Subject-variability effects on micron particle deposition in human nasal cavities

Abstract Validated computer simulations of the airflow and particle dynamics in human nasal cavities are important for local, segmental and total deposition predictions of both inhaled toxic and therapeutic particles. Considering three, quite different subject-specific nasal airway configurations, micron-particle transport and deposition for low-to-medium flow rates have been analyzed. Of special interest was the olfactory region from which deposited drugs could readily migrate to the central nervous system for effective treatment. A secondary objective was the development of a new dimensionless group with which total particle deposition efficiency curves are very similar for all airway models, i.e., greatly reducing the impact of intersubject variability. Assuming dilute particle suspensions with inhalation flow rates ranging from 7.5 to 20 L/min, the airflow and particle-trajectory equations were solved in parallel with the in-house, multi-purpose Alya program at the Barcelona Supercomputing Center. The geometrically complex nasal airways generated intriguing airflow fields where the three subject models exhibit among them both similar as well as diverse flow structures and wall shear stress distributions, all related to the coupled particle transport and deposition. Nevertheless, with the new Stokes-Reynolds-number group, Stk 1.23 Re 1.28 , the total deposition-efficiency curves for all three subjects and flow rates almost collapsed to a single function. However, local particle deposition efficiencies differed significantly for the three subjects when using particle diameters d p = 2, 10, and 20 μ m . Only one of the three subject-specific olfactory regions received, at relatively high values of the inertial parameter d p 2 Q , some inhaled microspheres. Clearly, for drug delivery to the brain via the olfactory region, a new method of directional inhalation of nanoparticles would have to be implemented.

[1]  M. M. Mozell,et al.  A numerical model of nasal odorant transport for the analysis of human olfaction. , 1997, Journal of theoretical biology.

[2]  A. Kuprat,et al.  Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways. , 2016, Journal of aerosol science.

[3]  Guillaume Houzeaux,et al.  Parallel uniform mesh multiplication applied to a Navier–Stokes solver , 2013 .

[4]  B. Wong,et al.  Experimental measurements and computational predictions of regional particle deposition in a sectional nasal model. , 2015, Journal of aerosol medicine and pulmonary drug delivery.

[5]  David L. Swift,et al.  Deposition of Ultrafine Aerosols in the Head Airways During Natural Breathing and During Simulated Breath Holding Using Replicate Human Upper Airway Casts , 1995 .

[6]  U. Piomelli,et al.  Wall-layer models for large-eddy simulations , 2008 .

[7]  O. Price,et al.  A lung dosimetry model of vapor uptake and tissue disposition , 2012, Inhalation toxicology.

[8]  Yung-Sung Cheng,et al.  CHARACTERISING THE VARIABILITY IN ADULT HUMAN NASAL AIRWAY DIMENSIONS , 1997 .

[9]  Rebecca Bascom,et al.  The effect of nasal passage characteristics on particle deposition , 1998 .

[10]  Gary H. Ganser,et al.  A rational approach to drag prediction of spherical and nonspherical particles , 1993 .

[11]  Clement Kleinstreuer,et al.  Dilute suspension flow with nanoparticle deposition in a representative nasal airway model , 2008 .

[12]  S. K. Robinson,et al.  Coherent Motions in the Turbulent Boundary Layer , 1991 .

[13]  G. Rettinger,et al.  The impact of expiration on particle deposition within the nasal cavity. , 2003, Clinical otolaryngology and allied sciences.

[14]  R A Guilmette,et al.  Effect of flow rate on particle deposition in a replica of a human nasal airway. , 2001, Inhalation toxicology.

[15]  Jeffry D Schroeter,et al.  Effects of Surface Smoothness on Inertial Particle Deposition in Human Nasal Models. , 2011, Journal of aerosol science.

[16]  Guillaume Houzeaux,et al.  Large-scale CFD simulations of the transitional and turbulent regime for the large human airways during rapid inhalation , 2016, Comput. Biol. Medicine.

[17]  Guillaume Houzeaux,et al.  Extension of fractional step techniques for incompressible flows: The preconditioned Orthomin(1) for the pressure Schur complement , 2011 .

[18]  Santiago Badia,et al.  Assessment of variational multiscale models for the large eddy simulation of turbulent incompressible flows , 2015 .

[19]  Purushottam W. Laud,et al.  Changes in nasal airflow and heat transfer correlate with symptom improvement after surgery for nasal obstruction. , 2013, Journal of biomechanics.

[20]  Clement Kleinstreuer,et al.  Nanoparticle mass transfer from lung airways to systemic regions--Part I: Whole-lung aerosol dynamics. , 2013, Journal of biomechanical engineering.

