Targeted Lung Delivery of Nasally Administered Aerosols

Using the nasal route to deliver pharmaceutical aerosols to the lungs has a number of advantages, including coadministration during noninvasive ventilation. The objective of this study was to evaluate the growth and deposition characteristics of nasally administered aerosol throughout the conducting airways based on delivery with streamlined interfaces implementing two forms of controlled condensational growth technology. Characteristic conducting airways were considered including a nose-mouth-throat (NMT) geometry, complete upper tracheobronchial (TB) model through the third bifurcation (B3), and stochastic individual path (SIP) model to the terminal bronchioles (B15). Previously developed streamlined nasal cannula interfaces were used for the delivery of submicrometer particles using either enhanced condensational growth (ECG) or excipient enhanced growth (EEG) techniques. Computational fluid dynamics (CFD) simulations predicted aerosol transport, growth, and deposition for a control (4.7 μm) and three submicrometer condensational aerosols with budesonide as a model insoluble drug. Depositional losses with condensational aerosols in the cannula and NMT were less than 5% of the initial dose, which represents an order-of-magnitude reduction compared to the control. The condensational growth techniques increased the TB dose by a factor of 1.1–2.6×, delivered at least 70% of the dose to the alveolar region, and produced final aerosol sizes ≥2.5 μm. Compared to multiple commercial orally inhaled products, the nose-to-lung delivery approach increased dose to the biologically important lower TB region by factors as large as 35×. In conclusion, nose-to-lung delivery with streamlined nasal cannulas and condensational aerosols was highly efficient and targeted deposition to the lower TB and alveolar regions.

Copyright 2014 American Association for Aerosol Research     

Comparison of ambient and spray aerosol deposition in a standard induction port and more realistic mouth–throat geometry

For inhalation aerosols, it is well known that spray momentum and geometry characteristics can significantly influence deposition in the mouth–throat (MT) region. However, little is know about the quantitative influence of spray momentum on aerosol transport and deposition. The objective of this study was to evaluate the effect of spray momentum on deposition in a standard induction port (IP) and a representative MT geometry using capillary-generated aerosols. Capillary aerosol generation (CAG) was selected as a model spray aerosol system that has not been previously tested in a realistic throat geometry. To evaluate the effects of spray momentum, the transport and deposition characteristics of transient capillary-generated aerosols were compared with ambient particles of the same size inhaled at a steady flow rate of 30 L/min. To evaluate the influence of geometry, aerosols were considered in a standard IP and a more realistic MT model. A previously tested CFD model was employed to simulate aerosol transport and deposition for ambient and CAG spray aerosols in both the IP and MT geometries. Considering the capillary-generated spray, good agreement was observed for the deposition of drug mass between the in vitro experiments (IP—15.3%, MT—19.4%) and CFD model predictions without droplet evaporation (IP—14.7%, MT—20.8%). In all cases considered, deposition was increased for spray vs. ambient aerosols and in the MT geometry vs. the IP model. Based on CFD results for a representative polydisperse aerosol distribution, the deposition of ambient particles was highly sensitive to the geometry considered, with 2.9 times more deposition in the MT compared to the IP model. In contrast, deposition was less influenced by the geometry for a CAG spray aerosol, with only a 25–40% deposition increase in the MT. As a result, use of the simple IP model may provide a reasonable approximation of total MT deposition for systems with high spray momentum. However, the IP model may be less useful for evaluating the total MT deposition in systems with reduced spray momentum effects.     

Condensational Growth May Contribute to the Enhanced Deposition of Cigarette Smoke Particles in the Upper Respiratory Tract

