Airway Bifurcation Model Research Articles

Direct numerical simulation of particle laden flow in a human airway bifurcation model

During the delivery of inhaled medicines, and depending on the size distribution of the particles in the formulation, airway bifurcations are areas of preferential deposition. Previous studies of laminar flow through airway bifurcations point to an interplay of inertial and centrifugal forces that leads to rich flow phenomena and controls particle deposition patterns. However, recent computational studies have shown that the airflow in the upper human airways is turbulent during much of the respiratory cycle. The question of how the presence of turbulence modifies these effects remains open. In this study, we perform for the first time Direct Numerical Simulations (DNS) of fully developed turbulent flow through a single human airway bifurcation model, emulating steady prolonged inspiration and expiration. We use the rich information obtained from the DNS in order to identify key structures in the flow field and scrutinize their role in determining deposition patterns in the bifurcation. We find that the vortical structures present in the bifurcation during expiration differ from those identified during inspiration. While Dean vortices are present in both cases, a set of three dimensional “carinal vortices” are identified only during expiration. A set of laminar simulations in the same geometries, but at lower Reynolds numbers, allow us to identify key differences in aerosol deposition patterns between laminar and turbulent respiration. We also report deposition fractions for representative Stokes numbers for both laminar and turbulent conditions. Given the suspected role of external mechanical stress on the airway epithelium in determining mucus clearance and chronic disease development, here we report wall shear stress distributions for both the turbulent and laminar cases. Finally, we also perform Large Eddy Simulations (LES) and Reynolds-Averaged Navier-Stokes (RANS) simulations for the same configuration in order to asses their performance as compared to DNS. We find that LES and RANS perform well and that they are able to capture the key characteristics of the flow field. The agreement between DNS and RANS holds true only for the mean flow field, which is primarily influenced by curvature effects.

Fiber transport and deposition in human upper tracheobronchial airways

Using a multi-level asymmetric lung bifurcation model, transport and deposition of ellipsoidal fibers in the human upper airways were analyzed. The first three generations (G0–G3) of the tracheobronchial tree were included in the study. The focus of this research is airflow simulation and fiber motion prediction in the multi-level human airway bifurcation model. The laryngeal jet at the trachea entrance was modeled as an equivalent turbulence generator, and downstream in the lower level of the bronchi a laminar flow model was used. Lagrangian simulation of ellipsoidal fiber transport and deposition was performed where the effects of coupled hydrodynamic drag and torque, shear induced lift, gravitational sedimentation, inertial impaction, turbulence diffusion were included in the analysis. The study showed that the multi-level asymmetric lung bifurcation model was flexible, easy to use, and computationally highly efficient. The particle simulation results showed that the elongated fibers were aligned with the main flow direction most of the time, but occasionally they experienced impulsive rotation along their pathway. The rotational motion was dependent on the fiber geometry and the local flow patterns. Fiber deposition pattern and deposition rate in the human upper airways were evaluated. The simulation results were compared with the experimental data. The equivalent sphere model for fiber transport and deposition was also discussed.

Airway Wall Stiffening Increases Peak Wall Shear Stress: A Fluid–Structure Interaction Study in Rigid and Compliant Airways

The airflow characteristics in a computed tomography (CT) based human airway bifurcation model with rigid and compliant walls are investigated numerically. An in-house three-dimensional (3D) fluid-structure interaction (FSI) method is applied to simulate the flow at different Reynolds numbers and airway wall stiffness. As the Reynolds number increases, the airway wall deformation increases and the secondary flow becomes more prominent. It is found that the peak wall shear stress on the rigid airway wall can be five times stronger than that on the compliant airway wall. When adding tethering forces to the model, we find that these forces, which produce larger airway deformation than without tethering, lead to more skewed velocity profiles in the lower branches and further reduced wall shear stresses via a larger airway lumen. This implies that pathologic changes in the lung such as fibrosis or remodeling of the airway wall-both of which can serve to restrain airway wall motion-have the potential to increase wall shear stress and thus can form a positive feed-back loop for the development of altered flow profiles and airway remodeling. These observations are particularly interesting as we try to understand flow and structural changes seen in, for instance, asthma, emphysema, cystic fibrosis, and interstitial lung disease.

