Monte Carlo modeling of aerosol deposition in human lungs. Part I: Simulation of particle transport in a stochastic lung structure

Koblinger, L.; Hofmann, Werner

doi:10.1016/0021-8502(90)90121-d

Cited by 282 publications

(180 citation statements)

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“…upper airways, bronchial airways, acinar airways), lobar, or airway generation number specific deposition fractions. The model was initially developed by Koblinger and Hofmann (1990). In this study the model has been adapted and validated for the case of medical aerosols.…”

Section: Description Of the Computational Methodsmentioning

confidence: 99%

Experimental and computational study of the effect of breath-actuated mechanism built in the NEXThaler® dry powder inhaler

Farkas

Lewis

Church

et al. 2017

International Journal of Pharmaceutics

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Link to publication record in Explore Bristol Research PDF-document This is the final published version of the article (version of record). It first appeared online via Elsevier at https://www.sciencedirect.com/science/article/pii/S0378517317309237 . Please refer to any applicable terms of use of the publisher. University of Bristol -Explore Bristol Research General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms A B S T R A C TThe breath-actuated mechanism (BAM) is a mechanical unit included in NEXThaler ® with the role of delaying the emission of the drug until the inhalation flow rate of the patient is sufficiently high to detach the drug particles from their carriers.The main objective of this work was to analyse the effect of the presence of BAM on the size distribution of the emitted drug and its airway deposition efficiency and distribution. Study of the hygroscopic growth of the emitted drug particles and its effect on the deposition was another goal of this study.Size distributions of Foster ® NEXThaler ® drug particles emitted by dry powder inhalers with and without BAM have been measured by a Next Generation Impactor. Three characteristic inhalation profiles of asthmatic patients (low, moderate and high flow rates) were used for both experimental and modelling purposes. Particle hygroscopic growth was determined by a new method, where experimental measurements are combined with simulations. Upper airway and lung deposition fractions were computed assuming 5 s and 10 s breath-hold times.By the inclusion of BAM the fine particle fraction of the steroid component increased from 24 to 30% to 47-51%, while that of bronchodilator from 25-34% to 52-55%. The predicted upper airway steroid and bronchodilator doses decreased from about 60% to 35-40% due to BAM. At the same time, predicted lung doses increased from about 20%-35% (steroid) and from 22% to 38% (bronchodilator) for the moderate flow profile and from about 25% to 40% (steroid) and from 29% to 47% (bronchodilator) for the high inhalation flow profile. Although BDP and FF upper airway doses decreased by a factor of about two when BAM was present, lung doses of both components were about the same in the BAM and no-BAM configurations at the weakest flow profile. However, lung dose increased by 2-3% even for this profile when hygroscopic growth was taken into account.In conclusion, the NEXThaler ® BAM mechanism is a unique feature enabling high emitted fine particle fraction and enhanced drug delivery to the lungs.

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Section: Description Of the Computational Methodsmentioning

confidence: 99%

Experimental and computational study of the effect of breath-actuated mechanism built in the NEXThaler® dry powder inhaler

Farkas

Lewis

Church

et al. 2017

International Journal of Pharmaceutics

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“…(23,24) For nebulized droplets and environmental aerosols, these models often match available in vivo data in terms of total tracheobronchial (TB) and alveolar deposition relatively well. (22,(25)(26)(27)(28)(29) Additional correlations can be included in 1D whole lung models to capture the effect of jet or spray momentum on deposition when dealing with pharmaceutical inhalers. (30) Katz et al (31) recently applied a whole-airway 1D model (25) to predict the deposition of nebulized droplets delivered through a relatively wide diameter mouthpiece and compared regional deposition results with the in vivo gamma scintigraphy study of Conway et al (32) Limitations of the model's predictive capabilities for this pharmaceutical aerosol were identified in the mouth-throat and tracheobronchial regions.…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, previous applications of 1D models to capture in vivo deposition of nebulized polydisperse aerosols have revealed limitations in predictions of alveolar deposition and exhaled mass fraction. (26,27,33) CFD simulations seek to capture the delivery and deposition of pharmaceutical aerosols from a first principles approach. 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.…”

Section: Introductionmentioning

confidence: 99%

“…Along each pathway, one daughter branch of each bifurcation is continued and one is not, which is similar to the 1D whole lung Monte Carlo modeling technique of Koblinger and Hofmann. (26) A sufficient number of stochastically generated pathways are simulated until deposition results converge to an ensemble average. (16) This approach is reported to reduce the required time to simulate the full TB region by a factor of 3 · 10 5 with only an estimated minor loss in accuracy.…”

Section: Introductionmentioning

confidence: 99%

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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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“…Complexities in the calculations include the effects of dead space, residual air in the lungs and air mixing due to asymmetric in/out airflows within the branchings of the respiratory tract. The approach just described is called 'deterministic', although sometimes a Monte-Carlo computational method is used that follows individual particles through a statistically-obtained pathway through the respiratory tract (Koblinger and Hofmann, 1990;Anjilvel and Asgharian, 1995). Table 3 presents sample calculations for predicted bronchial and pulmonary deposition of seven particle sizes in children and adults for two different dead space assumptions.…”

Section: Basic Considerationsmentioning

confidence: 99%

Methods for modeling particle deposition as a function of age

Phalen

Oldham

2001

Respiration Physiology

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The purpose of this paper is to review the application of mathematical models of inhaled particle deposition to people of various ages. The basic considerations of aerosol physics, biological characteristics and model structure are presented along with limitations inherent in modern modeling techniques. Application of the models to children and senescent adults has been largely based on extrapolating anatomical and physiological data from young adults to match the changes observed during growth and aging. Sample results are included for total particle deposition and deposition in the bronchial and pulmonary regions. The models proposed provide particle deposition predictions that are consistent with the scant measurements available. The models discussed appear to be on firm theoretical grounds, but they are largely limited in application to simple aerosols and average individuals. Also, additional validation of the computational predictions is needed.

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Monte Carlo modeling of aerosol deposition in human lungs. Part I: Simulation of particle transport in a stochastic lung structure

Cited by 282 publications

References 19 publications

Experimental and computational study of the effect of breath-actuated mechanism built in the NEXThaler® dry powder inhaler

Experimental and computational study of the effect of breath-actuated mechanism built in the NEXThaler® dry powder inhaler

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

Methods for modeling particle deposition as a function of age

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