Previous experimental studies have shown that concentrated cigarette smoke particles (CSPs) deposit in the upper airways like much larger 6 to 7 μ m aerosols. Based on the frequent assumption that relative humidity (RH) in the lungs does not exceed approximately 99.5%, the hygroscopic growth of initially submicrometer CSPs is expected to be a relatively minor factor. However, the inhalation of mainstream smoke may result in humidity values ranging from sub-saturated through supersaturated conditions. The objective of this study is to evaluate the effect of condensation particle growth on the transport and deposition of CSPs in the upper respiratory tract under various RH and temperature conditions. To achieve this objective, a computational model of transport in the continuous phase surrounding a CSP was developed for a multicomponent aerosol consisting of water soluble and insoluble species. To evaluate the transport and deposition of dilute hygroscopic CSPs in the upper airways, a model of the human mouth-throat (MT) through approximately respiratory generation G6 was considered with four steady inhalation conditions. These inhalation conditions were representative of inhaled ambient cigarette smoke as well as warm and hot saturated smoke. Results indicate that RH conditions above 100% are possible in the upper respiratory tract during the inhalation of a warm or hot saturated airstream. For sub-saturated inhalation conditions, initial evaporation of the CSPs was observed followed by hygroscopic growth and diameter increases less than approximately 50%. In contrast, the inhalation of warm or hot saturated air resulted in significant particle growth in the MT and tracheobronchial regions. For the inhalation of warm saturated air 3°C above body temperature, initially 200 and 400 nm particles were observed to increase in size to above 3 μ m near the trachea inlet. The upper boundary inhalation condition of saturated 47°C air resulted in 7 to 8 μ m droplets entering the trachea. These results do not prove that the enhanced deposition of CSPs in the upper airways is only a result of condensational growth. However, this study does highlight condensational growth as a potentially significant mechanism in the deposition of smoke particles under saturated inhalation conditions.     

Effectiveness of Direct Lagrangian Tracking Models for Simulating Nanoparticle Deposition in the Upper Airways

Direct Lagrangian particle tracking may provide an effective method for simulating the deposition of ultrafine aerosols in the upper respiratory airways that can account for finite inertia and slip correction effects. However, use of the Lagrangian approach for simulating ultrafine aerosols has been limited due to computational cost and numerical difficulties. The objective of this study is to evaluate the effectiveness of direct Lagrangian tracking methods for calculating ultrafine aerosol transport and deposition in flow fields consistent with the upper respiratory tract. Representative geometries that have been considered include a straight tubular flow field, a 90° tubular bend, and an idealized replica of the human oral airway. The Lagrangian particle tracking algorithms considered include the Fluent Brownian motion (BM) routine, a user-defined BM model, and a user-defined BM model in conjunction with a near-wall interpolation (NWI) algorithm. Lagrangian deposition results have been compared with a chemical species Eulerian model, which neglects particle inertia, and available experimental data. Results indicate that the Fluent BM routine incorrectly predicts the diffusion-driven deposition of ultrafine aerosols by up to one order of magnitude in all cases considered. For the tubular and 90° bend geometries, Lagrangian model results with a user-defined BM routine agreed well with the Eulerian model, available analytic correlations, and experimental deposition data. Considering the oral airway model, the best match to empirical deposition data over a range of particle sizes from 1 to 120 nm was provided by the Lagrangian model with user-defined BM and NWI routines. Therefore, a direct Lagrangian transport model with appropriate user-defined routines provides an effective approach to accurately predict the deposition of nanoparticles in the respiratory tract.     

CFD simulations of the Andersen cascade impactor: Model development and effects of aerosol charge

Cascade impactors are commonly used to assess the size characteristics of aerosols in toxicology and pharmaceutical applications. These aerosol instruments have been developed and refined over decades. However, a number of questions remain related to impactor performance, including the influence of electrostatic charge on measured size distributions. The objective of this study was to develop a validated CFD model of the Mark II Andersen cascade impactor (ACI) and apply this model to evaluate the effects of particle charge on deposition. The flow field was simulated using a commercial CFD code for incompressible laminar and transitional flows. Particle trajectories and deposition were evaluated using a well tested Lagrangian tracking approach that accounts for impaction, sedimentation, diffusion, and electrostatic attraction. Particle charge levels typical of dry powder inhaler (DPI) and metered dose inhaler (MDI) aerosols were considered for a particle size range of 0.3–12 μm. As a model validation, computational predictions of cutoff d₅₀ diameters for each of the eight ACI stages were found to be within 10% difference of existing experimental and manufacturer data. Results indicated that charges consistent with DPI and MDI aerosols increased deposition fraction in Stages 0–3 by up to 30% and increased deposition fraction in Stages 4–7 by up to an order of magnitude. For Stages 0–3, both DPI and MDI charges reduced the d₅₀ value by approximately 10% or less. In contrast, charged aerosols reduced the d₅₀ values in Stages 4 and 5 by 200% and 60%, respectively. All charged submicrometer aerosols considered deposited in Stages 6 and 7. Increasing the particle charge by an order of magnitude from DPI to MDI values had a relatively small effect on further decreasing the cutoff size of each stage. In conclusion, these results can be used to approximate the actual aerodynamic diameter of a charged pharmaceutical aerosol based on measurements in a standard ACI. Future applications of the developed ACI model include evaluating the influence of space charge on deposition and quantifying the effects of aerosol condensation and evaporation on size assessment.     

