Deposition Of Inhaled Particles Research Articles

Non-local impact of distal airway constrictions on patterns of inhaled particle deposition.

Airway constriction and blockage in obstructive lung diseases cause ventilation heterogeneity and create barriers to effective drug deposition. Established computational particle-deposition models have not accounted for these impacts of disease. We present a new particle-deposition model that calculates ventilation based on the resistance of each airway, such that ventilation responds to airway constriction. The model incorporates distal airway constrictions representative of cystic fibrosis, allowing us to investigate the resulting impact on patterns of deposition. Unlike previous models, our model predicts how constrictions affect deposition in airways throughout the lungs, not just in the constricted airways. Deposition is reduced in airways directly distal and proximal to constrictions. When constrictions are clustered together, central-airways deposition can increase significantly in regions away from constrictions, but distal-airways deposition in those regions remains largely unchanged. We use our model to calculate lung clearance index (LCI), a clinical measure of ventilation heterogeneity, after applying constrictions of varying severities in one lobe. We find an increase in LCI coinciding with significantly reduced deposition in the affected lobe. Our results show how the model provides a framework for development of computational tools that capture the impacts of airway disease, which could significantly affect predictions of regional dosing.

Design of a multilayer lung chip with multigenerational alveolar ducts to investigate the inhaled particle deposition.

We present the development and application of a multilayer microfluidic lung chip designed to accurately replicate the human respiratory bronchi, providing an innovative platform for controlled particle deposition in the lung. By employing a quantitative control method of fluid velocity through the deformation of an elastic PDMS membrane, this platform mimics the passive breathing process in humans and allows for precise simulation of the respiration cycle. We utilized time-lapse photography of fluorescent particles in a water/glycerol solution to qualitatively observe fluid morphology in the channel, while a chip-aerosol exposure device combined with microscopy imaging was employed to visualise aerosol deposition. Both experimental and numerical simulation results showed that particle concentration decreased towards the distal generations of the lung, and that changes in breathing pattern significantly affected particle deposition trends. Furthermore, we found that increasing the residence time of particles in the channel facilitated deeper particle deposition, achievable by adjusting parameters such as breath-hold time, exhalation time, respiration cycle length, and tidal volume. The proposed microfluidic lung chip device has significant potential for future research in respiratory health and inhaled drug delivery, providing an efficient, cost-effective, and ethical alternative to traditional in vivo studies.

A novel in-situ method to determine the respiratory tract deposition of carbonaceous particles reveals dangers of public commuting in highly polluted megacity

BackgroundExposure to air pollutants is one of the major environmental health risks faced by populations globally. Information about inhaled particle deposition dose is crucial in establishing the dose–response function for assessing health-related effects due to exposure to air pollution.ObjectiveThis study aims to quantify the respiratory tract deposition (RTD) of equivalent black carbon (BC) particles in healthy young adults during a real-world commuting scenario, analyze factors affecting RTD of BC, and provide key parameters for the assessment of RTD.MethodsA novel in situ method was applied to experimentally determine the RTD of BC particles among subjects in the highly polluted megacity of Metro Manila, Philippines. Exposure measurements were made for 40 volunteers during public transport and walking.ResultsThe observed BC exposure concentration was up to 17-times higher than in developed regions. The deposition dose rate (DDR) of BC was up to 3 times higher during commute inside a public transport compared to walking (11.6 versus 4.4 μg hr−1, respectively). This is twice higher than reported in similar studies. The average BC mass deposition fraction (DF) was found to be 43 ± 16%, which can in large be described by individual factors and does not depend on gender.ConclusionsCommuting by open-sided public transport, commonly used in developing regions, poses a significant health risk due to acquiring extremely high doses of carcinogenic traffic-related pollutants. There is an urgent need to drastically update air pollution mitigation strategies for reduction of dangerously high emissions of BC in urban setting in developing regions. The presented mobile measurement set-up to determine respiratory tract deposition dose is a practical and cost-effective tool that can be used to investigate respiratory deposition in challenging environments.

