Particle Clearance in Human Bronchial Airways: Comparison of Stochastic Model Predictions with Experimental Data
|
|
- Baldric O’Neal’
- 6 years ago
- Views:
Transcription
1 Ann. occup. Hyg., Vol. 46, Supplement 1, pp , British Occupational Hygiene Society Published by Oxford University Press DOI: /annhyg/mef659 Particle Clearance in Human Bronchial Airways: Comparison of Stochastic Model Predictions with Experimental Data R. STURM 1, W. HOFMANN 1 *, G. SCHEUCH 2, K. SOMMERER 2, P. CAMNER 3 and M. SVARTENGREN 3,4 1 Institute of Physics and Biophysics, University of Salzburg, Hellbrunner Strasse 34, A-5020 Salzburg, Austria; 2 InAMed, Taunus Strasse 12, D Gemuenden, Germany; 3 Institute of Environmental Medicine and 4 Department of Public Health Sciences, Karolinska Institute, S Stockholm, Sweden A stochastic bronchial clearance model has been developed that is based on a probabilistic asymmetric structure of the human lung. This model takes mucociliary transport rates to be a function of airway diameter, considers delayed mucus clearance at bifurcation sites, and uses an empirically derived expression for the slow clearance fraction as a function of particle diameter. For the calculation of retention curves, this bronchial clearance model was applied to predicted deposition patterns for different particle sizes and breathing conditions. Two sets of experimental data were used: (i) bolus inhalation at different volumetric depths, and (ii) extremely slow inhalation, providing a wide range of initial deposition patterns. In general, excellent agreement was found between theoretical predictions and experimental retention data (short-term retention curves and 24 h retention values) for different particle sizes, with maximum differences between 10 and 20%. Two different mechanisms are discussed to interpret the experimentally observed relation between the slow clearance fraction and particle diameter. Keywords: human lung; mucociliary clearance; particle retention; slow bronchial clearance INTRODUCTION Results of bolus inhalation experiments have suggested the existence of a slow bronchial clearance phase, exhibiting a distinct dependence on particle size (Stahlhofen, 1989; Scheuch and Stahlhofen, 1992). To investigate potential underlying mechanisms, the objectives of the present study were (i) to calculate short-term retention curves for different particle sizes, (ii) to compare them with the available experimental evidence, and (iii) to identify specific mechanisms for the slow bronchial clearance phase The retention calculations presented here are based on a stochastic bronchial clearance model. This model takes mucociliary transport rates to be a function of airway diameter, considers delayed mucus clearance at bifurcation sites, and uses an empirically derived expression for the slow clearance fraction as a function of particle diameter. For the calculation of *Author to whom correspondence should be addressed. Tel: ; fax: ; werner.hofmann@sbg.ac.at retention curves, this bronchial clearance model was applied to predicted deposition patterns for different particle sizes and breathing conditions and compared to two sets of experimental data: (i) bolus inhalation at different volumetric depths (Stahlhofen, 1989; Scheuch and Stahlhofen, 1992), and (ii) extremely slow inhalation (Philipson et al., 2000), thereby providing a wide range of initial deposition patterns. MATERIALS AND METHODS Bronchial clearance model The stochastic particle deposition model of Koblinger and Hofmann (1990) was extended by incorporating a bronchial clearance model which allows the calculation of particle retention within an asymmetrically branching tracheobronchial tree. Calculations of particle clearance by the mucociliary escalator are based on a positive correlation between airway diameter and mucus velocity in that airway, normalized to a measured tracheal mucus velocity of 5.5 mm/min (ICRP, 1994). Stochastically generated mucus vel- 329
2 330 R. Sturm et al. (a) (b) Fig. 1. (a) Comparison of mucus velocities calculated with the stochastic clearance model and the deterministic clearance model of Lee et al. (1979). (b) Dependence of average mucus velocities on average diameters of the human bronchial airway generations. ocities decrease in an almost exponential manner with increasing generation number (Fig. 1a), differing by <10% from the values reported by Lee et al. (1979) for a deterministic, symmetric lung. As illustrated in Fig. 1b, the relationship between computed average mucus velocities and airway diameters can be reasonably approximated by an exponential function. Since our present understanding of the mechanisms underlying slow bronchial clearance is still fragmentary, experimental data obtained by bolus experiments were used to derive an empirical relationship between the slow clearance fraction f s (fraction retained after 24 h) and the geometric particle diameter, d geom (µm): f s = d geom (1) indicating that only particles smaller than ~6.5 µm experience a slow bronchial clearance. The delay of mucus flow at carinal ridges is considered in our model by an adjustable average delay time t, which is selected randomly from a uniform distribution between 0 and t. At present, a default value of 10 min is used in the program. Experimental data Two sets of experimental clearance data were used for the comparison with predicted retention curves: (i) bolus inhalation at different volumetric depths (Stahlhofen, 1989; Scheuch and Stahlhofen, 1992), and (ii) extremely slow