Aerosol flow mechanics in human airways: Inter-subject variability in health and disease

Deposition of inhaled particles within lung tissue is a critical factor mediating the spread of airborne infections and the efficacy of pulmonary drug delivery. Particle trajectories in the human respiratory tract are strongly influenced by the unique anatomical features of each individual, contributing to considerable inter-subject variability in infection susceptibility and therapeutic outcomes. This variability, alongside differences in host immune responses, explains why individuals exposed to similar viral loads can exhibit divergent clinical manifestations, from asymptomatic to severe pneumonia, and why inhaled treatments show varied efficacy across patients. In this study, we employ physics-based reduced-order models of the human lung airway geometry and airflow to investigate the flow physics underpinning this structure-function variability. Our results elucidate key mechanisms controlling particle transport and deposition patterns that drive differential drug delivery efficiency and infection risk among individuals. Additionally, we analyze how obstructive airway diseases perturb local airflow dynamics, modifying particle deposition and potentially altering infection progression and treatment effectiveness. This work contributes new insights into the complex interactions between respiratory fluid mechanics, anatomy, and disease, with implications for personalized inhalation therapy design and infection control.