An Update on Advancements and Challenges in Inhalational Drug Delivery for Pulmonary Arterial Hypertension.

A lethal condition at the arterial–alveolar juncture caused the exhaustive remodeling of pulmonary arterioles and persistent vasoconstriction, followed by a cumulative augmentation of resistance at the pulmonary vascular and, consequently, right-heart collapse. The selective dilation of the pulmonary endothelium and remodeled vasculature can be achieved by using targeted drug delivery in PAH. Although 12 therapeutics were approved by the FDA for PAH, because of traditional non-specific targeting, they suffered from inconsistent drug release. Despite available inhalation delivery platforms, drug particle deposition into the microenvironment of the pulmonary vasculature and the consequent efficacy of molecules are influenced by pathophysiological conditions, the characteristics of aerosolized mist, and formulations. Uncertainty exists in peripheral hemodynamics outside the pulmonary vasculature and extra-pulmonary side effects, which may be further exacerbated by underlying disease states. The speedy improvement of arterial pressure is possible via the inhalation route because it has direct access to pulmonary arterioles. Additionally, closed particle deposition and accumulation in diseased tissues benefit the restoration of remolded arterioles by reducing fallacious drug deposition in other organs. This review is designed to decipher the pathological changes that should be taken into account when targeting the underlying pulmonary endothelial vasculature, especially with regard to inhaled particle deposition in the alveolar vasculature and characteristic formulations.

3D printer particle emissions: Translation to internal dose in adults and children

Desktop fused deposition modeling (FDM®) three-dimensional (3D) printers are becoming increasingly popular in schools, libraries, and among home hobbyists. FDM® 3D printers have been shown to release ultrafine airborne particles in large amounts, indicating the potential for inhalation exposure and consequent health risks among FDM® 3D printer users and other room occupants including children. These particles are generated from the heating of thermoplastic polymer feedstocks during the FDM® 3D printing process, with the most commonly used polymers being acrylonitrile butadiene styrene (ABS) and poly-lactic acid (PLA). Risk assessment of these exposures demands estimation of internal dose, especially to address intra-human variability across life stages. Dosimetry models have proven to effectively translate particle exposures to internal dose metrics relevant to evaluation of their effects in the respiratory tract. We used the open-access multiple path particle dosimetry (MPPD v3.04) model to estimate inhaled particle deposition in different regions of the respiratory tract for children of various age groups from three months to eighteen years old adults. Mass concentration data for input into the MPPD model were calculated using particle size distribution and density data from experimental FDM® 3D printer emissions tests using both ABS and PLA. The impact of changes in critical parameters that are principal determinants of inhaled dose, including: sex, age, and exposure duration, was examined using input parameter values available from the International Commission on Radiological Protection. Internal dose metrics used included regional mass deposition, mass deposition normalized by pulmonary surface area, surface area of deposited particles by pulmonary surface area, and retained regional mass. Total mass deposition was found to be highest in the 9-year-old to 18-year-old age groups with mass deposition by pulmonary surface area highest in 3-month-olds to 9-year-olds and surface area of deposited particles by pulmonary surface area to be highest in 9-year-olds. Clearance modeling revealed that frequent 3D printer users are at risk for an increased cumulative retained dose.

Assessing the relationship between movement and airflow in the upper airway using computational fluid dynamics with motion determined from magnetic resonance imaging

BackgroundComputational fluid dynamics simulations of respiratory airflow in the upper airway reveal clinically relevant information, including sites of local resistance, inhaled particle deposition, and the effect of pathological constrictions. Unlike previous simulations, which have been performed on rigid anatomical models from static medical imaging, this work utilises ciné imaging during respiration to create dynamic models and more closely represent airway physiology. MethodsAirway movement maps were obtained from non-rigid image registration of fast-cine MRI and applied to high-spatial-resolution airway surface models. Breathing flowrates were recorded simultaneously with imaging. These data formed the boundary conditions for large eddy simulation computations of the airflow from exterior mask to bronchi. Simulations with rigid geometries were performed to demonstrate the resulting airflow differences between airflow simulations in rigid and dynamic airways. FindingsIn the analysed rapid breathing manoeuvre, incorporating airway movement significantly changed the findings of the CFD simulations. Peak resistance increased by 19.8% and occurred earlier in the breath. Overall pressure loss decreased by 19.2%, and the proportion of flow in the mouth increased by 13.0%.Airway wall motion was out-of-phase with the air pressure force, demonstrating the presence of neuromuscular motion. In total, the anatomy did 25.2% more work on the air than vice versa. InterpretationsRealistic movement of the airway is incorporated into CFD simulations of airflow in the upper airway for the first time. This motion is vital to producing clinically relevant computational models of respiratory airflow and will allow novel analysis of dynamic conditions, such as sleep apnoea.

