CFD Simulation of Aerosol Deposition in an Anatomically Based Human Large–Medium Airway Model

Ma, Baoshun; Lutchen, Kenneth R.

doi:10.1007/s10439-008-9620-y

Cited by 122 publications

(79 citation statements)

References 64 publications

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“…The relevant governing transport equations are solved in 3D models of the airways, which are discretized into interconnected small spatial elements (or control volumes) such as hexahedral, tetrahedral, or prism cells. Recent CFD studies of inhaled pharmaceutical aerosols have captured the effects of inhalers on transport and deposition in the mouth-throat region (34)(35)(36) and have predicted aerosol deposition through numerous generations of the upper (37)(38)(39) and lower TB airways. (40) However, prediction of aerosol transport and deposition throughout the lungs with CFD simulations (i.e., a CFD whole-lung model) remains challenging and requires simplifying techniques, which are actively being developed.…”

Section: Introductionmentioning

confidence: 99%

Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates

Longest

Tian

Khajeh-Hosseini-Dalasm

et al. 2016

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: The objective of this study was to compare aerosol deposition predictions of a new whole-airway CFD model with available in vivo data for a dry powder inhaler (DPI) considered across multiple inhalation waveforms, which affect both the particle size distribution (PSD) and particle deposition. Methods: The Novolizer DPI with a budesonide formulation was selected based on the availability of 2D gamma scintigraphy data in humans for three different well-defined inhalation waveforms. Initial in vitro cascade impaction experiments were conducted at multiple constant (square-wave) particle sizing flow rates to characterize PSDs. The whole-airway CFD modeling approach implemented the experimentally determined PSDs at the point of aerosol formation in the inhaler. Complete characteristic airway geometries for an adult were evaluated through the lobar bronchi, followed by stochastic individual pathway (SIP) approximations through the tracheobronchial region and new acinar moving wall models of the alveolar region. Results: It was determined that the PSD used for each inhalation waveform should be based on a constant particle sizing flow rate equal to the average of the inhalation waveform's peak inspiratory flow rate (PIFR) and mean flow rate [i.e., AVG(PIFR, Mean)]. Using this technique, agreement with the in vivo data was acceptable with <15% relative differences averaged across the three regions considered for all inhalation waveforms. Defining a peripheral to central deposition ratio (P/C) based on alveolar and tracheobronchial compartments, respectively, large flow-rate-dependent differences were observed, which were not evident in the original 2D in vivo data. Conclusions: The agreement between the CFD predictions and in vivo data was dependent on accurate initial estimates of the PSD, emphasizing the need for a combination in vitro-in silico approach. Furthermore, use of the AVG(PIFR, Mean) value was identified as a potentially useful method for characterizing a DPI aerosol at a constant flow rate.

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Section: Introductionmentioning

confidence: 99%

Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates

Longest

Tian

Khajeh-Hosseini-Dalasm

et al. 2016

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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“…Thus, airflow modeling should consider upper as well as intra-thoracic airway geometry. Nevertheless, the relevant works mainly focused on the geometry from oral cavity to intra-thoracic excluding nasal cavity [29,30].…”

Section: Introductionmentioning

confidence: 99%

Numerical analysis of respiratory flow patterns within human upper airway

et al. 2009

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A computational fluid dynamics (CFD) approach is used to study the respiratory airflow dynamics within a human upper airway. The airway model which consists of the airway from nasal cavity, pharynx, larynx and trachea to triple bifurcation is built based on the CT images of a healthy volunteer and the Weibel model. The flow characteristics of the whole upper airway are quantitatively described at any time level of respiratory cycle. Simulation results of respiratory flow show good agreement with the clinical measures, experimental and computational results in the literature. The air mainly passes through the floor of the nasal cavity in the common, middle and inferior nasal meatus. The higher airway resistance and wall shear stresses are distributed on the posterior nasal valve. Although the airways of pharynx, larynx and bronchi experience low shear stresses, it is notable that relatively high shear stresses are distributed on the wall of epiglottis and bronchial bifurcations. Besides, two-dimensional fluid-structure interaction models of normal and abnormal airways are built to discuss the flow-induced deformation in various anatomy models. TheThe project was supported by the

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“…(59,(75)(76)(77)(78)(79) More recently, CFD applications have used surface models derived from imaging data from individual subjects. (80)(81)(82)(83) These models typically comprise the upper respiratory tract consisting of the oral airways, pharynx, and larynx, and upper lung airways from the trachea extending down through several generations of the lung. The limiting factor in determining how far down into the lung patientbased CFD models can go is driven by the resolution of the scanning procedure.…”

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confidence: 99%

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung

Darquenne

Fleming

Katz

et al. 2016

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Development of a new drug for the treatment of lung disease is a complex and time consuming process involving numerous disciplines of basic and applied sciences. During the 2015 Congress of the International Society for Aerosols in Medicine, a group of experts including aerosol scientists, physiologists, modelers, imagers, and clinicians participated in a workshop aiming at bridging the gap between basic research and clinical efficacy of inhaled drugs. This publication summarizes the current consensus on the topic. It begins with a short description of basic concepts of aerosol transport and a discussion on targeting strategies of inhaled aerosols to the lungs. It is followed by a description of both computational and biological lung models, and the use of imaging techniques to determine aerosol deposition distribution (ADD) in the lung. Finally, the importance of ADD to clinical efficacy is discussed. Several gaps were identified between basic science and clinical efficacy. One gap between scientific research aimed at predicting, controlling, and measuring ADD and the clinical use of inhaled aerosols is the considerable challenge of obtaining, in a single study, accurate information describing the optimal lung regions to be targeted, the effectiveness of targeting determined from ADD, and some measure of the drug's effectiveness. Other identified gaps were the language and methodology barriers that exist among disciplines, along with the significant regulatory hurdles that need to be overcome for novel drugs and/or therapies to reach the marketplace and benefit the patient. Despite these gaps, much progress has been made in recent years to improve clinical efficacy of inhaled drugs. Also, the recent efforts by many funding agencies and industry to support multidisciplinary networks including basic science researchers, R&D scientists, and clinicians will go a long way to further reduce the gap between science and clinical efficacy.

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CFD Simulation of Aerosol Deposition in an Anatomically Based Human Large–Medium Airway Model

Cited by 122 publications

References 64 publications

Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates

Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates

Numerical analysis of respiratory flow patterns within human upper airway

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung

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