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Keywords: Micro-Particle, Airflow, computational fluid dynamics, Lung Airway.
People may inhale 100 millions of particles each day, including toxic particulate matter as well as drug aerosols. Some of those deposited in the respiratory system can be either harmful or therapeutic to humans depending upon the particle material, deposition site, and local concentration. These transport and deposition phenomena as well as the resulting biomedical processes are greatly determined by the airflow field, particle properties, breathing pattern, and geometric airway characteristics. Realistic models of tracheobronchial and nasal⁄oral- tracheobronchial airways were built. Airflow and particle transport and deposition in these airway models were investigated in detail by mainly using the validated, in-house FORTRAN code CFPD (computational fluid-particle dynamics), which is a cell-centered, finite volume multi-block code. Both laminar and transitional-turbulent-laminar flows were considered for different transient and steady inhalation flow rates and inlet velocity profiles. The resulting effects of transients, upstream conditions and geometric characteristics, i.e., spatial angle and/or cartilaginous rings, are fully discussed. A new code based on the lattice-Boltzmann method (LBM) has been developed and validated to investigate airflow patterns and pressure changes in representative alveolar structures of the human respiratory zone. The new idea of targeted drug aerosol delivery technology was numerically tested for a more realistic human airway configuration and thereby addressing the problem of inter-subject variability. Specifically, controlled air-particle streams were studied using the oral and asymmetric tracheobronchial airway models. The results were compared with data obtained for a symmetric Weibel Type A tracheobronchial airway model.
Inhaled Particles integrates all that is known about inhaled particles in a unified treatment. It aims to provide a scientific framework essential to a reasonable understanding of inhaled particles. The emphasis is placed on demonstrating the key roles of lung morphology on airflow and particle transport as well as identifying physical and biological factors that influence deposition. Special attention is paid to maintaining consistency of treatment and a balance between theoretical modeling and experimental measurements. The book covers all important aspects of inhaled particles including inhalability, aerosol dispersion, particle deposition, and clearance. It reviews concisely the basic background of lung morphology, respiratory physiology, aerodynamics, and aerosol science pertinent to the subject. Essential aspects of health effects and applications are also included. An easy-to-read, self contained introduction to the field An excellent source of updated research information Useful for students and professionals in aerosol science, environmental health science, occupational hygiene, health physics and biomedical engineering
This wide-ranging, comprehensive reference presents the latest developments in aerosol science and interactions between particles and the respiratory tract-utilizing an inter-disciplinary approach that integrates advances in physics, chemistry, and engineering with the epidemiological and biomedical sciences, and focusing on the dynamics of particl
Traditional research methodologies in the human respiratory system have always been challenging due to their invasive nature. Recent advances in medical imaging and computational fluid dynamics (CFD) have accelerated this research. This book compiles and details recent advances in the modelling of the respiratory system for researchers, engineers, scientists, and health practitioners. It breaks down the complexities of this field and provides both students and scientists with an introduction and starting point to the physiology of the respiratory system, fluid dynamics and advanced CFD modeling tools. In addition to a brief introduction to the physics of the respiratory system and an overview of computational methods, the book contains best-practice guidelines for establishing high-quality computational models and simulations. Inspiration for new simulations can be gained through innovative case studies as well as hands-on practice using pre-made computational code. Last but not least, students and researchers are presented the latest biomedical research activities, and the computational visualizations will enhance their understanding of physiological functions of the respiratory system.
The context of this thesis is the modelling of particle deposition in the human lung in order to optimise the administration of inhaled drugs. As the alveolar region plays a crucial role both physiologically and functionally, especially for systemic delivery, the objective of this work is to set-up a particle deposition model specific to the acinar region which could be integrated in whole lung deposition model. The first two chapters concentrate on the anatomical and functional aspects of the lung and on the physical principles involved in the flow and particle transport mechanisms in the lung. Then a computational fluid dynamics model was setup in a simplified alveolar geometry. Aerosol bolus transport was studied through an Eulerian approach, for one or several breathing cycles. The impact of flow irreversibilities on bolus dispersion was quantified. The last chapter deals with the integration of the previous results in an analytical model of particle deposition in the whole lung. The results generated by this model are then compared to experimental data from the literature or obtained from an ongoing clinical trial. The results of the new theoretical model show an increase of particle deposition in the acinar region which improves correlation of theory with experimental data. This model could favourably help designing therapies targeting the alveolar region of the lung.