inhalation (Philipson et al., 2000). Applying the bolus technique, the retention of monodisperse 111 In-labelled polystyrene particles (d = 6.7 µm) was measured at different times after bolus inhalation. The volumetric bolus front depth V F varied between 54.6 and ml to target different regions of the bronchial tree. To investigate the dependence of particle retention on particle size, monodisperse aerosols with diameters of 1.7, 3.2 and 6.7 µm were injected as shallow boluses with a front depth of ~100 ml and a half-width between 40 and 50 ml. The philosophy of the extremely slow inhalation technique with a flow rate of l/s is to specifically increase deposition in small bronchiolar airways of the tracheobronchial tree (Philipson et al., 2000). To investigate slow thoracic clearance, volunteers inhaled 111 In-labelled polystyrene particles (d = 6.05 µm, 1.05 g/cm 3 ). The radioactivity in the thorax
3 Particle clearance in human bronchial airways 331 Fig. 2. Results of the stochastic clearance calculations. (a) Retention curves of 6.7 µm particles for different volumetric bolus front depths. (b) Comparison between measured and predicted 24 h retention values of 6.7 µm particles for different volumetric bolus front depths. (c) Measured and predicted retention curves for different particle sizes in shallow boluses. (d) 24 hour retention values was measured immediately after inhalation and at selected times between 24 h and 2 weeks. RESULTS Simulation of the bolus experiments In general, excellent agreement was found between theoretical predictions and experimental retention data (short-term retention curves and 24 h retention values) for different particle sizes, with maximum differences between 10 and 20%. As illustrated in Fig. 2a,b, the A-values (i.e. fraction retained after 24 h) of the experimentally derived retention curves for 6.7 µm particles exhibit a positive correlation with the volumetric bolus front depths, increasing from 0% for V F = 54.6 ml to 85% for V F = ml. For comparison, predicted A-values range from 0 to 76%. Shallow bolus experiments with different particle sizes (1.7, 3.2 and 6.7 µm) indicate a positive correlation between particle diameter and short-term retention (Fig. 2c). While >80% of the 6.7 µm particles are cleared from the tracheobronchial tree within the first 10 h after inhalation, only 20% of the deposited 1.7 µm particles leave the thorax during that time interval. Differences between predicted and measured data are again rather small, with a maximum of ~10%. Simulation of extremely slow inhalation experiments In their experiments, Philipson et al. (2000) observed a mean retention value after 24 h of 51 ± 5% for 6.05 µm particles (Fig. 2d). Corresponding experiments with a flow rate of 0.5 l/s yielded an A-value of 46 ± 11%. Simulation of these experiments with our clearance model produced A-values of 45 and 49%, thus agreeing very well with the experimental data. When extended to intermediate and very high flow rates, the clearance model predicts a slightly convex curve between and 0.5 l/s with a maximum at ~0.2 l/s (Fig. 2d), which has to be tested in future experiments. However, the main objective of that experiment was to study whether the slow bronchial clearance fraction depends on geometric or aerodynamic particle diameter (see equation 1). In contrast
4 332 R. Sturm et al. Fig. 3. Possible mechanisms responsible for slow bronchial clearance. (a) Particle capture in the sol phase after penetration through the gel layer. (b) Particle capture in the sol phase after direct deposition in mucus discontinuities (i.e. no gel layer). (c) Mucus delay at carinal ridges of airway bifurcations. to the bolus experiments discussed above, 24 h retention in this study did not depend on the geometric diameter. DISCUSSION Comparison with experimental retention curves indicates that the stochastic clearance model in its present formulation provides fair fits to both bolus and extremely slow inhalation data covering a wide range of initial deposition patterns. While the dependence of the slowly cleared fraction on particle size is expressed by an empirically derived linear equation, further refinement of the model will require a mechanistic understanding of potential mechanisms. At the moment, our mechanistic understanding of the slow clearance phase is mainly based on the results of Gehr et al. (1991), who found evidence for the capture of particles in the sol layer of the bronchial epithelium, assuming that they have passed through the gel layer (Fig. 3a). As these authors used only rather large particles (d = 6 µm), we do not have any comparable evidence for smaller particles. Recently, however, the penetration of the mucus layer was questioned by Podgorski and Sosnowski (2000) on theoretical grounds. An alternative mechanism of slow bronchial clearance is based on experimental findings (e.g. Mercer et al., 1992) that the mucus layer, particularly in the smaller airways, is not continuous but patchy. Particles being deposited in such holes (i.e. no gel layer) of a discontinuous mucus layer (Fig. 3b) may experience longer residence times than those initially deposited on the gel layer. Hence the slow clearance fraction may be interpreted as the probability of hitting such a hole which depends, among other parameters, on particle size. Mucus delay at bifurcations (Fig. 3c) due to local fluid dynamics or impairment of ciliary movement may be an additional effect contributing to slow bronchial clearance (Hofmann et al., 1990).
