Computational analysis of flow structure and particle deposition in a single asthmatic human airway bifurcation

This paper aims to improve current understanding of flow structure and particle deposition in asthmatic human airways. A single, symmetric airway bifurcation, corresponding to generations 10–11 of Weibel’s model, is investigated through validated numerical simulations. The parent airway segment is modelled as a smooth circular tube. The child segments are considered asthmatic and their cross-section is modelled as a constricted tube with sinusoidal folds uniformly distributed along the circumference. The flow structure and particle deposition pattern for normal (i.e., healthy) and asthmatic airway bifurcations are compared and discussed. The numerical results reveal that the secondary flow in the asthmatic airway bifurcation is much stronger than in the healthy one, resulting in higher particle deposition. The effects of size of the lumen area and number of folds on particle deposition and pressure drop are also investigated. It is found that particle deposition efficiency is significantly affected by lumen area of the asthmatic segment (the smaller the lumen area, the higher the particle deposition efficiency). The effect of number of folds is small. Particle deposition efficiency also increases with Reynolds number. The pressure drop in the asthmatic airway bifurcation depends mainly on size of the lumen area. The effect of number of folds becomes important for strongly collapsed airways.     

Effects of curved inlet tubes on air flow and particle deposition in bifurcating lung models

In vivo bifurcating airways are complex and the airway segments leading to the bifurcations are not always straight, but curved to various degrees. How do such curved inlet tubes influence the motion as well as local deposition and hence the biological responses of inhaled particulate matter in lung airways? In this paper steady laminar dilute suspension flows of micron-particles are simulated in realistic double bifurcations with curved inlet tubes, i.e., 0 degrees < or =theta< or =90 degrees, using a commercial finite-volume code with user-enhanced programs. The resulting air-flow patterns as well as particle transport and wall depositions were analyzed for different flow inlet conditions, i.e., uniform and parabolic velocity profiles, and geometric configurations. The curved inlet segments have quite pronounced effects on air-flow, particle motion and wall deposition in the downstream bifurcating airways. In contrast to straight double bifurcations, those with bent parent tubes also exhibit irregular variations in particle deposition efficiencies as a function of Stokes number and Reynolds number. There are fewer particles deposited at mildly curved inlet segments, but the particle deposition efficiencies at the downstream sequential bifurcations vary much when compared to those with straight inlets. Under certain flow conditions in sharply curved lung airways, relatively high, localized particle depositions may take place. The findings provide necessary information for toxicologic or therapeutic impact assessments and for global lung dosimetry models of inhaled particulate matter.     

Effects of tumors on inhaled pharmacologic drugs

Lung carcinomas are now the most common form of cancer. Clinical data suggest that tumors are found preferentially in upper airways, perhaps specifically at carina within bifurcations. The disease can be treated by aerosolized pharmacologic drugs. To enhance their efficacies site-specific drugs must be deposited selectively. Since inhaled particles are transported by air, flow patterns will naturally affect their trajectories. Therefore, in Part I of a systematic investigation, we focused on tumor-induced effects on airstreams, in Part II (the following article [p. 245]), particle trajectories were determined. To facilitate the targeted delivery of inhaled drugs, we simulated bifurcations with tumors on carinas using a commercial computational fluid dynamics (CFD) software package (FIDAP) with a Cray T90 supercomputer and studied effects of tumor sizes and ventilatory parameters on localized flow patterns. Critical tumor sizes existed; e.g., tumors had dominant effects when r/R > or = 0.8 for bifurcation 3-4 and r/R > or = 0.6 for bifurcation 7-8 (r = tumor radius and R = airway radius). The findings suggest that computer modeling is a means to integrate alterations to airway structures caused by diseases into aerosol therapy protocols.     

