Comparative Computational Modeling of Airflows and Vapor Dosimetry in the Respiratory Tracts of Rat, Monkey, and Human

Abstract

Computational fluid dynamics (CFD) models are useful for predicting site-specific dosimetry of airborne materials in the respiratory tract and elucidating the importance of species differences in anatomy, physiology, and breathing patterns. We improved the imaging and model development methods to the point where CFD models for the rat, monkey, and human now encompass airways from the nose or mouth to the lung. A total of 1272, 2172, and 135 pulmonary airways representing 17±7, 19±9, or 9±2 airway generations were included in the rat, monkey and human models, respectively. A CFD/physiologically based pharmacokinetic model previously developed for acrolein was adapted for these anatomically correct extended airway models. Model parameters were obtained from the literature or measured directly. Airflow and acrolein uptake patterns were determined under steady-state inhalation conditions to provide direct comparisons with prior data and nasal-only simulations. Results confirmed that regional uptake was sensitive to airway geometry, airflow rates, acrolein concentrations, air:tissue partition coefficients, tissue thickness, and the maximum rate of metabolism. Nasal extraction efficiencies were predicted to be greatest in the rat, followed by the monkey, and then the human. For both nasal and oral breathing modes in humans, higher uptake rates were predicted for lower tracheobronchial tissues than either the rat or monkey. These extended airway models provide a unique foundation for comparing material transport and site-specific tissue uptake across a significantly greater range of conducting airways in the rat, monkey, and human than prior CFD models.

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung

“…(59,(75)(76)(77)(78)(79) More recently, CFD applications have used surface models derived from imaging data from individual subjects. (80)(81)(82)(83) These models typically comprise the upper respiratory tract consisting of the oral airways, pharynx, and larynx, and upper lung airways from the trachea extending down through several generations of the lung. The limiting factor in determining how far down into the lung patientbased CFD models can go is driven by the resolution of the scanning procedure.…”

“…Another avenue that is receiving recent interest is the integration of distal lung mechanics through coupling of the 3D CFD model with 1D or 0D models at each outlet. (80,84,85) This should allow for a more realistic definition of airflow distribution at model outlets. DeBacker et al (86) showed good agreement between CFD predictions of airflow distribution and those derived from SPECT/CT by accounting for airway resistance.…”

The evolution of inhaled particle dose modeling: A review

“…Hofmann (2011) reviewed the development of morphometric data for particle deposition modeling, including simulations of population variability from the data of Weibel (1963), Raabe et al (1976), and others. Currently, modelers have access to a substantial number of quantitative physiological and anatomical data sets (e.g., Asgharian et al, 2001Asgharian et al, , 2006Asgharian et al, , 2012Corley, Kabilan, & Kuprat, 2012;Newton, 1995, Chapter 5;Yeh & Schum, 1980). Also, medical scanning techniques are often used to define respiratory airways for aerosol deposition modeling Rostami, 2009).…”

“…Kimbell and colleagues were probably the first to mesh a three-dimensional respiratory tract structure used to model the gas flow (in the nose of the rat). Such models have been applied to upper, bronchial, and alveolar airways (Asgharian et al, 2012;Balásházy & Hofmann, 1993;Balásházy, Hofmann, Farkas, & Madas, 2008;Corley et al, 2012;Darquenne, Harrington, & Prisk, 2009;Ferron et al, 1991;Heistracher & Hofmann, 1995;Schroeter, Asgharian, Price, & McClellan, 2013;Zhang, Kleinstreuer, & Kim, 2009;). CFD models have proven useful for calculating detailed deposition patterns, but validation of the results are still under development (Hofmann, 2011;Oldham, Phalen, & Budiman, 2009;Rostami, 2009).…”

“…nanoaerosols, and volatile particles), using additional species, and interfacing with CFD models of particle deposition (e.g., Corley et al, 2012). Nanoparticles smaller than 10 nm in physical diameter can readily move by diffusion through available pores directly into the blood passing intact through the air-to-blood cellular barrier of the gas-exchange regions of the lungs (Raabe, 1982).…”