Dynamic airways drive aerosol deposition in the human lung.

Most computational studies of aerosol transport in the lung treat airways as rigid tubes and breathing as a prescribed inflow problem. This simplification overlooks a fundamental reality that in the living lungs, airflow is generated by deforming airways, and not imposed at the inlet. As a result, the consequent predictions of where the inhaled particles deposit can remain fundamentally flawed. Here, we introduce a subject-specific, physiology-driven framework that directly couples airway motion with airflow and particle transport. Using Computed Tomography (CT)-derived tracheobronchial geometry, we compare two models on identical anatomy: a conventional rigid-wall formulation and a moving-wall model in which airway deformation follows lung expansion and contraction over a full breathing cycle. Airflow is resolved under unsteady conditions, while micron-sized particles (1-10 µm) are tracked with realistic force balances. Our results reveal that the airway motion is not a minor correction to the airway dynamics, but rather reshapes the same. Wall deformation intensifies secondary flows, drives particles closer to airway surfaces, and consistently increases the deposition across all sizes (e.g., from 6.68% to 7.47% for 1 µm, and from 9.94% to 10.75% for 10 µm). Importantly, an additional 2-3% deposition arises during the expiration phase, which is an effect commonly ignored in the standard models. The simulation framework thus offers a more reliable basis for predicting inhalation drug delivery, assessing the respiratory exposure in real time, and developing realistic lung deposition models that reflect true physiological dynamics from a subject-specific perspective.