Particle Deposition in Oral-tracheal Airway Models with Very Low Inhalation Profiles

Considerable progress has been made on modeling particle deposition in the oral-tracheal airway under some normal breathing conditions,i.e.,resting,light activity and moderate exercise.None of these standard breathing patterns correspond to very low inhalation profiles.It is known that particle deposition in the oral-tracheal airway is greatly influenced by flow and particle inlet conditions.In this work,very low inhalation flow rates are considered.Particle deposition is numerically investigated in different oral-tracheal airway models,i.e.,circular,elliptic and realistic oral-tracheal airway models.Both micro- and nano-particles that are normally present in cigarette smoke are considered.Results show that inhalation profiles greatly influence the particle deposition.Due to relatively low flow rate,for ultra-fine particles,the oral deposition is enhanced due to longer residence time in oral cavity and stronger Brownian motion.However,for larger particles,less particles deposit in the oral-tracheal airway due to the weaker impaction.The transition happens when particle size changes from 0.01 μm to 0.1 μm.The influence of the limited entrance area is shown and discussed.Under the low inhalation profiles,the highest deposition fraction could be in either circular or realistic models depending on the particle property and the geometric characteristic of oral cavity.The knowledge obtained in this study may be beneficial for the design of bionic inhaler and understanding of health effect from smoke particle on human being.     

Computational analysis of micron-particle deposition in a human triple bifurcation airway model

Steady laminar axisymmetric inhalation flow and wall deposition of micron-size particles in representative triple bifurcation airways have been simulated using a commercial finite-volume code with user-enhanced programs. Assuming spherical non-interacting particles (3 microm相似文献   

Computational Analysis of Micron-particle Deposition in a Human Triple Bifurcation Airway Model

Steady laminar axisymmetric inhalation flow and wall deposition of micron-size particles in representative triple bifurcation airways have been simulated using a commercial finite-volume code with user-enhanced programs. Assuming spherical non-interacting particles (3 μm≤ d p ≤7 μm), various inlet Reynolds numbers (Re=500-2000) and Stokes numbers (St=0.02-0.23) were considered. The resulting particle deposition patterns were analyzed and then summarized in terms of deposition efficiencies, i.e. DE=DE(Re,St) Surprisingly high DE-values occur at relatively low Reynolds numbers (e.g., Re=500 ) in the third bifurcation. The quantitative results are of interest to researchers either conducting health risk assessment studies for inhaled particulate pollutants or analyzing drug aerosol inhalation and deposition at desired lung target sites.     

Particle deposition in obstructed airways

One approach to tackle the particle deposition in human lungs in close proximity is to develop an understanding of the particle motion in bifurcation airways. Chronic obstructive pulmonary disease (COPD) is one of the most common diseases in humans. COPD always results in inflammation that leads to narrowing and obstructing of the airways. The obstructive airways can alter the respiratory flow and particle deposition significantly. In order to study the effect of obstruction on particle deposition, four three-dimensional four-generation lung models based on the 23-generation model of Weibel [1963. Morphometry of the Human Lung. New York Academic Press, Springer, Berlin.] have been generated. The fully three-dimensional incompressible laminar Navier-Stokes equations are solved using computational fluid dynamics (CFD) solver on structured hexahedral meshes. Subsequently, a symmetric four-generation airway model serves as the reference and the other three models are considered to be obstructed at each generation, respectively. The calculation results show that the obstructive airway has significant influence on the particle deposition down-stream of the obstruction. The skewed velocity profile in the bifurcation airway is modified by the throat; consequently, more particles impact on the divider which results in higher deposition efficiency.     

