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Particle Image Velocimetry (PIV) measurements with the aim of providing experimental data for the SimInhale benchmark case are presented within this work. We, therefore, present a refractive index matched, transparent model of the benchmark geometry, in which the velocity and turbulent kinetic energy fields are examined at flow rates comparable to 15, 30 and 60 L/min (Re ≈ 1000–4500) in air. Furthermore, these results are compared with Large Eddy Simulations (LES). The results reveal a Reynolds number independence of the qualitative velocity field in the range covered within this work. Good agreement is found between the PIV and LES data, with a slight over-prediction of turbulent kinetic energies by the simulations. The obtained experimental data will be part of a common, publicly accessible ERCOFTAC database along with additional results published recently. 133 183 189

Regional deposition of inhaled medicines is a valuable metric of effectiveness in drug delivery applications to the lung. In silico methods are now emerging as a valuable tool for the detailed description of localized deposition in the respiratory airways. In this context, there is a need to minimize the computational cost of high-fidelity numerical approaches. Motivated by this need, the present study is designed to assess the role of the extrathoracic airways in determining regional deposition in the upper bronchial airways. Three mouth-throat geometries, with significantly different geometric and filtering characteristics, are merged onto the same tracheobronchial tree that extends to generation 8, and Large Eddy Simulations are carried out at steady inhalation flowrates of 30 and 60 L / min . At both flowrates, large flow field differences in the extrathoracic airways across the three geometries largely die out below the main bifurcation. Importantly, localized deposition fractions are found to remain practically identical for particles with aerodynamic diameters of up to d p = 4 μ m and d p = 2.5 μ m at 30 and 60 L / min , respectively. For larger particles, differences in the localized deposition fractions are shown to be mainly due to variations in the mouth-throat filtering rather than upstream flow effects or differences in the local flow field. Deposition efficiencies in the individual airway segments exhibit strong correlations across the three geometries, for all particle sizes. The results suggest that accurate predictions of regional deposition in the tracheobronchial airways can therefore be obtained if the particle size distribution that escapes filtering in the mouth-throat (ex-cast dose) of a particular patient is known or can be estimated. These findings open the prospect for significant reductions in the computational expense, especially in the context of in silico population studies, where the aerosol size distribution and precomputed flow field from standardized mouth-throat models could be used with large numbers of tracheobronchial trees available in chest-CT databases.

Regional deposition effects are important in the pulmonary delivery of drugs intended for the topical treatment of respiratory ailments. They also play a critical role in the systemic delivery of drugs with limited lung bioavailability. In recent years, significant improvements in the quality of pulmonary imaging have taken place, however the resolution of current imaging modalities remains inadequate for quantifying regional deposition. Computational Fluid-Particle Dynamics (CFPD) can fill this gap by providing detailed information about regional deposition in the extrathoracic and conducting airways. It is therefore not surprising that the last 15 years have seen an exponential growth in the application of CFPD methods in this area. Survey of the recent literature however, reveals a wide variability in the range of modelling approaches used and in the assumptions made about important physical processes taking place during aerosol inhalation. The purpose of this work is to provide a concise critical review of the computational approaches used to date, and to present a benchmark case for validation of future studies in the upper airways. In the spirit of providing the wider community with a reference for quality assurance of CFPD studies, in vitro deposition measurements have been conducted in a human-based model of the upper airways, and several groups within MP1404 SimInhale have computed the same case using a variety of simulation and discretization approaches. Here, we report the results of this collaborative effort and provide a critical discussion of the performance of the various simulation methods. The benchmark case, in vitro deposition data and in silico results will be published online and made available to the wider community. Particle image velocimetry measurements of the flow, as well as additional numerical results from the community, will be appended to the online database as they become available in the future. This article is based upon work from COST Action MP1404 SimInhale ‘Simulation and pharmaceutical technologies for advanced patient-tailored inhaled medicines', supported by COST (European Cooperation in Science and Technology) www.cost.eu. The work conducted at Brno University of Technology was partly supported by the Czech Science Foundation [16-23675S].

To be able to predict the fate of therapeutic or pollutant xenobiotic inhaled particles in the human lungs, we need to understand the nature of airflow as it occurs throughout the entire respiratory tract. © 2018, Springer International Publishing AG. 24 343 349 343-349

High-fidelity simulations of the complete airway tree are still largely beyond current computational capabilities. Towards large-scale simulations of the human lung, the current study introduces a numerical methodology to predict particle deposition in a simplified approximation of the deep lung during a full breathing cycle. The geometrical model employed consists of an idealised bronchial tree that represents generations 10 to 19 of the conducting zone and a heterogeneous acinar model created using a space-filling algorithm. The computational cost of the coupled simulation is reduced by taking advantage of the flow similarity across the central conducting regions in order to decompose the bronchial tree into representative subunits. Topological information is used to account for the correct gravitational force on the particles in the representative bifurcations, emulating their transport characteristics in the actual bronchial tree. Eventually, airflow and particle transport are simulated in a single representative bifurcation and a single acinar model, resulting in great savings in computational cost. An Eulerian-Lagrangian approach has been used for solving the flow and particle equations during sinusoidal breathing in the decomposed domain. The resulting deposition estimates agree rather well with the known deposition trends reported in the literature, while offering additional insights. For 1 − 5μm particles, deposition during exhalation is comparable to deposition upon inhalation, suggesting the use of breath-hold maneuvers to further increase sedimentation of these particles. Airway orientation relative to gravity was found to have a significant impact on deposition rates, especially for particles above 2μm and to be higher in the more distal generations, due to the wider range of angles relative to the direction of gravity. In the acinus, particles in the 2 − 5μm range have a quite high average deposition efficiency that reaches approximately 75% and shows considerable variation (12.4%) due to airway orientation. Finally, a simplified semi-analytical approach is introduced that can lead to even further reduction in computational costs, while incurring only a small loss in accuracy. © 2017 Elsevier B.V. 113 132 144 132-144

