Regional Particle Deposition Research Articles

Asymmetric human lung morphology induce particle deposition variation

The effect of lung morphology on the heterogeneity of regional ventilation and particle deposition in the bronchial airways is studied using Horsfield's regular-asymmetric lung model. Flow distribution among the airways is calculated by solving the whole tree network, assuming laminar flow hydrodynamic resistances without accounting for gravitationally enhanced preferential airflow distribution. The variation of morphological properties, such as the lung volume and surface area distal to any airway generation, and physiological properties, such as ventilation and particle deposition, is calculated, and fractal dimensions that characterize these properties and processes are computed. The close agreement between the model fractal dimension characterizing ventilation and those found from clinical data assess the validity of the model. It is shown that the fractal dimensions that characterize the morphological properties and the physiological processes are similar, suggesting that all are related and stem from a common underlying attribute—the lung morphology. The variation of particle deposition in the lung, as well as the variation of ventilation and morphological attributes, increases moderately with the lung tree asymmetry. The deposition density, regarded as a key exposure metric or therapeutic index, does not follow a spatial scale-free distribution.

Numerical simulation of aerosol deposition in a 3-D human nasal cavity using RANS, RANS/EIM, and LES

Reynolds Averaged Navier–Stokes (RANS) simulations using a shear stress transport (SST) k - ω -based turbulence model with both mean flow tracking and random-walk/Lagrangian stochastic eddy interaction-models (EIMs) and large eddy simulation (LES) with Lagrangian particle tracking were used to model deposition of particles in a human nasal cavity geometry. Deposition of monodisperse particles (0.354– 16 μ m diameter) was studied for steady inhalation flow rates, Q, ranging from 7.5 to 60 L/min (through a single nasal passage) and various inlet turbulence intensities. Results show that the RANS/EIM approach tends to significantly over-predict particle deposition for small impaction parameters ( d a 2 Q < 200 ) whereas “mean flow particle tracking” tends to under-predict deposition over a wide range of d a 2 Q . LES particle deposition results show better agreement with in vivo data and detailed analysis shows that regional particle deposition efficiency is strongly affected by particle size. For larger particle sizes, inlet geometry of the nasal passage is thought to be important in calculating local deposition. Caution is needed when a standard RANS/EIM is used to predict deposition of particles in a human nasal cavity.

Deposition of Ultrafine (NANO) Particles in the Human Lung

Increased production of industrial devices constructed with nanostructured materials raises the possibility of environmental and occupational human exposure with consequent adverse health effects. Ultrafine (nano) particles are suspected of having increased toxicity due to their size characteristics that serve as carrier transports. For this reason, it is critical to refine and improve existing deposition models in the nano-size range. A mathematical model of nanoparticle transport by airflow convection, axial diffusion, and convective mixing (dispersion) was developed in realistic stochastically generated asymmetric human lung geometries. The cross-sectional averaged convective-diffusion equation was solved analytically to find closed-form solutions for particle concentration and losses per lung airway. Airway losses were combined to find lobar, regional, and total lung deposition. Axial transport by diffusion and dispersion was found to have an effect on particle deposition. The primary impact was in the pulmonary region of the lung for particles larger than 10 nm in diameter. Particles below 10 nm in diameter were effectively removed from the inhaled air in the tracheobronchial region with little or no penetration into the pulmonary region. Significant variation in deposition was observed when different asymmetric lung geometries were used. Lobar deposition was found to be highest in the left lower lobe. Good agreement was found between predicted depositions of ultrafine (nano) particles with measurements in the literature. The approach used in the proposed model is recommended for more realistic assessment of regional deposition of diffusion-dominated particles in the lung, as it provides a means to more accurately relate exposure and dose to lung injury and other biological responses.

Airflow Distribution in the Human Lung and its Influence on Particle Deposition

Realistic descriptions of lung geometry and physiology are the primary determinants of accurate predictions of inhaled particle deposition and distribution in the human lung. While there have been considerable efforts devoted to geometry reconstruction, little attention has been given to lung ventilation as applied to particle deposition applications. Models of lung ventilation based on pressure differential between extrathoracic airways and the pleural cavity were developed and used to calculate lobar and regional deposition of particles in the human lung. Local airflow in the lung varied in accordance with regional physiological properties. Calculations showed that airflow rate entering each lobe was different for compliant and noncompliant lung models and similar for uniform and nonuniform lung expansions. Regional particle deposition predictions were almost identical between the two compliance models. However, differences in lobar depositions were observed. The coupled lung ventilation and deposition models can be used in site-specific deposition predictions of inhaled particles in the human lungs.

