focus on the interactions of biochemically-induced events. For example, the effect of metabolic enzyme induction by one pollutant on the subsequent effect of another pollutant is often considered. Another important aspect of mixture interactions is the modulating effects exposure to one pollutant can have on the dosimetry of another pollutant and, indirectly, on the effects of the other pollutant. Dose-modulating effects may be particularly important when considering effects of inhaled mixtures on the lung. In this paper, the specific case of O3-induced changes on the human lung and the resulting effects on inhaled particle dose are considered as a specific example. Ozone has multiple effects on the lung ranging from alterations in pulmonary function to effects on lung defense mechanisms such as mucociliary transport of particles, and alveolar macrophage engulfment and translocation. To better understand how the O3-induced changes can affect particle dosimetry, the basic concepts of particle dosimetry are considered first. Then the specific O3-induced effects on the human lung are considered in the context of the factors governing inhaled particle dose.