5 Particle clearance in human bronchial airways 333 Acknowledgements This research was supported in part by the Commission of the European Communities, contract no. FIGD- CT REFERENCES Gehr P, Im Hof V, Geiser M, Schürch S. (1991) The fate of particles deposited in the intrapulmonary conducting airways. J Aerosol Med; 1: Hofmann W, Martonen TB, Ménache MG. (1990) A dosimetric model for localized radon progeny accumulations at tracheobronchial bifurcations. Radiat Protect Dosim; 30: ICRP. (1994) Human respiratory tract model for radiological protection. International Commission on Radiological Protection (ICRP) Publication 66, Ann ICRP; 24: 1 3. Oxford: Elsevier. Koblinger L, Hofmann W. (1990) Monte Carlo modeling of aerosol deposition in human lungs. Part I: Simulation of particle transport in a stochastic lung structure. J Aerosol Sci; 21: Lee PS, Gerrity TR, Hass FJ, Lourenco RV. (1979) A model for tracheobronchial clearance of inhaled particles in man and a comparison with data. IEEE Trans Biomed Eng; 26: Mercer RR, Russell ML, Crapo JD. (1992) Mucous lining layers in human and rat airways. Annu Rev Respir Dis; 145: 355. Philipson K, Falk R, Svartengren M et al. (2000) Does lung retention of inhaled particles depend on their geometric diameter? Exp Lung Res; 26: Podgorski A, Sosnowski TR. (2000) Dynamic analysis of the process of an aerosol particle deposition onto an extracellular lining layer in the human lung. J Aerosol Sci; 31 (suppl. 1): Scheuch G, Stahlhofen W. (1992) Deposition and dispersion of aerosol particles in the airways of the human respiratory tract: the effect of particle size. Exp Lung Res; 18: Stahlhofen W. (1989) Human lung clearance following bolus inhalation of radioaerosols. In Crapo JD, Smolko ED, Miller FJ, Graham JA, Hayes AW, editors. Extrapolation of dosimetric relationships for inhaled particles and gases. San Diego: Academic Press. pp
Inhalation von Radionukliden physikalische und biologische Mechanismen
Inhalation von Radionukliden physikalische und biologische Mechanismen Werner Hofmann Abteilung für Physik und Biophysik, Fachbereich Materialforschung und Physik, Universität Salzburg 1 LUNG DOSIMETRY
More informationMICRODOSIMETRY CALCULATION OF THE DOSE CONVERSION COEFFICIENT FOR RADON PROGENY. B.M.F. Lau, D. Nikezic, K.N. Yu
MICRODOSIMETRY CALCULATION OF THE DOSE CONVERSION COEFFICIENT FOR RADON PROGENY B.M.F. Lau, D. Nikezic, K.N. Yu Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue,
More informationTHE ROLE OF BRONCHIAL MUCUS LAYER THICKNESS IN RADON DOSIMETRY. Balázs Gergely Madas, Imre Balásházy
The Role of Bronchial Mucus Layer Thickness in Radon Dosimetry 181 THE ROLE OF BRONCHIAL MUCUS LAYER THICKNESS IN RADON DOSIMETRY Balázs Gergely Madas, Imre Balásházy Hungarian Academy of Sciences KFKI
More informationCHRONIC SMOKER LUNG DOSIMETRY OF RADON PROGENY
Romanian Reports in Physics, Vol. 61, No. 4, P. 669 675, 2009 NUCLEAR MEDICINE CHRONIC SMOKER LUNG DOSIMETRY OF RADON PROGENY PAUL F. BAIAS 1, WERNER HOFMANN 2, RENATE WINKLER-HEIL 2, OCTAVIAN G. DULIU
More informationTheoretical model of clearance in the tracheobronchial airways of healthy subjects and smokers
Original Article Page 1 of 8 Theoretical model of clearance in the tracheobronchial airways of healthy subjects and smokers Robert Sturm Division of Physics and Biophysics, Department of Chemistry and
More informationClearance of carbon nanotubes in the human respiratory tract a theoretical approach
Original Article Page 1 of 9 Clearance of carbon nanotubes in the human respiratory tract a theoretical approach Robert Sturm Brunnleitenweg 41, A-561 Elsbethen, Salzburg, Austria Correspondence to: Dr.
More informationALPHA PARTICLE MICRODOSIMETRY IN THE LUNG
ALPHA PARTICLE MICRODOSIMETRY IN THE LUNG Werner Hofmann Division of Physics and Biophysics, Department of Materials Research and Physics, University of Salzburg, Austria 1 Alpha particle microdosimetry
More informationTracheobronchial deposition and clearance in small airways in asthmatic subjects
Eur Respir J, 1996, 9, 1123 1129 DOI: 1.1183/931936.96.961123 Printed in UK - all rights reserved Copyright ERS Journals Ltd 1996 European Respiratory Journal ISSN 93-1936 Tracheobronchial deposition and
More informationAN ABSTRACT OF THE THESIS OF. Jason D. Hout for the degree of Master of Science in Radiation Health Physics presented. Abstract Approved:
AN ABSTRACT OF THE THESIS OF Jason D. Hout for the degree of Master of Science in Radiation Health Physics presented on September 2nd, 2010. Title: Development of a Dose Conversion Factor from Uptakes
More informationPossible Consequences of Inhomogeneous Suborgan Distribution of Dose and the Linear No-Threshold Dose-Effect Relationship
Possible Consequences of Inhomogeneous Suborgan Distribution of Dose and the Linear No-Threshold Dose-Effect Relationship Balázs G. Madas, Imre Balásházy Centre for Energy Research, Hungarian Academy of
More informationDeposition of Inhaled Particle in the Human Lung for Different Age Groups
Deposition of Inhaled Particle in the Human Lung for Different Age Groups Xilong Guo 1, Qihong Deng 1* 1 Central South University (CSU), Changsha, China * Corresponding email: qhdeng@csu.edu.cn, qhdeng@gmail.com.