A Modeling Study of the Effect of Gravity on Airflow Distribution and Particle Deposition in the Lung

Inhalation of particles generated as a result of thermal degradation from fire or smoke, as may occur on spacecraft, is of major health concern to space-faring countries. Knowledge of lung airflow and particle transport under different gravity environments is required to addresses this concern by providing information on particle deposition. Gravity affects deposition of particles in the lung in two ways. First, the airflow distribution among airways is changed in different gravity environments. Second, particle losses by sedimentation are enhanced with increasing gravity. In this study, a model of airflow distribution in the lung that accounts for the influence of gravity was used for a mathematical description of particle deposition in the human lung to calculate lobar, regional, and local deposition of particles in different gravity environments. The lung geometry used in the mathematical model contained five lobes that allowed the assessment of lobar ventilation distribution and variation of particle deposition. At zero gravity, it was predicted that all lobes of the lung expanded and contracted uniformly, independent of body position. Increased gravity in the upright position increased the expansion of the upper lobes and decreased expansion of the lower lobes. Despite a slight increase in predicted deposition of ultrafine particles in the upper lobes with decreasing gravity, deposition of ultrafine particles was generally predicted to be unaffected by gravity. Increased gravity increased predicted deposition of fine and coarse particles in the tracheobronchial region, but that led to a reduction or even elimination of deposition in the alveolar region for coarse particles. The results from this study show that existing mathematical models of particle deposition at 1 G can be extended to different gravity environments by simply correcting for a gravity constant. Controlled studies in astronauts on future space missions are needed to validate these predictions.

Calculated Deposition in Growing Tracheobronchial Airways: Effect of Growth-Rate Assumptions

Most current deterministic computer dosimetry models use idealized dichotomous symmetrical infant, child, and adolescent tracheobronchial geometries for dosimetry predictions. These tracheobronchial geometries were derived from either the morphometric measurements of J. D. Mortensen and colleagues or those of R. F. Phalen and colleagues. The airway growth curves used to create these geometries are typically means from all airways within a single generation in the tracheobronchial tree. This idealized approach implies that the growth rate of all airways in the same generation is identical (symmetric growth, SG), which is unlikely. In this study, existing morphometric measurements of airway dimensions were used to determine growth equations for airway length, diameter, branch angle, and inclination to gravity as a function of body height for each airway in the first four tracheobronchial generations. Tracheobronchial geometries (asymmetrical growth, AG) were created from these growth curves for the first 4 tracheobronchial generations representing a 4- and 11-yr-old child and an adult. Particle deposition predictions for steady inspiratory flow using 0.1- to 20-μm diameter monodisperse particles in these AG geometries were compared with predictions using the SG geometries using the uniform growth rate approach. Each airway in the first four generations had a unique airway length and diameter growth rate. Airway branch angle and inclination to gravity did not change as a function of body height. The unique airway growth rates resulted in significant differences in predicted deposition efficiency between the AG and SG geometry. Use of AG geometry may provide improved estimates of regional particle deposition in infants, children, and adolescents.

Artificial Neural Network Prediction of the Patterns of Deposition of Polydisperse Aerosols Within Human Lungs

For optimum therapeutic response from drug administered to the lungs, it is paramount that the aerosolised drug is able to deposit in the lower airways. The filtering characteristics of the respiratory tract, however, make this a particularly challenging task. Computational tools afford a cost-effective means of studying the problem, and here we report on the development of a rapid and reliable method for predicting the pattern of deposition of polydisperse aerosols within human lungs using artificial neural networks (ANNs). Literature (experimental) data on lung deposition of monodisperse aerosols were used to train a single ANN to allow for simultaneous predictions of regional and total aerosol particle deposition patterns in human lungs. When used in modelling the fate of polydisperse aerosols in human lungs, the trained ANN was found to give highly accurate predictions for all lung regions, and all (pharmaceutically relevant) particle sizes and breathing conditions (with errors typically <0.025%). Further testing of the ANN, using 'unseen' in vitro and in vivo data, gave good agreement of lung dosages. It is thus concluded that the ANN produced can be used to provide highly reliable estimates of particle deposition from polydisperse pharmaceutical aerosols generated from breath-actuated dry powder inhalers, nebulizers and metered dose inhalers with spacers.