[21]  Rainald Löhner,et al.  A linelet preconditioner for incompressible flow solvers , 2003 .

[22]  Clement Kleinstreuer,et al.  Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part I: Theory and model validation , 2016, Comput. Biol. Medicine.

[23]  J. Y. Tu,et al.  Numerical analysis of micro- and nano-particle deposition in a realistic human upper airway , 2012, Comput. Biol. Medicine.

[24]  Michelle Noga,et al.  In vitro deposition measurement of inhaled micrometer-sized particles in extrathoracic airways of children and adolescents during nose breathing , 2011 .

[25]  Robert H. Nelson,et al.  A Comparison of the Nasal Cross-Sectional Areas and Volumes Obtained with Acoustic Rhinometry and Magnetic Resonance Imaging , 1997, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[26]  R A Guilmette,et al.  Characterization of nasal spray pumps and deposition pattern in a replica of the human nasal airway. , 2001, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[27]  Guilherme J M Garcia,et al.  Toward personalized nasal surgery using computational fluid dynamics. , 2011, Archives of facial plastic surgery.

[28]  Lisbeth Illum,et al.  Nanoparticles for direct nose-to-brain delivery of drugs. , 2009, International journal of pharmaceutics.

[29]  Goodarz Ahmadi,et al.  Numerical Simulations Investigating the Regional and Overall Deposition Efficiency of the Human Nasal Cavity , 2008, Inhalation toxicology.

[30]  Harvey J. Clewell,et al.  Application of Physiological Computational Fluid Dynamics Models to Predict Interspecies Nasal Dosimetry of Inhaled Acrolein , 2008 .

[31]  D. A. Field Laplacian smoothing and Delaunay triangulations , 1988 .

[32]  G. Ahmadi,et al.  CFD simulation of total and regional fiber deposition in human nasal cavities , 2014 .

[33]  Jeffry D Schroeter,et al.  A computational fluid dynamics approach to assess interhuman variability in hydrogen sulfide nasal dosimetry , 2010, Inhalation toxicology.

[34]  Clement Kleinstreuer,et al.  Computational particle-hemodynamics analysis and geometric reconstruction after carotid endarterectomy , 2001, Comput. Biol. Medicine.

[35]  Yang Na,et al.  Patient specific CFD models of nasal airflow: overview of methods and challenges. , 2013, Journal of biomechanics.

[36]  David L. Swift,et al.  Nasal Deposition of Ultrafine Particles in Human Volunteers and Its Relationship to Airway Geometry , 1996 .

[37]  J. Tu,et al.  A Numerical Study of Spray Particle Deposition in a Human Nasal Cavity , 2006 .

[38]  Jeffry D Schroeter,et al.  Analysis of particle deposition in the turbinate and olfactory regions using a human nasal computational fluid dynamics model. , 2006, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[39]  E. Matida,et al.  Creation of a standardized geometry of the human nasal cavity. , 2009, Journal of applied physiology.

[40]  D. Swift,et al.  Aerosol Deposition in Human Nasal Airway for Particles 1nm to 20 µm: A Model Study , 1991 .

[41]  William Yang,et al.  Optimising nasal spray parameters for efficient drug delivery using computational fluid dynamics , 2008, Comput. Biol. Medicine.

[42]  Jiyuan Tu,et al.  Numerical study of fibre deposition in a human nasal cavity , 2008 .

[43]  Yung Sung Cheng,et al.  Aerosol Deposition in the Extrathoracic Region , 2003, Aerosol science and technology : the journal of the American Association for Aerosol Research.

[44]  J. Xi,et al.  Modeling of inertial deposition in scaled models of rat and human nasal airways: Towards in vitro regional dosimetry in small animals , 2016 .

[45]  Julia S. Kimbell,et al.  Particle Deposition in Human Nasal Airway Replicas Manufactured by Different Methods. Part I: Inertial Regime Particles , 2004 .

[46]  Jinxiang Xi,et al.  Numerical predictions of submicrometer aerosol deposition in the nasal cavity using a novel drift flux approach , 2008 .

[47]  Kevin R Minard,et al.  Comparative Risks of Aldehyde Constituents in Cigarette Smoke Using Transient Computational Fluid Dynamics/Physiologically Based Pharmacokinetic Models of the Rat and Human Respiratory Tracts. , 2015, Toxicological sciences : an official journal of the Society of Toxicology.

[48]  Goodarz Ahmadi,et al.  Fibrous particle deposition in human nasal passage : The influence of particle length, flow rate, and geometry of nasal airway , 2008 .

