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Prediction of the Focal Sites of Tissue Injury Caused by Reactive Gas Uptake In the Respiratory Tract

Banafsheh Keshavarzi, The Pennsylvania State University, Department of Chemical Engineering, University Park, PA 16802, James Ultman, Chemical Engineering, The Pennsylvania State University, University Park, PA 16802, and Ali Borhan, Chemical Engineering, Pennsylvania State University, 122 Fenske Laboratory, University Park, PA 16802.

Inhalation of reactive gases such as ozone results in a reproducible pattern of tissue injury in the respiratory tract which is believed to depend on the local dose delivered to the walls. To predict the focal sites of tissue injury, we perform numerical simulations of reactive gas transport and uptake in anatomically-accurate models of the respiratory tract. The model geometry is created through three-dimensional reconstruction of MRI images of the respiratory tract, including the nasal passages, larynx and tracheobronchial tree. Three-dimensional flow and concentration distributions within the resulting structure are subsequently obtained through numerical solution of the Navier-Stokes, continuity, and species convection-diffusion equations. A quasi-steady diffusion-reaction model is used to account for the interaction between the reactive gas and endogenous substrates in the respiratory tract lining fluid (RTLF). The total rate of reactive gas uptake within different sections of the respiratory tract is determined, and hot spots of reactive gas flux on the respiratory tract wall are identified. For steady inspiratory flow under quiet breathing conditions, high flux regions are predicted to appear at the nasal atrium, middle turbinates, inferior meatus, laryngopharynx, rima glottidis, and downstream of bifurcations. These predictions are qualitatively consistent with experimental observations of formaldehyde-induced nasal lesions in rhesus monkeys [Monticello et al. 1989], and focal sites of epithelial damage in rat lungs exposed to ozone [Postlethwait et al., 2000].