Effect of static vs. dynamic imaging on particle transport in CT-based numerical models of human central airways

Advances in quantitative computed tomography (CT) has provided methods to assess the detailed structure of the pulmonary airways and parenchyma, providing the means of applying computational fluid dynamics-based modeling to better understand subject-specific differences in structure-to-function relationships. Most of the previous numerical studies, seeking to predict patterns of inhaled particle deposition, have considered airway geometry and regional ventilation derived from static images. Because geometric alterations of the airway and parenchyma associated with regional ventilation may greatly affect particle transport, we have sought to investigate the effect of rigid vs. deforming airways, linear vs. nonlinear airway deformations, and step-wise static vs. dynamic imaging on particle deposition with varying numbers of intermediate lung volume increments. Airway geometry and regional ventilation at different time points were defined by four-dimensional (space and time) dynamic or static CT images. Laminar, transitional, and turbulent air flows were reproduced with a three-dimensional eddy-resolving computational fluid dynamics model. Finally, trajectories of particles were computed with the Lagrangian tracking algorithm. The results demonstrated that static-imaging-based models can contribute 7% uncertainty to overall particle distribution and deposition primarily due to regional flow rate (ventilation) differences as opposed to geometric alterations. The effect of rigid vs. deforming airways on serial distribution of particles over generations was significantly smaller than reported in a previous study that used the symmetric Weibel geometric model with smaller flow rate. Rigid vs. deforming airways were also shown to affect parallel particle distribution over lobes by 8% and the differences associated with use of static vs. dynamic imaging was 18%. These differences demonstrate that estimates derived from static vs. dynamic imaging can significantly affect the assessment of particle distribution heterogeneity. The effect of linear vs. nonlinear airway deformations was within the uncertainty due to mesh size.

Novel multi-functional europium-doped gadolinium oxide nanoparticle aerosols facilitate the study of deposition in the developing rat lung.

Ambient ultrafine particulate matter (UPM), less than 100 nm in size, has been linked to the development and exacerbation of pulmonary diseases. Age differences in susceptibility to UPM may be due to a difference in delivered dose as well as age-dependent differences in lung biology and clearance. In this study, we developed and characterized aerosol exposures to novel metal oxide nanoparticles containing lanthanides to study particle deposition in the developing postnatal rat lung. Neonatal, juvenile and adult rats (1, 3 and 12 weeks old) were nose only exposed to 380 μg m(-3) of ∼30 nm europium doped gadolinium oxide nanoparticles (Gd2O3:Eu(3+)) for 1 h. The deposited dose in the nose, extrapulmonary airways and lungs was determined using inductively-coupled plasma mass spectroscopy. The dose of deposited particles was significantly greater in the juvenile rats at 2.22 ng per g body weight compared to 1.47 ng per g and 0.097 ng per g for the adult and neonate rats, respectively. Toxicity was investigated in bronchoalveolar lavage fluid (BALF) by quantifying recovered cell types, and measuring lactate dehydrogenase activity and total protein. The toxicity data suggests that the lanthanide particles were not acutely toxic or inflammatory with no increase in neutrophils or lactate dehydrogenase activity at any age. Juvenile and adult rats had the same mass of deposited NPs per gram of lung tissue, while neonatal rats had significantly less NPs deposited per gram of lung tissue. The current study demonstrates the utility of novel lanthanide-based nanoparticles to study inhaled particle deposition in vivo and has important implications for nanoparticles delivery to the developing lung either as therapies or as a portion of particulate matter air pollution.

