The extent to which laryngeal-induced flow features penetrate into the upper tracheobronchial (TB) airways and their related impact on particle transport and deposition are not well understood. The objective of this study was to evaluate the effects of including the laryngeal jet on the behavior and fate of inhaled aerosols in an approximate model of the upper TB region. The upper TB model was based on a simplified numerical reproduction of a replica cast geometry used in previous in vitro deposition experiments that extended to the sixth respiratory generation along some paths. Simulations with and without an approximate larynx were performed. Particle sizes ranging from 2.5 nm to 12 mum were considered using a well-tested Lagrangian tracking model. The model larynx was observed to significantly affect flow dynamics, including a laryngeal jet skewed toward the right wall of the trachea and a significant reverse flow in the left region of the trachea. Inclusion of the laryngeal model increased the tracheal deposition of nano- and micrometer particles by factors ranging from 2 to 10 and significantly reduced deposition in the first three bronchi of the model. Considering localized conditions, inclusion of the laryngeal approximation decreased deposition at the main carina and produced a maximum in local surface deposition density in the lobar-to-segmental bifurcations (G2-G3) for both 40-nm and 4-microm aerosols. These findings corroborate previous experiments and highlight the need to include a laryngeal representation in future computational and in vitro models of the TB region.

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Experimental deposition patterns of cigarette smoke in surrogate human airway systems are very heterogeneous. Particle deposits are enhanced at predictable, well-defined morphological regions; most specifically, carinal ridges within bifurcation zones and along posterior sections of tubular airways. The efficiency of the mucociliary transport mechanism in vivo is also reduced at airway branchings. The geometrical sites of preferential particle deposition and impaired clearance can be correlated with clinically observed anatomical sites exhibiting increased incidences of bronchogenic carcinomas. These locations are not compatible with current theoretical models simulating only the usual particle deposition processes of inertial impaction, sedimentation, and diffusion, while intending to account for particle hygroscopicity. Moreover, data from human subject exposures indicate that heretofore unknown factors affect the distribution of inhaled cigarette smoke. Herein, a new mathematical model is presented that explains cigarette smoke deposition patterns, including bifurcation "hot spots," in terms of composition and cumulative density. The behavior of mainstream cigarette smoke can be related to physicochemical parameters of its particulate and vapor-gas phases and is a result of two distinct effects: (1) particle cloud motion and (2) vapor-gas behavior. In lung airways, Effect 1 is the most prominent. The high particle number,ns approximately equal to 3 x 10(9) cm-3, and mass,rho s approximately equal to 10(-4) g cm-3, concentrations of smoke dictate that a bolus of it has kinetic properties of an entity (Effect 1 above), independent of the aerodynamic size characteristics of individual constituent particles. This motion may be exacerbated by the bulk movement (Effect 2 above) of the vapor-gas phase density of smoke.

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Key factors that contribute to the aerodynamic properties of aerosol particles are found in Stokes' law. These factors may be monitored or controlled to optimize drug delivery to the lungs. Predictions of the aerodynamic behavior of therapeutic aerosols can be derived in terms of the physical implications of particle slip, shape and density. The manner in which each of these properties have been used or studied by pharmaceutical scientists to improve lung delivery of drugs is readily understood in the context of aerosol physics. Additional improvement upon current aerosol delivery of particulates may be predicted by further theoretical scrutiny.

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