Particle Deposition in a Cast of Human Tracheobronchial Airways

Abstract Regional particle deposition efficiency and deposition patterns were studied experimentally in a human airway replica made from an adult cadaver. The replica includes the oral cavity, pharynx, larynx, trachea, and four generations of bronchi. This study reports deposition results in the tracheobronchial (TB) region. Nine different sizes of monodispersed, polystyrene latex fluorescent particles in the size range of 0.93–30 μm were delivered into the lung cast with the flow rates of 15, 30, and 60 l min− 1. Deposition in the TB region appeared to increase with the increasing flow rate and particle size. Comparison of deposition data obtained from physical casts showed agreement with results obtained from realistic airway replicas that included the larynx. Deposition data obtained from idealized airway models or replicas showed lower deposition efficiency. We also compared experimental data with theoretical models based on a simplified bend and bifurcation model. A deposition equation derived from t...

Deposition of Coarse Particles in Cystic Fibrosis: Model Predictions Versus Experimental Results

In patients with cystic fibrosis (CF), the lung regions most affected by infection are presumed to be poorly ventilated and, hence, difficult to treat with inhaled therapeutic aerosols. Current dosimetric models do not adequately describe regional particle deposition in CF. We have developed a multiple-path particle deposition model and compared model predictions with the observed pattern of coarse particle (5 microm, mass median aerodynamic diameter) deposition in ten CF patients and eight healthy volunteers. Our model divides the lung into quadrants, separated at lobar bronchi, representing apical and basal lung regions. The volume and ventilation of quadrants were experimentally determined from a xenon equilibrium and multi-breath washout, respectively. Regional ventilation in the healthy lung was assumed to be determined largely by regional compliance. In CF patients, the deviations in regional ventilation from that observed in the healthy subjects were assumed to be due to regional resistance. A "custom" lung morphology was calculated for each subject based on their lung volume (functional residual capacity plus one-half tidal volume) and ventilation to each quadrant. Input parameters for particle deposition calculations were "custom" lung morphology, breathing pattern, and inhaled particle size. Relative to healthy subjects, the CF patients had reduced ventilation to the apices and increased ventilation to the bases of the lung. In healthy subjects, the general pattern of particle deposition followed ventilation. However, in the CF patients, the model predicted increased particle deposition in the large airways of the apices (an obstructed and poorly ventilated region) and to a lesser extent in the basal lung (relatively healthier and better-ventilated region), whereas particle deposition in the parenchyma was only increased in the basal lung and was decreased or absent in the apical lung. Our modeling strategy improves estimates of regional aerosol deposition and may be useful for predicting breathing conditions and particle size for optimal drug delivery in a given CF patient.

Gas–solid two-phase flow in a triple bifurcation lung airway model

Laminar oscillatory flow as well as micron-particle transport and wall deposition in a triple bifurcation airway model have been simulated using a validated finite-volume code with user-enhanced programs. Three realistic breathing patterns, i.e., resting, light activity and moderate exercise, were considered. Transient air flow, particle transport, and wall deposition results are shown and summarized in terms of regional particle deposition efficiencies (DEs). The effects of skewed inlet profiles on the flow field and particle deposition were recorded as well. Particle deposition may increase under cyclic flow conditions, i.e., DE-values are typically larger for cyclic flow than for steady flow evaluated at the mean flow rate of a given inhalation or exhalation pulse. While particles deposit mainly around the carinal ridges, i.e., flow dividers, during inspiratory flow due to direct impaction, they deposit on the tubular surfaces during exhalation because of strong secondary flows. Moreover, particle deposition during exhalation is much lower than for inhalation at the same local Stokes number. The comparisons of DEs among different lung generations or bifurcation areas for both cyclic inhalation and exhalation show that DEs in the third bifurcation region may be quite different from those at previous bifurcations due to upstream geometry and flow effects.