Particle transport modeling in pulmonary airways with high-order elements

Inhaled particles can be either harmful (e.g., smoke, exhaust, viruses) or beneficial (e.g., a therapeutic drug). The accurate and computationally efficient simulation of particle transport and deposition remains a challenge because it requires the simultaneous solution of the Navier-Stokes equations and multiple advection-diffusion mass transport equations when the particles are modeled as multiple mono-dispersed populations. The solution of these equations requires that multiple length scales be resolved since the ratio of advection to diffusion varies among the different equations. Here, the spectral element method is examined because the high-order approximation provides greater flexibility in resolving multiple length scales. The problem geometry is based on the Weibel model A of the human airway for convergence tests and the first three generations of a typical rat airway for experimental validation. Particles in the size range 1 to 100 nm are simulated for deposition results. The particle concentration and flux were determined using meshes of varying coarseness to represent the geometry along with basis polynomials of order 5 to 11. The higher-order elements accurately propagate the short wavelengths contained in the advection-diffusion solution without sacrificing efficiency for the more computationally expensive Navier-Stokes solution. As the diffusion coefficient in the advection-diffusion equation decreases (i.e., particle size increases) the advantages of the spectral elements become apparent for the coupled system.     

Ozone exposure alters tracheobronchial mucociliary function in humans

Mucociliary function is a primary defense mechanism of the tracheobronchial airways, and yet the response of this system to an inhalational hazard, such as ozone, is undefined in humans. Utilizing noninvasive techniques to measure deposition and retention of insoluble radiolabeled particles on airway mucous membranes, we studied the effect on mucus transport of 0.2 and 0.4 ppm ozone compared with filtered air (FA) in seven healthy males. During 2-h chamber exposures, subjects alternated between periods of rest and light exercise with hourly spirometric measurement of lung function. Mechanical and mucociliary function responses to ozone by lung airways appeared concentration dependent. Reduction in particle retention was significant (P less than 0.005) (i.e., transport of lung mucus was increased during exposure to 0.4 ppm ozone and was coincident with impaired lung function; e.g., forced vital capacity and midmaximal flow rate fell by 12 and 16%, respectively, and forced expiratory volume at 1 s by 5%, of preexposure values). Regional analysis indicated that mucus flow from distal airways into central bronchi was significantly increased (P less than 0.025) by 0.2 ppm ozone. This peripheral effect, however, was buffered by only a marginal influence of 0.2 ppm ozone on larger bronchi, such that the resultant mucus transport for all airways of the lung in aggregate differed only slightly from FA exposures. These data may reflect differences in regional diffusion of ozone along the respiratory tract, rather than tissue sensitivity. In conclusion, mucociliary function of humans is acutely stimulated by ozone and may result from fluid additions to the mucus layer from mucosal and submucosal secretory cells and/or alteration of epithelial permeability.     

Distribution of airway narrowing responses across generations and at branching points,assessed in vitro by anatomical optical coherence tomography

Background

Previous histological and imaging studies have shown the presence of variability in the degree of bronchoconstriction of airways sampled at different locations in the lung (i.e., heterogeneity). Heterogeneity can occur at different airway generations and at branching points in the bronchial tree. Whilst heterogeneity has been detected by previous experimental approaches, its spatial relationship either within or between airways is unknown.

Methods

In this study, distribution of airway narrowing responses across a portion of the porcine bronchial tree was determined in vitro. The portion comprised contiguous airways spanning bronchial generations (#3-11), including the associated side branches. We used a recent optical imaging technique, anatomical optical coherence tomography, to image the bronchial tree in three dimensions. Bronchoconstriction was produced by carbachol administered to either the adventitial or luminal surface of the airway. Luminal cross sectional area was measured before and at different time points after constriction to carbachol and airway narrowing calculated from the percent decrease in luminal cross sectional area.

Results

When administered to the adventitial surface, the degree of airway narrowing was progressively increased from proximal to distal generations (r = 0.80 to 0.98, P < 0.05 to 0.001). This ''serial heterogeneity'' was also apparent when carbachol was administered via the lumen, though it was less pronounced. In contrast, airway narrowing was not different at side branches, and was uniform both in the parent and daughter airways.

Conclusions

Our findings demonstrate that the bronchial tree expresses intrinsic serial heterogeneity, such that narrowing increases from proximal to distal airways, a relationship that is influenced by the route of drug administration but not by structural variations accompanying branching sites.     