Deposition Characteristics of Aerosol Particles in Sequentially Bifurcating Airway Models

Local deposition efficiencies and deposition patterns of aerosol particles were studied experimentally in sequential double bifurcation tube models with two different branching geometries: one with in-plane (model A) and another with 90 out-of-plane bifurcation (model B). The dimensions of the model were similar to those of 3rd-5th generation human bronchial airways. Monodispersed oil particles (2.9-6.7 mu m diameter range) tagged with uranine were generated as test aerosols and were drawn through the model at flow rates in the Reynolds number (Re) of 283-4718. Both symmetric (1:1) and asymmetric (1:2, 1:3, and 1:0) flow patterns were used at the first bifurcation. Results showed that deposition efficiencies (DE) in each bifurcation increased with increasing Stokes number (Stk), ranging from ～1% at Stk=0.02 to ～40% at Stk=0.2, and could be fitted well with modified logistic functions. With symmetric flow conditions, DE was some what smaller in the second than the first bifurcation in both models. DE was greater in model B than model A in the second bifurcation. With asymmetric flows, DE was greater in the low-flow side compared to the high-flow side at a given Stk and this was consistent in both model A and model B. However, the average DE of the combined data for both the high- and low-flow side was similar to that with symmetric flows. Deposition pattern analysis showed highly localized deposition on and in the immediate vicinity of each bifurcation ridge at Stokes numbers as low as 0.02, regardless of branching patterns and flow distribution patterns used. These results showing detailed deposition characteristics in the sequential bifurcation geometry may prove useful for estimating local deposition dose in the airways and for developing improved lung dosimetry models.     

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.     

Deposition of Ultrafine Particles in Human Tracheobronchial Airways of Adults and Children

Inhalation exposure to ultrafine particles, including radon progeny and other combustion aerosols, has been implicated in potential health risks of ambient and indoor environments. These particles deposit in the respiratory tract mainly by diffusion. The purpose of this study was to determine the deposition pattern of nanometer-sized particles in the human tracheobronchial (TB) airways of children and young adults. The deposition was determined for 1.75, 10, and 40 nm ²¹²Pb particles at flow rates corresponding to respiratory minute volumes at rest and during moderate exercise. The 1.75 nm particles were unattached clusters, whereas the 10 and 40 nm particles were silver particles with attached ²¹²Pb clusters. Replicate casts of the upper TB airways of 3, 16, and 23 year old humans were used, including the larynx, trachea, and bronchial airways down to generations 5-8. Deposition in each generation and total deposition were measured by counting the ²¹²Pb gamma photopeak in a NaI (Tl) detector. The effects of airway geometry, particle size, and flow rate on deposition efficiency were studied. The deposition of the 1.75 nm particle, corresponding to unattached indoor radon progeny, was substantially higher than that of the 10 and 40 nm particles. The dependence of particle deposition on the flow rate was relatively weak, and deposition efficiencies were only slightly higher at the lower flow rates. The deposition models for diffusion from parabolic flow underestimated aerosol deposition, whereas the diffusion deposition predicted for plug flow overestimated the TB deposition. The deposition models resulting from this study can be used for developing lung deposition models and in the risk assessment of radon progeny and ultrafine ambient particles.     

Particle deposition in a hollow cast of the human tracheobronchial tree

The deposition of particles within the human airways was studied using a hollow silicone rubber cast of the larynx and tracheobronchial tree which extended to bronchi of approximately 0.2 cm dia. The cast was exposed to radioactively tagged, ferric oxide aerosols, having mass median aerodynamic diameters ranging from 2.5 to 8.1 μm. at three constant “inspiratory” flow rates. The detection system was designated for the determination of deposition within airways of all sizes and at various branch levels, and to allow selective measurements of the deposited activity within bifurcation and length regions of individual bronchi. Deposition efficiencies were determined and classified according to branch generation. Bifurcations were sites of preferential deposition over the range of particle sizes and flow rates used; bifurcation deposition generally peaked in generation 3.     