Categorization of Lung Morphology Based on FRC and Height: Computer Simulations of Aerosol Deposition

The aim of this study was to compare the human subject experimental measurements of particle deposition within the lungs using the aerosol bolus technique with the results of analytical modeling as a basis for assessing the influence of lung morphology on inhaled particle deposition patterns. A methodology for scaling the lung morphology, based on a classic symmetric dichotomous model, as a function of both functional residual capacity and height of the investigated population is presented. Because of the availability of deposition data for male and female lung morphologies, these were used as an example to address the importance of adjusting lung morphology in calculating the aerosol deposition rates. In order to represent the 2 groups based on gender enrolled in the experimental study, 2 lung morphologies have been built. An analytical and mechanistic model was used to mimic the bolus delivery technique and simulate the aerosol deposition in each of the 2 groups. Predicted results were compared with exp...

New developments in aerosol dosimetry

Dosimetry provides information linking environmental exposures to sites of deposition, removal from these sites, and translocation of deposited materials. Dosimetry also aids in extrapolating laboratory animal and in vitro data to humans. Recent progress has shed light on: properties of particles in relation to their fates in the body; influence of age, gender, body size, and lung diseases on inhaled particle doses; particle movement to the brain via the olfactory nerves; and particle deposition hot spots in the respiratory tract. Ultrafine size has emerged as an important dosimetric characteristic. Particle count, composition, and surface properties are recognized as potentially important toxicology-related considerations. Differences in body size influence airway sizes, inhaled particle deposition, specific ventilation, and specific doses (e.g. per unit body mass). Related to body size, age, gender, species, and strain are also dosimetric considerations. Diseases, such as chronic obstructive pulmonary disease (COPD) and bronchitis, produce uneven doses within the respiratory tract. Traditional concepts of the translocation and clearance of deposited particles have been challenged. Ultrafine particles can translocate to the brain via olfactory nerves, and from the lung to other organs. The clearance rates of particles from tracheobronchial airways are slowed by respiratory tract infections, but newer evidence implies that slow particle clearance from this region also exists in healthy lungs. Finally, hot spots of particle deposition are seen in hollow models, lung tissue, and dosimetric simulations. Local doses to groups of epithelial cells can be much greater than those to surrounding cells. The new insights challenge dosimetry scientists.

Deposition and biokinetics of inhaled nanoparticles.

Particle biokinetics is important in hazard identification and characterization of inhaled particles. Such studies intend to convert external to internal exposure or biologically effective dose, and may help to set limits in that way. Here we focus on the biokinetics of inhaled nanometer sized particles in comparison to micrometer sized ones.The presented approach ranges from inhaled particle deposition probability and retention in the respiratory tract to biokinetics and clearance of particles out of the respiratory tract. Particle transport into the blood circulation (translocation), towards secondary target organs and tissues (accumulation), and out of the body (clearance) is considered. The macroscopically assessed amount of particles in the respiratory tract and secondary target organs provides dose estimates for toxicological studies on the level of the whole organism. Complementary, microscopic analyses at the individual particle level provide detailed information about which cells and subcellular components are the target of inhaled particles. These studies contribute to shed light on mechanisms and modes of action eventually leading to adverse health effects by inhaled nanoparticles.We review current methods for macroscopic and microscopic analyses of particle deposition, retention and clearance. Existing macroscopic knowledge on particle biokinetics and microscopic views on particle organ interactions are discussed comparing nanometer and micrometer sized particles. We emphasize the importance for quantitative analyses and the use of particle doses derived from real world exposures.

