Application of both a physical theory and statistical procedure in the analyses of an in vivo study of aerosol deposition

Abstract

Regional deposition of inhaled aerosols in the respiratory tract is a significant factor in assessing the biological effects from exposure to a variety of environmental particles. Understanding the deposition efficiency of inhaled aerosol particles in the nasal and oral airways can help evaluate doses to the extrathoracic region as well as to the lung. Dose extrapolation from laboratory animals to humans has been questioned due to significant physiological and anatomical variations. Although human studies are considered ideal for obtaining in vivo toxicity information important in risk assessment, the number of subjects in the study is often small compared to epidemiological and animal studies. This study measured in vivo the nasal airway dimensions and the extrathoracic deposition of ultrafine aerosols in 10 normal adult males. Variability among individuals was significant. The nasal geometry of each individual was characterized at a resolution of 3 mm using magnetic resonance imaging (MRI) and acoustic rhinometry (AR). The turbulent diffusion theory was used to describe the nonlinear nature of extrathoracic aerosol deposition. To determine what dimensional features of the nasal airway were responsible for the marked differences in particle deposition, the MIXed-effects NonLINear Regression (MIXNLIN) procedure was used to account for the random effort of more » repeated measurements on the same subject. Using both turbulent diffusion theory and MIXNLIN, the ultrafine particle deposition is correlated with nasal dimensions measured by the surface area, minimum cross-sectional area, and complexity of the airway shape. The combination of MRI and AR is useful for characterizing both detailed nasal dimensions and temporal changes in nasal patency. We conclude that a suitable statistical procedure incorporated with existing physical theories must be used in data analyses for experimental studies of aerosol deposition that involve a relatively small number of human subjects. « less