Improving Pulmonary Nanotherapeutics Using Helical Aerosol Streams: An In Silico Study.

The increasing prevalence of pulmonary ailments including asthma, chronic obstructive pulmonary disorder, lung tuberculosis, and lung cancer, coupled with the success of pulmonary therapy, has led to a plethora of scientific research focusing on improving the efficacy of pulmonary drug delivery systems. Recent advances in nanoscience and nano-engineering help achieve this by developing stable, potent, inhalable nanosize drug formulations that potentially increase dosages at target sites with significant therapeutic effects. In this study, we numerically analyze a novel methodology of incorporating helical air-nanoparticle streams for pulmonary nanotherapeutics, using a customized version of the open-source computational fluid dynamics (CFD) toolbox openfoam. As nanoparticles predominantly follow streamlines, helical airflow transports them in a centralized core along the human upper respiratory tract, thereby minimizing deposition and hence waste on the oropharyngeal walls, potentially also reducing the risk of drug-induced toxicity in healthy tissues. Advancing our previous study on micron-particle dynamics, helical streams are shown to improve the delivery of nanodrugs, to deeper lung regions when compared to a purely axial fluid-particle jet. For example, an optimal helical stream featuring a volumetric flow rate of 30 L/min, increased the delivery of 300-nm particles to regions beyond generation 3 by 5%, in comparison to a conventional axial jet. Results from regional deposition studies are presented to demonstrate the robustness of helical flows in pulmonary drug delivery, thus paving the way toward successful implementation of the novel methodology in nanotherapeutics.

A Lagrangian Approach for Calculating Microsphere Deposition in a One-Dimensional Lung-Airway Model.

Using the open-source software openfoam as the solver, a novel approach to calculate microsphere transport and deposition in a 1D human lung-equivalent trumpet model (TM) is presented. Specifically, for particle deposition in a nonlinear trumpetlike configuration a new radial force has been developed which, along with the regular drag force, generates particle trajectories toward the wall. The new semi-empirical force is a function of any given inlet volumetric flow rate, micron-particle diameter, and lung volume. Particle-deposition fractions (DFs) in the size range from 2 µm to 10 µm are in agreement with experimental datasets for different laminar and turbulent inhalation flow rates as well as total volumes. Typical run times on a single processor workstation to obtain actual total deposition results at comparable accuracy are 200 times less than that for an idealized whole-lung geometry (i.e., a 3D-1D model with airways up to 23rd generation in single-path only).

Computational analysis of non-spherical particle transport and deposition in shear flow with application to lung aerosol dynamics--a review.

All naturally occurring and most man-made solid particles are nonspherical. Examples include air-pollutants in the nano- to micro-meter range as well as blood constituents, drug particles, and industrial fluid-particle streams. Focusing on the modeling and simulation of inhaled aerosols, theories for both spherical and nonspherical particles are reviewed to analyze the contrasting transport and deposition phenomena of spheres and equivalent spheres versus ellipsoids and fibers.

Nanoparticle mass transfer from lung airways to systemic regions--Part I: Whole-lung aerosol dynamics.

This is a two-part paper describing inhaled nanoparticle (NP) transport and deposition in a model of a human respiratory tract (Part I) as well as NP-mass transfer across barriers into systemic regions (Part II). Specifically, combining high-resolution computer simulation results of inhaled NP deposition in the human airways (Part I) with a multicompartmental model for NP-mass transfer (Part II) allows for the prediction of temporal NP accumulation in the blood and lymphatic systems as well as in organs. An understanding of nanoparticle transport and deposition in human respiratory airways is of great importance, as exposure to nanomaterial has been found to cause serious lung diseases, while the use of nanodrugs may have superior therapeutic effects. In Part I, the fluid-particle dynamics of a dilute NP suspension was simulated for the entire respiratory tract, assuming steady inhalation and planar airways. Thus, a realistic airway configuration was considered from nose/mouth to generation 3, and then an idealized triple-bifurcation unit was repeated in series and parallel to cover the remaining generations. Using the current model, the deposition of NPs in distinct regions of the lung, namely extrathoracic, bronchial, bronchiolar, and alveolar, was calculated. The region-specific NP-deposition results for the human lung model were used in Part II to determine the multicompartmental model parameters from experimental retention and clearance data in human lungs. The quantitative, experimentally validated results are useful in diverse fields, such as toxicology for exposure-risk analysis of ubiquitous nanomaterial as well as in pharmacology for nanodrug development and targeting.