Prolonged exposure to inhaled micron-sized airborne particles is a known public health concern. These particles impact the health of staggering numbers of residents of polluted urban areas, as well as significant portions of the third world where it is still common to burn wood or charcoal indoors for cooking or heating. An understanding of the fate of inhaled particles in the lungs is useful for assessing their associated health risks, as well as improving the effectiveness of respiratory drug delivery techniques. The transport of microparticles is inseparable from behavior of the suspending airflow and this is studied using computational fluid dynamics techniques. The anatomy of the airways seems to have evolved to encourage turbulent airflow for functions such as mixing of flow to promote the warming and humidification of inhaled air, as well as for filtration. Large eddy simulation models are employed to capture turbulent flow in extremely complex patient-specific airway geometries. These collectively comprise the oral and nasal cavities, larynx, trachea, and the bronchial tree. The flow in anatomically-accurate rhesus macaque airways is also studied. Simulations are carried out for inspiratory flow rates corresponding to nominal Reynolds numbers in the hundreds to low-thousands yet somewhat surprisingly yield unsteady flows due to local geometric factors. A computed mean flow field is compared extensively with magnetic resonance velocimetry measurements carried out in the same computed-tomography--based lung geometry, showing good agreement. Microparticle deposition predictions are also verified. Focus is placed on the dynamics of the flow in the nasal airway, trachea, and bronchial tree. After becoming unsteady at constrictions in the upper airways, the flow is found to be chaotic, exhibiting fluctuations with broad-band spectra even at the most distal simulated airways in which the Reynolds numbers are as low as 300. The unsteadiness is attributed to the convection of turbulent structures produced in the upper airways as well as to local kinetic energy production throughout the bronchial tree.
The pulmonary acinus, known as the gas exchange region of the lung, encompasses the complex of millions of sub-millimeter alveoli and may represent a potential host for pulmonary complications and diseases. These health disorders may require the inhalation of therapeutic drugs typically administered in the form of aerosolized particles. Both a precise understanding of the mechanisms leading to particle deposition as well as the need to target aerosols to specific pulmonary sites, remain ongoing challenges and depend directly on the fluid dynamics in the lung, and specifically on the microflows present in the acinar region. These considerations call not only for a deepening of our understanding of the fluid mechanics pertinent to the acinar region of the lung, but also, for the potential development of novel strategies towards improved and enhanced particle deposition inside the lung. The present thesis, which lies at the interface between engineering and medicine, is concerned with the role of convective respiratory flows in the acinar region of the lung, in conjunction with the transport and deposition of inhaled particles.
"Particle deposition in the acinus region of the lung is a significant area of interest, because particles can potentially travel into the bloodstream through the capillaries in the lung. Drugs, in the form of aerosols, small particulates in a volume of air, may be delivered through the respiratory system. Also, toxic, airborne, particles could enter the body through the pulmonary capillaries in the acinus region of the lung. In order to accurately predict particle deposition, the aspects that influence deposition needs to be understood. Many physiological features may influence flow and particle deposition in the lung; the geometry of the acinus, expansion and contraction of the alveolar walls due to breathing mechanics, heterogeneities in the lung, breathing flow rate, and the number of breaths. In literature, streamlines and pathlines have been examined, both experimentally and computationally, in models representing the alveolar region of the lung. Some of these studies suggest the presence of irreversible flow, which would significantly influence particle deposition. However, none of these models incorporated all significant features: non-symmetric, three dimensional, expanding geometry. Therefore, flow mechanics, behind particle deposition, in the alveolar region are not well understood. Furthermore, lung disease influences the physiological factors that impact particle deposition. Emphysema physically changes the structure of the alveolar region of the lung. How particle deposition changes with emphysema is not fully understood. In this work, two different alveolar geometries were examined using Particle Image Velocimetry (PIV). The first model represented a healthy alveolar sac, while the second model represented an emphysematous alveolar sac. The same, realistic flow rate was used for both models, which allowed for the fluid flow to be examined as only a function of geometry. The PIV technique was validated by comparing to CFD results, using a simple balloon geometry. Pathlines were plotted in the models in order to examine the fluid flow with respect to time. The fluid was examined, by use of streamlines and pathlines, at the entrance of the alveolar sacs and in areas of high probability for irreversible flow. It was found that the fluid flow inside both alveolar sac geometries was completely reversible, and therefore no mixing was taking place. The comparison between the healthy and emphysematic alveolar sac models showed that the pathlines in health traveled closer to the alveolar walls. Particle deposition by Brownian Diffusion was estimated for particle diameter range of 0.1 [micron] to 0.01 [micron]. For the pathlines that began at the duct entrance, the pathlines came approximately 1.5 times closer to the wall in the healthy case when compared to emphysema. Because the pathline traveled closer to the alveolar walls, the particle diffusion was greater in the healthy than emphysema. In the healthy geometry particles with a diameter less then 0.02 [micron] were estimated to diffuse to all of the alveolar walls within a 5 second time frame, where in emphysema 7 seconds would be needed. It was also determined that if a particle diffuses off of the original streamline, it will remain in the alveolar sac, therefore allowing it to deposit in later breaths."--Abstract.