Airway remodeling in allergen-challenged Brown Norway rats: distribution of proteoglycans

Proteoglycans (PG) have important effects on the mechanical properties of tissues and the phenotype of various structural cells. Little is known about changes in PG deposition in the airways in animal models of asthma. We studied changes in PG in the airway wall of Brown Norway rats sensitized to ovalbumin (OA) and exposed to repeated OA challenge. Control (Sal) animals were sensitized and challenged with saline. After the 3rd challenge, animals were killed and lungs fixed in formalin. Tissue sections were incubated with antibodies to the small, leucine-rich PG, decorin, and biglycan and collagen type I. Airways were classified according to basement membrane perimeter length (< or =0.99, 1-2.99, and > or =3 mm). Decorin, biglycan, and collagen type I were increased in the airways of OA vs. Sal rats. Remodeling was most prominent in central airways. The distribution of PG differed with respect to the subepithelial vs. airway smooth muscle (ASM) vs. adventitial layer. Whereas biglycan was readily detected within the ASM, decorin and collagen were detected outside the ASM and especially in the adventitial layer. Differences in the distribution of these molecules within the layers of the airway wall may reflect their specific functional roles.     

Effect of resting smooth muscle length on contractile response in resistance airways

We studied the effect of resting smooth muscle length on the contractile response of the major resistance airways (generations 0-5) in 18 mongrel dogs in vivo using tantalum bronchography. Dose-response curves to 10(-10) to 10(-7) mol/kg methacholine (MCh) were generated [at functional residual capacity (FRC)] by repeated intravenous bolus administration using tantalum bronchography after each dose. Airway constriction varied substantially with dose-equivalent stimulation and varied sequentially from trachea (8.8 +/- 2.2% change in airway diam) to fifth-generation bronchus (49.8 +/- 3.0%; P less than 0.001). Length-tension curves were generated for each airway to determine the airway diameter (i.e., resting in situ smooth muscle length) at which maximal constriction was elicited using bolus intravenous injection of 10(-8) mol/kg MCh. A Frank-Starling relationship was obtained for each airway; the transpulmonary pressure at which maximal constriction was elicited increased progressively from 2.50 +/- 1.12 cmH2O for trachea (approximately FRC) to 18.3 +/- 1.05 cmH2O for fifth-generation airways (approximately 50% TLC) (P less than 0.001). A similar relationship was obtained when change in airway diameter was plotted as a function of airway radius. We demonstrate substantial heterogeneity in the lung volumes at which maximal constriction is elicited and in distribution of parasympathomimetic constriction within the first few generations of resistance bronchi. Our data also suggest that lung hyperinflation may lead to augmented airway contractile responses by shifting resting smooth muscle length toward optimum resting smooth muscle length.     

Aerosol transport and deposition in sequentially bifurcating airways

Deposition patterns and efficiencies of a dilute suspension of inhaled particles in three-dimensional double bifurcating airway models for both in-plane and 90 deg out-of-plane configurations have been numerically simulated assuming steady, laminar, constant-property air flow with symmetry about the first bifurcation. Particle diameters of 3, 5, and 7 microns were used in the simulation, while the inlet Stokes and Reynolds numbers varied from 0.037 to 0.23 and 500 to 2000, respectively. Comparisons between these results and experimental data based on the same geometric configuration showed good agreement. The overall trend of the particle deposition efficiency, i.e., an exponential increase with Stokes number, was somewhat similar for all bifurcations. However, the deposition efficiency of the first bifurcation was always larger than that of the second bifurcation, while in general the particle efficiency of the out-of-plane configuration was larger than that of the in-plane configuration. The local deposition patterns consistently showed that the majority of the deposition occurred in the carinal region. The distribution pattern in the first bifurcation for both configurations were symmetric about the carina, which was a direct result of the uniaxial flow at the inlet. The deposition patterns about the second carina showed increased asymmetry due to highly nonuniform flow generated by the first bifurcation and were extremely sensitive to bifurcation orientation. Based on the deposition variations between bifurcation levels and orientations, the use of single bifurcation models was determined to be inadequate to resolve the complex fluid-particle interactions that occur in multigenerational airways.     

