Mucociliary escalator

Nonciliated cells separate fields of ciliated epithelial cells from each other. Synchronized ciliary movement, with a beat frequency in human proximal airways under normal conditions of 8-15 EIz, propels mucus along the mucociliary escalator at a rate of up to 25 mm/min. Beat frequencies appear to slow to roughly 7 Hz in more distal airways. Cilia move in the same direction and in phase within each field but cilia in adjacent fields move in slightly different directions and are phase shifted. These beat patterns result in metachronal waves that steadily move mucus at higher velocities ( -12-18 mm/min) than would be achievable by summing the motion of individual cilia. 

Mucociliary escalator Mechanism that removes extracellularly-derived materials from the conducting airways by entrapping these materials in mucus that is continuously moved toward the epiglottis by synchronized ciliary movement. 

Lungs also secrete nonvolatile compounds. Lipid-soluble compounds may thus be transported with the alveobronchotracheal mucus to the pharynx, where they are swallowed. They may then be excreted or reabsorbed. Particles are also removed by this mucociliary escalator. 

The particle size is the most important factor that contributes to the clearance of particles. For particles deposited in the anterior parts of the nose, wiping and blowing are important mechanisms whereas particles on the other areas of the nose are removed with mucus. The cilia move the mucus toward the glottis where the mucus and the particles are swallowed. In the tracheobronchial area, the mucus covering the tracheobronchial tree is moved upward by the cilia beating under the mucus. This mucociliary escalator transports deposited particles and particle-filled macrophages to the pharynx, where they are also swallowed. Mucociliary clearance is rapid in healthy adults and is complete within one to two days for particles in the lower airways. Infection and inflammation due to irritation or allergic reaction can markedly impair this form of clearance. 

Mucociliary clearance Inhaled particles are cleared from the airways through trapping of the particles in mucus upon deposition and subsequent clearance of the mucus (with trapped particles) which is propelled by the coordinated beating of cilia towards the throat. This is termed the mucociliary escalator system. The mucociliary function is regulated by a variety of factors, such as bradykinin, histamine and cytokines [20-24],... 

There are two important defense mechanisms against inhaled particles. The first of these involves the mucociliary escalator and consists of the trapping of particles in mucus followed by the upward movement of the mucus brought about by the upward beating of cilia on the airway epithelial airway cells. The material is then either swallowed or expectorated. The second mechanism is macrophage mediated. Macrophages engulf particles and either deposit them on the mucociliary escalator or enter the lymphatic system. 

In the nasal cavity and the upper and central lungs, an efficient self-cleansing mechanism referred to as the mucociliary escalator is in place to remove any foreign material, including undissolved drag particles. Particulates entering the airways are entrapped within a mucus blanket and ciliary action propels the mucus along the airways, to the... 

Alveolar macrophages account for 3% of cells in the A region. These phagocytic cells scavenge and transport particulate matter to the lymph nodes and the mucociliary escalator (see below). 

Tracheobronchial deposition of such carriers may not be desirable as clearance on the mucociliary escalator will occur in a relatively short time providing insufficient time for release from these controlled-release systems. Alveolar deposition will, in contrast, result in extended clearance times which are dependent on the nature of the carrier particle and may therefore be a better option for the effective use of such carrier systems for pulmonary drag delivery. 

Figure 27.5. Structure and dynamics of the airway epithelium. (A) Illustration of tracheal and bronchial epithelial cell types. (B) The mucociliary escalator wherein epithelial cell cilia move in a low-viscosity periciliary layer to propel mucus with their tips.

Figure 1 Fate of inhaled drugs depositing in the airways. Aerosolized compounds delivered to the lumenal surface of central (i.e., tracheobronchial) and peripheral (i.e., alveolus) airways may be subject to different pharmacokinetic pressures. The sites of loss of a drug in passage from the airway lumen to the site of therapeutic action in the central airways (e.g., smooth muscle) and peripheral airways (e.g., blood in pulmonary circulation) are depicted in upper and lower diagrams, respectively. In the central airways, a drug may (1) interact with the mucus layer, (2) be removed by the mucociliary escalator, (3) have restricted access through the epithelium and be biotransformed or be complexed by epithelium-associated...

To increase the residence times of drugs in the conducting airways served by the mucociliary escalator, mucoadhesive formulations were investigated [134]. This approach can be effective, but safety consequences of slowing down this natural clearance mechanism will need to be investigated. 

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