Non-linear relationship of cell hit and transformation probabilities in a low dose of inhaledradon progenies

Cellular hit probabilities of alpha particles emitted by inhaled radon progenies in sensitivebronchial epithelial cell nuclei were simulated at low exposure levels to obtain useful datafor the rejection or support of the linear-non-threshold (LNT) hypothesis. In this study,local distributions of deposited inhaled radon progenies in airway bifurcation models werecomputed at exposure conditions characteristic of homes and uranium mines. Then,maximum local deposition enhancement factors at bronchial airway bifurcations, expressedas the ratio of local to average deposition densities, were determined to characterise theinhomogeneity of deposition and to elucidate their effect on resulting hit probabilities. Theresults obtained suggest that in the vicinity of the carinal regions of the central airways theprobability of multiple hits can be quite high, even at low average doses. Assuming auniform distribution of activity there are practically no multiple hits and the hitprobability as a function of dose exhibits a linear shape in the low dose range.The results are quite the opposite in the case of hot spots revealed by realisticdeposition calculations, where practically all cells receive multiple hits and thehit probability as a function of dose is non-linear in the average dose range of10–100 mGy.

Fluid Dynamics of Gas Exchange in High-Frequency Oscillatory Ventilation: In Vitro Investigations in Idealized and Anatomically Realistic Airway Bifurcation Models

The objective of this work is to develop understanding of the local fluid dynamic mechanisms that underpin gas exchange in high-frequency oscillatory ventilation (HFOV). The flow field during HFOV was investigated experimentally using particle image velocimetry in idealized and realistic models of a single bifurcation. Results show that inspiratory and expiratory fluid streams coexist in the airway at flow reversal, and mixing between them is enhanced by secondary flow and by vortices associated with shear layers. Unsteady flow separation and recirculation occurs in both geometries. The magnitude of secondary flow is greater in the realistic model than in the idealized model, and the structure of secondary flow is quite different. However, other flow structures are qualitatively similar.

Simulation of the effect of local obstructions and blockage on airflow and aerosol deposition in central human airways

Investigation of the effect of sidewall and carinal tumours, airway constrictions and airway blockage on the inspiratory airflow and particle deposition in the large central human airways was the primary objective of this study. A computational fluid and particle dynamics model was implemented, validated and applied in order to simulate the air and particle transport and to quantify the aerosol deposition in double airway bifurcation models. Our investigations revealed that surface abnormalities and tubular constrictions can significantly alter the airstreams and the related local aerosol deposition distributions. Sidewall tumours have lead to an enhanced deposition of large particles and caused lower deposition efficiency values of nano-particles compared to the deposition efficiency in healthy airways. Central tumours multiplied the deposition efficiency of large particles but hardly affected the deposition efficiency of nano-particles. Airway blockage caused a significant redistribution of particle deposition sites. The deposition efficiency of the inhaled aerosols in constricted airways was much higher than the same deposition efficiency in healthy airways. Current results might help in the understanding of the adverse health effects of the inhaled air-pollutants in patients with lung disease and might be integrated into future aerosol therapy protocols.

Computational investigation of particle inertia effects on submicron aerosol deposition in the respiratory tract

Current models of submicron particle transport and deposition often ignore particle inertia for aerosols smaller than 200 nm. In the absence of inertial effects, a highly efficient Eulerian transport model can be applied that treats the particle phase as a dilute chemical species. However, the effects of inertia have not been fully quantified for aerosols in the fine and ultrafine ranges. The objective of this study is to evaluate conditions for which current chemical species Eulerian and Lagrangian particle transport models can be applied in order to predict submicron particle deposition characteristics on a regional and local basis in upper and central respiratory models. Differences between the chemical species Eulerian and Lagrangian model results have been used to evaluate conditions for which particle inertia becomes important relative to diffusional effects. The deposition characteristics of particles ranging from 5 nm to 1 μ m have been evaluated in a tubular entrance flow geometry, a double bifurcation model of upper respiratory generations G3–G5 and a double bifurcation model of central respiratory generations G7–G9. Considering the regional area-averaged deposition of submicron aerosols, the minimum particle diameters (and Stokes numbers) for which particle inertia became significant were approximately 20 nm ( St = 6.1 × 10 - 6 ) for the tubular entrance flow geometry, 70 nm ( St = 5.1 × 10 - 5 ) for the upper bifurcation model, and 140 nm ( St = 4.4 × 10 - 5 ) for the central bifurcation model. Below these critical particle diameters, numerical estimates of regional deposition were shown to be consistent with currently available analytic correlations of diffusional deposition efficiencies. In comparison to regional-averaged values, the effects of particle inertia on localized deposition characteristics were found to be much more dramatic. For the upper airway bifurcation model, inclusion of particle inertia increased the maximum local microdosimetry factor by one order of magnitude for 40 nm particles at an inhalation flow rate of 30 L/min. Results of this study indicate that particle inertia may be more significant in regional and local depositions of fine and ultrafine aerosol than previous considered. Therefore, effective models of particle transport are necessary that can maintain the efficiency of the chemical species Eulerian approach while accounting for local finite particle inertia.