[49]  H P Lee,et al.  A review of the implications of computational fluid dynamic studies on nasal airflow and physiology. , 2010, Rhinology.

[50]  Guillaume Houzeaux,et al.  Deflated preconditioned conjugate gradient solvers for the pressure‐Poisson equation: Extensions and improvements , 2011 .

[51]  W. Frey,et al.  Intranasal delivery to the central nervous system: mechanisms and experimental considerations. , 2010, Journal of pharmaceutical sciences.

[52]  Robert H. Nelson,et al.  Normative standards for nasal cross-sectional areas by race as measured by acoustic rhinometry , 1998, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[53]  Jeffry D Schroeter,et al.  Olfactory deposition of inhaled nanoparticles in humans , 2015, Inhalation toxicology.

[54]  J. Kesavan,et al.  The relationship between particle deposition in the anterior nasal passage and nasal passage characteristics. , 2000, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[55]  Effect of Race on Fine Particle Deposition for Oral and Nasal Breathing , 2005, Inhalation toxicology.

[56]  Clement Kleinstreuer,et al.  Modeling of inertial particle transport and deposition in human nasal cavities with wall roughness , 2007 .

[57]  Yu Feng,et al.  Drug-targeting methodologies with applications: A review. , 2014, World journal of clinical cases.

[58]  R. G. Thorne,et al.  Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration , 2004, Neuroscience.

[59]  L. Illum Transport of drugs from the nasal cavity to the central nervous system. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[60]  D. J. Taylor,et al.  Nasal architecture: form and flow , 2008, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[61]  G. Houzeaux,et al.  A variational subgrid scale model for transient incompressible flows , 2008 .

[62]  Jana Kesavanathan,et al.  Human Nasal Passage Particle Deposition: The Effect of Particle Size, Flow Rate, and Anatomical Factors , 1998 .

[63]  S. Simpson,et al.  In vivo measurements of nasal airway dimensions and ultrafine aerosol deposition in the human nasal and oral airways , 1996 .

[64]  C. Woodard,et al.  A Computational Study of Nasal Spray Deposition Pattern in Four Ethnic Groups. , 2016, Journal of aerosol medicine and pulmonary drug delivery.

[65]  Jesús Labarta,et al.  Dynamic load balance applied to particle transport in fluids , 2016 .

[66]  R. Thorne,et al.  Quantitative analysis of the olfactory pathway for drug delivery to the brain , 1995, Brain Research.

[67]  Matthew R. Johnson,et al.  Experimental measurements and computational modeling of aerosol deposition in the Carleton-Civic standardized human nasal cavity , 2010 .

[68]  Guilherme J M Garcia,et al.  Interindividual variability in nasal filtration as a function of nasal cavity geometry. , 2009, Journal of aerosol medicine and pulmonary drug delivery.

[69]  J. Morris,et al.  A physiologically based pharmacokinetic model for nasal uptake and metabolism of nonreactive vapors. , 1993, Toxicology and applied pharmacology.

[70]  C. Kleinstreuer,et al.  Computational analysis of airflow and nanoparticle deposition in a combined nasal–oral–tracheobronchial airway model , 2011 .

[71]  Alberto M. Gambaruto,et al.  Wall shear stress and near-wall convective transport: Comparisons with vascular remodelling in a peripheral graft anastomosis , 2010, J. Comput. Phys..

[72]  Grace M. Kepler,et al.  Effects of Differences in Nasal Anatomy on Airflow Distribution: A Comparison of Four Individuals at Rest , 2008, Annals of Biomedical Engineering.

[73]  Guilherme J M Garcia,et al.  Atrophic rhinitis: a CFD study of air conditioning in the nasal cavity. , 2007, Journal of applied physiology.

[74]  Jeffry D. Schroeter,et al.  Dosimetry of nasal uptake of water-soluble and reactive gases: A first study of interhuman variability , 2009, Inhalation toxicology.

[75]  Michelle Noga,et al.  Deposition of micrometer-sized aerosol particles in infant nasal airway replicas , 2008 .

[76]  F. J. Miller,et al.  Upper respiratory tract surface areas and volumes of laboratory animals and humans: considerations for dosimetry models. , 1997, Journal of toxicology and environmental health.

[77]  Jeffry D Schroeter,et al.  Characterization of deposition from nasal spray devices using a computational fluid dynamics model of the human nasal passages. , 2007, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[78]  Clement Kleinstreuer,et al.  Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part II: Dry powder inhaler application , 2017, Comput. Biol. Medicine.