Fate of inhaled aerosols under the influence of glottal motion in a realistic in silico human tracheobronchial tree model

Abstract

Despite the prevalence of inhalation therapy in the treatment of various respiratory diseases, predicting and optimizing lung deposition fractions of inhaled drugs for maximal efficacy remains challenging due to the complex anatomical structures of the extra-thoracic airways, notably the glottal region. One of the widespread speculations in current insilico simulations lies in assuming a static glottis during inhalation, while in reality inhalation leads to significant glottis cross-sectional area expansion. The present work attempts to explore, insilico, the influence of transient movement of the glottal structures on inhalation therapy outcomes. To this end, we adopted a CT-based realistic human tracheobronchial tree (TB) model and explored transient airflows and deposition outcomes for a broad range of inhaled aerosols (i.e., dp=1-12 μm) under a dry powder inhaler (DPI) maneuver. Three different glottal expansion ratios, spanning static to 40 percent cross-sectional area expansion have been considered for the analysis. Our findings point to the tangible impact of glottal motion on airflow and particle deposition along the respiratory tract for a DPI maneuver, where a static glottis underpredicts the total particle deposition in the TB model for lower sized particles (dp≤ 3 μm) compared to predictions for all dynamic glottal motions. In contrast, for larger size particles (i.e., 5 ≤dp≤ 10 μm), a static glottis yields lower total deposition in the TB model compared with dynamic glottal motions. Our study also underlines that regional deposition of smaller micron-sized particles is most affected by glottal deformation in the conducting airways.