Respiratory Deposition

Introduction

Particles suspended in the air enter our body when we breathe. These particles include natural materials such as bacteria, viruses, pollens, sea salt, road dust as well as anthropogenic emissions such as cigarette smoke, vehicle exhaust, boilers, agricultrual or forest burns. The hazard posed by these particles depends on their chemical composition as well as where they deposit within our respiratory system. The recent outbreak of SARS (Severe Acute Respiratory Syndrome) is a good example of disease transmission through the inhalation route. Interestingly, the same process applies to the administration of pharmaceutical aerosols or diagnostic aerosol by inhalation. Hence, the understanding of aerosol deposition in our respiratory system is critcal to our health so that we can reduce the deposition of "BAD" aerosol and enhance the deposition of "GOOD" aerosol in the desired region.
In order to evaluate aerosol deposition, first we need to learn our respiratory system. The system is typically divided into three regions (from the viewpoint of respiratory deposition): Head Airways region, Lung Airways Region and Pulmonary Region.
The head airways region is also called extra thoracic or nasopharyngeal region, and it includes nose, mouth, pharynx and larynx. The lung airways region is also called tracheobronchial region, and it is from the trachea to the terminal bronchioles. In this region, the trachea subdivides into smaller and smaller branches just like an inverted tree. From the trachea to the alveolar surface, there are 23 airway branchings. The pulmonary region is also called alveolar region. This is where gas exchange takes place. If fully unfolded, the surface area for this gas exchange region is about 75m², approximately half of a singles tennis court!
The following animation show the anatomy of our respiratory system.

In order to evaluate aerosol deposition, first we need to learn our respiratory system. The system is typically divided into three regions (from the viewpoint of respiratory deposition): Head Airways region, Lung Airways Region and Pulmonary Region.
The head airways region is also called extra thoracic or nasopharyngeal region, and it includes nose, mouth, pharynx and larynx. The lung airways region is also called tracheobronchial region, and it is from the trachea to the terminal bronchioles. In this region, the trachea subdivides into smaller and smaller branches just like an inverted tree. From the trachea to the alveolar surface, there are 23 airway branchings. The pulmonary region is also called alveolar region. This is where gas exchange takes place. If fully unfolded, the surface area for this gas exchange region is about 75m², approximately half of a singles tennis court!
The following animation show the anatomy of our respiratory system.
Characteristics of the various regions in the respiratory system are shown in the table below. As you can see from the table, as it goes deeper in the system, the diameter and the length decrease while the number of branchings increases. This increase results in a decreasing velocity and increasing residence time that have great impact on the "effective mechanisms" responsible for deposition.

Airway	Gener- ation of Branchings	Number of Branchings	Diameter of Airway (mm)	Length of Airway (mm)	Total Cross- Section Area (cm2)	Velocity (mm/s)	Residence Time in the Airway (ms)
Trachea	0	1	18	120	2.5	3900	30
Main bronchus	1	2	12	48	2.3	4300	11
Segmental bronchus	4	16	4.5	13	2.5	3900	3.2
Terminal bronchus	11	2000	1.1	3.9	20	520	7.4
Terminal bronchiole	16	66000	0.6	1.6	180	54	31
Alveolar duct	21	2 x 106	0.43	0.7	3200	3.2	210
Alveolar sac	23	8 x 106	0.41	0.5	72000	0.9	550
Alveoli		3 x 108	0.28	0.2

Retention and Clearance

The retention of deposited particles varies significantly depending on their physicochemical properties, deposition location and clearance mechanism involved. In the head airways and lung airways, the surface is covered with a layer of mucus. This layer is slowly propelled by ciliary action to the pharynx and is then subconsciously swallowed to the gastrointestinal tract. Generally, this mucociliary transport can get the deposited particles out of the respiratory system in a matter of hours. If the inhaled air contains low doses of irritating gases or aerosols, this clearance mechanism can be accelerated. However, it can be slowed down if doses are high.
The alveolar region, however, does not have the same mucociliary mechanism because BY NATURE it's designed for gas exchange. Insoluble particles deposited in this region may be engulfed by alveolar macrophages and transported to lymph nodes although generally it can take months or years to clear them. Fibrogenic dusts, such as silica, asbestos and coal dust, interfere with this mechanism resulting in fibrosis of this region. Due to its long retention time and subsequently continuous radiation, insoluble radioactive material deposited in this region causes significant damages to the local region. Soluble materials can pass through the thin alveolar membrane and be transported to other parts of our body. Hence, it is the region where viruses love to invade and it is also the target region for therapeutic aerosol delivery.