Nanoparticle mass transfer from lung airways to systemic regions--Part II: Multi-compartmental modeling.

This is the second article of a two-part paper, combining high-resolution computer simulation results of inhaled nanoparticle deposition in a human airway model (Kolanjiyil and Kleinstreuer, 2013, "Nanoparticle Mass Transfer From Lung Airways to Systemic Regions--Part I: Whole-Lung Aerosol Dynamics," ASME J. Biomech. Eng., 135(12), p. 121003) with a new multicompartmental model for insoluble nanoparticle barrier mass transfer into systemic regions. Specifically, it allows for the prediction of temporal nanoparticle accumulation in the blood and lymphatic systems and in organs. The multicompartmental model parameters were determined from experimental retention and clearance data in rat lungs and then the validated model was applied to humans based on pharmacokinetic cross-species extrapolation. This hybrid simulator is a computationally efficient tool to predict the nanoparticle kinetics in the human body. The study provides critical insight into nanomaterial deposition and distribution from the lungs to systemic regions. The quantitative results are useful in diverse fields such as toxicology for exposure-risk analysis of ubiquitous nanomaterial and pharmacology for nanodrug development and targeting.

Analysis of improved oral drug delivery with different helical stream inhalation modes.

A challenging aspect of pulmonary drug delivery devices, e.g., metered dose inhalers (MDIs), is to deliver therapeutic drugs to prescribed target locations at the required dosage level. In this study, validated computer simulations of micron-drug inhalation with angled or radially positioned helical fluid-particle streams are simulated and analyzed. For a suitable swirl number significant improvements in drug delivery, especially to deeper lung regions, have been achieved. Specifically, considering realistic polydisperse particle distributions at the mouth inlet for a subject-specific upper lung airway geometry, a 10-degree angled helical stream increased the local efficacy by up to 26% in comparison to a conventional helical stream, causing an overall dosage of about 60% to the deep lung. Considering lobe-specific drug targeting scenarios, while using an off-center, i.e., radially well positioned, helical-flow mouthpiece, the local particle-deposition efficacy increased from 9% to 24% in the left lobe and from 25% to 38% in the right lobe in comparison to conventional drug-aerosol stream released from the central position. The efficacy of helical streams for pulmonary drug delivery applications has been established.

Deposition of naphthalene and tetradecane vapors in models of the human respiratory system.

Jet-propulsion fuel (particularly JP-8) is currently being used worldwide, exposing especially Air Force personnel and people living near airfields to JP-8 vapors and aerosols during aircraft fueling, maintenance operations, and/or cold starts. JP-8 is a complex mixture containing >200, mostly toxic, aliphatic and aromatic hydrocarbon compounds of which tetradecane and naphthalene were chosen as two representative chemical markers for computer simulations. Thus, transport and deposition of naphthalene and tetradecane vapors have been simulated in models of the human respiratory system. The inspiratory deposition data were analyzed in terms of regional deposition fractions (DFs) and deposition enhancement factors (DEF). The vapor depositions are affected by vapor properties (e.g. diffusivity), airway geometric features, breathing patterns, inspiratory flow rates, as well as airway-wall absorption parameter. Specifically, the respiratory uptake of vapors is greatly influenced by the degree of airway-wall absorption. For example, being an almost insoluble species in the mucus layer, the deposition of tetradecane vapor is nearly zero in the extrathoracic and tracheobronchial (TB) airways, that is, the DF is <1%. The remaining vapors may penetrate further and deposit in the alveolar airways. The DF of tetradecane vapors during inhalation in the alveolar region can range from 7% to 24%, depending on breathing waveform, inhalation rate, and thickness of the mucus layer. In contrast, naphthalene vapor almost completely deposits in the extrathoracic and TB airways and hardly moves downstream and deposits in the respiratory zone. The DFs of naphthalene vapor in the extrathoracic airways from nasal/oral to trachea under normal breathing conditions (Q = 15-60 L/min) are about 12-34%, although they are about 66-87% in the TB airways. In addition, the variation of breathing routes (say, from nasal breathing to oral breathing) may influence the vapor deposition in the regions of nasal and oral cavities, nasopharynx and oropharynx, but hardly affects the deposition at and beyond the larynx. The different deposition patterns of naphthalene and tetradecane vapors in the human respiratory system may indicate different toxic and hence health effects of these toxic jet-fuel components.

