Chapter 2 - Deposition of Aerosols in the Lungs
This chapter includes following sub-chapters:
Chapter 2.1 Particle Size Distributions by Warren H. Finlay, PhD and Chantal Darquenne, PhD
This chapter describes the effects that respiratory disease has on particle deposition in the lungs. The geometry of airways, breathing patterns, and regional ventilation are all affected by various lung diseases, including COPD, asthma, and cystic fibrosis, and in turn modify total and regional deposition from normal. Total particle deposition in the lung is increased by airways obstruction and increased ventilation at rest compared to healthy individuals. Regional particle deposition is 1) shifted from distal to more proximal bronchial airways by airway obstruction, and 2) becomes more heterogeneous due to uneven lung ventilation. The net effect of the changes in total and regional particle deposition from normal is to greatly enhance bronchial airway surface doses for particle deposition while leaving unventilated lung regions inaccessible to the particles.
Chapter 2.2 Deposition Mechanisms by Chantal Darquenne, PhD
The success of inhalation therapy is not only dependent upon the pharmacology of the drugs being inhaled but also upon the site and extent of deposition in the respiratory tract. Similarly, the toxicity of environmental and industrial particulate matter is affected not only by the nature of the dust but also by the amount and spatial distribution of deposited particles in the lung. Aerosol deposition is primarily governed by the mechanisms of inertial impaction, gravitational sedimentation, Brownian diffusion, and to a lesser extent, by turbulence, electrostatic precipitation and interception. The relative contribution of these different mechanisms is a function of the physical characteristics of the particles, the lung structure and the flow patterns. Large particles (> 5 μm) tend to deposit mainly in the upper and large airways, limiting the amount of aerosols that can be delivered to the lung.
Chapter 2.3 Regional Lung Deposition: In vivo Data by Sabine Häußermann, PhD, Knut Sommerer, and Gerhard Scheuch, PhD
The method section of this chapter on in vivo regional lung deposition highlights a nonradioactive method to measure regional deposition, which uses a photometer to quantify inhaled and exhaled particles and in that way is able to estimate the lung region from which the particles are exhaled and to what amount. The radioactive methods cover the measurement of clearance of the deposited particles as well as different imaging techniques to determine regional deposition. The result section reviews in vivo trials in human subjects. It also addresses different parameters that influence the regional deposition in the lungs: particle size, inhalation maneuver, carrier gas, disease, and inhalation device. All of these factors can affect regional deposition significantly.
Chapter 2.4 Regional Deposition: Deposition Models by Werner Hofmann, PhD
Modeling particle deposition in the human lung requires information about the morphology of the lung in terms of simple geometric units, e.g. characterizing bronchial airways by straight cylindrical tubes. Five different regional deposition models are discussed in this section with respect to morphometric lung models and related mathematical modeling techniques: 1) one- dimensional cross-section or “trumpet” model, 2) deterministic symmetric generation or “single- path” model, 3) deterministic asymmetric generation or “multiple-path” model, 4) stochastic asymmetric generation or “multiple-path” model, and 5) single-path computational fluid and particle dynamics (CFPD) model.
Chapter 2.5 Regional Deposition: Targeting by Andrew R. Martin, PhD
Patterns of regional aerosol deposition within the lungs are known to vary in a predictable manner with a number of factors, most notably aerodynamic particle size and inhalation pattern. Targeting deposition involves the intentional manipulation of one or more of these factors to promote aerosol deposition in certain locations within the respiratory tract. This section will begin by exploring existing evidence supporting the need to target regional deposition. Thereafter, various approaches to targeting will be introduced. In addition to control of aerodynamic particle size and inhalation pattern, a collection of approaches are available through which to passively target deposition to more central or peripheral lung regions.
Chapter 2.6 Additional Factors: Particle Characteristics / Warren H. Finlay, PhD
Of the various particle properties that affect deposition in the respiratory tract, particle diameter and particle density are the most commonly considered, since their effect on deposition is well known and important, as has been discussed earlier in this chapter. However, there are several other particle properties that can affect particle deposition in the lungs. These include: 1) electrostatic charge on the particle, which can cause electrostatic forces to enhance deposition; 2) the shape of the particle, which can cause its trajectory to differ from that of a spherical particle and thereby alter its deposition; and 3) volatility of the particle i.e. its ability to condense or evaporate at its surface, which can change its diameter and in turn affect its deposition. In this section, we examine each of these three factors individually.
Chapter 2.7 Additional Factors: Carrier Gases and Their Effects on Aerosol Drug Delivery by Tim Corcoran, PhD.
Carrier gases provide the medium for delivery of inhaled aerosol therapies. The physical properties of these gases substantially affect both fluid and aerosol mechanics in the lung. Gas density affects both the pressure/flow relationship in the airways and the extent of turbulence within the flow. These physical properties also affect the operation of some components of respiratory and aerosol drug delivery equipment. The lower resistance associated with breathing low density gases has prompted many studies of therapeutic applications.
Chapter 2.8 Additional Factors: Physiological Factors by Chong S. Kim, PhD.
Ventilation and mechanics of breathing are an integral part of respiratory physiology that directly affect aerosol transport and deposition in the lung. Although natural breathing pattern varies widely among individuals, breathing pattern is controllable, and by using an appropriate breathing pattern, aerosol deposition can be substantially modified for desired purposes. Effects of breathing pattern have been investigated under carefully controlled inhalation conditions covering a wide range of tidal volumes (VT) and breathing frequencies (f) or respiratory times (T=1/f). The studies have shown that lung deposition can increase or decrease as much as two times by changing the breathing pattern.
Chapter 2.9 Effect of Respiratory Tract Disease on Particle Deposition by William D. Bennett, PhD
This chapter describes the effects that respiratory disease has on particle deposition in the lungs. The geometry of airways, breathing patterns, and regional ventilation are all affected by various lung diseases, including COPD, asthma, and cystic fibrosis, and in turn modify total and regional deposition from normal. Total particle deposition in the lung is increased by airways obstruction and increased ventilation at rest compared to healthy individuals. Regional particle deposition is 1) shifted from distal to more proximal bronchial airways by airway obstruction, and 2) becomes more heterogeneous due to uneven lung ventilation. The net effect of the changes in total and regional particle deposition from normal is to greatly enhance bronchial airway surface doses for particle deposition while leaving unventilated lung regions inaccessible to the particles.