More informationBronchial Dosimeter for Radon Progeny
Bronchial Dosimeter for Radon Progeny T.K. Cheung 1, K.N. Yu 1, D. Nikezic 1, A.K.M.M. Haque 1 and D. Vucic 2 1 Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue,
More informationChoice of Nebulizer for Inhaled Tobramycin Treatment in Cystic Fibrosis
Respiratory Drug Delivery 2010 Müllinger et al. Choice of Nebulizer for Inhaled Tobramycin Treatment in Cystic Fibrosis Bernhard Müllinger, 1 Thomas C. Topini, 2 Anna L. Valeri, 2 Juliane Gleske, 1 Philipp
More informationRecommendations for Aerosol Applications of Silicone-Based Materials
Recommendations for Aerosol Applications of Silicone-Based Materials September 2001 Revised March 2018 This document provides information and recommendations relevant to formulating aerosol products containing
More informationModeling of Internal Dose from Insoluble Cesium
Modeling of Internal Dose from Insoluble Cesium Kentaro Manabe 1 and Masaki Matsumoto 2 1. Japan Atomic Energy Agency 2. National Institutes for Quantum and Radiological Science and Technology ICRP-RERF-JHPS
More informationUse of Math Modelling to Understand Delivery of Biopharmaceutical Molecules to the Lung
Use of Math Modelling to Understand Delivery of Biopharmaceutical Molecules to the Lung Nia Stevens 9 th November 2016 Thanks to Richard Kaye, James Mitchell, Dave Prime at GSK Bahman Asgharian and Owen
More informationRegional deposition and retention of particles in shallow, inhaled boluses: effect of lung volume
Regional deposition and retention of particles in shallow, inhaled boluses: effect of lung volume WILLIAM D. BENNETT, 1 GERHARD SCHEUCH, 2 KIRBY L. ZEMAN, 1 JAMES S. BROWN, 1 CHONG KIM, 3 JOACHIM HEYDER,
More informationRADON RISK IN URANIUM MINING AND ICRP
Submitted to 13 th International Congress of the International Radiation Protection Association Glasgow, Scotland, 13-18 May 2012 RADON RISK IN URANIUM MINING AND ICRP D. Chambers*, R. Stager* and N. Harley**
More informationAdvanced Drug Delivery Reviews
ADR-12134; No of Pages 16 Advanced Drug Delivery Reviews xxx (2011) xxx xxx Contents lists available at ScienceDirect Advanced Drug Delivery Reviews journal homepage: www.elsevier.com/locate/addr In silico
More informationAerosol Therapy. Aerosol Therapy. RSPT 1410 Humidity & Aerosol Therapy Part 4
1 RSPT 1410 Humidity & Part 4 Wilkins Chapter 36; p. 801-806 2 Stability: the tendency for aerosol particles to remain in Size: the the particle, the greater the tendency toward stability the the particle,
More informationPARTICLE DEPOSITION IN THE LUNG
300 PARTICLE DEPOSITION IN THE LUNG See also: Bronchiectasis. Bronchiolitis. Chemokines, CXC: IL-8. Defensins. Interstitial Lung Disease: Cryptogenic Organizing Pneumonia. Further Reading Epler GR and
More informationARTICLE IN PRESS. Experimental Measurements of Regional Lung Deposition in Taiwanese
Aerosol and Air Quality Research, x: 1 8, xxxx Copyright Taiwan Association for Aerosol Research ISSN: 1680-8584 print / 2071-1409 online doi: 10.4209/aaqr.2018.06.0213 Experimental Measurements of Regional
More informationTheoretical deposition of variably sized platelets in the respiratory tract of healthy adults
Original Article Page of Theoretical deposition of variably sized platelets in the respiratory tract of healthy adults Robert Sturm Department of Material Sciences and Physics, Division of Physics and
More information7/12/2012. Respiratory system. Respiratory Response to Toxic Injury (Lung) Ninth Industrial Toxicology and Pathology Short Course.
Ninth Industrial Toxicology and Pathology Short Course 23 27 July, 2012 Contemporary Concepts in Target Organ Toxicologic Pathology Respiratory system Respiratory Response to Toxic Injury (Lung) Eric Wheeldon
More informationTransactions on Biomedicine and Health vol 2, 1995 WIT Press, ISSN
Biomedical application of the supercomputer: targeted delivery of inhaled Pharmaceuticals in diseased lungs T.B. Martonen,* I. Katz,* D. Hwang,' Y.Yang* "Health Effects Research Laboratory, U.S.Environmental
More informationLung Physiology and How Aerosol Deposits in the Lungs. 1. Physiological and Anatomical Background
XA0100097 43 Lung Physiology and How Aerosol Deposits in the Lungs Toyoharu Isawa, M.D. 1. Physiological and Anatomical Background Weibel's morphologic data has been referred to not only for predicting
More informationCSP Deposition to the Alveolar Region of the Lung: Implications of Cigarette Design
Risk Analysis, Vol. 27, No. 6, 2007 DOI: 10.1111/j.1539-6924.2007.00986.x CSP Deposition to the Alveolar Region of the Lung: Implications of Cigarette Design Stephanie Gower 1, and David Hammond 2 Ventilated
More informationThe optimal particle size for beta-adrenergic aerosols in mild asthmatics*
The optimal particle size for beta-adrenergic aerosols in mild asthmatics* Introduction The treatment of asthma and chronic obstructive pulmonary diseases (COPD) has improved considerably with the introduction