In silico methods offer a valuable approach to predict localized deposition in the tracheobronchial tree, important in the topical treatment of respiratory diseases and the systemic administration of drugs with limited lung bioavailability. In this study, we examine the effect of extrathoracic airway variation on regional deposition in order to assess whether standard mouth-throat models can be adopted for more efficient predictions. Despite large qualitative differences in the extrathoracic airways, deposition patterns and efficiencies in the tracheobronchial region remain largely unaffected for particles smaller than 6 microns. The findings suggest that for drug delivery applications, standard mouth-throat models could be adopted to predict deposition in the central airways.

Understanding the multitude of factors that control pulmonary deposition is important in assessing the therapeutic or toxic effects of inhaled particles. The use of increasingly sophisticated in silico models has improved our overall understanding, but model realism remains elusive. In this work, we use Large Eddy Simulations (LES) to investigate the deposition of inhaled aerosol particles with diameters of dp=0.1,0.5,1,2.5,5dp=0.1,0.5,1,2.5,5 and 10μm (particle density of 1200 kg/m3). We use a reconstructed geometry of the human airways obtained via computed tomography and assess the effects of inlet flow conditions, particle size, electrostatic charge, and flowrate. While most computer simulations assume a uniform velocity at the mouth inlet, we found that using a more realistic inlet profile based on Laser Doppler Anemometry measurements resulted in enhanced deposition, mostly on the tongue. Nevertheless, flow field differences due to the inlet conditions are largely smoothed out just a short distance downstream of the mouth inlet as a result of the complex geometry. Increasing the inhalation flowrate from sedentary to activity conditions left the mean flowfield structures largely unaffected. Nevertheless, at the higher flowrates turbulent intensities persisted further downstream in the main bronchi. For dp>2.5μm, the overall Deposition Fractions (DF) increased with flowrate due to greater inertial impaction in the oropharynx. Below dp=1.0μm, the DF was largely independent of particle size; it also increased with flowrate, but remained significantly lower. Electrostatic charge increased the overall DF of smaller particles by as much as sevenfold, with most of the increase located in the mouth–throat. Moreover, significant enhancement in deposition was found in the left and right lung sub-regions of our reconstructed geometry. Although there was a relatively small impact of inhalation flowrate on the deposition of charged particles for sizes dp

Understanding the multitude of factors that control pulmonary deposition is important in assessing the therapeutic or toxic effects of inhaled particles. The use of increasingly sophisticated in silico models has improved our overall understanding, but model realism remains elusive. In this work, we use Large Eddy Simulations (LES) to investigate the deposition of inhaled aerosol particles with diameters of dp=0.1,0.5,1,2.5,5 and 10μm (particle density of 1200 kg/m3). We use a reconstructed geometry of the human airways obtained via computed tomography and assess the effects of inlet flow conditions, particle size, electrostatic charge, and flowrate. While most computer simulations assume a uniform velocity at the mouth inlet, we found that using a more realistic inlet profile based on Laser Doppler Anemometry measurements resulted in enhanced deposition, mostly on the tongue. Nevertheless, flow field differences due to the inlet conditions are largely smoothed out just a short distance downstream of the mouth inlet as a result of the complex geometry. Increasing the inhalation flowrate from sedentary to activity conditions left the mean flowfield structures largely unaffected. Nevertheless, at the higher flowrates turbulent intensities persisted further downstream in the main bronchi. For dp>2.5μm, the overall Deposition Fractions (DF) increased with flowrate due to greater inertial impaction in the oropharynx. Below dp=1.0μm, the DF was largely independent of particle size it also increased with flowrate, but remained significantly lower. Electrostatic charge increased the overall DF of smaller particles by as much as sevenfold, with most of the increase located in the mouth–throat. Moreover, significant enhancement in deposition was found in the left and right lung sub-regions of our reconstructed geometry. Although there was a relatively small impact of inhalation flowrate on the deposition of charged particles for sizes dp

In the current study, Large Eddy Simulations (LES) are used to investigate the transport and deposition of inhaled aerosol particles (dp = 0.1, 0.5, 1, 2.5, 5, 10 μm) in a realistic geometry of the human airways under steady inhalation. The effects of electrostatic charge and lower generation airway narrowing caused by Chronic Obstructive Pulmonary Disease (COPD) on particle transport and deposition are examined for various flowrates (sedentary - 15.2 lt/min, light - 30 lt/min and heavy activity - 60 lt/min). Results show that the mean flow structures at the three flowrates are qualitatively similar regardless of Reynolds number. Similar swirling motions are generated from the impingement of the laryngeal jet on the tracheal front wall. However, higher turbulent intensities that persist further downstream in the trachea and the main bronchi are observed as the flowrate is increased. The Deposition Efficiency (DE) of particles is increased with the flowrate due to greater inertial impaction. The majority of the larger particles are filtered in the mouththroat region, while 0.1, 0.5 and 1μm diameter particles have similar DE at a given flowrate. The effect of charge on DE of particles is more pronounced for smaller particles 1000 elementary charge units on 0.1, 0.5,1 and 2.5 μm diameter particles results in approximately 7, 3, 2.5 and 1.5 times greater overall DE than that with no charge, respectively. Obstructed lower generation airways result in enhanced deposition due to impaction caused by higher velocities in these airways. 2