A computer model for the clearance of insoluble particles from the tracheobronchial tree of the human lung

A multi-compartment model for the clearance of insoluble particles from the tracheobronchial tree of the human lung was created. As a significant innovation, the model considers specific mass transfer paths that may play an important role for slow bronchial clearance. These include the accumulation of particulate mass in the periciliary sol layer, an uptake of stored particles by airway macrophages, and the endocytosis of deposited mass by epithelial cells. Besides the gel layer representing fast mucociliary clearance, all cellular and extracellular units involved into the slow clearance process are described by respective compartments which are connected by specific transfer paths. The gastrointestinal tract (GIT), lymph nodes (LN), and blood capillaries are included into the model as final accumulation compartments, to which mass is transferred via the airway route and the transepithelial path. Besides a basic version of the model describing the whole tracheobronchial region by one set of compartments, also an advanced approach is introduced which, in accordance with the International Commission on Radiation Protection (ICRP), subdivides the conducting airways into a bronchial (BB) and bronchiolar (bb) part. Preliminary results were generated with MS-Excel from deposition data of 1-mummass median aerodynamic diameter (MMAD) particles, calculating local slow clearance fractions according to mathematical procedures introduced in previous publications. While mucociliary clearance is completely finished within 24h after exposure, slow clearance takes place in distinct phases and needs several days to weeks. This multi-stage event is also reflected in the respective retention curves which correspond well to previously published graphs.

[1]  Werner Stöber,et al.  Alveolar clearance and retention of inhaled insoluble particles in rats simulated by a model inferring macrophage particle load distributions , 1994 .

[2]  H. Yeh,et al.  Models of human lung airways and their application to inhaled particle deposition. , 1980, Bulletin of mathematical biology.

[3]  Bahman Asgharian,et al.  Mucociliary clearance of insoluble particles from the tracheobronchial airways of the human lung , 2001 .

[4]  Gerhard Scheuch,et al.  Clearance of Particles Deposited in the Lungs , 2000 .

[5]  L. Grant,et al.  Aerosols research, risk assessment and control strategies , 1985 .

[6]  E R Weibel,et al.  Morphometry of the human pulmonary acinus , 1988, The Anatomical record.

[7]  Marianne Geiser,et al.  The Fate of Particles Deposited in the Intrapulmonary Conducting Airways , 1991 .

[8]  Otto G. Raabe,et al.  Tracheobronchial Geometry: Human, Dog, Rat, Hamster - A Compilation of Selected Data from the Project Respiratory Tract Deposition Models , 1976 .

[9]  J. Sturgess,et al.  The mucous lining of major bronchi in the rabbit lung. , 1977, The American review of respiratory disease.

[10]  Magnus Svartengren,et al.  Particle Clearance in Human Bronchial Airways: Comparison of Stochastic Model Predictions with Experimental Data , 2002 .

[11]  Günter Oberdörster,et al.  Lung Clearance of Inhaled Insoluble and Soluble Particles , 1988 .

[12]  R O McClellan,et al.  Pulmonary retention and clearance of inhaled biopersistent aerosol particles: data-reducing interpolation models and models of physiologically based systems--a review of recent progress and remaining problems. , 1997, Critical reviews in toxicology.

[13]  Marianne Geiser,et al.  Assessment of particle retention and clearance in the intrapulmonary conducting airways of hamster lungs with the fractionator 1 , 1990, Journal of microscopy.

[14]  Gerhard Scheuch,et al.  Measurement of lung clearance with pulses of radioactively-labelled aerosols , 1986 .

[15]  James D. Crapo,et al.  Extrapolation of Dosimetric Relationships for Inhaled Particles and Gases , 1989 .

[16]  R. Kavet,et al.  Airway macrophages. The importance of the fixation method. , 1984, The American review of respiratory disease.

[17]  E. Weibel.  Morphometry of the Human Lung , 1965, Springer Berlin Heidelberg.

[18]  A Birchall,et al.  In vivo measurement of unattached radon progeny deposited in the human respiratory tract. , 2001, Radiation protection dosimetry.

[19]  Donald L. Dungworth,et al.  Inhalation toxicology : the design and interpretation of inhalation studies and their use in risk assessment , 1988 .

[20]  Alan Birchall,et al.  In-vivo measurement of deposition and absorption of unattached radon progeny , 2005 .

[21]  W. Hofmann,et al.  Monte Carlo modeling of aerosol deposition in human lungs. Part I: Simulation of particle transport in a stochastic lung structure , 1990 .

[22]  R. G. Cuddihy,et al.  Respiratory Tract Clearance of Particles and Substances Dissociated from Particles , 1988 .

[23]  J J DiStefano,et al.  Multiexponential, multicompartmental, and noncompartmental modeling. I. Methodological limitations and physiological interpretations. , 1984, The American journal of physiology.

[24]  P Camner,et al.  Does lung retention of inhaled particles depend on their geometric diameter? , 2000, Experimental lung research.

[25]  G Scheuch,et al.  An approach to deposition and clearance measurements in human airways. , 1996, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[26]  R. V. Lourenço,et al.  A, Model for Tracheobronchial Clearance of Inhaled Particles in Man and a Comparison with Data , 1979, IEEE Transactions on Biomedical Engineering.

[27]  L Morawska,et al.  Environmental tobacco smoke deposition in the human respiratory tract: differences between experimental and theoretical approaches. , 2001, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[28]  P. Morrow,et al.  Possible mechanisms to explain dust overloading of the lungs. , 1988, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[29]  Peter Gehr,et al.  Particle-Lung Interactions , 2000 .

[30]  W. Hulbert,et al.  An improved method for fixation of the respiratory epithelial surface with the mucous and surfactant layers. , 1982, Laboratory investigation; a journal of technical methods and pathology.