Retention is used here to describe the amount of material previously deposited in the respiratory tract that remains there at a later time of interest. Clearance (removal) of the material is used here to represent the dynamic process whereby the deposited material is removed from the respiratory tract.

For all regions of the respiratory tract, clearance of deposited material can be described in terms of competing processes. Two key processes are (1) transport in mucous (mechanical clearance) and (2) absorptive processes. The mucous is moved along by underlying cilia, hence the term "mechanical clearance." This process is also called mucocilliary transport.

Absorptive processes can lead to the transfer of deposited material from the respiratory tract and lymph nodes to the blood circulation.

Absorption into the blood mainly occurs for substances that dissolve or elute from surfaces of inhaled material. These substances may react with tissue constituents and could remain in the respiratory tract for a long time.

Small, undissolved, free particles may pass into the blood and translocate to other organs, or be excreted from the body. However, this direct passing of very small particles into blood should rarely occur for particles larger than 0.1 µm in diameter.

Particle solubility is influenced by particle surface characteristics (e.g., ratio of particle surface to particle volume). Solubility increases as the surface-to-volume ratio increases. The rates at which dissolution and absorption occur are influenced by the chemical composition of particles and by other factors.

Once deposited materials enter the blood, other sites in the body in addition to the respiratory tract can become critical targets.

4.1 Upper Respiratory Tract. Soluble material can be cleared from the nasal passages via mucociliary transport. Some material can also be cleared via absorptive processes into the blood.

Insoluble material that deposit in the nasal passage clear mainly via mucociliary transport. The mucous generally flows toward the nasopharynx.

The epithelium in the most anterior (front) part of the nasal passages does not contain cilia. The mucus flows slowly toward the entrance to the nose and is moved by traction associated with actions of more distal cilia.

Particles depositing in the nonciliated front portion of the nasal passages are thought to be moved along at a rate of about 1-2 mm/h. Because clearance via the indicated mechanism may take up to 12 h, deposited particles are usually more rapidly removed by sneezing, wiping, or nose blowing.

Insoluble materials that deposit in the oral passages (mouth, throat) can be translocated to the gastrointestinal tract by swallowing. Some material inhaled through the nose can also end up being swallowed.

4.2 Tracheobronchial Region. When soluble particles deposit in the tracheobronchial region, diffusion of material that dissolved between cells and biological processes may lead to absorption into the blood. Intact soluble particles may also be cleared mechanically via the mucociliary transport pathway.

The mucociliary escalator is the main clearance pathway in the tracheobronchial region for insoluble particles. The escalator consists of the ciliated epithelium moving a mucous layer on top of it. This layer is composed of a sol phase of low viscosity (hypophase) in which the cilia beat, and an overlaying gel phase of high viscosity (epiphase) thought to be moved by ciliary motion toward the pharynx.

Clearance of particles depositing in the tracheobronchial region may also occur through phagocytosis (consumption) by airway macrophages.

Another clearance mechanism, which is considered less important, is penetration of insoluble particles of submicronic size through the epithelium. Some free particles may go through the epithelium, entering the peribronchial region.

Cough can be an efficient clearance mechanism, but clearance of particles via this mode is likely to be limited to the upper generations of the conducting airways.

The mucous transport rate varies in different areas of the tracheobronchial region. In healthy nonsmokers, average tracheal mucous transport rates range from about 4 to 6 mm/min. For insoluble particles, the transport rate appears not to depend on particle shape, size, and composition. The indicated transport rates may therefore apply to insoluble particles.

The mean mucous velocity in the main bronchi is about 2 mm/min. Medium size bronchi have an estimated mucous velocity of between about 0.2 and 1 mm/min. For the most distal ciliated airways, the mucous velocity may be as low as 0.001 mm/min.

In healthy, nonsmoking soldiers, about 90% of insoluble particles depositing on the tracheobronchial tree would be expected to be cleared from 3 to 13 h after deposition, depending on the individual and particle size.

In some studies using laboratory animals, a small fraction of the inhaled particles has been shown to be retained in the nasal and tracheobronchial epithelium for several weeks after exposure. The mechanisms responsible for the prolonged retention are not fully understood. However, the mechanisms may include the following:

Pinocytosis (fluid uptake and pinching off of the cell membrane) by epithelial cells.

Phagocytosis (material consumption) by macrophages with subsequent translocation into epithelial tissue and passive movement along normal fluid clearance pathways.

Trapping in areas of the respiratory tract where clearance mechanisms have been damaged.

The bronchial surfaces are not homogeneous. Islands (small areas) of nonciliated cells occur at bifurcation regions, whereby the progress of mucous movement can be disrupted. A bifurcation is a location where a branch of the respiratory tree separates into two other branches. Bifurcations could be sites of retarded clearance of particles.

4.3 Pulmonary Region. Clearance of particles from the pulmonary region is thought to depend on their size, shape, and composition. Deposited particles smaller than 1 µm and down to molecular sizes can be found in almost all types of cells in this region. They can be taken into cells by phagocytosis or pinocytosis and can be cleared to the lymphatic vessels, tracheobronchial airways, or blood circulation.

Larger particles are mainly taken up by phagocytic cells, then cleared to the tracheobronchial airways or lymph vessels. However, soluble material leaving the surface of particles can pass directly into the blood circulation.

Clearance kinetics in the pulmonary region for insoluble particles are highly uncertain. However, insoluble particles that deposit there generally remain much longer than those deposited in the conducting airways (e.g., trachea and bronchi).

For insoluble particles in healthy, nonsmoking humans, clearance has generally been observed to consist of two components (fast and slow): the fast component having a clearance half time on the order of days and the slow component on the order of hundreds of days.

Greater harm to the respiratory tract can be associated with the slow clearance component than with the fast component depending on what fraction of the deposited material is removed via the slow-component mode. There is a large variation in clearance rates among different individuals.

The effective half life for removal of deposited material from the respiratory tract is the time required for half of the deposited material to be removed (cleared) by all processes involved.

For radioactive material, the rate of radioactive decay influences the effective clearance half time. The faster the rate of radioactive decay, the shorter the effective clearance half time.