Convective flow dominates aerosol delivery to the lung segments.

Most previous computational studies on aerosol transport in models of the central airways of the human lung have focused on deposition, rather than transport of particles through these airways to the subtended lung regions. Using a model of the bronchial tree extending from the trachea to the segmental bronchi (J Appl Physiol 98: 970-980, 2005), we predicted aerosol delivery to the lung segments. Transport of 0.5- to 10-μm-diameter particles was computed at various gravity levels (0-1.6 G) during steady inspiration (100-500 ml/s). For each condition, the normalized aerosol distribution among the lung segments was compared with the normalized flow distribution by calculating the ratio (R(i)) of the number of particles exiting each segmental bronchus i to the flow. When R(i) = 1, particle transport was directly proportional to segmental flow. Flow and particle characteristics were represented by the Stokes number (Stk) in the trachea. For Stk < 0.01, R(i) values were close to 1 and were unaffected by gravity. For Stk > 0.01, R(i) varied greatly among the different outlets (R(i) = 0.30-1.93 in normal gravity for 10-μm particles at 500 ml/s) and was affected by gravity and inertia. These data suggest that, for Stk < 0.01, ventilation defines the delivery of aerosol to lung segments and that the use of aerosol tracers is a valid technique to visualize ventilation in different parts of the lung. At higher Stokes numbers, inertia, but not gravitational sedimentation, is the second major factor affecting the transport of large particles in the lung.

[1]  E. Hoffman,et al.  On intra- and intersubject variabilities of airflow in the human lungs. , 2009, Physics of fluids.

[2]  Samir Vinchurkar,et al.  Validating CFD predictions of respiratory aerosol deposition: effects of upstream transition and turbulence. , 2007, Journal of biomechanics.

[3]  M. Dolovich,et al.  Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. , 2003, British journal of clinical pharmacology.

[4]  Pieter Zanen,et al.  The optimal particle size for β-adrenergic aerosols in mild asthmatics , 1994 .

[5]  P. Valberg,et al.  Deposition of aerosol in the respiratory tract. , 1979, The American review of respiratory disease.

[6]  A. Wilson,et al.  Dose-response effects of two sizes of monodisperse isoproterenol in mild asthma. , 1990, The American review of respiratory disease.

[7]  F L Wuyts,et al.  Flow analyses in the lower airways: patient-specific model and boundary conditions. , 2008, Medical engineering & physics.

[8]  W. Finlay,et al.  Experimental measurements of particle deposition in three proximal lung bifurcation models with an idealized mouth-throat. , 2005, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[9]  Gordon Kim Prisk,et al.  Deposition and dispersion of 1-μm aerosol boluses in the human lung: effect of micro- and hypergravity , 1998 .

[10]  P T Macklem,et al.  Gas mixing and distribution in the lung. , 1977, International review of physiology.

[11]  H. Atkins,et al.  Utility of technetium-99m-DTPA in determining regional ventilation. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[12]  D E Olson,et al.  Models of the human bronchial tree. , 1971, Journal of applied physiology.

[13]  Norman Chigier,et al.  Inertial deposition effects: a study of aerosol mechanics in the trachea using laser Doppler velocimetry and fluorescent dye. , 2002, Journal of biomechanical engineering.

[14]  M. Zgoda,et al.  Balloon-facilitated percutaneous dilational tracheostomy tube placement: preliminary report of a novel technique. , 2005, Chest.

[15]  O. Usmani,et al.  Regional Lung Deposition and Bronchodilator Response as a Function of β2-Agonist Particle Size , 2005 .

[16]  Chris Lacor,et al.  Fluid flow and particle deposition analysis in a realistic extrathoracic airway model using unstructured grids , 2007 .

[17]  Clement Kleinstreuer,et al.  Laminar-to-turbulent fluid-particle flows in a human airway model , 2003 .

[18]  T. Martonen,et al.  Three-dimensional computational study of inspiratory aerosol flow through the larynx: the effect of glottal aperture modulation , 1997 .