Comparison of micron- and nano-particle transport in the human nasal cavity with a focus on the olfactory region.

Intranasal administration of drugs serves as a promising, noninvasive option for the treatment of various disorders of the central nervous system and upper respiratory tract. Predictive, ie, realistic and accurate, particle tracking in the human nasal cavities is an essential step to achieve these goals. The major factors affecting aerosol transport and deposition are the inhalation flowrate, the particle characteristics, and the nasal airway geometry. In vivo and in vitro studies using nasal cavity casts provide realistic images regarding particle-deposition pattern. Computational Fluid-Particle Dynamics (CF-PD) studies can offer a flexible, detailed and cost effective solution to the problem of direct drug delivery. The open-source software OpenFOAM was employed to conduct, after model validation, laminar and turbulent fluid-particle dynamics simulations for representative nasal cavities. Specifically, micron particles and nanoparticles were both individually tracked for different steady airflow rates to determine sectional deposition efficiencies. For micron particles, inertial forces were found to be the dominating factor, resulting in higher deposition for larger particles, mainly due to impaction. In contrast, diffusional effects are more important for nanoparticles. With a focus on the olfactory region, the detailed analysis of sectional deposition concentrations, considering a wide range of particle diameters, provide new physical insight to the particle dynamics inside human nasal cavities. The laminar/turbulent Euler-Lagrange modelling approach for simulating the fate of nanoparticles form a foundation for future studies focusing on targeted drug delivery. A major application would be direct nanodrug delivery to the olfactory region to achieve large local concentrations for possible migration across the blood-brain-barrier.

Modeling Airflow and Particle Deposition in a Human Acinar Region.

The alveolar region, encompassing millions of alveoli, is the most vital part of the lung. However, airflow behavior and particle deposition in that region are not fully understood because of the complex geometrical structure and intricate wall movement. Although recent investigations using 3D computer simulations have provided some valuable information, a realistic analysis of the air-particle dynamics in the acinar region is still lacking. So, to gain better physical insight, a physiologically inspired whole acinar model has been developed. Specifically, air sacs (i.e., alveoli) were attached as partial spheroids to the bifurcating airway ducts, while breathing-related wall deformation was included to simulate actual alveolar expansion and contraction. Current model predictions confirm previous notions that the location of the alveoli greatly influences the alveolar flow pattern, with recirculating flow dominant in the proximal lung region. In the midalveolar lung generations, the intensity of the recirculating flow inside alveoli decreases while radial flow increases. In the distal alveolar region, the flow pattern is completely radial. The micron/submicron particle simulation results, employing the Euler-Lagrange modeling approach, indicate that deposition depends on the inhalation conditions and particle size. Specifically, the particle deposition rate in the alveolar region increases with higher inhalation tidal volume and particle diameter. Compared to previous acinar models, the present system takes into account the entire acinar region, including both partially alveolated respiratory bronchioles as well the fully alveolated distal airways and alveolar sacs. In addition, the alveolar expansion and contraction have been calculated based on physiological breathing conditions which make it easy to compare and validate model results with in vivo lung deposition measurements. Thus, the current work can be readily incorporated into human whole-lung airway models to simulate/predict the flow dynamics of toxic or therapeutic aerosols.

Mice-to-men comparison of inhaled drug-aerosol deposition and clearance.