More informationLower Respiratory Tract Structure of Laboratory Animals and Humans: Dosimetry Implications
Aerosol Science and Technology ISSN: 0278-6826 (Print) 1521-7388 (Online) Journal homepage: http://www.tandfonline.com/loi/uast20 Lower Respiratory Tract Structure of Laboratory Animals and Humans: Dosimetry
More informationMisty Max 10 nebulizer
AirLife brand Misty Max 10 nebulizer Purpose Introduction Delivery of nebulized medication to the lungs is a complex process dependant upon a variety of clinical and device-related variables. Patient breathing
More informationEffect of particle size of bronchodilator aerosols on lung distribution and pulmonary function in patients
Thorax 1987;42:457-461 Effect of particle size of bronchodilator aerosols on lung distribution and pulmonary function in patients with chronic asthma D M MITCHELL, M A SOLOMON, S E J TOLFREE, M SHORT,
More information21/03/2011 AEROSOL DEPOSITION AND THE ASSESSMENT OF PULMONARY DRUG DELIVERY. Fundamentals of aerosols
AEROSOL DEPOSITION AND THE ASSESSMENT OF PULMONARY DRUG DELIVERY AEROSOL DEPOSITION AND THE ASSESSMENT OF PULMONARY DRUG DELIVERY Steve Newman Scientific Consultant Norfolk, UK steve.newman@physics.org
More informationConsiderations for Inhalation Safety Assessment: Approaches and Application
Considerations for Inhalation Safety Assessment: Approaches and Application Madhuri Singal, PhD, RRT, DABT Inhalation Toxicologist, Senior Consumer Safety Associate Reckitt Benckiser, LLC CIR Expert Panel
More informationIndividual Monitoring Conducted by the Health Protection Agency in the London Polonium-210 Incident
Individual Monitoring Conducted by the Health Protection Agency in the London Polonium-210 Incident Michael Bailey a*, Alan Birchall a, Louise Bishop b, George Etherington a, Barry Evans c, Graham Fraser
More information22 nd ETH-Conference on Combustion Generated Nanoparticles June 18 21, 2018; Zürich, Switzerland. Wolfgang G. Kreyling
22 nd ETH-Conference on Combustion Generated Nanoparticles June 18 21, 2018; Zürich, Switzerland Engineered nanoparticles versus ambient ultrafine particles: how comparable are their interactions with
More informationPulmonary Drug Delivery: A Promising Approach
ISSN: 2231-3354 Received on: 10-04-2012 Revised on: 27-04-2012 Accepted on: 23-05-2012 DOI: 10.7324/JAPS.2012.2632 Pulmonary Drug Delivery: A Promising Approach ND Shah, VV Shah and ND Chivate ABSTRACT
More informationLong-term Excretion of Thorium with Faeces and Urine from TIG Welders after Continuos Occupational Handling of Thoriated Electrodes
Long-term Excretion of Thorium with Faeces and Urine from TIG Welders after Continuos Occupational Handling of Thoriated Electrodes P. Ostapczuk 1, R. Hille 1, A Titze 2, N. Witkowski 1 1 Division of Safety
More informationChanges in International Standards (ICRP) and Potential Implications
Changes in International Standards (ICRP) and Potential Implications Overview Who is the ICRP? Brief Sojourn Epidemiology Studies vs. Dosimetric Modelling What does the ICRP say about radon? What is the
More informationThree-Dimensional Quantitative Co-Mapping of Pulmonary Morphology and. Nanoparticle Distribution with Cellular Resolution in Nondissected Murine
Three-Dimensional Quantitative Co-Mapping of Pulmonary Morphology and Nanoparticle Distribution with Cellular Resolution in Nondissected Murine Lungs Lin Yang,,, Annette Feuchtinger, Winfried Möller,,
More informationUnited Nations Scientific Committee on the Effects of Atomic Radiation
United Nations Scientific Committee on the Effects of Atomic Radiation ATTACHMENT D-1 ESTIMATION OF THE POSSIBLE CONTRIBUTION OF INTAKES OF SHORT-LIVED RADIONUCLIDES TO EFFECTIVE DOSE AND ABSORBED DOSES
More informationAerosol Characterisation of e-cigarettes. Ross Cabot, Anna Koc, Caner U. Yurteri & John McAughey
Aerosol Characterisation of e-cigarettes Ross Cabot, Anna Koc, Caner U. Yurteri & John McAughey European Aerosol Conference, Prague 2-6 September 2013 1 Organisation Background Description History Regulation
More informationPredictive modeling of deposition, dissolution, absorption and systemic exposure
Predictive modeling of deposition, dissolution, absorption and systemic exposure IPAC-RS/UF Orlando Inhalation Conference March 20, 2014 Per Bäckman and Bo Olsson, AstraZeneca R&D, Mölndal Sweden The views
More information9th ETH Conference on CGP: 16. August 2005 Distribution and Clearance of Inhaled Ultrafine TiO 2 Particles in Rat Lungs
9th ETH Conference on CGP: 16. August 2005 Distribution and Clearance of Inhaled Ultrafine TiO 2 Particles in Rat Lungs Marianne Geiser University of Bern Airways & alveoli - rodent lung TiO 2 particle
More informationCitation for published version (APA): Schans, C. P. V. D. (1991). Physiotherapy and bronchial mucus transport s.n.