Effects of Inertia and Gravity on Liquid Plug Splitting at a Bifurcation

Liquid plugs may form in pulmonary airways during the process of liquid instillation or removal in many clinical treatments. During inspiration the plug may split at airway bifurcations and lead to a nonuniform final liquid distribution, which can adversely affect treatment outcomes. In this paper, a combination of bench top experimental and theoretical studies is presented to study the effects of inertia and gravity on plug splitting in an airway bifurcation model to simulate the liquid distributions in large airways. The splitting ratio, Rs, is defined as the ratio of the plug volume entering the upper (gravitationally opposed) daughter tube to the lower (gravitationally favored) one. Rs is measured as a function of parent tube Reynolds number, Rep; gravitational orientations for roll angle, phi, and pitch angle, gamma; parent plug length LP; and the presence of pre-existing plug blockages in downstream daughter tubes. Results show that increasing Rep causes more homogeneous splitting. A critical Reynolds number Rec is found to exist so that when Rep < or = Rec, Rs = 0, i.e., no liquid enters the upper daughter tube. Rec increases while Rs decreases with increasing the gravitational effect, i.e., increasing phi and gamma. When a blockage exists in the lower daughter, Rec is only found at phi = 60 deg in the range of Rep studied, and the resulting total mass ratio can be as high as 6, which also asymptotes to a finite value for different phi as Rep increases. Inertia is further demonstrated to cause more homogeneous plug splitting from a comparison study of Rs versus Cap (another characteristic speed) for three liquids: water, glycerin, and LB-400X. A theoretical model based on entrance flow for the plug in the daughters is developed and predicts Rs versus Rep. The frictional pressure drop, as a part of the total pressure drop, is estimated by two fitting parameters and shows a linear relationship with Rep. The theory provides a good prediction on liquid plug splitting and well simulates the liquid distributions in the large airways of human lungs.

Effect of Gravity on Liquid Plug Transport Through an Airway Bifurcation Model

Many medical therapies require liquid plugs to be instilled into and delivered throughout the pulmonary airways. Improving these treatments requires a better understanding of how liquid distributes throughout these airways. In this study, gravitational and surface mechanisms determining the distribution of instilled liquids are examined experimentally using a bench-top model of a symmetrically bifurcating airway. A liquid plug was instilled into the parent tube and driven through the bifurcation by a syringe pump. The effect of gravity was adjusted by changing the roll angle (phi) and pitch angle (gamma) of the bifurcation (phi = gamma =0 deg was isogravitational). Phi determines the relative gravitational orientation of the two daughter tubes: when phi not equal to 0 deg, one daughter tube was lower (gravitationally favored) compared to the other. Gamma determines the component of gravity acting along the axial direction of the parent tube: when gamma not equal to 0 deg, a nonzero component of gravity acts along the axial direction of the parent tube. A splitting ratio Rs, is defined as the ratio of the liquid volume in the upper daughter to the lower just after plug splitting. We measured the splitting ratio, Rs, as a function of: the parent-tube capillary number (Cap); the Bond number (Bo); phi; gamma; and the presence of pre-existing plugs initially blocking either daughter tube. A critical capillary number (Cac) was found to exist below which no liquid entered the upper daughter (Rs = 0), and above which Rs increased and leveled off with Cap. Cac increased while Rs decreased with increasing phi, gamma, and Bo for blocked and unblocked cases at a given Cap > Ca,. Compared to the nonblockage cases, Rs decreased (increased) at a given Cap while Cac increased (decreased) with an upper (lower) liquid blockage. More liquid entered the unblocked daughter with a blockage in one daughter tube, and this effect was larger with larger gravity effect. A simple theoretical model that predicts Rs and Cac is in qualitative agreement with the experiments over a wide range of parameters.

