Comparing Lung Regions of Interest in Gamma Scintigraphy for Assessing Inhaled Therapeutic Aerosol Deposition

Biddiscombe, Martyn; Meah, Sally; Underwood, S. Richard; Usmani, Omar

doi:10.1089/jamp.2010.0845

Cited by 58 publications

(51 citation statements)

References 23 publications

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“…(67,68) In the previous validation study of Tian et al, (61) acceptable agreement was found between the in vivo results of Newman et al (62) and CFD computed airway predictions transferred to 2D planar images for the Novolizer inhaler, which was considered only at the PIFR of 99 LPM (fast inhalation), as well as a softmist inhaler also considered at a single flow rate. The methods established in the previous study of Tian et al (61) are repeated in the current study to evaluate the more challenging scenario of a single DPI evaluated at multiple flow rates generating different aerosol size distributions and tested in two separate airway geometries.…”

Section: Selection Of the In Vivo Dataset And Inhalation Waveformmentioning

confidence: 78%

“…As described, the method used to segment the 2D planar image can influence the predictions of regional lung deposition, (67) and a newly recommend method for dividing planar images was described (68) after the publication of Newman et al (62) However, for validation purposes, the goal was to match the techniques used in the selected in vivo experiments as closely as possible. For the purpose of comparison, acceptable agreement between the CFD predictions and in vivo data will be determined based on the average relative error evaluated in the three regions of interest ( MT, C, and I+P) having a value of 15% or less.…”

Section: Deposition Fraction Calculations and Mappingmentioning

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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Section: Selection Of the In Vivo Dataset And Inhalation Waveformmentioning

confidence: 78%

Section: Deposition Fraction Calculations and Mappingmentioning

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

View full text Add to dashboard Cite

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“…(126) Indeed, it was observed that larger particles visually deposited more proximally, whereas smaller particles distributed deeper into the lungs and had a greater penetration index. (125,148) The paradox of overall less total lung deposition with the 6 lm particles but greater efficacy in FEV 1 was explained by better matching of the inhaled therapeutic to its receptor distribution.…”

Section: Importance Of Aerosol Deposition Distribution To Clinical Efmentioning

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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“…29 Classically, scintigraphy underestimates the peripheral deposition due to the alveolar spaces included in the inner region due to how regions of interest are defined. 32 The choice of regions of interest was discussed in a recent recommendation. 24 Our results confirm that the Akita device offers a better method for drug administration to the peripheral lung compared with other modalities of nebulization, but they suggest that it is the device itself rather than the settings that are supposed to target differentially central or peripheral airways.…”

Section: Discussionmentioning

confidence: 99%

Effect of Drug Targeting Nebulization on Lung Deposition: A Randomized Crossover Scintigraphic Comparison Between Central and Peripheral Delivery

et al. 2014

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BACKGROUND: Recent technological advances in nebulization permit researchers to target specific parts of the lungs by modifying delivery method. The aim of this study was to compare the central and peripheral targeted modalities of administration. METHODS: Lung and regional deposition of inhaled technetium-99m diethylene triamine penta-acetic was measured by scintigraphy after peripheral and central targeted modalities of administration with an Akita device in 6 healthy subjects. RESULTS: Drug targeting nebulization delivered a large amount of drug into the peripheral part of the lung independent of the modality (outer-to-inner deposition ratio of 1.24 ؎ 0.21 vs 1.22 ؎ 0.14 for central and peripheral modalities, respectively), but there was no difference in lung deposition (whole-body deposition, 83.3 ؎ 6.5% vs 82.8 ؎ 7.3%, P ‫؍‬ .86) or regional deposition (P ‫؍‬ .77) between both modalities. The extrathoracic deposition was < 20% of the wholebody deposition, without a difference between modalities (P ‫؍‬ .86). CONCLUSIONS: This study shows for the first time that choosing 2 different specific drug targeting nebulization modes does not influence the amount of drug delivered into the lung in healthy male subjects. Moreover, the modes do not modify the site of deposition under the conditions of our study.

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Comparing Lung Regions of Interest in Gamma Scintigraphy for Assessing Inhaled Therapeutic Aerosol Deposition

Abstract: Different approaches used to determine pulmonary regions of interest and quantify aerosol deposition produce different results. Our research highlights a genuine need for a consensus to standardize the methodology to facilitate data comparison between laboratories on aerosol deposition.

Cited by 58 publications

References 23 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

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

Effect of Drug Targeting Nebulization on Lung Deposition: A Randomized Crossover Scintigraphic Comparison Between Central and Peripheral Delivery

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