[19]  R W Glenny,et al.  High-resolution maps of regional ventilation utilizing inhaled fluorescent microspheres. , 1997, Journal of applied physiology.

[20]  M. Hayward,et al.  Ventilation agents--what agents are currently used? , 1991, Nuclear medicine communications.

[21]  Eric A Hoffman,et al.  Regional Deposition of Particles in an Image-Based Airway Model: Large-Eddy Simulation and Left-Right Lung Ventilation Asymmetry , 2011, Aerosol science and technology : the journal of the American Association for Aerosol Research.

[22]  A. Dobs,et al.  Time to peak insulin level, relative bioavailability, and effect of site of deposition of nebulized insulin in patients with noninsulin-dependent diabetes mellitus. , 1998, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[23]  Charles Hirsch,et al.  Anatomically based three-dimensional model of airways to simulate flow and particle transport using computational fluid dynamics. , 2005, Journal of applied physiology.

[24]  J. Sandeau,et al.  CFD simulation of particle deposition in a reconstructed human oral extrathoracic airway for air and helium-oxygen mixtures , 2010 .

[25]  Kenneth R. Lutchen,et al.  CFD Simulation of Aerosol Deposition in an Anatomically Based Human Large–Medium Airway Model , 2009, Annals of Biomedical Engineering.

[26]  Jinxiang Xi,et al.  Effects of the laryngeal jet on nano- and microparticle transport and deposition in an approximate model of the upper tracheobronchial airways. , 2008, Journal of applied physiology.

[27]  J. Heyder,et al.  Deposition of particles in the human respiratory tract in the size range 0.005–15 μm , 1986 .

[28]  B Jonson,et al.  Comprehensive ventilation/perfusion SPECT. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[29]  Yung-sung Cheng,et al.  Particle Deposition in a Cast of Human Tracheobronchial Airways , 2005 .

[30]  J. Patton,et al.  Mechanisms of macromolecule absorption by the lungs , 1996 .

[31]  Warren H. Finlay,et al.  On the suitability of k–ε turbulence modeling for aerosol deposition in the mouth and throat: a comparison with experiment , 2000 .

[32]  G. Kim Prisk,et al.  Deposition of inhaled particles in the human lung is more peripheral in lunar than in normal gravity , 2008, European Journal of Applied Physiology.

[33]  Ted B. Martonen,et al.  A numerical study of particle motion within the human larynx and trachea , 1999 .

[34]  P. Byron Prediction of drug residence times in regions of the human respiratory tract following aerosol inhalation. , 1986, Journal of pharmaceutical sciences.

[35]  M. Lippmann,et al.  Particle deposition in casts of the human upper tracheobronchial tree. , 1972, American Industrial Hygiene Association journal.

[36]  S J Farr,et al.  Pulmonary administration of aerosolised fentanyl: pharmacokinetic analysis of systemic delivery. , 1998, British journal of clinical pharmacology.

[37]  Peter R. Byron,et al.  Inhaling medicines: delivering drugs to the body through the lungs , 2007, Nature Reviews Drug Discovery.

[38]  J. Ultman Gas transport in the conducting airways , 1985 .

[39]  S. Newman Deposition and Effects of Inhaled Corticosteroids , 2003, Clinical pharmacokinetics.

[40]  J B West,et al.  Effect of microgravity and hypergravity on deposition of 0.5- to 3-micron-diameter aerosol in the human lung. , 1997, Journal of applied physiology.

[41]  W. Finlay,et al.  In vitro intersubject and intrasubject deposition measurements in realistic mouth-throat geometries , 2004 .

[42]  Gordon Kim Prisk,et al.  Dispersion of 0.5- to 2-μm aerosol in μG and hypergravity as a probe of convective inhomogeneity in the lung , 1999 .

[43]  Ananth V. Annapragada,et al.  Computational Fluid Dynamics Simulation of Airflow and Aerosol Deposition in Human Lungs , 2004, Annals of Biomedical Engineering.