ALVEOLAR DEPOSITION OF MONODISPERSE AEROSOL PARTICLES IN THE LUNG OF PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Knowledge about the regional deposition of aerosol particles is essential in order to perform efficient inhalation therapy or to minimize health risks due to environmental or occupational aerosol particles. In this study, 2 techniques were used to measure thoracic deposition and to differentiate between bronchial and alveolar deposition. The first technique was the clearance-derived regional deposition (CRD) technique and the second the single-breath regional deposition (SBRD) technique. Deposition was measured in 12 patients with α 1 -antitrypsin deficiencyand symptoms of moderate to severe chronic obstructive pulmonary disease (COPD)using monodisperse test particles with aerodynamic diameters of 2, 3, and 4 μ m. In CRD, the kinetic of particle clearance within the first 24 hours after inhalation was used to determine bronchial and alveolar deposition. In SBRD, the longitudinal distribution of deposited inert test particles was used to calculate the particle fraction deposited within and distal to the dead space. Both techniques delivered very similar mean values for total and alveolar deposition. Due to controlled slow and deep inhalations, alveolar deposition was as much as 50%. Therefore, SBRD can be considered as an easy tool in patients.

Artificial neural network prediction of aerosol deposition in human lungs.

To develop a rapid and reliable method for predicting the pattern of aerosol particle deposition within the human lungs, using artificial neural networks (ANNs). Experimental data from the literature were used to train multi-layer perceptron (MLP) networks to allow for prediction of regional and total aerosol particle deposition patterns in human lungs. These data covered particle sizes in the range 0.05-15 microm and three different breathing patterns (ranging from "quiet" breathing to breathing "under physical work conditions"). Three different MLPs were trained, to provide separate predictions of aerosol particle deposition in the laryngeal, bronchial, and alveolar regions. The total deposition fraction for a given set of breathing conditions was computed simply as the sum of the outputs produced from the corresponding regional deposition MLPs. The ANNs developed are shown to give highly accurate predictions for both regional and total aerosol deposition patterns for all particle sizes and breathing conditions (with errors typically less than 0.04%). We conclude that the current set of ANNs can be used to give good predictions of particle deposition from polydisperse pharmaceutical aerosols generated from breath-actuated dry powder inhalers, nebulizers, and metered dose inhalers with spacers.

Estimation of regional deposition of hygroscopic sulphur particles in canine lungs

Estimation of regional deposition of hygroscopic sulphur particles in canine lungs

Extrathoracic Deposition of Inhaled, Coarse Particles (4.5 μm) in Children vs Adults

Recent epidemiological studies suggest that children have increased morbidity from particulate air pollution (Dockery et al., 1989; Schwartz et al., 1994), primarily characterised by increased incidence of cough and bronchitis in the children. In general the morbidity associations with particulate pollution have been with inhalable particles (PM10). It is not clear, however, which fraction of PM10, the coarse (2.5-10 urn MMAD) or the fine (< 2.5 urn MMAD) mode, is most responsible for these associations. While children may be especially predisposed to acute toxic effects from airborne particulates, they may also receive an increased dose of particles to their lungs compared to adults. Theoretical calculations by Xu and Yu (1986) predict enhanced deposition of particles (greater than 2 urn) in the head region for children when compared to adults. This model and others (Hoffman et al., 1989) also predict enhanced airway (tracheobronchial) deposition for particles < 5 urn MMAD in children when compared to adults. As a result of this increased filtering in the conducting airways, a smaller fraction of particles in the size range of 2-10 urn are predicted to deposit in the pulmonary region of childrens' lungs. There are limited data on the regional deposition of particles within the respiratory tract of children. Such measurements in humans have generally relied on the use of radiolabelled particles and gamma camera analysis. While the potential radiation risk has been deemed justified for studying normal adult volunteers, most investigators are reluctant to perform such studies in normal children. It may be that this risk is higher in children than in adults (Everard, 1994). Studies of children with cystic fibrosis lung disease, however, have been justified to assess regional deposition of inhaled therapeutic aerosols (Alderson et al., 1974) or to assess mucociliary clearance following inhalation therapy (App et al., 1990). In a retrospective study we analysed regional deposition of radiolabelled (Tc-99m) Fe2O3 particles (4.5 um MMAD) by gamma camera analysis in a group of children and adults with mild cystic fibrosis (CF). Because the CF patients have only mild lung disease and their upper airway anatomy is likely not dissimilar from normal, intra vs extrathoracic deposition in these patients should be similar to normals.