Computational fluid dynamics simulations of particle deposition in large-scale, multigenerational lung models

Computational fluid dynamics (CFD) has emerged as a useful tool for the prediction of airflow and particle transport within the human lung airway. Several published studies have demonstrated the use of Eulerian finite-volume CFD simulations coupled with Lagrangian particle tracking methods to determine local and regional particle deposition rates in small subsections of the bronchopulmonary tree. However, the simulation of particle transport and deposition in large-scale models encompassing more than a few generations is less common, due in part to the sheer size and complexity of the human lung airway. Highly resolved, fully coupled flowfield solution and particle tracking in the entire lung, for example, is currently an intractable problem and will remain so for the foreseeable future. This paper adopts a previously reported methodology for simulating large-scale regions of the lung airway (Walters, D. K., and Luke, W. H., 2010, "A Method for Three-Dimensional Navier-Stokes Simulations of Large-Scale Regions of the Human Lung Airway," ASME J. Fluids Eng., 132(5), p. 051101), which was shown to produce results similar to fully resolved geometries using approximate, reduced geometry models. The methodology is extended here to particle transport and deposition simulations. Lagrangian particle tracking simulations are performed in combination with Eulerian simulations of the airflow in an idealized representation of the human lung airway tree. Results using the reduced models are compared with those using the fully resolved models for an eight-generation region of the conducting zone. The agreement between fully resolved and reduced geometry simulations indicates that the new method can provide an accurate alternative for large-scale CFD simulations while potentially reducing the computational cost of these simulations by several orders of magnitude.     

Disposition of Mulberry Pollen in the Human Respiratory System: A Mathematical Model

Inhaled particle deposition sites must be identified to effectively treat human airway diseases. We have determined distribution patterns of a selected aeroallergen, mulberry pollen, among human extrathoracic (ET: i.e., oronasopharyngeal) regions and the lung. A predictive model validated by inhalation exposure data from human subjects was utilized. Deposition locations were primarily functions of (1) mulberry particle parameters (geometric size, 11–18 μm; shape, spherical; and density, 1.14 g cm^?3), and (2) mode of breathing. In the general population, two styles of inhalation are prevalent, normal augmentors (NAs) and mouth breathers (MBs). Their clinical definitions are based on intra-ET airflow divisions. For a NA-mode breathing sedentary (minute ventilation = V_E = 10 L min^?1) adult, 93% of inhaled mulberry pollen was removed by the ET compartment and 7% collected within the lung. For a MB, the respective deposition efficiencies were 75% and 25%. To apply the model, we used a daily springtime mulberry pollen concentration of 1748 grains m^?3 and an exposure time of 0.5 hour to calculate actual doses for the respiratory system. Under the stipulated conditions, a MB would inhale 524 pollen grains per day and 131 would be deposited in the lung; the value is 37 grains for a NA. Preliminary epidemiological results suggest 15% of the study population are MBs in whom such pollen deposits are likely contributors to airway disease.     

Flow distribution through human and canine airways during inhalation and exhalation

Airflow distribution through the tracheobronchial tree is influenced by many factors. In a hollow cast of the central airways, the only factors involved are resistance and inertia of the airflow. Distribution of steady flow during both inhalation and exhalation was measured at different total flow rates in human and canine tracheobronchial casts. The resulting airflow rates in peripheral segments were measured with a sensitive apparatus, which did not disturb the distribution of flow. Inertia of the airflow was found to be small but significant in airways of the human cast and substantially greater in the canine airway cast than in the human cast during inhalation. The influence of airflow inertia during inhalation was largely responsible for the different distributions of flow during inhalation and exhalation through the airway casts. Airflow resistance was found to be considerably greater during exhalation and may have contributed to the redistribution of flow. The forces involved are small but should be considered when modeling the in vivo distribution of airflow.     

