Airway mucus viscosity

The rate of removal of mucus from the airways is determined by such factors as mucus viscosity, the amount of mucus produced, and the degree of ciliary activity. These processes may be influenced by a variety of diseases, including asthma, cystic fibrosis, and chronic bronchitis [82,83], In patients suffering from cystic fibrosis or chronic bronchitis, mucus hypersecretion is evident and mucociliary function is impaired. The failure to clear mucus from the airways leads to airway obstruction and to chronic colonization of the airways with bacterial organisms (which leads to lung infections and airway inflammation and damage). In asthmatic subjects, airway mucus is more viscous and ciliary transport mechanisms are inhibited [82,83]. In these diseases, the therapeutic objective is to improve mucus clearance from the airways. For example, aerosols of water or saline (especially hypertonic saline) promote clearance of mucus by... 

The exudative inflammatory process and sloughing of epithelial cells into the airway lumen impair mucociliary transport. The bronchial glands are increased in size, and the goblet cells are increased in size and number. Expectorated mucus from patients with asthma tends to have high viscosity. 

Patients suffering from cystic fibrosis often use various aerosolized drugs. To reduce the viscosity of the mucus in the airways, recombinant human deoxyribonuclease is used. This enzyme is the first recombinant protein that has been developed for specific delivery to the lungs via the airways. It has a local action on the mucus in the airways and its absorption is minimal. Another drug that decreases the viscosity of the mucus is acetylcysteine. Aerosolized antibiotics are a further group of therapeutics that is widely used by cystic fibrosis patients. Solutions of antibiotics like tobramycin or colistin are used in nebulizers to prevent exacerbation of the disease. Pentamidine has been used for the prophylaxis of Pneumocystis pneumonia in patients infected with HIV virus, while chronic rejection of lung transplants provided a reason to develop an aerosol formulation of cyclosporine A. 

Mucous airway obstruction. Mu-colytics, such as acetylcysteine, split disulfide bonds in mucus, hence reduce its viscosity and promote clearing of bronchial mucus. Other expectorants (e.g., hot beverages, potassium iodide, and ipecac) stimulate production of watery mucus. Acetylcysteine is indicated in cystic fibrosis patients and inhaled as an aerosol. Whether mucolytics are indicated in the common cold and whether expectorants like bromohexine or am-broxole effectively lower viscosity of bronchial secretions may be questioned. 

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.

Parvolex ) is used a MUCOLYTIC agent, which reduces the viscosity of sputum, so can be used as an expectorant in patients with disorders of the upper respiratory airways, such as chronic asthma and bronchitis. It is also used orally to treat abdominal complications associated with cystic fibrosis, and locally in the eye to increase lacrimation and mucus secretion. It is also used intravenously as an antidote in paracetamol poisoning. 

Aerosol preparations of drugs are most commonly used for the treatment of diseases involving airway obstruction, namely bronchodilators and antiinflammatory agents in asthma, bronchitis, and emphysema. Other uses of aerosol therapies include mucolytics (for decreasing the thickness or viscosity of mucus in diseases involving abnormal mucus secretion, e.g., pneumonia,... 

The prolonged retention of viscous airway secretions in the diseased lung (e.g., CF and COPD) can lead to recurring bacterial infections, resulting in a viscous, more purulent sputum [155]. Increased mucus viscoelasticity may be attributed to extensive disulphide and lectin bonding, poor hydration, and/or excess concentrations of extracellular DNA or actin [155], In these situations, therapeutics have been used to reduce the viscosity of airway secretions to improve the rate of mucociliary clearance. 

A well operating ciliary epithelium is important in prevention as well as cure of many diseases of the airways. The activity of the cilia depends on a number of factors, including temperature and humidity of the air, pH and viscosity of the mucus layer. Besides pathological conditions (allergic diseases, sinusitis, measles) also chemical influence may inhibit the action or even destroy the ciliary epithelium. This is called ciHotoxicity. CUiotoxicity is an important reason to restrict the period of use of nasal preparations. 

The relation between the viscosity and elasticity of the secretions is one of the determining factors in transport velocity. If the gel phase is in practice the only one really transported, the sol phase creates a low-resistance milieu where the cilia can beat, an environment that is essential for transport in the direction of the upper airways. One of the most important rheological properties of mucus is viscosity. Viscosity is resistance to flow and represents the capacity of a material to absorb energy while it moves. Elasticity is the capacity to store the energy used to move or deform material. The ratio between viscosity and elasticity appears to be an important determinant of the transport rate (6,10). Mucus transport by ciliary beating is influenced by the viscoelastic and surface properties of the mucus. Theoretical models suggest that a decrease in the ratio of viscosity to elasticity can result in an increase in mucociliary transport (13). 

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