Computation of local enhancement factors for the quantification of particle deposition patterns in airway bifurcations

Spatial deposition patterns in two different geometric models of bronchial airway bifurcations were computed by solving numerically the 3D Navier–Stokes equations and simulating particle trajectories under the simultaneous action of impaction, sedimentation, diffusion, and interception by Monte Carlo techniques. To quantify the inhomogeneities of the predicted deposition patterns the whole surface of the bifurcation was scanned with a prespecified surface area element to determine the number of particles deposited per unit surface area. The local deposition density in a given surface element, relative to the average deposition density, was then defined as the local deposition enhancement factor.In the present study, the computation of local deposition enhancement factors focused on inspiratory particle deposition patterns. Our results revealed that the distributions of local deposition enhancement factors along the surface of a bifurcation exhibit strong inhomogeneities for all particle sizes and bifurcation geometries considered here. The maximum enhancement factor in a bifurcation was found to be about 100 in the upper bronchial airways for any particle size in the diameter range from 0.01 to 10 μm, obtained with a 100 μm×100 μm scanning element. These numerically computed local deposition enhancement factors can be directly applied to inhalation health effect protocols to consider the effects of highly localized doses.     

DEPOSITION OF SALINE DROPLETS IN A MODEL OF THE HUMAN BRONCHIAL TREE

Deposition velocities were experimentally determined for aerosols of saline droplets moving in a physical model of the human airways consisting of the first two generations of bifurcations. The aerosols were generated from aqueous solutions containing 0.9 and 1.35% NaCl (by weight) by a Collison nebulizer. The size distributions of the saline droplets were approximately lognormal, with a geometric standard deviation of 1.7. The mass median diameters were 1.04 and 1.23 jim for 0.9 and 1.35% saline droplets. The constant flow rale through the trachea was 255 cm³/scc and the relative humidity of the stream was 99.7% at 22°C, The first bifurcation consisting of the trachea and the two main bronchi, was placed horizontally, while the two second bifurcations were placed in planes normal to the first bifurcation. Because the saline droplets were not monodispersed, larger droplets tended to deposit on the lower edges of the main bronchi. The average deposition velocities on the lower edge were 1.4 ×10^?2cm/sec for 1.35% saline droplets and 1.0 × 10^?2 cm/sec for 0.9% saline droplets. The average deposition velocity on the inner edges of the main bronchi was 3.25 × 10^?3 cm/sec. for both 0.9 and 1.35% saline droplets. These results show that the deposition is nonuniform and that the degree of nonuniformity depends to a great extent on the droplet size. These factors should be taken into consideration in aerosol therapy.     

DEPOSITION OF SALINE DROPLETS IN A MODEL OF THE HUMAN BRONCHIAL TREE

Deposition velocities were experimentally determined for aerosols of saline droplets moving in a physical model of the human airways consisting of the first two generations of bifurcations. The aerosols were generated from aqueous solutions containing 0.9 and 1.35% NaCl (by weight) by a Collison nebulizer. The size distributions of the saline droplets were approximately lognormal, with a geometric standard deviation of 1.7. The mass median diameters were 1.04 and 1.23 jim for 0.9 and 1.35% saline droplets. The constant flow rale through the trachea was 255 cm³/scc and the relative humidity of the stream was 99.7% at 22°C, The first bifurcation consisting of the trachea and the two main bronchi, was placed horizontally, while the two second bifurcations were placed in planes normal to the first bifurcation. Because the saline droplets were not monodispersed, larger droplets tended to deposit on the lower edges of the main bronchi. The average deposition velocities on the lower edge were 1.4 ×10^-2cm/sec for 1.35% saline droplets and 1.0 × 10^-2 cm/sec for 0.9% saline droplets. The average deposition velocity on the inner edges of the main bronchi was 3.25 × 10^-3 cm/sec. for both 0.9 and 1.35% saline droplets. These results show that the deposition is nonuniform and that the degree of nonuniformity depends to a great extent on the droplet size. These factors should be taken into consideration in aerosol therapy.     

Measurements of the total and regional deposition of inhaled particles in the human respiratory tract

The total and regional deposition of monodisperse aerosols in the human respiratory tract has been measured in 12 healthy subjects breathing through the mouth. Radioactively labelled polystyrene particles in the aerodynamic diameter range 3.5–10.0 μm were employed. The total deposition results are similar to those reported by Stahlhofen et al. (1980), showing only a slight progressive increase with particle size, from a mean fraction of 0.79 of the inhaled aerosol at 3.5 μm, to 0.88 for 10 μm particles. The extrathoracic airways show a very marked deposition at all sizes, predominantly in the throat. The throat values rise rapidly from a mean of 0.09 at 3.5 μm to 0.36 at 10 μm particle diameter. Two intrathoracic fractions were also obtained by the widely accepted method of measuring the relative amounts of activity cleared from the thorax as a function of time. Alveolar deposition was apparently still some 0.06 of the inhaled aerosol at 10 μm particle diameter. Tracheo-bronchial deposition showed little change at any particle size except at 3.5 μm, when it was 0.24 of the inhaled aerosol.     

