Airway Replicas Research Articles

Deposition of Man-Made Fibers in a Human Nasal Airway

Many occupational lung diseases are associated with exposure to aerosolized fibers in the workplace. The nasal airway is a critical route for fiber aerosol to enter the human respiratory tract. The fiber deposition efficiency in the nasal airway could be used as an index to indicate the fraction of the inhaled fibers potentially transported to the lower airways. In this research, experiments of fiber deposition in the human nasal airway were conducted. Man-made carbon, glass, and titanium dioxide fibers in the inertia regime were used as the test fiber materials. The deposition studies were carried out by delivering aerosolized fibers into a human nasal airway replica at constant human inspiratory flow rates ranging from 15 l/min to 43.5 l/min. The deposition results were compared in detail between these fiber materials to study how the fiber characteristics affected the nasal airway deposition. The results showed that the deposition efficiency of the carbon fiber increases as the fiber impaction parameter increases. Many carbon fibers deposited in the anterior region of the nasal airway. In contrast, very few glass or titanium dioxide fibers deposited in the nasal airway, but relatively more of these two fibers deposited in the turbinate region. This result implies that, if a fiber in the inertia regime is inhaled during normal human breathing, the smaller the fiber, the more easily it could enter the human lower respiratory tract, possibly causing harm to the human respiratory tract.

Fiber Deposition in the Tracheobronchial Region: Deposition Equations

A lung deposition model for fibrous aerosol needs accurate deposition equations for different regions of the human respiratory tract. For fiber deposition in the tracheobronchial region there are several theoretical and empirical equations to predict deposition efficiency in the impaction-dominant region. However, few were verified with experimental data. We have obtained experimental data of fiber deposition in realistic human airway replicas using carbon fibers. Comparison of experimental data and existing deposition models yield variable results, with some models performing better than other models. There was no consistent agreement found over the Stokes number range of experimental data. A generic empirical model for fiber deposition in the tracheobronchial region was developed based on all carbon fiber deposition data in human lung replicas. This model includes the size of fibers and the geometry of the tracheobronchial bifurcation. Because it is difficult to develop only one equation for all data from the trachea to the major bronchial bifurcations, the deposition patterns in the trachea and first generation were each predicted by their own equations. An additional equation was developed for the second to fourth generations. This model, combined with oral and nasal deposition predictions which will be published elsewhere, can be used to investigate the inhalation dosimetry and deposition patterns of fibers in human lungs for assessing occupational hazards and air pollutants.

Modeling of Aerosol Deposition with Interface Devices

Various approaches can be used to mathematically model the performance of different masks, mouthpieces, and aerosol delivery devices. The sophistication of such models can vary widely, from the use of simple algebraic empirical correlations to advanced computational fluid dynamics simulations. Bench-top testing is also often used to model aspects of devices, since it is difficult to capture certain aspects of device behavior with mathematical models. These various approaches to modeling differ in their limitations. Empirical correlations exist for predicting the effects of varying mouthpiece diameter and mouth-throat dimensions on extrathoracic losses, but are restricted to stable, nonballistic aerosols in certain flow rate ranges. Computational fluid dynamics (CFD) simulations that solve the Reynolds-averaged Navier-Stokes (RANS) equations typically require near-wall turbulence corrections in order to adequately model mouth-throat deposition, while Large Eddy Simulation (LES) removes this deficiency. Bench-top models that use replicas of the extrathoracic airways vary in their accuracy and generality in replicating the filtering properties of these airways. Choosing and using these various modeling approaches for evaluating patient-device interfaces requires knowledge of their merits and pitfalls, a brief discussion of which is given here.

Fiber Deposition in the Tracheobronchial Region: Experimental Measurements

Fiber deposition efficiency in the tracheobronchial region was studied by using two human airway replicas. Carbon fibers with a monodisperse diameter of 3.66 μ were delivered into lung casts at the flow rates of 15, 45, and 60 L/min. Deposition efficiencies in each airway bifurcation were obtained individually. Even though the data shows large variability among the bifurcations within the same generation, there is a general trend for the data obtained in these two replicas. Our results show that fiber deposition for carbon fibers increases with the Stokes number, indicating that inertial impaction is the dominant mechanism. Also, fiber deposition in the tracheobronchial region is lower than that of spherical particles at a given Stokes number, and is similar to the deposition found in the nasal and oral airways as reported previously. This finding implies that it is easier for fibers to penetrate the upper respiratory tract and to reach the lower airways as compared to spherical particles. Our measurements are in general agreement with data obtained with asbestos fiber as reported in another study using a hollow airway replica. Our study appears to give a higher deposition efficiency than the results obtained using idealized single symmetrical bifurcation models. This demonstrates, again, the importance of using a realistic airway model, including larynx, to simulate the airway geometry and flow pattern of the human respiratory tract.