Study on airflow and inhaled particle deposition within realistic human upper respiratory tract

Based on the CT (Computerized Tomography) scanned images of a 19-years-old healthy boy, a realistic geometric model of URT from nasal cavity to the upper six-generation bronchial is rebuilt. To investigate airflow and particle deposition in the obtained realistic human upper respiratory tract, RNG k-ϵ turbulence model was used to describe the primary flow and particle deposition under three breathing intensity such as 15 L/min, 30 L/min and 60 L/min. The particle is tracked and analyzed in the Lagrangian frame. The velocity fields of airflow under different airflow rates were computed and discussed. The trapping of particles with diameter 1μm on the wall surfaces was monitored, and the locations of trapping in different region were visualized.In order to study the characteristics of particles movement and the effect of particles diameter on the deposition pattern, eleven kinds of sphere particles with different diameters are selected as research object. The diameters of selected particles as follows: 0.1μm, 0.5μm, 1μm, 2.5μm, 3μm, 3.5μm, 4μm, 4.5μm, 5μm, 6.5μm and 8μm. The variation of inhalable particles deposition in realistic human upper respiratory tract with respiratory intensity and particle size was researched and compared.

The Relevance of Animal Models for Aerosol Studies

Animal models are essential for understanding the fates and effects of inhaled materials, because invasive methods are frequently necessary to provide the desired information. Because of the variability in humans of particle deposition, clearance, and effects, numerous animal models have been used in inhalation studies. Furthermore, humans are not typical mammals in some ways that affect inhalation phenomena. Humans have less fur, longer gestation and life times, simplified nasal structure, and symmetric bronchial branching in relation to other mammals. However, experience, plus the genetic similarity among mammals, underpins the use of animal models. Mammals are varied with respect to their inhaled particle deposition and clearance phenomena. Total inhaled aerosol deposition probability versus particle-size curves are qualitatively similar for various mammals of similar body mass, despite airway anatomy differences. However, more species variation is seen in regional particle deposition curves, complicating aerosol study design. The rates of clearance of deposited slowly dissolving particles are animal species dependent, apparently due to differences in gross, subgross, and cellular respiratory tract biology. Clearance rates for rapidly dissolving particles are not strongly species dependent. Inhalation toxicology studies require several animal species. Rodents are among the most frequently used, but for studies of lung development, diseases, exercise, etc., and for extrapolation to humans, larger mammals are also needed. Fortunately, the research database, and excellent monographs on inhalation phenomena provide ample guidance for study design.

Large eddy simulation of inhaled particle deposition within the human upper respiratory tract

A three-dimensional (3-D) computer geometrical model of the human upper respiratory tract (URT), including the airway from mouth, pharynx, larynx and trachea to triple bifurcation was created. A large eddy simulation (LES) based on this model investigated the deposition of inhaled particles within the human URT. Steady respiration mode was first considered with three kinds of breathing intensity Q = 30 , 60 and 90 L/min and then compared with an unsteady respiration mode at the breathing intensity of Q = 60 L / min . The deposition efficiencies (DEs) of different particles with density of ρ = 600 , 912 kg / m 3 and particle diameter of d = 1 , 5, 6.5 μ m was studied, respectively. The results showed that the increases of particle diameter, particle density and breathing intensity improves the particle DEs in the human URT; and the particle DEs in unsteady respiration mode are higher than those in steady mode. The results agree well with corresponding experimental data.

Inhaled Particle Deposition in Unsteady-State Respiratory Flow at a Numerically Constructed Model of the Human Larynx

To evaluate the clinical effectiveness of aerosol therapy for the lower and upper respiratory airways, particle deposition at the human laryngeal region has been analyzed with various unsteady-state respiratory flow-patterns. The flow profiles and trajectory of aerosol particles were calculated by 3-D thermo-fluid analysis of a finite volume method (FVM) with 8-CPUs parallel computational system. A reconstructed physical model of the real laryngeal airways was modified from 3-D CAM modeling function of Rhinoceros based on the images of Magnetic Resonance Imaging (MRI). By using 104 MRI images taken vertically and horizontally at intervals of 2 mm on the oral cavity and the pharynx-larynx respectively, 3-D physical model of the laryngeal airways was obtained. The numerical results of flow profile analyzed by the unsteady-state respiration model showed that vortex flow was occurred with time at near larynx, showing uniform flow profile in both the oral cavity and upper side of pharynx. The vortex was appeared at the anterior part of the epiglottis and downward of the vocal cord. However, it was confirmed that few particles deposit in the vocal cord. In these cases, the particle deposition was taken place mostly at the oral cavity and the oropharynx. On the other hand, the relationship between the particle deposition efficiency and the impaction in the laryngeal region was well agreement with the data sets of ICRP task group (1993) for the larynx deposition.