Inspiratory Deposition Efficiency of Ultrafine Particles in a Human Airway Bifurcation Model

The inspiratory deposition efficiency of ultrafine particles in a physiologically realistic bronchial airway bifurcation model, approximating the airway generation 3-4 juncture, was computed for different particle sizes, ranging from 1 to 500 nm, under three different flow conditions, representing resting to heavy exercise breathing conditions. For the smallest particle sizes, say between 1 and 10 nm, molecular diffusion is the primary deposition mechanism, as indicated by the inverse relationship with flow rate, except for the highest flow rate where the additional effect of convective diffusion has to be considered as well. For the larger particle sizes, say above 20 nm, the independence from particle size and dependence on flow rate suggests that convective diffusion plays the major role for ultrafine particle deposition in bifurcations. A semiempirical equation for the inspiratory deposition efficiency, m (D, Q), as a function of diffusion coefficient D and flow rate Q, due to the combined effect of m...

Simulation of deposition and clearance of inhaled particles in central human airways.

In this study local distributions of deposited inhaled particles such as radon progenies in realistic human airway bifurcation models of bronchial generations one to six are computed for different geometries, inlet flow profiles, flow rates and particle sizes with computational fluid particle dynamics methods. The movement of the mucus layer in the large central human airways is also simulated by computational fluid dynamic techniques. There is experimental evidence that bronchogenic carcinomas mainly originate at the central zone of the large airway bifurcations, where primary hot-spots of deposition have been found. However, current lung deposition models do not take into consideration the inhomogeneity of deposition within the airways. The inhomogeneous movement of the mucus layer may strongly influence the effect of primary deposition. On the basis of our results, both the deposition and the clearance patterns are highly non-uniform, especially in the vicinity of the carinal ridge of the bifurcations.

Modeling carcinogenic effects of low doses of inhaled radionuclides

Clinical studies have indicated that carinal regions of the airway generation 3–5 are preferential sites of tumor development following inhalation of radon progenies. These coincide with the locations where primary hot spots of deposition have been found. However, current lung dosimetry models do not take into consideration the inhomogeneity of deposition within the airways. In this study, computed local distributions of deposited inhaled radionuclides, such as radon progenies in morphologically realistic human airway bifurcation models, are analyzed for different flow rates and particle sizes. Then, local deposition enhancement factors (EF), defined as the ratio of local to average deposition densities, are computed by scanning along the surface of the bifurcation with prespecified surface area elements. The computed enhancement factors indicate that cells located at carinal ridges may receive localized doses, which are two orders of magnitude higher than the average values. Here, the probability of multiple hits can be quite high even at low doses. If the number of multiple cellular hits plays a crucial role in lung cancer development, then the maximum enhancement factor could serve as a useful parameter for a mechanism-based risk analysis of inhaled radionuclides.

Local deposition distributions of inhaled radionuclides in the human tracheobronchial tree.

There is experimental evidence that bronchogenic carcinomas originate mainly at the carinal ridges of the large central airways, where primary hot spots of deposition have been found. However, current lung dosimetry models do not take into consideration the inhomogeneity of deposition within the airways. In this study, computed local distributions of deposited inhaled radionuclides such as radon progenies in morphologically realistic human airway bifurcation models are analysed for different flow rates and particle sizes. Then, local deposition enhancement factors, defined as the ratio of local to average deposition densities, are computed by scanning along the surface of the bifurcation with pre-specified surface area elements. Computed enhancement factors indicate that cells located at carinal ridges or at the inner sides of the progeny branches may receive localised doses which are two orders of magnitude higher than the average values.