University of Groningen Physiotherapy and bronchial mucus transport van der Schans, Cees P. IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from
More informationSave Our Sievert! Ches Mason BHP Billiton Uranium, 55 Grenfell Street, Adelaide, SA5000, Australia
Save Our Sievert! Ches Mason BHP Billiton Uranium, 55 Grenfell Street, Adelaide, SA5000, Australia Abstract The protection quantity effective dose was devised by the International Commission on Radiological
More informationA Radiation Carcinogenesis Model Applied to Radon- Induced Lung Cancer Risk Prediction Using a Sugarscape Cellular Automaton
International Research Journal of Biological Sciences ISSN 2278-3202 A Radiation Carcinogenesis Model Applied to Radon- Induced Lung Cancer Risk Prediction Using a Sugarscape Cellular Automaton Abstract
More informationAerosol bolus dispersion in healthy subjects
Eur Respir J 1997; 10: 460 467 DOI: 10.1183/09031936.97.10020460 Printed in UK - all rights reserved Copyright ERS Journals Ltd 1997 European Respiratory Journal ISSN 0903-1936 Aerosol bolus dispersion
More informationUse of Target Tissue Concentrations in PK-PD Modeling of Inhaled Drugs Ramon Hendrickx, AstraZeneca, RIA IMed Gothenburg, Sweden
Use of Target Tissue Concentrations in PK-PD Modeling of Inhaled Drugs Ramon Hendrickx, AstraZeneca, RIA IMed Gothenburg, Sweden IQ DMPK Leadership Group 31 May 2017 What s On? Lung as target organ Benefit
More informationEffect of cigarette smoking on nasal mucociliary
Effect of cigarette smoking on nasal mucociliary clearance and ciliary beat frequency PJ STANLEY, R WILSON, MA GREENSTONE, L MACWILLIAM, PJ COLE From the Host Defence Unit, Department ofmedicine, Cardiothoracic
More informationReview. Deposition and retention of inhaled fibres: effects. on incidence of lung cancer and mesothelioma
Occupational and Environmental Medicine 1994;51:793-798 Review Nelson Institute of Environmental Medicine, New York University Medical Center, Tuxedo, NY, USA M Lippmann Correspondence to: Professor M
More informationIndian J Med Res 117, April 2003, pp R. Guleria, T.R. Singh, S. Sinha, A.K. Padhy*, K. Gupta* & J.N. Pande
158 INDIAN J MED RES, APRIL 2003 Indian J Med Res 117, April 2003, pp 158-163 Effect of inhalation of salbutamol, beclomethasone dipropionate & ipratropium bromide on mucociliary clearance in some patients
More informationSpray Nebulizer Deposition Efficiency as a Function of Age. University of Denver Denver, CO Denver, CO
ILASS Americas, 23 rd Annual Conference on Liquid Atomization and Spray Systems, Ventura, CA, May 2011 Spray Nebulizer Deposition Efficiency as a Function of Age L. Weber * and C.S. Lengsfeld 1 Department
More informationChallenges in Nonclinical Development of Inhalation Drug Products
Challenges in Nonclinical Development of Inhalation Drug Products Luqi Pei, Ph.D. Senior Pharmacologist DPARP, CDER August 6, 2015 Rockville, MD Disclaimer This speech reflects the views of the speaker
More informationY90 SIRT Therapy Dosimetric Aspects
Y90 SIRT Therapy Dosimetric Aspects David Chee-Eng Ng MBBS, BSc, MSc, MRCP, FAMS, FRCP (Edin) Head and Senior Consultant, Department of Nuclear Medicine and PET Singapore General Hospital Adjunct Assistant
More informationPlutonium Worker Dosimetry
Plutonium Worker Dosimetry A Birchall M Puncher, J Harrison, A Riddell, V Khokhryakov, S Romanov Bridging the Experimental and Epidemiologic Divide Georgetown University Hotel, Washington DC May 4-6 (2009)
More informationThe Pressure Losses in the Model of Human Lungs Michaela Chovancova, Pavel Niedoba
The Pressure Losses in the Model of Human Lungs Michaela Chovancova, Pavel Niedoba Abstract For the treatment of acute and chronic lung diseases it is preferred to deliver medicaments by inhalation. The
More informationMEASUREMENT OF THE DEGREE OF PROTECTION AFFORDED BY RESPIRATORY PROTECTIVE EQUIPMENT AGAINST MICROBIOLOGICAL AEROSOLS
PII: S0003-^878(96)00082-8 Ann. occup. Hyg., Vol. 41, Supplement 1, pp. 636-640, 1997 British Occupational Hygiene Society Crown Copyright 1997 Published by Elsevier Science Ltd Printed in Great Britain
More informationTargeting Aerosolized Drugs to the Conducting Airways Using Very Large Particles and Extremely Slow Inhalations
JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY Volume 23, Number &, 2010 ª Mary Ann Liebert, Inc. Pp. 1 7 DOI: 10.1089=jamp.2008.0711 Original Research Targeting Aerosolized Drugs to the Conducting
More informationA mathematical model of particle retention in the air-spaces of human lungs
British Journal ofindustrial Medicine 1983;4:121-13 mathematical model of particle retention in the air-spaces of human lungs T R GERRITY, C S GRRRD, ND D B YETES From the Section ofenvironmental Medicine,
More informationCOPYRIGHTED MATERIAL INTRODUCTION AND BACKGROUND. Morton Lippmann and George D. Leikauf
1 INTRODUCTION AND BACKGROUND Morton Lippmann and George D. Leikauf This book identifies and critically reviews current knowledge on human exposure to selected chemical agents and physical factors in the
More informationDeposition of particle-attached radon progeny in the respiratory tract - an experimental study of children and adults in home environments
Deposition of particle-attached radon progeny in the respiratory tract - an experimental study of children and adults in home environments Pagels, Joakim; Falk, Rolf; Gudmundsson, Anders; Bohgard, Mats
More informationA PB-PK model to explore ALX-0171 PK in infants following inhalation
A PB-PK to explore ALX-0171 PK in infants following inhalation Massimiliano Germani 27 th Nov. 2014 Nanobodies - Inspired by nature Background Respiratory syncytial virus (RSV): respiratory tract infections
More informationICRP Perspective on Internal Dosimetry OIR and Radiopharmaceuticals
ICRP Perspective on Internal Dosimetry OIR and Radiopharmaceuticals Dietmar Noßke dnosske@web.de 1 Disclaimer The information and views set out in this presentation are those of the author and do not necessarily
More informationLung Dosimetry: Pulmonary Clearance of Inhaled Particles
Aerosol Science and Technology ISSN: 0278-6826 (Print) 1521-7388 (Online) Journal homepage: http://www.tandfonline.com/loi/uast20 Lung Dosimetry: Pulmonary Clearance of Inhaled Particles G. Oberdörster
More informationEURADOS Work on Internal Dosimetry
B. Breustedt (KIT, Germany), E. Blanchardon (IRSN, France), C.-M. Castellani (ENEA, Italy), G. Etherington (PHE (retired), UK), D. Franck (IRSN, France), A. Giussani (BfS, Germany), W. Hofmann (U Salzburg,
More informationAdvanced Inhaler Technique. Learning Outcomes. Disclosure 1.1. Belgian Chocolate, French Champagne and Inhaled Medication: Too Good To Waste?