Deposition of fiber in a human airway replica

Fiber is a notorious occupational hazard. Exposures to airborne asbestos fiber in the workplace increase the incidence of lung cancer for asbestos workers. Due to the lack of experimental data, the nature of fiber deposition in the human airway is unclear. In this study, a set of experiments were carried out to investigate the effect of fiber dimension and fiber inertia on the deposition pattern in the human airway replica. The deposition study was conducted by delivering aerosolized carbon fibers into the replica at constant inspiratory flow rates of 15–60 l/min. The results showed that impaction is the dominant deposition mechanism in this study. Most of the high-inertia fibers deposited in the oropharynx and the carina ridges of the bifurcations in tracheobronchial airways. A series of fiber deposition patterns were obtained and the deposition efficiencies were acquired for certain regions in the human airway replica.

Deposition of Fiber in the Human Nasal Airway

Inhalation is the main route for aerosol entering the human body. Many occupational lung diseases are associated with exposure to fiber aerosol in the workplace. However, very few studies to date have been conducted for investigating fiber deposition in the human airway. As a result, there is a notable lack of information on the nature of the fiber deposition pattern in the human respiratory tract. With this in mind, this research consisted of a large number of experimental works to investigate the effects of fiber dimension on the deposition pattern for a human nasal airway. Carbon fibers with uniform diameter (3.66 μm) and polydispersed length were adopted as the test material. Deposition studies were conducted by delivering aerosolized carbon fibers into a nasal airway replica (encompassing the nasal airway regions from vestibule to nasopharynx) at constant inspiratory flow rates of 7.5, 15, 30, and 43.5 l/min. Fibers deposited in each nasal airway region were washed out and the length distribution was...

Particle Deposition in a Cast of Human Tracheobronchial Airways

Abstract Regional particle deposition efficiency and deposition patterns were studied experimentally in a human airway replica made from an adult cadaver. The replica includes the oral cavity, pharynx, larynx, trachea, and four generations of bronchi. This study reports deposition results in the tracheobronchial (TB) region. Nine different sizes of monodispersed, polystyrene latex fluorescent particles in the size range of 0.93–30 μm were delivered into the lung cast with the flow rates of 15, 30, and 60 l min− 1. Deposition in the TB region appeared to increase with the increasing flow rate and particle size. Comparison of deposition data obtained from physical casts showed agreement with results obtained from realistic airway replicas that included the larynx. Deposition data obtained from idealized airway models or replicas showed lower deposition efficiency. We also compared experimental data with theoretical models based on a simplified bend and bifurcation model. A deposition equation derived from t...

Particle Deposition in Human Nasal Airway Replicas Manufactured by Different Methods. Part I: Inertial Regime Particles

Information on the deposition efficiency of aerosol particles in the nasal airways is used for optimizing the delivery of therapeutic aerosols into the nose and for risk assessment of toxic airborne pollutants inhaled through the nose into the respiratory system. Nasal particle deposition is often studied using plastic replicas of nasal airways. Deposition efficiency in a nasal replica manufactured by stereolithography has not been reported to date. We determined the inertial particle deposition efficiency of two replicas of the same nasal airways manufactured by different stereolithography machines and compared results with deposition efficiencies reported for models manufactured by other techniques from the same magnetic resonance imaging scans. Deposition in the replicas was measured for particles of aerodynamic diameter between 1 and 10 μm and constant inspiratory flow rates ranging from 20–40 Ipm. Deposition efficiency of the replicas increased from nearly 0–100% with increasing particle inertia. For...

Particle Deposition in Human Nasal Airway Replicas Manufactured by Different Methods. Part II: Ultrafine Particles

Particle Deposition in Human Nasal Airway Replicas Manufactured by Different Methods. Part II: Ultrafine Particles

Particle characteristics and lung deposition patterns in a human airway replica of a dry powder formulation of polylactic acid produced using supercritical fluid technology.