Deposition Mechanism

Our respiratory system is essentially a filter. Thus, the mechanisms involved in filtration (industrial or domestic applications) are also valid here. The viscous surface of the airway walls almost guarantees the deposition without re-entrainment when a particle is in contact with it. The most important mechanisms are IMPACTION, SETTLING, DIFFUSION and INTERCEPTION.

. Impaction

Collection by impaction is due to a particle's inertia that makes the particle deviate from the air stream when the air stream makes a turn. That is, the particle likes to stick to its original linear path and does not want to follow the curved air streamlines. Impaction is important when the particle size or the velocity is large in a curved pathway. Hence, it is the primary concern in the bronchial region.

Settling

When flow velocity is small and the airway dimension is small, settling then becomes an important role for large particles. Just like all objects on earth are subject to the gravitational force, a particle settles onto the airway surface when it moves toward the earth. It's especially effective in horizontally oriented airways. Therefore, it is the most important in the distal airways (those farthest from the trachea).

Diffusion/Brownian Motion

In the small airway where the distance is short and residence time is long, diffusion is an important mechanism for the deposition of small particles (< 0.5 μm). Brownian motion is the microscopic random motion of small particles due to the numerous random collisions by gas molecules. Macroscopically, we see the overall movement of particles from a high concentration region (in this case, the center of air stream) to a lower concentration region (in this case, the airway wall). Since it is caused by gas molecule collisions, the effectiveness of this mechanism increases as particle size decreases.

Interception

When a particle follows the air stream without deviation, it can still contact the airway surface because of its physical size. This mechanism is called interception. Its likelihood depends on how close the gas streamline is to the airway surface and also on the ratio of particle size to airway diameter. Usually interception is not critically important in our respiratory system except for long fibers that are long in one dimension. They can easily traverse the tortuous pathway to the alveolar region but they have a higher possibility of being trapped there due to interception. 

Total Deposition

A particle entering our respiratory system is subject to all the deposition mechanisms described previously. The actual deposition efficiency of a given particle size has been determined experimentally. Several models have been developed to predict the deposition based on experimental data. Two advanced and widely used ones are those developed by the International Commission on Radiological Protection (ICRP) and the National Council on Radiation Protection and Measurement (NCRP). The total deposition fraction (DF) in the respiratory system according to ICRP model is

where d_p is particle size in μm, and IF is the inhalable fraction defined as

The entry of aerosols into the mouth or nose is affected by the human head that distorts the airflow approaching the mouth or nose (i.e. inhalability). The impact is greater on larger particles (> 3 μm) and hence their actual entry efficiency is reduced.
The total deposition fractions considering inhalability are shown in the plot below. Large particles have a high deposition fraction due to impaction and settling. The fraction decreases for particles larger than 3μm is due to the reduced entry into the mouth or nose. Small particles also get a high deposition fraction due to diffusion. The minimum efficiency is between 0.1 and 1.0 μm, where none of the above mechanisms dominates.

Regional Deposition

Regional deposition is of more interest because it's more relevant in assessing the potential hazard of inhaled particles and the effectiveness of therapeutic delivery. The deposition fraction in the three regions can be approximated by the following equations.
For the Head Airways,

For the Tracheobronchial region,

For the Alveolar region,

The largest particles are removed by settling and impaction in the Head Airways. Ultrafine particles less than 0.01 μm can also have significant deposition in this region due to their high diffusivity. In the Tracheobronchial region, impaction and settling are important for particles larger than 0.5 μm although the overall deposition fraction in this size range is quite small. This is because the majority has been removed in the preceding head airways. Ultrafine particles also have a high deposition efficiency in this region due to their rapid Brownian motion. Particles entering the Alveolar region have high deposition efficiency no matter they are larger or small: settling for large particles and diffusion for small particles. As see in the figure, Alveolar deposition is not significant whenever head airways and tracheobronchial airways deposition is high. Again, these two rapid cleared regions are very important in protecting the more vulnerable alveolar region from irritating or harmful particles.

Now enter a particle size and find out its deposition fraction in different regions

Deposition Assessment

Now, ready to assess the deposition fraction of the particles from different sources? Provide particle loading and its size distribution, the deposition calculator based on the formula shown in sections 5 and 6 can compute the total deposition and regional deposition for you. Before the web calculator shows you the answer, have an educated guess of where the given particles will deposit based on what you have learned from previous sections. Also think about why (i.e. what is the dominant mechanism).
The default value is taken from cigarette smoke. You may also want to try the particles from the outlet of the control device module (e.g. cyclone) or other types of aerosols.