Deposition and Clearance of Fine Particles in the Human Respiratory Tract

Total deposition of respirable particles in the human respiratory tract is well determined by experimental data and model calculations whereas regional deposition is still under discussion, particularly in the size range from 0.1-1.0 urn particle diameter. Experimental data on regional deposition of radiolabelled aerosol particles can be derived from gamma camera images on the basis of the particle clearance kinetics during the first few days after inhalation, since the limited resolution of the planar image allows no separation between the peripheral and the bronchial airways. When particles are deposited in the human respiratory tract, two distinct phases of clearance from the thorax are usually observed: a fast cleared fraction during the first hours after inhalation followed by much slower clearance. It is generally assumed that the fast phase, completed within about 24 h, represents predominantly mucociliary clearance of particles deposited in the tracheobronchial tree, whereas the slow phase represents predominantly clearance from the alveolar region (Lippmann, 1977; Stahlhofen etal., 1980). Nevertheless, during recent years the assumption that there also exists a slow cleared component from the tracheobronchial region has been confirmed by a large number of experiments (Scheuch, 1991; Stahlhofen et al, 1994). Recently, a new radio-aerosol Technegas (TcG; Tetley Manufacturing Ltd, Lucas Heights, Australia) was developed for lung ventilation scans in nuclear medicine. Technegas (TcG) is a condensation type aerosol consisting of hydrophobic inert graphite particles. For the production of TcG 20-100 \i of Na m TcO4 in saline is put into the cavity of a graphite crucible which is dried at 50-70°C. Thereafter the cavity of the crucible is heated to 2500°C in an atmosphere of pure argon for 5 s such that carbon as well as the salt and 99m Tc evaporates, followed by condensation during cooling. This procedure is similar to the production of the C-60 molecules, named buckminster-fullerenes (Kroto et al., 1985). Therefore, it was assumed that TcG consists of ultrafine spherical particles which are formed via homogenous condensation from fullerene vapor at temperatures > 500°C. More recent investigations have shown that these ultrafine particles agglomerate rapidly to fine particles (Lemb et al., 1993). The latter is in agreement with the fact that the distribution of deposited TcG applied to the lungs of normal subjects was found in the entire ventilated lungs, that is, it is transported in the lungs like a gas.

In VivoDeposition of Inhaled Ultrafine Particles in the Respiratory Tract of Rhesus Monkeys

ABSTRACT Radon progeny are usually associated with ultrafine particles with diameters ranging from 0.001–0.005 μm for “unattached” progeny and from 0.005–0.2 μm for those attached to indoor aerosols. To assess the health effects of inhaling indoor radon progeny, it is necessary to study the regional deposition of these ultrafine particles when inhaled. Laboratory animals are often used in studies of the toxicity of inhaled particles and vapors. Information is available on the deposition of particles with diameters > 0.2 μm in the nasal passages of laboratory animals. However, there are very few data on the deposition of ultrafine particles < 0.2 μm in diameter, and most of the information has come from studies in nasal casts. In this article we describe in vivo deposition of inhaled ultrafine particles in the airways of rhesus monkeys. Two types of aerosols were used: 220Rn progeny and monodisperse 59Fe2O3 particles, in particle diameters ranging from 0.005–0.1 μm. Eight monkeys were exposed for 5–8 min a...

Repeatability of airway deposition and tracheobronchial clearance rate over three days in chronic bronchitis

Previous investigations on tracheobronchial clearance in chronic bronchitis or chronic obstructive pulmonary disease (COPD) have usually referred to measurements during a short time-period, i.e. a few hours. The purpose of this study, therefore, was to study regional particle deposition and tracheobronchial clearance during 72 h. In 14 patients with chronic bronchitis clearance of 111In-labelled 3.6 micrograms Teflon particles and lung function were measured on two occasions, with an interval of 2 weeks. Lung retention of test particles was measured at 0, 24, 48 and 72 h using a profile scanner. The weight of expectorated sputum samples was measured after the two clearance measurements. The particle retentions at all time-points were reproducible, as seen from the two measurements ( r > 0.90). The fast clearance phase was completed within 72 h. No correlation between sputum volume and clearance was seen. There was a significant negative correlation between airway resistance and the 72 h retention (r= -0.66), and an even better correlation between specific airway resistance and the 72 h retention (r = -0.82), indicating more central deposition in obstructed airways. There was no significant correlation between lung function tests reflecting smaller airways and the 72 h retentions. Deposition data agreed well with theoretical calculations and experimental data in healthy subjects. In spite of earlier findings that mucociliary transport is usually severely impaired in chronic bronchitis and COPD, the present results indicate that overall tracheobronchial mucus clearance in these patients is fairly effective, probably due to a productive cough. Alveolar deposition may be estimated by measurements of the 72 h retention in subjects with chronic obstructive pulmonary disease. The 72 h retention is dependent mainly on the calibre of larger airways. The present method of studying airway clearance during 3 days is highly reproducible.

