(182k) The Impact of Glottis Opening on Drug Aerosol Delivery in a Subject-Specific Lung-Airway Model: A Numerical Study

Computational fluid-particle dynamics (CFPD) simulations have been widely used to investigate transport phenomena of airflow and inhaled aerosols in human pulmonary routes. Compared to in-vitro and in-vivo methods, CFPD models are non-invasive, time-saving, and cost-effective. Properly validated, they can provide high-resolution results of and new physical insight to the transport and deposition of inhalable drugs or toxicants in human respiratory systems. Existing CFPD studies assume that glottis openings are identical between the respiratory system geometries reconstructed from CT/MRI images and the real scenarios when subjects draw drug aerosols from inhalers. However, this assumption is not physiologically correct and hence will influence the accuracy of simulation results of aerosol transport and deposition. As a result, the changing glottis geometry significantly influences the airflow structure and inhaled particle deposition in tracheobronchial airways. Thus, it is necessary to investigate such glottis-opening effects on aerosol transport and deposition in human upper respiratory systems. It will provide patient-specific guidance for operating the drug inhalation process, i.e., breathing patterns, inhaler activation timing, inhaler type/configuration and administered dosage, with the overall goal of best drug delivery efficacy. In this study, the impact of glottis opening on aerosol transport is investigated in a human upper lung model, i.e., from mouth to Generation 8 (G8). Specifically, using an experimentally validated Euler-Lagrange CFPD model, the transport and deposition of drug-aerosol particles on the micro/nanoscale were performed with three different glottis openings, i.e., 86.39 mm², 163.47 mm², and 253.00 mm². At different inhalation flowrates, significant influences were discovered among different glottis openings regarding airflow structures, i.e., laryngeal jet and turbulence intensity, as well as particle transport characteristics and local deposition values. Results support the importance of physiological correctness of glottis openings associated with realistic drug inhalation patterns. Furthermore, the numerical results provide physical insight and preliminary data for fluid-structure interaction (FSI) modeling of the real-time glottis motion during drug inhalation, as part of future inter-subject variability studies.