Part of the effective prediction of the pharmacokinetics of drugs (or toxic particles) requires extrapolation of experimental data sets from animal studies to humans. As the respiratory tracts of rodents and humans are anatomically very different, there is a need to study airflow and drug-aerosol deposition patterns in lung airways of these laboratory animals and compare them to those of human lungs. As a first step, interspecies computational comparison modeling of inhaled nano-to-micron size drugs (50 nm < d<15µm) was performed using mouse and human upper airway models under realistic breathing conditions. Critical species-specific differences in lung physiology of the upper airways and subsequently in local drug deposition were simulated and analyzed. In addition, a hybrid modeling methodology, combining Computational Fluid-Particle Dynamics (CF-PD) simulations with deterministic lung deposition models, was developed and predicted total and regional drug-aerosol depositions in lung airways of both mouse and man were compared, accounting for the geometric, kinematic and dynamic differences. Interestingly, our results indicate that the total particle deposition fractions, especially for submicron particles, are comparable in rodent and human respiratory models for corresponding breathing conditions. However, care must be taken when extrapolating a given dosage as considerable differences were noted in the regional particle deposition pattern. Combined with the deposition model, the particle retention and clearance kinetics of deposited nanoparticles indicates that the clearance rate from the mouse lung is higher than that in the human lung. In summary, the presented computer simulation models provide detailed fluid-particle dynamics results for upper lung airways of representative human and mouse models with a comparative analysis of particle lung deposition data, including a novel mice-to-men correlation as well as a particle-clearance analysis both useful for pharmacokinetic and toxicokinetic studies.

Modeling airflow and particle transport/deposition in pulmonary airways.

A review of research papers is presented, pertinent to computer modeling of airflow as well as nano- and micron-size particle deposition in pulmonary airway replicas. The key modeling steps are outlined, including construction of suitable airway geometries, mathematical description of the air-particle transport phenomena and computer simulation of micron and nanoparticle depositions. Specifically, diffusion-dominated nanomaterial deposits on airway surfaces much more uniformly than micron particles of the same material. This may imply different toxicity effects. Due to impaction and secondary flows, micron particles tend to accumulate around the carinal ridges and to form "hot spots", i.e., locally high concentrations which may lead to tumor developments. Inhaled particles in the size range of 20nm< or =dp< or =3microm may readily reach the deeper lung region. Concerning inhaled therapeutic particles, optimal parameters for mechanical drug-aerosol targeting of predetermined lung areas can be computed, given representative pulmonary airways.

Direct nanodrug delivery for tumor targeting subject to shear-augmented diffusion in blood flow.

The advent of multifunctional nanoparticle has enabled numerous innovative strategies in diagnostics, imaging, and cancer therapy. Despite the intense research efforts in developing new nanoparticles and surface bonding ligands, one major obstacle in achieving highly effective treatment, including minimizing detrimental side effects, is the inability to deliver drug-carrying nanoparticles from the injection point directly to the tumor site. The present study seeks to employ a direct nanodrug delivery methodology to feed multifunctional nanoparticles directly to tumor vasculatures, sparing healthy tissue. An important aspect to examine is how the interactions between such nanoparticles and relatively large red blood cells would affect the transport and delivery efficiency of nanodrugs. So, a novel computer simulation model has been developed to study nanoparticle transport in a representative human hepatic artery system, subject to shear-induced diffusion of nanoparticles due to hydrodynamic interactions with red blood cells. The particle-size effect was also evaluated by comparing the dynamics of nanoparticles with microspheres. Results from computer simulations under physiologically realistic conditions indicate that shear-induced diffusion has a significant effect on nanoparticle transport, even in large arteries. Nevertheless, as documented, direct nanodrug delivery to tumor-feeding hepatic artery branches is feasible. Graphical abstract Direct nanodrug delivery from injection point to tumor-feeding artery branch.

Computational analyses of a pressurized metered dose inhaler and a new drug-aerosol targeting methodology.