Advanced Inhaler Technique Learning Outcomes Describe the mechanism of different inhalers Explain how inspiratory flow can effect drug delivery for different inhalers Counsel a patient on the correct use
More informationAerosols in Medicine
Aerosols in Medicine Principles, Diagnosis and Therapy Second, revised edition Edited by F. Moren M.B. Dolovich M.T. Newhouse S.P. Newman 1993 ELSEV1ER AMSTERDAM - LONDON - NEW YORK TOKYO Contents Preface
More informationReal-time measurement of particulate matter deposition in the lung
Biomarkers, MayJune 2006; 11(3): 221 232 Real-time measurement of particulate matter deposition in the lung G. INVERNIZZI 1, R. BOFFI 1, A. A. RUPRECHT 1, P. J. BARNES 2, S. A. KHARITONOV 2, & P. PAREDI
More informationFUNDAMENTAL SAFETY OVERVIEW VOLUME 2: DESIGN AND SAFETY CHAPTER S: RISK REDUCTION CATEGORIES 3. RADIOLOGICAL CONSEQUENCES OF SEVERE ACCIDENTS
PAGE : 1 / 10 3. RADIOLOGICAL CONSEQUENCES OF SEVERE ACCIDENTS 3.1. SAFETY REQUIREMENTS 3.1.1. Safety objectives The safety approach for EPR reactors is deterministic, complemented by probabilistic analyses,
More informationDeposition, retention, and clearance of inhaled
British Journal ofindustrial Medicine 198;37:337-362 Deposition, retention, and clearance of inhaled particles* M LIPPMANN, D B YEATES,t AND R E ALBERT From the Institute of Environmental Medicine, New
More informationInternational Radiation Protection Association 11 th International Congress Madrid, Spain - May 23-28, 2004
International Radiation Protection Association 11 th International Congress Madrid, Spain - May 23-28, 2004 Refresher Course Programmes for Internal Dose Monitoring Part 1: Basic Aspects and Essential
More informationOn October 21 22, 2008, experts on the physiology of. Mucociliary and Cough Clearance as a Biomarker for Therapeutic Development.
JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY Volume 23, Number 5, 2010 ª Mary Ann Liebert, Inc. Pp. 261 272 DOI: 10.1089/jamp.2010.0823 Invited Review Mucociliary and Cough Clearance as a Biomarker
More informationSmall Volume Nebulizer Treatment (Hand-Held)
Small Volume Aerosol Treatment Page 1 of 6 Purpose Policy Physician's Order Small Volume Nebulizer Treatment To standardize the delivery of inhalation aerosol drug therapy via small volume (hand-held)
More informationA Primer on Acute Inhalation Toxicity Testing
A Primer on Acute Inhalation Toxicity Testing Where do Alternative Methods Fit? Jon A. Hotchkiss, PhD Toxicology and Environmental Research and Consulting The Dow Chemical Company 1 Outline Why do we test?
More informationParticle Size and Dust Inhalation
Pneumoconiosis A disease of the lungs characterized by fibrosis and caused by the chronic inhalation of mineral dusts, especially silica and asbestos. Helen Lang Dept. Geology & Geography West Virginia
More informationPulse Nebulization in Pneumatic Devices
INTERNATIONAL JOURNAL OF OCCUPATIONAL SAFETY AND ERGONOMICS 1999, VOL. 5, NO. 1, 31-42 Pulse Nebulization in Pneumatic Devices Leon Gradori Tomasz R. Sosnowski Warsaw University of Technology, Poland Zygmunt
More informationFRI aerosol. deposition. A unique way to look at regional inhaled drug deposition.
FRI aerosol deposition A unique way to look at regional inhaled drug deposition www.fluidda.com EXECUTIVE SUMMARY Since 2005, Functional Respiratory Imaging (FRI) has been used many times to evaluate the
More informationThe Effects of Simulated Airway Diseases and Affected Flow Distributions on Aerosol Deposition
The Effects of Simulated Airway Diseases and Affected Flow Distributions on Aerosol Deposition Gabriela Apiou-Sbirlea PhD, Ira M Katz PhD, and Ted B Martonen PhD BACKGROUND: Experimental and theoretical
More informationApplication of the Commission's Recommendations for the Protection of People in
ICRP Publication 127 ICRP Publication 126 ICRP Publication 125 ICRP Publication 124 ICRP Publication 123 ICRP Publication 122 ICRP Publication 121 ICRP Publication 120 ICRP 2011 Proceedings Radiological
More informationField calibration of the glass-based retrospective radon detectors for epidemiologic applications
University of Iowa Iowa Research Online Theses and Dissertations 2008 Field calibration of the glass-based retrospective radon detectors for epidemiologic applications Kainan Sun University of Iowa Copyright
More informationDose Estimates for Nuclear Medicine Procedures: What are they? Where do they come from?
