Aerosol Deposition in the Human Lung Periphery Is Increased by Reduced-Density Gas Breathing

Peterson, Jonathan B.; Prisk, G. Kim; Darquenne, Chantal

doi:10.1089/jam.2007.0651

Cited by 14 publications

(28 citation statements)

References 19 publications

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“…(43) The differences in the physical properties of heliox compared to air (lower density, higher viscosity, and higher mean free path) have a direct effect on the mechanics of particle motion and deposition, but also on the fluid mechanics of the gas that can indirectly change the ADD in the respiratory tract. (44) When breathing heliox rather than air, particle deposition tends to occur deeper in the respiratory tract (45,46) and ADD tends to be more homogeneous in particular in obstructed lungs. (44) On one hand, the lower density of heliox compared to air reduces the extent of turbulent flow, and as such reduces extrathoracic (ET) deposition due to turbulent mixing.…”

Section: Parameters Affecting Addmentioning

confidence: 99%

“…(44) On one hand, the lower density of heliox compared to air reduces the extent of turbulent flow, and as such reduces extrathoracic (ET) deposition due to turbulent mixing. (45) On the other hand, the higher viscosity of heliox compared to air tends to reduce impaction of >1 lm particles in the tracheobronchial (TB) region by keeping particle paths aligned with flow streamlines. For <1 lm particles, the larger mean free path of heliox results in a lower effective viscosity for the particles (i.e., particles are less likely to follow flow streamlines).…”

Section: Parameters Affecting Addmentioning

confidence: 99%

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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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Section: Parameters Affecting Addmentioning

confidence: 99%

Section: Parameters Affecting Addmentioning

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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“…Other techniques can be used to assess the regional deposition. The aerosol bolus delivery technique, initially designed as a diagnostic tool, provides very useful information on the repartition of deposited particles within the lungs Bennett et al 1998;Kim and Hu 1998;Bennett et al 1999;Peterson et al 2008). Among these experimental studies, only the work conducted by Kim and Hu (1998) investigated the differences in regional aerosol deposition in male and female populations.…”

mentioning

confidence: 99%

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

Pichelin

Caillibotte

Katz

et al. 2012

Aerosol Science and Technology

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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 experimental data for both total deposition fraction and bolus recovery (fraction of exhaled particles compared with inhaled particles) for 3 flow rates and 3 particle sizes. Good agreement was found between theoretical and measured data, showing the primary importance of the differentiation of the lung morphology to predict the aerosol deposition within human lungs. This study presents a morphological lung model that is adaptable to specific populations (e.g., gender or race), groups (e.g., a clinical study population), or even individuals.

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“…(31,32) Studies in 1G of aerosol transport while breathing lowdensity gas [80% helium, 20% oxygen (80:20 heliox); about one third of sea-level air density] showed a reduction in deposition in the upper respiratory tract and large airways, and an increase in deposition in the peripheral lung. (33)(34)(35) The combination of reduced gravity and reduced gas density (11) on aerosol deposition that was representative of a lunar habitat was investigated with the hypothesis that such combination would increase the deposition of aerosol particles in the peripheral lung in a synergistic manner. Similar to previous experiments performed with air, (9,11) deposition of 1-lm-diameter particles while breathing the low-density gas was less in lG than in 1G (Fig.…”

Section: Implications For Space Explorationmentioning

confidence: 99%

“…This contrasts with a previous study of aerosol transport in 1G that showed a reduction in deposition in the upper respiratory tract and large airways while breathing heliox (80:20) instead of air, and a slight increase in deposition in the peripheral lung. (34) Reduction in deposition in the upper respiratory tract and large airways was attributed to the reduction in deposition by turbulent mixing as heliox reduces turbulent flow in the trachea and secondary transitional flows in the conducting airways because of its reduced density. Data shown in Figure 5 suggest that the reduction in gas density for the proposed lunar habitat is insufficient to significantly reduce turbulence in the upper respiratory tract and large conducting airways, and hence for deposition to be significantly reduced compared with sea-level conditions.…”

Section: Implications For Space Explorationmentioning

confidence: 99%

Aerosol Deposition in the Human Lung in Reduced Gravity

Darquenne

2014

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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The deposition of aerosol in the human lung occurs mainly through a combination of inertial impaction, gravitational sedimentation, and diffusion. For 0.5-to 5-lm-diameter particles and resting breathing conditions, the primary mechanism of deposition in the intrathoracic airways is sedimentation, and therefore the fate of these particles is markedly affected by gravity. Studies of aerosol deposition in altered gravity have mostly been performed in humans during parabolic flights in both microgravity (lG) and hypergravity (*1.6G), where both total deposition during continuous aerosol mouth breathing and regional deposition using aerosol bolus inhalations were performed with 0.5-to 3-lm particles. Although total deposition increased with increasing gravity level, only peripheral deposition as measured by aerosol bolus inhalations was strongly dependent on gravity, with central deposition (lung depth < 200 mL) being similar between gravity levels. More recently, the spatial distribution of coarse particles (mass median aerodynamic diameter & 5 lm) deposited in the human lung was assessed using planar gamma scintigraphy. The absence of gravity caused a smaller portion of 5-lm particles to deposit in the lung periphery than in the central region, where deposition occurred mainly in the airways. Indeed, 5-lm-diameter particles deposit either by inertial impaction, a mechanism most efficient in the large and medium-sized airways, or by gravitational sedimentation, which is most efficient in the distal lung. On the contrary, for fine particles (*1 lm), both aerosol bolus inhalations and studies in small animals suggest that particles deposit more peripherally in lG than in 1G, beyond the reach of the mucociliary clearance system.

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Aerosol Deposition in the Human Lung Periphery Is Increased by Reduced-Density Gas Breathing

Cited by 14 publications

References 19 publications

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

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

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

Aerosol Deposition in the Human Lung in Reduced Gravity

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