Particle deposition in the lungs

One important factor that has to be considered for all types of pulmonary delivery particles deposit in the lungs based on their aerodynamic diameter (Equation 1). For a spherical particle, the aerodynamic diameter (daer) is equal to the product of actual diameter (d) times the square root of particle density (p) (Gonda 1992). 

Aerosol particles deposit in the lung by three principal mechanisms inertial impaction gravitational sedimentation and Brownian diffusion. Particles with a larger MMAD are deposited by the first two mechanisms, while smaller particles access the peripheral region of the lung by diffusion. 

List the physiological factors affecting particle deposition in the lung. 

Segal, R. A., Martonen, T. B., Kim, C. S., and Shearer, M. (2002), Computer simulations of particle deposition in the lungs of chronic obstructive pulmonary disease patients, Inhal. Toxicol., 14,705-720. 

Ciliary action removes deposited particles from both the bronchi and bronchioles. Though it is generally thought that mucocilliary action rapidly transports most particles deposited here toward the pharynx, a fraction of these particles are cleared more slowly. Evidence for this is found in human studies. For humans, retention of particles deposited in the lungs (BB and bb) is apparently biphasic. The slow action of the cilia may remove as many as half of the bronchi- and bronchiole-deposited particles. In human bronchi and bronchiole regions, mucus moves more slowly the closer to the alveoli it is. For the faster compartment it has been estimated that it takes about 2 days for particles to travel from the bronchioles to the bronchi and 10 days from the bronchi to the pharynx. The second (slower) compartment is assumed to have approximately equal fractions deposited between BB2 and bb2 and both with clearance... 

Aerosol properties, such as particle size distribution, aerosol velocity, and hygroscopicity, affect aerosol deposition in the human lungs. Aerosol size distribution, including mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD), is one of the most important variables in governing the site of droplet or particle deposition in the lungs. ... 

Panicle size, concentration, and chemical composition arc usually the aerosol properties of most interest. Also imponant in certain applications arc particle charge, crystal stmeture and optical properties. In Industry, particles are collected to recover a desirable product or reduce emissions and occiiputional exposures. The efficiency of filters, scrubbers and other such devices depends primarily on particle size. As shown in Chapter a minimum is often found when the efficiency of particle rentoval is plotted a.s a function of particle size. The efficiency minimum or window" occurs in the particle size range near a few tenths of a micron for reasons that differ depending on the mechani.sms of particle collection. A similar efficiency mintniLini is observed for particle deposition in the lung as a function of particle size. The explanations for the efficiency minima in the lung and certain types of filters are similar. 

Sanders C. 1975a. Effects of Pu02 particles deposited in the lung following intraperitoneal injection. Health Phys 28 84-86. 

Figure 2 shows the deposition of particles of different sizes in the various regions of the respiratory tract during quiet breathing. The data presented in Fig. 2 are calculated on the basis of a theoretical model developed by the International Commission on Radiation Protection (ICRP 1994). It takes into account that particle deposition in the lung is predominantly governed by three physical processes impaction, sedimentation and diffusion. The model reproduces quite well the available experimental data. The efficiency of deposition in the respiratory tract may generally be described as a U-shaped curve on a plot of deposition efficiency versus the of log particle diameter as in Fig. 2. Total deposition shows a minimum for particle diameters in the range of 0.1 to 1.0 pm, where particles are small enough to have minimal sedimentation or impaction and sufficiently large so...

The two main determinants for medicine deposition in the respiratory tract are the aerodynamic size distribution of the aerosol and the manoeuvre with which the aerosol is inhaled. They govern the mechanisms that are respraisible for particle deposition in the lungs. By varying the inhalation manoeuvre, not only the distribution in the airways for the same aerosol is changed in many cases also the amount and properties of the delivered fine particle dose are affected. The complex interplay between inhalation manoeuvre, aerosol properties and site of deposition has led to many misconceptions regarding the best inhaler choice for individual patients and the way these inhalers need to be operated to achieve optimal therapy for the patient. In this chapter the medicine deposition mechanisms for inhaled aerosols are explained as functions of the variables involved. In addition, the working principles of different inhaler types are described and it is discussed how their performance depends on many inhalation variables. Finally, some persistent misconceptions in the literature about the most preferable dry powder inhaler properties and performance are umaveUed. 

Effects of airflow and turbulence on particle deposition in the lung were examined by Chan et al. using the airflow measurements in hollow casts and airway bifurcation models. Heyder et al. measured total and regional aerosol depositions through the mouth and the nose. Experimental studies for inspiratory particle depositions in single and double bifurcation airways were reported by Johnston and Schroter, Kim and Iglesias, Kim et al., and Kim and Fisher. ... 

This chapter does not attempt to review the entire range of clearance mechanisms provided by the respiratory tract for all kinds of deposited particles. It does not address the clearance of particles that are readily soluble in the epithelial lining fluid, nor specific immune reactions triggered by viable particles. It reviews clearance mechanisms of particles deposited in the lung, with emphasis on slow-clearance mechanisms. 

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