Aerosol deposition in 3D models of the upper airways and trachea of rhesus macaques

Abstract

Little is known about aerosol deposition in macaques, variability in deposition between animals, or how deposition in macaques and humans compare. This is despite the use of macaques in assessments of toxic aerosols that are often translated to estimates of human exposure. We used three dimensional (3D) physical models of the upper airways and trachea (UAT) of Rhesus macaques to begin to fill in this information gap. Models of the UAT of five, living rhesus macaques were produced from CT scans, using 3D printing technology. Models were exposed to a polydisperse aerosol containing 0.54 to 9.65 micron particles, during constant flowrates of 2, 4, and 6 liters per min. Percent deposition in UAT models was quantified using an Aerodynamic Particle Sizer and was compared to in vivo upper airway deposition in ten, adult human subjects. Deposition in the UAT models increased as Stokes number increased. Deposition also varied significantly between models, but intermodel variability was reduced when plotted as a function of Stokes number. Using Stokes number, deposition in four of the five UAT models overlapped with each other and also overlapped with human upper airway deposition. These models could be used to explore the relationship between factors that affect toxic aerosol deposition in the UAT in vitro and pathology following toxic aerosol exposure in Rhesus macaques in vivo. Results from those experiments could also be applicable to humans because of deposition similarities.

Copyright © 2020 American Association for Aerosol Research     

Aerosol Deposition Efficiencies and Upstream Release Positions for Different Inhalation Modes in an Upper Bronchial Airway Model

Accurate predictions of micron-particle deposition patterns and surface concentrations in lung airways are most desirable for researchers assessing health effects of toxic particles or those concerned with inhalation delivery of therapeutic aerosols. Focusing on a rigid, symmetric triple bifurcation lung airway model, i.e., Weibel's generations G3-G6, a user-enhanced and experimentally validated finite volume program has been employed to simulate the airflow and particle transport under transient laminar three-dimensional flow conditions. Specifically, the effects of 3 inhalation modes, i.e., resting and light and moderate activities, were analyzed for typical ranges of Stokes numbers (St h 0.2) and Reynolds numbers (0 h Re h 2100). The detailed results show particle deposition patterns and efficiencies in the triple bifurcation under cyclic as well as steady-state inhalation conditions. Cyclic inhalation generates higher local and segmentally-averaged deposition rates when compared to steady mean Reynolds number inhalation; however, matching Stokes and Reynolds numbers, i.e., the average between mean and peak values, were found to provide fully equivalent results for all inhalation modes and bifurcations. In addition, particle maps were developed that show the release positions of deposited aerosols.     

Method to Determine the Number of Bacterial Spores Within Aerosol Particles

We describe methodology to reveal the number of microbial spores within aerosol particles. The procedure involves visualization under differential- interference-contrast microscopy enhanced by high-resolution photography and further analysis by computer-assisted imaging. The method was used to analyze spore of Bacillus globigii in aerosols generated by a small (pressured metered-dose inhaler type) generator. Particles consisting in 1 or 2 spores accounted for 85% of all generated particles. This percentage rose to 91% when the same aerosol was collected on an Andersen cascade impactor that collected particles larger than 0.65 μm and was even higher (96%) when particles larger than 3.3 μm were also eliminated. These results demonstrate that the imaging analysis of aerosol particles collected on glass slides is sensitive to even relatively small changes in aerosol particle composition. The accuracy of the enhanced microscopic method described herein (differences between visual and computer analysis were approximately 3% of the total particle counts) seems adequate to determine the spore composition of aerosols of interest in biodefense.     

HUMAN TRACHEOBRONCHIAL DEPOSITION AND EFFECT OF A HISTAMINE AEROSOL INHALED BY EXTREMELY SLOW INHALATIONS

Twelve subjects inhaled the same amounts of histamine aerosol in both a normal provocation test and in a test with extremely slow inhalations (ESI), a method which gives deposition in small airways. The purpose was to compare dose-effect relationships in large (diameter >1 mm) and small (diameter <1 mm) ciliated airways. The effect on large airways was estimated by measurement of airway resistance (R_aw), and the effect on small airways was measured by the single-breath nitrogen test phase III slope (N₂-delta). Mouth and throat deposition of the histamine aerosol was calculated from human experimental data, and deposition in the lower airways was calculated using a computerised model for particle deposition in the lungs. The study showed that only half the dose inhaled with ESI (0.65 mg) of that inhaled with normal inhalations (1.3 mg), was needed to obtain the same degree of obstruction for large airways in spite of that the calculated deposition in large airways was 40% higher for normal inhalations than for ESI. The threefold stronger effect in large airways was probably caused by a more uniform distribution of particles within each generation with ESI compared to normal inhalations with particle deposition near the bifurcation. There was slightly higher N₂-delta with ESI, and the calculated dose to the smaller airways for the same inhaled dose was 10 times higher with ESI than with normal inhalations.     