The popular pressurized metered dose inhaler (pMDI), especially for asthma treatment, has undergone various changes in terms of propellant use and valve design. Most significant are the choice of hydrofluoroalkane-134a (HFA-134a) as a new propellant (rather than chlorofluorocarbon, CFC), a smaller exit nozzle diameter and attachment of a spacer in order to reduce ultimately droplet size and spray inhalation speed, both contributing to higher deposition efficiencies and hence better asthma therapy. Although asthma medicine is rather inexpensive, the specter of systemic side effects triggered by inefficient pMDI performance and the increasing use of such devices as well as new targeted drug-aerosol delivery for various lung and other diseases make detailed performance analyses imperative. For the first time, experimentally validated computational fluid-particle dynamics technique has been applied to simulate airflow, droplet spray transport and aerosol deposition in a pMDI attached to a human upper airway model, considering different device propellants, nozzle diameters, and spacer use. The results indicate that the use of HFA (replacing CFC), smaller valve orifices (0.25 mm instead of 0.5 mm) and spacers (ID = 4.2 cm) leads to best performance mainly because of smaller droplets generated, which penetrate more readily into the bronchial airways. Experimentally validated computer simulations predict that 46.6% of the inhaled droplets may reach the lung for an HFA-pMDI and 23.2% for a CFC-pMDI, both with a nozzle-exit diameter of 0.25 mm. Commonly used inhalers are nondirectional, and at best only regional drug-aerosol deposition can be achieved. However, when inhaling expensive and aggressive medicine, or critical lung areas have to be reached, locally targeted drug-aerosol delivery is imperative. For that reason the underlying principle of a future line of "smart inhalers" is introduced. Specifically, by generating a controlled air-particle stream, most of the inhaled drug aerosols reach predetermined lung sites, which are associated with specific diseases and/or treatments. Using the same human upper airway model, experimentally confirmed computer predictions of controlled particle transport from mouth to generation 3 are provided.

Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part II: Dry powder inhaler application.

Pulmonary drug delivery is becoming a favored route for administering drugs to treat both lung and systemic diseases. Examples of lung diseases include asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD) as well as respiratory distress syndrome (ARDS) and pulmonary fibrosis. Special respiratory drugs are administered to the lungs, using an appropriate inhaler device. Next to the pressurized metered-dose inhaler (pMDI), the dry powder inhaler (DPI) is a frequently used device because of the good drug stability and a minimal need for patient coordination. Specific DPI-designs and operations greatly affect drug-aerosol formation and hence local lung deposition. Simulating the fluid-particle dynamics after use of a DPI allows for the assessment of drug-aerosol deposition and can also assist in improving the device configuration and operation. In Part I of this study a first-generation whole lung-airway model (WLAM) was introduced and discussed to analyze particle transport and deposition in a human respiratory tract model. In the present Part II the drug-aerosols are assumed to be injected into the lung airways from a DPI mouth-piece, forming the mouth-inlet. The total as well as regional particle depositions in the WLAM, as inhaled from a DPI, were successfully compared with experimental data sets reported in the open literature. The validated modeling methodology was then employed to study the delivery of curcumin aerosols into lung airways using a commercial DPI. Curcumin has been implicated to possess high therapeutic potential as an antioxidant, anti-inflammatory and anti-cancer agent. However, efficacy of curcumin treatment is limited because of the low bioavailability of curcumin when ingested. Hence, alternative drug administration techniques, e.g., using inhalable curcumin-aerosols, are under investigation. Based on the present results, it can be concluded that use of a DPI leads to low lung deposition efficiencies because large amounts of drugs are deposited in the oral cavity. Hence, the output of a modified DPI has been evaluated to achieve improved drug delivery, especially needed when targeting the smaller lung airways. This study is the first to utilize CF-PD methodology to simulate drug-aerosol transport and deposition under actual breathing conditions in a whole lung model, using a commercial dry-powder inhaler for realistic inlet conditions.

Nanomedicine for Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome.