Polylactic acid (PLA) powders have been used as vector particles to carry pharmaceutical material. Drugs incorporated in the PLA powder can be retained in the lung for a longer period and may be more effective than free-form drugs. A new formulation of L-PLA dry powder, which was easy to disperse in the air, was produced by using a supercritical technology. The L-PLA powder was characterized in terms of physical particle size and aerodynamic size as generated with a Turbuhaler dry powder inhaler (DPI). Electron microscopy analysis of the particles indicated that they were individual particles in bulk form and became aggregate particles after generation by the Turbuhaler. Aerodynamic particle size analysis using both an Aerodynamic Particle Sizer (APS) aerosol spectrometer and Andersen impactor showed that the aerodynamic size decreased as the flow rate in the Turbuhaler increased from 28.3 to 90 L min(-1). Deposition patterns in the human respiratory tract were estimated using a realistic physical replica of human airways. Deposition of the L-PLA was high (80.8%) in the oral airway at 28.3 L min(-1) and an average of 73.4% at flow rates of 60 and 90 L min(-1). In the lung region, the deposition totaled 7.2% at 28.3 L min(-1), 18.3% at 60 L min(-1), and 17.6% at 90 L min(-1). These deposition patterns were consistent with aerodynamic size measurement, which showed 76 to 86% deposition in the USP/EP (US Pharmacopoeia/European Pharmacopoeia) induction port. As the flow rate increased, fewer aggregates were formed resulting in the smaller aerodynamic particles. As a result, more particles penetrated the oral airways and were available for deposition in the lung. Our results showed that L-PLA particles as manufactured by the supercritical technology could be used in a DPI that does not require the use of carrier particles to facilitate aerosol delivery.

Respiratory Deposition Patterns of Salbutamol pMDI with CFC and HFA-134a Formulations in a Human Airway Replica

This paper describes a technique that uses a well-defined human airway replica and gamma counting as a standard method for evaluating and comparing the performance of medical inhalers and spacers. High-fidelity replicas reproduced as needed from master casts made from human cadavers include the oropharyngeal cavity, larynx, trachea, and five to nine generations of bronchi. Deposition in the small airways and alveoli region of the cast is simulated by material that passes through the upstream airways and is collected on foam filters. Deposition patterns in the respiratory tract replica were obtained by using radiolabel in the medical inhaler and by gamma scintigraphy. This technique was used to determine respiratory deposition patterns of salbutamol in a pressurized metered dose inhaler (pMDI) with chlorofluorocarbon (CFC, in-house formulation) and HFA-134 formulations (Proventil hydrofluoroalkane [HFA]). At an inspiration flow of 30 L/min, patterns in the salbutamol/CFC formula showed a high deposition in the oropharyngeal airway (78%) and a 16% deposition in the lung, similar to in vivo measurements reported in the literature. However, the salbutamol/HFA formula showed lower oral deposition (56%) but higher lung deposition (24%). The difference in the oral deposition patterns may be attributed to lower initial spray velocity, initial droplet evaporation rate, and possibly initial droplet sizes of Proventil HFA. The small orifice diameter (0.25 mm) of the Proventil HFA actuator produced a softer plume with a smaller impact force, resulting in lower oropharyngeal deposition. Cascade impactor measurements showed similar aerodynamic particle size distribution of the CFC and HFA formulations. We also showed that using spacers in the Proventil HFA resulted in a lower oropharyngeal deposition and higher lung deposition, indicating beneficial effects. Comparison of oropharyngeal deposition and those predicted by artificial throats used in the impactor measurements showed that, in general, the artificial throat predicted a lower deposition.

Particle Deposition in a Cast of Human Oral Airways

Oral and nasal airways are entryways to the respiratory tract. Most people breathe through the nasal airway during rest or light exercise, then switch to oral/nasal breathing during heavy exercise or work. Resistance through the oral airways is much lower than through the nasal airways, so fewer aerosol particles are deposited in the oral airways. Aerosol drugs are usually delivered by inhalation to the lung via the oral route for that reason. Oral deposition data from humans are limited, and those available show great intersubject variability. The purpose of this study was to investigate the effects of particle size and breathing rate on the deposition pattern in a human oral airway cast with a defined geometry. The airway replica included the oral cavity, pharynx, larynx, trachea, and 3 generations of bronchi. The oral portion of the cast was molded from a dental impression of the oral cavity in a human volunteer, while the other airway portions of the cast were made from a cadaver. Nine different sizes...