Empirical Modeling of Particle Deposition in the Alveolar Region of the Lungs: A Basis for Interspecies Extrapolation

Empirical Modeling of Particle Deposition in the Alveolar Region of the Lungs: A Basis for Interspecies Extrapolation. Asgharian, B., Wood, R., and Schlesinger, R. B. (1995). Fundam. Appl. Toxicol. 27, 232-238. Different species exposed to the same particle atmosphere may not receive identical initial doses in comparable respiratory tract regions, and the selection of a certain species for toxicologic evaluation of inhaled particles may, thus, influence the estimated human lung, or systemic, dose, as well as its relationship to potential adverse health effects. Estimating regional particle deposition patterns is important for establishing the comparability of animal models, for understanding interspecies differences in the expression of chemical toxicities, and, ultimately, for the human risk assessment process. A method is described which offers a strategy for summarizing published data on regional deposition of particles of different diameters and calculating a deposited fraction for a particular particle size distribution. This involved the construction of nomograms to allow estimation of alveolar deposition fractions in three species, namely the human, monkey, and rat. A regression model was then developed to permit the calculation of more exact deposition fractions. Although this paper describes the procedure for one region of the lungs, the same technique can be applied to other regions of the respiratory tract or to the total system for which deposition data are available. While this technique may facilitate the interpretation of available experimental results and their application to human health risk assessment, appropriate caution should be exercised in applying the developed nomograms given limitations of the deposition database upon which it is based.

Regional Deposition and Regional Ventilation During Inhalation of Pentamidine

In most patients, the deposition of aerosolized pentamidine (AP) is less in the apex of the lung relative to the base. As the apex of the lung is relatively less ventilated than the base, it is possible that reduced regional ventilation may explain the inhomogeneity in regional drug deposition. The purpose of this study was to measure the relationship between regional deposition of AP and regional ventilation, and the influence of particle size and airway caliber on this relationship. Ten subjects with HIV infection who were receiving prophylaxis with AP were recruited. Using krypton (81mKr), we measured regional ventilation during treatment with AP, labeled with 99mTc. Two nebulizers were used (Respirgard II and Fisoneb) that produced particles of different size. In addition, patients were studied with and without a bronchodilator because changes in airway geometry can affect sites of particle deposition. There was no significant correlation between regional ventilation and regional particle deposition (r = 0.00, linear regression). Particle deposition in the upper lobes relative to the lower lobes was less than would be predicted by regional ventilation, by a ratio of 0.84 +/- 0.03 (mean +/- SE). Using two-way analysis of variance (ANOVA), the upper to lower zone deposition pattern was not affected by either nebulizer or by the use of albuterol. The Fisoneb had significantly more central deposition relative to the jet nebulizer (mean +/- SE, skC/P: Fisoneb 1.3 +/- 0.1, Respirgard 1.1 +/- 0.1, p = 0.005, two-way ANOVA). The use of a bronchodilator did not significantly affect the central/peripheral deposition pattern. We conclude that differences in deposition between upper and lower lung regions are not accounted for simply by differences in regional ventilation in patients undergoing prophylaxis with AP. In assessing the cause of regional inhomogeneities of pharmaceutical aerosol deposition (and in devising strategies to achieve more uniform distribution), regional ventilation should be measured directly rather than be inferred from the deposition pattern of the aerosol.

Regional Deposition of Particles in the Erect Human Lung Following Chamber Exposure to Ozone

Regional Deposition of Particles in the Erect Human Lung Following Chamber Exposure to Ozone