Acute lung injury and acute respiratory distress syndrome (ARDS) represent a heterogenous group of lung disease in critically ill patients that continues to have high mortality. Despite the increased understanding of the molecular pathogenesis of ARDS, specific targeted treatments for ARDS have yet to be developed. ARDS represents an unmet medical need with an urgency to develop effective pharmacotherapies. Multiple promising targets have been identified that could lead to the development of potential therapies for ARDS; however, they have been limited because of difficulty with the mode of delivery, especially in critically ill patients. Nanobiotechnology is the basis of innovative techniques to deliver drugs targeted to the site of inflamed organs, such as the lungs. Nanoscale drug delivery systems have the ability to improve the pharmacokinetics and pharmacodynamics of agents, allowing an increase in the biodistribution of therapeutic agents to target organs and resulting in improved efficacy with reduction in drug toxicity. Although attractive, delivering nanomedicine to lungs can be challenging as it requires sophisticated systems. Here we review the potential of novel nanomedicine approaches that may prove to be therapeutically beneficial for the treatment of this devastating condition.

Hemodynamic Parameters and Early Intimal Thickening in Branching Blood Vessels.

Intimal thickening due to atherosclerotic lesions or intimal hyperplasia in medium to large blood vessels is a major contributor to heart disease, the leading cause of death in the Western World. Balloon angioplasty with stenting, bypass surgery, and endarterectomy (with or without patch reconstruction) are some of the techniques currently applied to occluded blood vessels. On the basis of the preponderance of clinical evidence that disturbed flow patterns play a key role in the onset and progression of atherosclerosis and intimal hyperplasia, it is of interest to analyze suitable hemodynamic wall parameters that indicate susceptible sites of intimal thickening and/or favorable conditions for thrombi formation. These parameters, based on the wall shear stress, wall pressure, or particle deposition, are applied to interpret experimental/clinical observations of intimal thickening. Utilizing the parameters as "indicator" functions, internal branching blood vessel geometries are analyzed and possibly altered for different purposes: early detection of possibly highly stenosed vessel segments, prediction of future disease progression, and vessel redesign to potentially improve long-term patency rates. At the present time, the focus is on the identification of susceptible sites in branching blood vessels and their subsequent redesign, employing hemodynamic wall parameters. Specifically, the time-averaged wall shear stress (WSS), its spatial gradient (WSSG), the oscillatory shear index (OSI), and the wall shear stress angle gradient (WSSAG) are compared with experimental data for an aortoceliac junction. Then, the OSI, wall particle density (WPD), and WSSAG are segmentally averaged for different carotid artery bifurcations and compared with clinical data of intimal thickening. The third branching blood vessel under consideration is the graft-to-vein anastomosis of a vascular access graft Suggested redesigns reduce several hemodynamic parameters (i.e., the WSSG, WSSAG, and normal pressure gradient [NPG]), thereby reducing the likelihood of restenosis, especially near the critical toe region.

Analysis and computer program for rupture-risk prediction of abdominal aortic aneurysms.

BACKGROUND: Ruptured abdominal aortic aneurysms (AAAs) are the 13th leading cause of death in the United States. While AAA rupture may occur without significant warning, its risk assessment is generally based on critical values of the maximum AAA diameter (> 5 cm) and AAA-growth rate (> 0.5 cm/year). These criteria may be insufficient for reliable AAA-rupture risk assessment especially when predicting possible rupture of smaller AAAs. METHODS: Based on clinical evidence, eight biomechanical factors with associated weighting coefficients were determined and summed up in terms of a dimensionless, time-dependent severity parameter, SP(t). The most important factor is the maximum wall stress for which a semi-empirical correlation has been developed. RESULTS: The patient-specific SP(t) indicates the risk level of AAA rupture and provides a threshold value when surgical intervention becomes necessary. The severity parameter was validated with four clinical cases and its application is demonstrated for two AAA cases. CONCLUSION: As part of computational AAA-risk assessment and medical management, a patient-specific severity parameter 0 < SP(t) < 1.0 has been developed. The time-dependent, normalized SP(t) depends on eight biomechanical factors, to be obtained via a patient's pressure and AAA-geometry measurements. The resulting program is an easy-to-use tool which allows medical practitioners to make scientific diagnoses, which may save lives and should lead to an improved quality of life.

Transport and uptake of MTBE and ethanol vapors in a human upper airway model.

