Computational Study of Regional and Global Aerosol Deposition in Human Airways during Realistic Breathing Cycles

The effectiveness of aerosolized drug delivery in human airways to treat various pulmonary diseases is strongly influenced by the temporal dynamics of breathing patterns. While examining steady-state inhalation conditions, as typically considered in high-fidelity computational studies, can provide insights into the airflow dynamics and deposition characteristics of particles within the airways, real human breathing involves complex cyclic flow patterns with distinct inhalation and exhalation phases that can significantly affect aerosol transport and deposition. In this study, we employ point-particle-based large-eddy simulation (LES) as a computational modeling strategy to examine airflow dynamics and aerosol transport and deposition characteristics during realistic breathing cycles in the upper human airways. The geometric model includes the extrathoracic and part of the intrathoracic airways, representing a truncated version of a realistic human airway based on the SimInhale benchmark case. LES is performed using the Eulerian-Lagrangian framework, where the airflow is simulated using the Eulerian formulation, while therapeutic aerosol particles ranging from 1 micron to 10 microns are injected at the beginning of inhalation and tracked in a Lagrangian manner under dilute suspension conditions. We first validate the LES results by comparing turbulence statistics and regional/global aerosol deposition with previously reported studies conducted on the full airway geometry at the steady inflow Reynolds number based on the bulk inflow velocity (Re) of 3745. Afterwards, the effects of breathing cycles on airflow behavior and aerosol deposition are analyzed over multiple cycles by considering a physiologically realistic inhalation-exhalation sequence, with average Re of 1170 during inhalation and 605 during exhalation phases. The results show that particle deposition occurs predominantly during the early stages of inhalation, with global deposition rates lower than those observed under steady-state conditions. The study highlights the influence of particle size and flow unsteadiness on both regional and global deposition behaviors, offering new insights for optimizing aerosol drug delivery strategies.