Deposition of micrometer particles in pulmonary airways during inhalation and breath holding

We investigated how breath holding increases the deposition of micrometer particles in pulmonary airways, compared with the deposition during inhalation period. A subject-specific airway model with up to thirteenth generation airways was constructed from multi-slice CT images. Airflow and particle transport were simulated by using GPU computing. Results indicate that breath holding effectively increases the deposition of 5μm particles for third to sixth generation (G3-G6) airways. After 10s of breath holding, the particle deposition fraction increased more than 5 times for 5μm particles. Due to a small terminal velocity, 1μm particles only showed a 50% increase in the most efficient case. On the other hand, 10μm particles showed almost complete deposition due to high inertia and high terminal velocity, leading to an increase of 2 times for G3-G6 airways. An effective breath holding time for 5μm particle deposition in G3-G6 airways was estimated to be 4-6s, for which the deposition amount reached 75% of the final deposition amount after 10s of breath holding.     

Changes in airway length after unilateral pneumonectomy in weanling ferrets

We have previously shown that airway cross-sectional area increases 15-20% after pneumonectomy in weanling ferrets by measuring bronchial casts. We have now reanalyzed these same casts to quantitate changes in airway length after pneumonectomy. In each cast the distance from each of 120 airways to the terminal bronchiole along its axial pathway was measured. The relationship between the logarithm of this distance and that of the fraction of the lobe subtended by an airway could be described by a quadratic equation with a correlation coefficient greater than 0.85. Subsegmental and more distal airways of postpneumonectomy animals were 33-47% longer than those of controls. Overall the main axial pathway of airways in the left lower lobes was 12% longer in operated animals, but this increase was primarily accounted for by an increase in the length of the more peripheral airways. Central airways were little if any longer in operated animals. After pneumonectomy in weanling ferrets, subsegmental and peripheral airway lengths increase to a greater degree than lung volume and airway cross-sectional area, whereas central airway lengths increase to a lesser extent if at all. The mechanisms responsible for this difference between central and intralobar compensatory airway growth are unknown.     

Rat airway morphometry measured from in situ MRI-based geometric models

Rodents have been widely used to study the environmental or therapeutic impact of inhaled particles. Knowledge of airway morphometry is essential in assessing geometric influence on aerosol deposition and in developing accurate lung models of aerosol transport. Previous morphometric studies of the rat lung performed ex situ provided high-resolution measurements (50-125 μm). However, it is unclear how the overall geometry of these casts might have differed from the natural in situ appearance. In this study, four male Wistar rat (268 ± 14 g) lungs were filled sequentially with perfluorocarbon and phosphate-buffered saline before being imaged in situ in a 7-T magnetic resonance (MR) scanner at a resolution of 0.2 × 0.2 × 0.27 mm. Airway length, diameter, gravitational, bifurcation, and rotational angles were measured for the first four airway generations from 3D geometric models built from the MR images. Minor interanimal variability [expressed by the relative standard deviation RSD (=SD/mean)] was found for length (0.18 ± 0.07), diameter (0.15 ± 0.15), and gravitational angle (0.12 ± 0.06). One rat model was extended to 16 airway generations. Organization of the airways using a diameter-defined Strahler ordering method resulted in lower interorder variability than conventional generation-based grouping for both diameter (RSD = 0.12 vs. 0.42) and length (0.16 vs. 0.67). Gravitational and rotational angles averaged 82.9 ± 37.9° and 53.6 ± 24.1°, respectively. Finally, the major daughter branch bifurcated at a smaller angle (19.3 ± 14.6°) than the minor branch (60.5 ± 19.4°). These data represent the most comprehensive set of rodent in situ measurements to date and can be used readily in computational studies of lung function and aerosol exposure.