Tracheobronchial Particle Dose Considerations for In Vitro Toxicology Studies

The purpose of this paper is to present a method for estimating particle doses that may be used to reconcile particle deposition doses used in in vitro toxicology studies with in vivo exposure levels. The focus is on the tracheobronchial (TB) tree of heavily exposed individuals. A review of the factors that influence inhaled particle deposition doses in environmental exposures leads to the identification of cases in which greater than average TB tree doses are received. Exercising individuals and those with chronic obstructive pulmonary disease not only inhale increased volumes of air but they also may have uneven ventilation that leads to greater than average particle deposition doses per unit of TB tree surface area. In addition, deposition hot spots, as occur at airway bifurcations, will greatly increase the particle exposures of target cells in the TB tree. Three particle exposure scenarios are proposed, and the average and local doses to the TB epithelium are calculated. When various factors that enhance particle doses (enhancement factors, or EFs) in vivo are considered, substantial particle doses may be justified for in vitro tissue culture studies that use TB target cells, such as epithelial cell cultures. The use of such EFs is intended to improve in vitro dosing with particles. Although the exposure of cells in vitro cannot fully replicate the complexity of in vivo exposures, it is possible to calculate toxicologically relevant doses that may define adverse health effects in potentially sensitive human populations. Local groups of TB cells in high-dose individuals are predicted to receive particle doses that are 3000-25,000 times higher than the doses averaged over the entire TB region.

Prediction of particle deposition in the human lung using realistic models of lung ventilation

Realistic predictions of inhaled particle deposition in various locations of the human lung depend mainly on accurate descriptions of the lung geometry and ventilation. Models of airflow distribution in the human lung by uniform and nonuniform lung expansions were used to calculate particle deposition in various lobes and regions of stochastically generated human lungs. To study the influence of lung geometry, 30 asymmetric stochastic lungs were generated and used in the calculations. Lobar airflow in each lung varied in accordance with lobar properties. The calculated airflow distributions indicated that the airflow rate entering each lobe of a given lung was similar for uniform and nonuniform lung expansions. Particle deposition was also found to be similar for uniform and nonuniform lung expansion models at rest breathing. The predicted deposition was in agreement with experimental measurements of regional and total depositions when considering lung size variation in a population. The coupled lung ventilation and deposition models can aid in detailed predictions of inhaled particle deposition in the human lungs.

Challenges in Validating CFD-Derived Inhaled Aerosol Deposition Predictions

Computational fluid dynamic (CFD) techniques have provided unprecedented opportunity for investigating inhaled particle deposition in realistic human airway geometries. Several recent articles describing local aerosol deposition predictions based upon “validated” CFD models have highlighted the challenges in validating local aerosol deposition predictions. These challenges include: (1) defining what is meant by validation; (2) defining appropriate experimental data for validation; and (3) determining when the agreement is not fortuitous. The term validation has numerous meanings, depending on the field and context in which it is used. For example, in computer programming it means the code executes as intended, to the experimentalist it means predicted results agree with matched experimental measurements, and to the risk assessor it implies that predictions using new parameters can be trusted. Based on the current literature it is not clear that a consensus exists for what constitutes a validated CFD model. It is also not clear what types of experimental data are needed or how closely the CFD input values and experimental conditions should be matched (similar or identical airway geometries, entrance airflow, or aerosol profiles) to validate CFD derived predictions. Due to the complexity of CFD computer codes and the multiplicity of deposition mechanisms, it is possible that total aerosol deposition may be accurately predicted and the resulting local particle deposition patterns are incorrect, or vice versa. Specific examples and suggestions for several challenges to experimentalists and modelers are presented.

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.

Air sampling in occupational asthma

Air sampling in occupational asthma