The effects of simulated airway diseases and affected flow distributions on aerosol deposition.

Background: Experimental and theoretical aspects of targeted drug delivery have been addressed several times in this journal. Herein, a computational study of particle deposition patterns within healthy and diseased lungs has been performed, using a validated aerosol dosimetry model and a flow-resistance model.

Objective: To evaluate to what extent the uneven flow distributions produced by the physical manifestations of respiratory diseases affect the deposition patterns of inhaled aerosolized drugs.

Measurements of electrodynamic effects on the deposition of MDI and DPI aerosols in a replica cast of human oral-pharyngeal-laryngeal airways.

Metered dose inhalers (MDIs) and dry powder inhalers (DPIs) are popular drug delivery devices used in the treatment of respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Integrated effects of electrostatic charges and aerodynamic sizes on the deposition of MDI and DPI particles in a replica cast of human oral-pharyngeal-laryngeal (OPL) airways were examined. Experimental aerosols were generated from commercially available MDI and DPI devices.

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.

Three-dimensional computational fluid dynamics simulations of particle deposition in the tracheobronchial tree.

Simulation of the dynamics and disposition of inhaled particles within human lungs is an invaluable tool in both the development of inhaled pharmacologic drugs and the risk assessment of environmental particulate matter (PM). The goal of the present focused study was to assess the utility of three-dimensional computational fluid dynamics (CFD) models in studying the local deposition patterns of PM in respiratory airways. CFD models were validated using data from published experimental studies in human lung casts.

Comparison of SPECT aerosol deposition data with a human respiratory tract model.

Three-dimensional (3D) radionuclide imaging provides detailed information on the distribution of inhaled aerosol material within the body. Analysis of the data can provide estimates of the deposition per airway generation. In this study, two different nebulizers have been used to deliver radiolabeled aerosols of different particle size to 12 human subjects.

Comparison of SPECT aerosol deposition data with twenty-four-hour clearance measurements.

Three-dimensional (3D) radionuclide imaging provides detailed information on the distribution of inhaled aerosol material within the body. Analysis of the data can provide estimates of the deposition per airway generation. Information on regional distribution of deposited aerosol can also be obtained from 24-hour clearance measurements.

Particle deposition in children's lungs: theory and experiment.

A mathematical model of inhaled aerosol particle deposition for children is presented and validated with data from two published experimental studies. The model accurately predicts deposition fraction (DF) in children as a function of particle size for particles in the size range 1-3 microns for both sedentary and exercise breathing conditions. When the experimental data are grouped according to age, the model is able to predict age-dependent trends in DF at the studied particle sizes under sedentary breathing conditions.

Airway identification within planar gamma camera images using computer models of lung morphology.

Purpose: Quantification of inhaled aerosols by planar gamma scintigraphy could be improved if a more comprehensive assessment of aerosol distribution patterns among lung airways were obtained. The analysis of planar scans can be quite subjective because of overlaying of small, peripheral airways with large, conducting airways. Herein, a computer modeling technique of the three-dimensional (3-D) branching structure of human lung airways was applied to assist in the interpretation of planar gamma camera images.

Issues in drug delivery: concepts and practice.

Understanding the transport and deposition of inhaled aerosols is of fundamental importance to inhalation therapy. Herein we address issues that affect drug delivery from experimental and theoretical perspectives. Accordingly, we shall limit our comments to a focused review of laboratory work (ie, an in vitro perspective) and the development of a computer-based 3-dimensional (3D) oral morphology with related computational fluid dynamics (CFD) and particle deposition studies (ie, an "in silico" perspective).

Validation of the conceptual anatomical model of the lung airway.

The conceptual anatomical model of the lung airway considers each lung volume divided into ten concentric shells. It specifies the volume of each airway generation in each shell, using Weibel morphometry. This study updates and validates the model and evaluates the errors obtained when using it to estimate inhaled aerosol deposition per generation from spatial imaging data.

Computer reconstruction of a human lung boundary model from magnetic resonance images.

A mathematical description of the morphology of the lung is necessary for modeling and analyzing the deposition of inhaled aerosols A model of the lung boundary was generated from magnetic resonance images, with the goal of creating a framework for anatomically realistic morphological models of the human airway network. We used data visualization and analysis software to reconstruct the lung volume from a series of transverse magnetic resonance images collected at many vertical locations in the lung, ranging from apex to base. The lung model was then built using isosurface extraction techniques.

Fine particle deposition within human nasal airways.

An original mathematical model describing particle diffusion in human nasal passages is presented. A unique feature of the model is that it combines effects of both turbulent and laminar flows. To account for turbulence, concentration equations written in cylindrical coordinates are first simplified by a scaling technique and then solved analytically based on momentum/mass transfer analogy.

Risk assessment dosimetry model for inhaled particulate matter: II. Laboratory surrogates (rat).

Inhalation toxicology investigations are often performed with laboratory animals to address the potential health effects of inhaled air pollutants on human beings. In Part II of this risk assessment study we have considered the deposition of inhaled particulate matter in the laboratory rat as the surrogate of choice. Calculations were performed in an analogous manner to those conducted in Part I for human subjects.

Risk assessment dosimetry model for inhaled particulate matter: I. Human subjects.

Pollutant particulate matter (PM) is a serious global problem, presenting a threat to the health and well being of human subjects. Inhalation exposures tests with surrogate animals can be performed to estimate the threat. However, it is difficult to extrapolate the findings of animal tests to human conditions.

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.

Factors affecting the deposition of inhaled porous drug particles.

Recent findings indicate that the inhalation of large manufactured porous particles may be particularly effective for drug delivery. In this study, a mathematical model was employed to systematically investigate the effects of particle size, particle density, aerosol polydispersity, and patient ventilatory parameters on deposition patterns of inhaled drugs in healthy human lungs. Aerodynamically similar particles with densities of 0.

A computer model of lung morphology to analyze SPECT images.

Measurement of the spatial distribution of aerosol deposition in human lungs can be performed using single photon emission computed tomography (SPECT). To relate deposition patterns to real lung structures, a computer model of the airway network has been developed. Computer simulations are presented that are compatible with the analysis of SPECT images.

Fundamental effects of particle morphology on lung delivery: predictions of Stokes' law and the particular relevance to dry powder inhaler formulation and development.

Key factors that contribute to the aerodynamic properties of aerosol particles are found in Stokes' law. These factors may be monitored or controlled to optimize drug delivery to the lungs. Predictions of the aerodynamic behavior of therapeutic aerosols can be derived in terms of the physical implications of particle slip, shape and density.