CFD simulations of enhanced condensational growth (ECG) applied to respiratory drug delivery with comparisons to in vitro data

Enhanced condensational growth (ECG) is a newly proposed concept for respiratory drug delivery in which a submicrometer aerosol is inhaled in combination with saturated or supersaturated water vapor. The initially small aerosol size provides for very low extrathoracic deposition, whereas condensation onto droplets in vivo results in size increase and improved lung retention. The objective of this study was to develop and evaluate a CFD model of ECG in a simple tubular geometry with direct comparisons to in vitro results. The length (29 cm) and diameter (2 cm) of the tubular geometry were representative of respiratory airways of an adult from the mouth to the first tracheobronchial bifurcation. At the model inlet, separate streams of humidified air (25, 30, and 39 °C) and submicrometer aerosol droplets with mass median aerodynamic diameters (MMADs) of 150, 560, and 900 nm were combined. The effects of condensation and droplet growth on water vapor concentrations and temperatures in the continuous phase (i.e., two-way coupling) were also considered. For an inlet saturated air temperature of 39 °C, the two-way coupled numerical (and in vitro) final aerosol MMADs for initial sizes of 150, 560, and 900 nm were 1.75 μm (vs. 1.23 μm), 2.58 μm (vs. 2.66 μm), and 2.65 μm (vs. 2.63 μm), respectively. By including the effects of two-way coupling in the model, agreements with the in vitro results were significantly improved compared with a one-way coupled assumption. Results indicated that both mass and thermal two-way coupling effects were important in the ECG process. Considering the initial aerosol sizes of 560 and 900 nm, the final sizes were most influenced by inlet saturated air temperature and aerosol number concentration and were not largely influenced by initial size. Considering the growth of submicrometer aerosols to above 2 μm at realistic number concentrations, ECG may be an effective respiratory drug delivery approach for minimizing mouth–throat deposition and maximizing aerosol retention in a safe and simple manner. However, future studies are needed to explore effects of in vivo boundary conditions, more realistic respiratory geometries, and transient breathing.     

Enhanced deposition of high aspect ratio aerosols in small airway bifurcations using magnetic field alignment

The present work describes a new approach for non-invasively targeting respiratory tract deposition of high aspect ratio aerosols loaded with magnetic nanoparticles by controlling particle orientations through magnetic field alignment. Enhanced deposition of aligned particles is measured in vitro in a physical model of the small, bifurcating airways found in the lung. Unlike previous approaches to magnetic drug targeting, the approach presented herein requires no gradient in the magnetic field strength, and can be accomplished with small amounts of magnetic material compared to active drug. This approach shows promise for targeting aerosol drug delivery to specific locations within the lung.     

The influence of lung volume during imaging on CFD within realistic airway models

In this article, we address a fundamental question regarding computational fluid dynamics (CFD) modeling within lung airways: does the inhaled volume during imaging have a significant effect on CFD computations of aerosol deposition? High resolution computed tomography (HRCT) images taken at mean lung volume (MLV) and at total lung capacity (TLC) obtained as part of a previous study of ventilation and aerosol deposition using positron emission tomography (PET) in challenged asthmatics were utilized to construct two airway models for each subject, and the differences in CFD calculated deposition metrics were subsequently quantified. These models included all the airway generations that could be rendered from the HRCT images. CFD calculations for three inhalation flow rates and four monodisperse aerosol sizes used images at MLV and at TLC from 24 volunteer subjects. Both large scale and detailed measures of particle deposition distribution were used in the analysis. The influence of lung volume during imaging is to increase airway dimensions in realistic models and thus reduce flow velocity and deposition due to impaction in the upper airways as calculated by CFD. However, large-scale deposition measures are confounded when the TLC models include deeper generations in the lung that increase the total airway deposition. These trends are modulated by the flow and particle characteristics of the aerosol, making consistent quantifiable differences between MLV and TLC difficult to predict unless both models consider the same anatomical airways.

© 2017 American Association for Aerosol Research