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BACKGROUND:The human respiratory airway undergoes dramatic growth during infancy and childhood, which induces substantial variability in air flow pattern and particle deposition. However, deposition studies have typically focused on adult subjects, the results of which cannot be readily extrapolated to children. We developed models to quantify the growth of human nasallaryngeal airways at early ages, and to evaluate the impact of that growth on breathing resistance and aerosol deposition. METHODS: Four image-based nasal-laryngeal models were developed from 4 children, ages 10 days, 7 months, 3 years, and 5 years, and were compared to a nasallaryngeal model of a 53-year-old adult. The airway dimensions were quantified in terms of different parameters (volume, cross-section area, and hydraulic diameter) and of different anatomies (nose, pharynx, and larynx). Breathing resistance and aerosol deposition were computed using a highfidelity fluid-particle transport model, and were validated against the measurements made with the 3-dimensional models fabricated from the same airway computed tomography images. RESULTS: Significant differences in nasal morphology were observed among the 5 subjects, in both morphology and dimension. The turbinate region appeared to experience the most noticeable growth during the first 5 years of life. The nasal airway volume ratios of the 10-day, 7-month, 3-year, and 5-year-old subjects were 6.4%, 18.8%, 24.2%, and 40.3% that of the adult, respectively. Remarkable inter-group variability was observed in air flow, pressure drop, deposition fraction, and particle accumulation. The computational fluid dynamics predicted pressure drops and deposition fractions were in close agreement with in vitro measurements. CONCLUSIONS: Age effects are significant in both breathing resistance and micrometer particle deposition. The image/computational-fluid-dynamics coupled method provides an efficient and effective approach in understanding patient-specific air flows and particle deposition, which have important implications in pediatric inhalation drug delivery and respiratory disorder diagnosis.

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The objective of this study is to systematically assess the influences of the larynopharyneal anatomical details on airflow and particle behaviors during exhalation by means of image-based modeling. A physiologically realistic nose-throat airway was developed with medical images. Individual airway anatomy such as uvula, pharynx, and larynx were then isolated for examination by progressively simplifying this image-based model geometry. Low Reynolds number (LRN) k- model and Langrangian tracking model were used to simulate the dynamics of airflow and particle transport for a wide range of exhalation conditions (4-45 L/min) and particle sizes (1 nm-1 μm). Results showed that pharyngeal anatomical details exerted a significant impact on breathing resistance and particle profiles. Abrupt pressure drop resulting from the uvula-related airway obstruction was observed. Even though the total deposition rate in the nasal airway is largely unaffected by the upstream effect, the local deposition patterns vary notably. Results of this study also indicate that the pressure drop appears to be an appropriate parameter to characterize the geometric variations for diffusive depositions. Inclusion of pressure drop (D 0.5 Q −0.62 dp 0.07) gives an improved correlation than using the conventional diffusion factor (D 0.5 Q −0.28).

Accurate knowledge of the delivery of locally acting drug products, such as metered-dose inhaler (MDI) formulations, to large and small airways is essential to develop reliable in vitro/in vivo correlations (IVIVCs). However, challenges exist in modeling MDI delivery, due to the highly transient multiscale spray formation, the large variability in actuation–inhalation coordination, and the complex lung networks. The objective of this study was to develop/validate a computational MDI-releasing-delivery model and to evaluate the device actuation effects on the dose distribution with the newly developed model. An integrated MDI–mouth–lung (G9) geometry was developed. An albuterol MDI with the chlorofluorocarbon propellant was simulated with polydisperse aerosol size distribution measured by laser light scatter and aerosol discharge velocity derived from measurements taken while using a phase Doppler anemometry. The highly transient, multiscale airflow and droplet dynamics were simulated by using large eddy simulation (LES) and Lagrangian tracking with sufficiently fine computation mesh. A high-speed camera imaging of the MDI plume formation was conducted and compared with LES predictions. The aerosol discharge velocity at the MDI orifice was reversely determined to be 40 m/s based on the phase Doppler anemometry (PDA) measurements at two different locations from the mouthpiece. The LES-predicted instantaneous vortex structures and corresponding spray clouds resembled each other. There are three phases of the MDI plume evolution (discharging, dispersion, and dispensing), each with distinct features regardless of the actuation time. Good agreement was achieved between the predicted and measured doses in both the device, mouth–throat, and lung. Concerning the device–patient coordination, delayed MDI actuation increased drug deposition in the mouth and reduced drug delivery to the lung. Firing MDI before inhalation was found to increase drug loss in the device; however, it also reduced mouth–throat loss and increased lung doses in both the central and peripheral regions.

The use of impulse oscillometry (IOS) for lung function testing does not need patient cooperation and has gained increasing popularity among both young and senior populations, as well as in patients with breathing difficulties. However, studies of the IOS sensitivity to regional lung obstructions are limited and have shown mixed results. The objective of this study was to evaluate the performance of an IOS system in 3D-printed lung models with structural abnormalities at different locations and with different severities. Lung trees of two complexity levels were tested, with one extending to the sixth generation (G6) and the other to G12. The IOS responses to varying glottal apertures, carina ridge tumors, and segmental bronchial constrictions were quantified in the G6 lung geometry. Both the G6 and G12 lung casts were prepared using high-resolution 3D printers. Overall, IOS detected the progressive airway obstructions considered in this study. The resonant frequency dropped with increasing obstructions for all three disease phenotypes in the G6 lung models. R20Hz increased with the increase in airway obstructions. Specifically, R20Hz in the airway model with varying glottal apertures agreed reasonably well with complementary measurements using TSI VelociCalc. In contrast to the high-resistance (R) sensitivity to the frequency in G6 lung models, R was nearly independent of frequency in G12 lung models. IOS R20Hz demonstrated adequate sensitivity to the structural remodeling in the central airways. However, the changes of R5Hz and X5Hz vs. airway obstructions were inconclusive in this study, possibly due to the rigid lung casts and the difference of a container–syringe system from human lungs.

The rabbit nose’s ability to filter out inhaled agents is directly related to its defense to infectious diseases. The knowledge of the rabbit nose anatomy is essential to appreciate its functions in ventilation regulation, aerosol filtration and olfaction. The objective of this study is to numerically simulate the inhalation and deposition of nanoparticles in a New Zealand white (NZW) rabbit nose model with an emphasis on the structure–function relation under normal and sniffing conditions. To simulate the sniffing scenario, the original nose model was modified to generate new models with enlarged nostrils or vestibules based on video images of a rabbit sniffing. Ventilations into the maxilloturbinate and olfactory region were quantified with varying nostril openings, and deposition rates of inhaled aerosols ranging from 0.5 nm to 1000 nm were characterized on the total, sub-regional and local basis. Results showed that particles which deposited in the olfactory region came from a specific area in the nostril. The spiral vestibule played an essential role in regulating flow resistance and flow partition into different parts of the nose. Increased olfactory doses were persistently predicted in models with expanded nostrils or vestibule. Particles in the range of 5–50 nm are more sensitive to the geometry variation than other nanoparticles. It was also observed that exhaled aerosols occupy only the central region of the nostril, which minimized the mixing with the aerosols close to the nostril wall, and potentially allowed the undisruptive sampling of odorants. The results of this study shed new light on the ventilation regulation and inhalation dosimetry in the rabbit nose, which can be further implemented to studies of infectious diseases and immunology in rabbits.

Starting with an extended Gibbs-Duhem equation and an expression for stress-deformation behavior derived by Oh and Slattery for elastic crystalline solids, we derive a new compatibility constraint on stress at coherent interfaces. Its use is demonstrated in determining the residual stresses developed during oxidation on the surface of a cylinder.