Ted B. Martonen

Effects of the laryngeal jet on nano- and microparticle transport and deposition in an approximate model of the upper tracheobronchial airways

The extent to which laryngeal-induced flow features penetrate into the upper tracheobronchial (TB) airways and their related impact on particle transport and deposition are not well understood. The objective of this study was to evaluate the effects of including the laryngeal jet on the behavior and fate of inhaled aerosols in an approximate model of the upper TB region. The upper TB model was based on a simplified numerical reproduction of a replica cast geometry used in previous in vitro deposition experiments that extended to the sixth respiratory generation along some paths. Simulations with and without an approximate larynx were performed. Particle sizes ranging from 2.5 nm to 12 mum were considered using a well-tested Lagrangian tracking model. The model larynx was observed to significantly affect flow dynamics, including a laryngeal jet skewed toward the right wall of the trachea and a significant reverse flow in the left region of the trachea. Inclusion of the laryngeal model increased the tracheal deposition of nano- and micrometer particles by factors ranging from 2 to 10 and significantly reduced deposition in the first three bronchi of the model. Considering localized conditions, inclusion of the laryngeal approximation decreased deposition at the main carina and produced a maximum in local surface deposition density in the lobar-to-segmental bifurcations (G2-G3) for both 40-nm and 4-microm aerosols. These findings corroborate previous experiments and highlight the need to include a laryngeal representation in future computational and in vitro models of the TB region.

Deposition Patterns of Aerosolized Drugs Within Human Lungs: Effects of Ventilatory Parameters

A mathematical model for inhaled aerosolized drugs is validated by comparisons of predicted particle deposition values with experimental data from adult subject inhalation exposure tests. The model is subsequently used to study the effects of ventilatory parameters on particle deposition patterns within the human lung. By altering breathing profiles, deposition values can be affected regarding quantity delivered and spatial location. Increased tidal volumes and breath-holding times increase deposition in the pulmonary region, while increased inspiratory flow rates increase deposition in the tracheobronchial region. Based upon fluid dynamics considerations (Reynolds numbers), an original method of partitioning the lung is also presented. The model has implications with regard to aerosol therapy, indicating that the efficacies of inhaled pharmacological drugs in the prophylaxis and treatment of airway diseases can be improved by regulating breathing profiles to deposit particles selectively at prescribed sites within the lung.

Behavior of Hygroscopic Pharmaceutical Aerosols and the Influence of Hydrophobic Additives

The high temperature and relative humidity in the lung can result in the hygroscopic growth of susceptible aerosol particles or droplets. The term hygroscopic growth describes the increase in particle diameter which occurs as the result of association with water vapor. The influence of hygroscopicity upon lung deposition of aerosols has been a productive area of research in industrial hygiene, environmental sciences, and inhalation toxicology. Many pharmaceutical inhalation aerosols display hygroscopic behavior in their passage through the airways; however, the effect has been neglected. Controlling the phenomenon of hygroscopic growth and, thus, the related lung deposition of aerosols might result in the therapeutic advantage of targeting the site of action. Such an approach might also allow identification of the location of pharmacologic receptor sites in the lung. This Review discusses an approach to achieving control of hygroscopic growth of aerosol particles. Theoretical and experimental studies have indicated that inhaled particle diameters increased significantly for drugs commonly administered to the lung. The presence of certain additives, notably glycerol, cetyl alcohol, and lauric and capric acids, has been demonstrated to reduce the growth of particles under conditions approaching those in the lung. Very few quantitative studies of the nature discussed herein have appeared in the literature. It is conceivable that an aerosol particle could be fabricated of known initial size and density, and by implication, deposition characteristics, and this might be induced to follow specific growth kinetics to enhance deposition in a particular region of the lung. Thus, physical targeting of regions within the lung might be achieved.

A numerical study of particle motion within the human larynx and trachea

In this paper, particle trajectories are calculated using a stochastic model for turbulent fluctuations incorporated into the particle momentum equation, in combination with the time-averaged solutions of flow fields in the larynx and trachea. The manner in which turbulence may affect overall deposition is investigated through illustrative numerical experiments of the effects of flow rate, initial particle location, density, and size, from which results are given in the form of probability density histograms of final particle locations (i.e. deposition sites). The histogram bins are defined in a unique manner that highlight the deposition mechanisms associated with turbulent dispersion. It is observed that turbulence may play a key role in enhancing particle deposition in the larynx and trachea.

Influences of Cartilaginous Rings on Tracheobronchial Fluid Dynamics

AbstractFluid dynamics patterns within tracheobronchial (TB) airways reflect interactions between cartilaginous rings and inspiratory flow rates. The results of supercomputer simulations performed herein were complex, yet systematic. The effects of cartilaginous rings upon TB fluid dynamics patterns were investigated using FIDAP software. A sequence of cartilaginous ring morphologies was examined. The distributions of rings varied from contiguous to spaced. A range of physiologically realistic flow conditions was simulated corresponding to these physical states: sedentary, light, and heavy activity. At the lowest inspiratory flow rate (14 L min−1) the primary convection flow within an airway occupied a prominent portion of its cross-sectional area and ring effects were confined along the rough surface. At the highest inspiratory flow rate (120 L min−1) the core flow was very narrow, with the disturbances created at the irregular walls being propagated to the very center of the airway. The fluid dynamics a...