Potential human exposure to vapors of methyl tertiary-butyl ether (MTBE) and ethanol is of increasing concern because these materials are widely used as gasoline additives. In this study we analyzed numerically the transport and deposition of MTBE and ethanol vapors in a model of the human upper respiratory airway, consisting of an oral airway and the first four generations of the tracheobronchial tree. Airflow characteristics and mass transfer processes were analyzed at different inspiratory flow conditions using a three-dimensional computational fluid and particle dynamics method. The deposition data were analyzed in terms of regional deposition fractions (DF = regional uptake/mouth concentration) and deposition enhancement factors (DEF = local DF/average DF) at local micro surface areas. Results show that DF in the entire upper airway model is 21.9%, 12.4%, and 6.9% for MTBE and 67.5%, 51.5%, and 38.5% for ethanol at a flow rate of 15, 30, and 60 L/min, respectively. Of the total DF, 65-70% is deposited in the oral airway for both vapors. Deposition is localized at various sites within the upper airway structure, with a maximum DEF of 1.5 for MTBE and 7.8 for ethanol. Local deposition patterns did not change with inhalation conditions, but DF and the maximum DEF increased with diffusivity, solubility, and the degree of airway wall absorption of vapors, as shown by a greater deposition of ethanol than MTBE. The vapor deposition efficiency as expressed by the dimensionless mass transfer coefficient correlated well with a product of Reynolds (Re) and Schmidt (Sc) numbers. In conclusion, MTBE and ethanol vapors deposit substantially in the upper airway structure with a marked enhancement of dose at local sites, and the deposition dose may be reasonably estimated by a functional relationship with dimensionless fluid flow and diffusion parameters.

Isotonic and hypertonic saline droplet deposition in a human upper airway model.

The evaporative and hygroscopic effects and deposition of isotonic and hypertonic saline droplets have been simulated from the mouth to the first four generations of the tracheobronchial tree under laminar-transitional-turbulent inspiratory flow conditions. Specifically, the local water vapor transport, droplet evaporation rate, and deposition fractions are analyzed. The effects of inhalation flow rates, thermodynamic air properties and NaCl-droplet concentrations of interest are discussed as well. The validated computer simulation results indicate that the increase of NaCl-solute concentration, increase of inlet relative humidity, or decrease of inlet air temperature may reduce water evaporation and increase water condensation at saline droplet surfaces, resulting in higher droplet depositions due to the increasing particle diameter and density. However, solute concentrations below 10% may not have a very pronounced effect on droplet deposition in the human upper airways.

Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part I: Theory and model validation.

Computational predictions of aerosol transport and deposition in the human respiratory tract can assist in evaluating detrimental or therapeutic health effects when inhaling toxic particles or administering drugs. However, the sheer complexity of the human lung, featuring a total of 16 million tubular airways, prohibits detailed computer simulations of the fluid-particle dynamics for the entire respiratory system. Thus, in order to obtain useful and efficient particle deposition results, an alternative modeling approach is necessary where the whole-lung geometry is approximated and physiological boundary conditions are implemented to simulate breathing. In Part I, the present new whole-lung-airway model (WLAM) represents the actual lung geometry via a basic 3-D mouth-to-trachea configuration while all subsequent airways are lumped together, i.e., reduced to an exponentially expanding 1-D conduit. The diameter for each generation of the 1-D extension can be obtained on a subject-specific basis from the calculated total volume which represents each generation of the individual. The alveolar volume was added based on the approximate number of alveoli per generation. A wall-displacement boundary condition was applied at the bottom surface of the first-generation WLAM, so that any breathing pattern due to the negative alveolar pressure can be reproduced. Specifically, different inhalation/exhalation scenarios (rest, exercise, etc.) were implemented by controlling the wall/mesh displacements to simulate realistic breathing cycles in the WLAM. Total and regional particle deposition results agree with experimental lung deposition results. The outcomes provide critical insight to and quantitative results of aerosol deposition in human whole-lung airways with modest computational resources. Hence, the WLAM can be used in analyzing human exposure to toxic particulate matter or it can assist in estimating pharmacological effects of administered drug-aerosols. As a practical WLAM application, the transport and deposition of asthma drugs from a commercial dry-powder inhaler is discussed in Part II.