Dose Estimates for Nuclear Medicine Procedures: What are they? Where do they come from? SNM Continuing Education Lecture Salt Lake City, UT -- June 6, 2010 Darrell R. Fisher Pacific Northwest National
More informationChapter 16. Respiratory System
Chapter 16 Respiratory System Introduction Respiration = the entire process of exchanging gases between the atmosphere and body cells 1. Ventilation 2. Gas exchange 3. Gas transport : 4. Cellular respiration
More informationPENETRATION OF AN AEROSOL, PRODUCED BY FILM ATOMIZATION, THROUGH THE CARINAL BIFURCATION
British Journal of Anaesthesia 1993; 70: 527-531 PENETRATION OF AN AEROSOL, PRODUCED BY FILM ATOMIZATION, THROUGH THE CARINAL BIFURCATION T. J. J. INGLIS, J. G. JONES AND S. PAXTON SUMMARY We have measured
More informationToxicology of Inhaled Materials
Zoo Toxicology of Inhaled Materials General Principles of Inhalation Toxicology Contributors I.Y. R. Adamson B. D. Beck M. R. Becklake J. D. Brain J. D. Crapo R. T. Drew D. L. Dungworth A. B. Fisher T.
More informationComputational toxicology: an in silico dosimetry model for risk assessment of air pollutants
Computational toxicology: an in silico dosimetry model for risk assessment of air pollutants T. Martonen 1,2 & K. K. Isaacs 1,3 1 Experimental Toxicology Division, National Health and Environmental Effects
More informationAEROSOL THERAPY: THE PRACTICALITIES
AEROSOL THERAPY: THE PRACTICALITIES Lester I. Harrison, PhD Section Head, Clinical Pharmacokinetics, 3M Pharmaceuticals, 3M Center 270-3S-05, St. Paul, MN, USA 55144 liharrison@mmm.com Introduction: Horses,
More informationFRI aerosol. deposition. A unique way to look at regional inhaled drug deposition.
FRI aerosol deposition A unique way to look at regional inhaled drug deposition www.fluidda.com EXECUTIVE SUMMARY FRI - AN UPDATE OF SCINTIGRAPHY FRI deposition technology is based on CT imaging, and uses
More informationWhat Do Cascade Impaction Measurements Tell Us: In Vitro Aspects. Context of Presentation
What Do Cascade Impaction Measurements Tell Us: In Vitro Aspects Jolyon P. Mitchell, Ph.D. Trudell Medical International London, Canada IPAC-RS Conference November 2006 1 Context of Presentation This talk
More informationICRP 128 ICRP ICRP ICRP 1928
ICRP 1928 129 ICRP 1928 ICRP ICRP ICRP 1928 129 ICRP 129 ICRP 128 Radiological Protection in Cone Beam Computed Tomography (CBCT) Radiation Dose to Patients from Radiopharmaceuticals: A Compendium of Current
More informationChapter 13. The Respiratory System.
Chapter 13 The Respiratory System https://www.youtube.com/watch?v=hc1ytxc_84a https://www.youtube.com/watch?v=9fxm85fy4sq http://ed.ted.com/lessons/what-do-the-lungs-do-emma-bryce Primary Function of Breathing
More informationAN INVESTIGATION INTO THE USE OF BIOKINETIC MODELS WHEN ASSESSING INTAKES OF PLUTONIUM. A Thesis BRIAN ANDREW HRYCUSHKO
AN INVESTIGATION INTO THE USE OF BIOKINETIC MODELS WHEN ASSESSING INTAKES OF PLUTONIUM A Thesis by BRIAN ANDREW HRYCUSHKO Submitted to the Office of Graduate Studies of Texas A&M University in partial
More informationRisks from Internal Emitters - misuse of equivalent and effective dose
Risks from Internal Emitters - misuse of equivalent and effective dose EU Scientific Seminar, Luxembourg, November 2010 John Harrison Science / policy / regulations UNSCEAR Reports on doses and effects
More informationRadon dose coefficients
Strahlenschutzkommission Geschäftsstelle der Strahlenschutzkommission Postfach 12 06 29 D-53048 Bonn http://www.ssk.de Radon dose coefficients Recommendation by the German Commission on Radiological Protection
More informationRespiratory System. Organization of the Respiratory System
Respiratory System In addition to the provision of oxygen and elimination of carbon dioxide, the respiratory system serves other functions, as listed in (Table 15 1). Respiration has two quite different
More informationProgress in understanding radon risk
Progress in understanding radon risk D LAURIER Institute for Radiological Protection and Nuclear Safety (IRSN) Fontenay-aux-Roses, France EU Scientific Seminar 2010 "Issues with internal emitters Luxembourg,
More informationA Real-Time Monte Carlo System for Internal Dose Evaluation Using an Anthropomorphic Phantom with Different Shapes of Tumors Inserted
A Real-Time Monte Carlo System for Internal Dose Evaluation Using an Anthropomorphic Phantom with Different Shapes of Tumors Inserted J. Wu, S. J. Chang, B. J. Chang, I. J. Chen, J. H. Chiu Health Physics
More informationUncertainties on internal dosimetry
Uncertainties on internal dosimetry Augusto Giussani 2 March 2017 agiussani@bfs.de Internal dosimetry Internal dose is evaluated with mathematical models Intake Biokinetic Model Time-activity curves in
More informationRisk of secondary cancer induced by radiotherapy
Risk of secondary cancer induced by radiotherapy Iuliana Toma-Dasu Medical Radiation Physics Stockholm University and Karolinska Institutet Radiation - the two-edged sword Risk of secondary cancer induced
More informationChronic cell death may play a crucial role in mutagenesis and carcinogenesis due to radon exposure
Chronic cell death may play a crucial role in mutagenesis and carcinogenesis due to radon exposure Balázs G. Madas, Imre Balásházy MTA Centre for Energy Research,, Hungary balazs.madas@energia.mta.hu Low
More informationThe objectives of this presentation are to
1 The objectives of this presentation are to 1. Review the mechanics of airway clearance 2. Understand the difference between secretion mobilization and secretion clearance 3. Identify conditions that
More information