The Relationship between Secondary Flows and Particle Deposition Patterns in Airway Bifurcations

The relationship between localized fluid dynamics and localized particle deposition patterns within bronchial airway bifurcations upon inspiration and expiration was analyzed for different bifurcation geometries, flow conditions, and particle sizes. For the simulation of three-dimensional airflow patterns in airway bifurcation models, the Navier-Stokes and continuity equations were solved numerically by the finite volume Computational Fluid Dynamics (CFD) program package FIRE. Spatial particle deposition patterns were determined by the intersection of randomly selected particle trajectories with the surrounding wall surfaces. While three-dimensional flow patterns were characterized by their corresponding two-dimensional secondary flow fields, three-dimensional deposition patterns were represented by their related two-dimensional deposition density plots. Two particle sizes were selected to explore the relationship between secondary flows and localized particle deposition patterns: 0.01 μm, to illustrate the effects of Brownian motion, and 10 μm, to display the effects of impaction and sedimentation. Changes in bifurcation geometry (shape of bifurcation zone, branching angle) and flow conditions (flow rate, inlet flow profile, direction of flow) lead to variations in resulting secondary flow patterns, which were reflected by corresponding differences in related particle deposition patterns. In conclusion, a distinct relationship could be observed between secondary flow patterns and deposition density plots, demonstrating that particle deposition patterns in airway bifurcations are not only determined by physical forces acting upon individual particles, but also by convective transport processes of the carrier fluid.

Deposition of rigid fibers in three-dimensional airway bifurcation models

Deposition of rigid fibers in three-dimensional airway bifurcation models

31.O.02 Simulation of airflow in a physiologically realistic airway bifurcation model

31.O.02 Simulation of airflow in a physiologically realistic airway bifurcation model

Inspiratory particle deposition in airway bifurcation models

Particle deposition in a three-dimensional bifurcation model of the human lung was computed for simultaneous effects of inertial impaction and gravitational settling. In the present approach an anatomical bifurcation unit is characterized as a contiguous system of three straight tubes with two intermediate bends, with defined radius of curvature and an effective branching angle. Idealized flow profiles of uniform velocity in the straight segments and of rotational velocity in the bend portions were assumed, the latter being corrected for physiologically realistic flow conditions. Our theoretical results show excellent agreement with published experimental data. This model is then used to predict aerosol deposition in the symmetrical Model A of Weibel [Weibel, E. R. (1963) Morphometry of the Human Lung. Springer, Berlin] and to study the effect of airway variability and asymmetry on particle deposition in the human lung.

Periodic flow at airway bifurcations. III. Energy dissipation

We measured the energy dissipation associated with large-amplitude periodic flow through airway bifurcation models. Each model consisted of a single asymmetric bifurcation with a different branching angle and area ratio, with each branch terminated into an identical elastic load. Sinusoidal volumetric oscillations were applied at the parent duct so that the upstream Reynolds number (Re) varied from 30 to 77,000 and the Womersley parameter (alpha) from 4 to 30. Pressures were measured continuously at the parent duct and at both terminals, and instantaneous branch flow rates were calculated. Time-averaged energy dissipation in the bifurcation was computed from an energy budget over a control volume integrated over a cycle and was expressed as a friction factor, F. We found that when tidal volume was small [ratio of tidal volume to resident (dead space) volume, VT/VD less than 1], F was independent of branching angle and fell with increasing alpha and VT/VD. When tidal volume was large (VT/VD greater than 1), F increased with increasing branching angle and varied less strongly with alpha and VT/VD. No simple benchmark flow represented the data well over the entire experimental range. This study demonstrates that only two nondimensional parameters, alpha and VT/VD, are necessary and are sufficient to describe time-averaged energy dissipation in a given bifurcation geometry during sinusoidal flow.

Effect of the laryngeal jet on particle deposition in the human trachea and upper bronchial airways

Abstract Preferential sites of particle deposition within the human respiratory system are known to correlate with primary cancer sites, and are therefore important in the etiology of neoplastic respiratory diseases. In this study, we characterized the intrabronchial and intratracheal patterns of deposition in a hollow cast of a human larynx-tracheobronchial tree, and examined the effects of airflow and turbulence on particle deposition by performing airflow measurements in the hollow cast and an “ideal” airway bifurcation model. Experimental results revealed a deposition “hot spot” for particles greater than 2 μm in mass median aerodynamic diameter in the trachea at 2 cm below the larynx. The enhancement of deposition in the trachea was studied by making comparative airflow and detailed morphometry measurements in a hollow lung cast and in an “ideal” model. The larynx had a significant effect on the local flow field in the trachea of the hollow cast and this effect extended to and beyond the tracheal bifurcation. This accounted for some of the difference in flow field at the bifurcation between the cast and an “ideal” model. Additional differences were related to the different shapes of the transitional regions near the bifurcation.