title: Simulation of the uptake of a reactive gas in a rat respiratory tract model with an asymmetric tracheobronchial region patterned on complete conducting airway cast data.
abstract: Generally, the uptake of reactive gases by the respiratory tract is simulated assuming that all paths from the trachea to the most distal airspaces are equivalent. As this is not the case, especially for nonhumans, the adequacy of this approach to predict doses that can be useful in the fields of toxicology and risk assessment is subject to question. To explore this issue, a dosimetry model is developed which combines the use of one-dimensional convection-dispersion equations in conjunction with multiple path anatomic models so that the dosimetry model simultaneously simulates transport and uptake in all the airways and airspaces of the anatomic model. For this work, the anatomic model of the tracheobronchial (TB) region is patterned on cast data which describe the dimensions and branching network of the 4807 airways of the TB region of a rat. Distal to each of the 2404 terminal bronchioles of the anatomical model, the air space is modeled as a single path. The results presented are preliminary; they focus on the predictions themselves to obtain an understanding of what the model has to say about uptake in a complex set of branching airways. Results include the following predictions: (1) Regardless of path there is a similarity along different paths in the shape of concentration profiles as well as a similarity in the shape of dose profiles. (2) Along a path in the TB or pulmonary region, dose decreases distally. (3) Generally, proximal alveolar region (PAR, a region of major morphological damage due to O3 and NO2) dose decreases the more distal the PAR. (4) There is considerable variation in the doses of the different airways or alveolar surfaces in the same generation. (5) The maximum and minimum PAR doses do not correspond to paths with, respectively, the smallest and largest number of generations from the trachea to the PAR. (6) The ratio of the maximum to minimum PAR dose is very sensitive to tidal volume. These results give a more realistic understanding of respiratory tract gas transport and uptake. The model also predicts aspects that equivalent path models cannot, such as the dose distribution of different but morphologically equivalent sites.
authors.affiliation: Pulmonary Toxicology Branch, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Overton
authors.forename: R C
authors.initials: RC
authors.lastname: Graham
mesh_terms: D000465:Algorithms; D000818:Animals; D001980:Bronchi / Q000378:metabolism*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005544:Forecasting; D005652:Functional Residual Capacity; D008953:Models, Anatomic; D008954:Models, Biological; D009585:Nitrogen Dioxide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010126:Ozone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011650:Pulmonary Alveoli / Q000378:metabolism; D012123:Pulmonary Ventilation; D051381:Rats; D012119:Respiration; D015657:Respiratory Transport; D013990:Tidal Volume; D014132:Trachea / Q000378:metabolism*
chemical_list: D010126:Ozone; D009585:Nitrogen Dioxide