Metered Dose Inhaler Aerosol Deposition in a Model of the Human Respiratory System and a Comparison with Clinical Deposition Studies

Journal of Aerosol MedicineVol. 11, No. s1 International Society for Aerosols in Medicine Focus Symposium TOWARDS MEANINGFUL LABORATORY TESTS FOR EVALUATION OF PHARMACEUTICAL AEROSOLS Puerto Rico, January 29–31,1997Metered Dose Inhaler Aerosol Deposition in a Model of the Human Respiratory System and a Comparison with Clinical Deposition StudiesDAVID J. VELASQUEZ and BRIAN GABRI0DAVID J. VELASQUEZSearch for more papers by this author and BRIAN GABRI0Search for more papers by this authorPublished Online:25 Mar 2010https://doi.org/10.1089/jam.1998.11.Suppl_1.S-23AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byUse of Airway Replicas in Lung Delivery Applications Laleh Golshahi, Warren H. Finlay, and Herbert Wachtel30 March 2022 | Journal of Aerosol Medicine and Pulmonary Drug Delivery, Vol. 35, No. 2In vitro-in vivo correlations (IVIVCs) of deposition for drugs given by oral inhalationAdvanced Drug Delivery Reviews, Vol. 167Determination of Passive Dry Powder Inhaler Aerodynamic Particle Size Distribution by Multi-Stage Cascade Impactor: International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS) Recommendations to Support Both Product Quality Control and Clinical Programs30 May 2019 | AAPS PharmSciTech, Vol. 20, No. 5Developing Ways to Evaluate in the Laboratory How Inhalation Devices Will Be Used by Patients and Care-Givers: The Need for Clinically Appropriate Testing4 June 2014 | AAPS PharmSciTech, Vol. 15, No. 5Improved laboratory test methods for orally inhaled productsTherapeutic Delivery, Vol. 4, No. 8Applying the AIM Concept in Support of Developing Improved In Vitro–In Vivo Relationships for OIPs25 February 2013Development of the Premature Infant Nose Throat-Model (PrINT-Model)—An Upper Airway Replica of a Premature Neonate for the Study of Aerosol DeliveryPediatric Research, Vol. 64, No. 2Studies of the Human Oropharyngeal Airspaces Using Magnetic Resonance Imaging. II. The Use of Three-Dimensional Gated MRI to Determine the Influence of Mouthpiece Diameter and Resistance of Inhalation Devices on the Oropharyngeal Airspace Geometry Susan E. Pritchard and Donald W. McRobbie11 January 2005 | Journal of Aerosol Medicine, Vol. 17, No. 4Entry Port Selection for Detecting Particle Size Differences in Metered Dose Inhaler Formulations Using Cascade Impaction2 February 2004 | Drug Development and Industrial Pharmacy, Vol. 30, No. 1Studies of the Human Oropharyngeal Airspaces using Magnetic Resonance Imaging. I. Validation of a Three-Dimensional MRI Method for Producing Ex Vivo Virtual and Physical Casts of the Oropharyngeal Airways During Inspiration Donald W. McRobbie, Susan Pritchard, and Rebecca A. Quest7 July 2004 | Journal of Aerosol Medicine, Vol. 16, No. 4The Sophia Anatomical Infant Nose-Throat (Saint) Model: A Valuable Tool to Study Aerosol Deposition in Infants Hettie M. Janssens, Johan C. de Jongste, Wytske J. Fokkens, Simon G.F. Robben, Kris Wouters, and Harm A.W.M. Tiddens7 July 2004 | Journal of Aerosol Medicine, Vol. 14, No. 4A new method to evaluate plume characteristics of hydrofluoroalkane and chlorofluorocarbon metered dose inhalersInternational Journal of Pharmaceutics, Vol. 186, No. 1Assessing lung deposition of inhaled medicationsRespiratory Medicine, Vol. 93, No. 2 Volume 11Issue s1Jun 1998 To cite this article:DAVID J. VELASQUEZ and BRIAN GABRI0.Metered Dose Inhaler Aerosol Deposition in a Model of the Human Respiratory System and a Comparison with Clinical Deposition Studies.Journal of Aerosol Medicine.Jun 1998.S-23-S-28.http://doi.org/10.1089/jam.1998.11.Suppl_1.S-23Published in Volume: 11 Issue s1: March 25, 2010PDF download

Deposition of 0.005-12 μm Monodisperse Particles in A Computer-Milled, Mri-Based Nasal Airway Replica

Deposition of 0.005-12 μm Monodisperse Particles in A Computer-Milled, Mri-Based Nasal Airway Replica