Inter-species Variabilities of Droplet Transport, Size Change, and Deposition in Human and Rat Respiratory Systems: An In Silico Study.

To speculate on human responses from animal studies, scale-up factors (body weight, lung volume, or lung surface area ratios) are currently used to extrapolate aerosol lung deposition from animal to human. However, those existing scale-up methods between animals and humans neglected two important inter-subject variability factors: (1) the effect of anatomical differences in respiratory systems from mouth/nose to peripheral lungs between human and rat, and (2) the effect of spatial distributions and temporal evolutions of temperature and relative humidity (RH) on droplet size change dynamics between the two species. To test the above-mentioned inter-species variability effects on droplet fates in pulmonary routes and generate correlations as a precise scale-up method for lung deposition estimation, this study simulated the transport of pure-water droplets in both human and Sprague-Dawley (SD) rat respiratory systems. Employing an experimentally validated Euler-Lagrange based Computational Fluid-Particle Dynamics (CFPD) model, simulations were performed for droplets with Stk/Fr between 8.36×10-5 and 1.25×10-2. Droplets were inhaled through human and rat nostrils with resting breathing conditions. Numerical results indicate that RH becomes uniformly distributed in rat airways sooner than in human airways, which significantly influences droplet size change dynamics and the resultant trajectories in pulmonary paths. Using the Stokes-Froude dimensionless number group (i.e., Stk/Fr) as the independent variable, the regional deposition fractions and evaporation fractions in both rat and human respiratory systems collapsed into unified correlations. The correlations can be used as a new rat-to-human scale-up method, estimating the lung depositions with consideration of anatomical differences. Furthermore, the necessity to employ realistic RH and temperature boundary conditions at airway walls was also confirmed for the accurate prediction of droplet size change using CFPD. Employing idealized boundary conditions leads the droplets to evaporate slower and deposit more than using realistic RH and temperature boundary conditions.