Effects of Carinal Ridge Shapes on Lung Airstreams

Experimental tests cited herein have established that the deposits of inhaled particles may be highly concentrated at carinal ridges within lung bifurcations. Airway cells located at these sites will receive relatively massive doses of toxic substances and pharmacologic drugs. The deposition patterns, therefore, have immediate implications to risk assessment programs and aerosol therapy protocols. Herein, the software FIDAP was employed to study the effects of carinal ridge shapes upon fluid dynamics patterns. A series of well-defined geometric shapes (symmetric and asymmetric) were examined. For each case, a wide range of physiologically realistic flows were considered which corresponded to respiratory intensities for sedentary, light, and heavy activities. The results varied in a systematic manner. For example, at the lowest inspiratory flow rate of 14 L/min the effects were highly localized for all carinal ridge shapes, whereas at the highest inspiratory flow rate of 120 L/min the effects were propagat...

The use of combined single photon emission computed tomography and X-ray computed tomography to assess the fate of inhaled aerosol

BACKGROUND Gamma camera imaging is widely used to assess pulmonary aerosol deposition. Conventional planar imaging provides limited information on its regional distribution. In this study, single photon emission computed tomography (SPECT) was used to describe deposition in three dimensions (3D) and combined with X-ray computed tomography (CT) to relate this to lung anatomy. Its performance was compared to planar imaging. METHODS Ten SPECT/CT studies were performed on five healthy subjects following carefully controlled inhalation of radioaerosol from a nebulizer, using a variety of inhalation regimes. The 3D spatial distribution was assessed using a central-to-peripheral ratio (C/P) normalized to lung volume and for the right lung was compared to planar C/P analysis. The deposition by airway generation was calculated for each lung and the conducting airways deposition fraction compared to 24-h clearance. RESULTS The 3D normalized C/P ratio correlated more closely with 24-h clearance than the 2D ratio for the right lung [coefficient of variation (COV), 9% compared to 15% p < 0.05]. Analysis of regional distribution was possible for both lungs in 3D but not in 2D due to overlap of the stomach on the left lung. The mean conducting airways deposition fraction from SPECT for both lungs was not significantly different from 24-h clearance (COV 18%). Both spatial and generational measures of central deposition were significantly higher for the left than for the right lung. CONCLUSIONS Combined SPECT/CT enabled improved analysis of aerosol deposition from gamma camera imaging compared to planar imaging. 3D radionuclide imaging combined with anatomical information from CT and computer analysis is a useful approach for applications requiring regional information on deposition.

Fluid Dynamics of the Human Larynx and Upper Tracheobronchial Airways

The deposition sites of inhaled particles must be known to (1) promote therapeutic effects of airborne pharmacologic drugs via targeted delivery and (2) improve risk assessments of ambient contaminants. Because particle trajectories are affected by the motion of an entraining fluid, it is important to determine the character of an inhaled airstream. In this report, an original theory is presented for the simulation of laryngeal and tracheobronchial fluid dynamics. The mathematical model describes conditions in such respiratory tract airways of adult human subjects under various breathing conditions. The data describing fluid dynamics patterns are presented in two formats: graphical displays of mean streamlines and color illustrations of velocity distributions. In the defined airway system, fluid dynamics patterns are heterogeneous. Conditions within the larynx are especially complex, encompassing localized eddies, and a jet formed at the vocal folds. Moreover, the data indicate that the larynx exerts a pr...

Consensus statement: aerosols and delivery devices.

MYRNA B. DOLOVICH, P.Eng., NEIL R. MacINTYRE, F.A.A.R.C, PAULA J. ANDERSON, M.D., CARLOS A. CAMARGO, JR., M.D., Dr.P.H, NANCY CHEW, M.S., R.A.C., CYNTHIA H. COLE, M.D., M.P.H., RAJIV DHAND, M.D., JAMES B. FINK, M.S., R.R.T., F.A.A.R.C., NICHOLAS J. GROSS, M.D., Ph.D., DEAN R. HESS, Ph.D., R.R.T., F.A.A.R.C, ANTHONY J. HICKEY, Ph.D., CHONG S. KIM, Ph.D., TED B. MARTONEN, Ph.D., DAVID J. PIERSON, M.D., F.A.A.R.C, BRUCE K. RUBIN, M.D., and GERALD C. SMALDONE, M.D., Ph.D.

Flow simulation in the human upper respiratory tract

Computer simulations of airflow patterns within the human upper respiratory tract (URT) are presented. The URT model includes airways of the head (nasal and oral), throat (pharyngeal and laryngeal), and lungs (trachea and main bronchi). The head and throat morphology was based on a cast of a medical school teaching model; tracheobronchial airways were defined mathematically. A body-fitted three-dimensional curvilinear grid system and a multiblock method were employed to graphically represent the surface geometries of the respective airways and to generate the corresponding mesh for computational fluid dynamics simulations. Our results suggest that for a prescribed phase of breath (i.e., inspiration or expiration), convective respiratory airflow patterns are highly dependent on flow rate values. Moreover, velocity profiles were quite different during inhalation and exhalation, both in terms of the sizes, strengths, and locations of localized features such as recirculation zones and air jets. Pressure losses during inhalation were 30–35% higher than for exhalation and were proportional to the square of the flow rate. Because particles are entrained and transported within airstreams, these results may have important applications to the targeted delivery of inhaled drugs.