Asthma mucociliary clearance

Respiratory allergies and infections are the most common form of illness in the United States and Europe and account for more missed school and work days than any other disease [1], A substantial body of experimental work has clearly shown that airborne toxicants such as tobacco smoke, ozone, and other air pollutants can alter many aspects of the host defense network to either decrease resistance to infection, or exacerbate respiratory allergies and asthma [2], Exposure to air toxicants can suppress a number of key host defenses including mucociliary clearance in the airways, pulmonary macrophage function, and development of specific immune responses such as IgG antibody production and cell mediated immunity. In contrast, immune stimulation in the form of increased T cell activity and IgE antibody formation has also has been shown to occur under some circumstances, resulting in increased incidence or severity of allergic lung disease. 

Baum GL, Zwas T, Katz I, Roth Y. Changes in mucociliary clearance during acute exacerbations of asthma. Am Rev Respir Dis 1992 145(l) 237-238. 

The rate of mucociliary clearance can be affected by the pathophysiological condition of the nasal cavity and this will also affect the rate of clearance of administered drag. Such conditions include rhinitis, the common cold, hayfever, sinusitis, asthma, nasal polyposis, Sjogren s and Kartagener s syndromes. In addition, environmental factors such as humidity, temperature and pollution can also affect the rate of nasal clearance. 

Ipratropium and tiotropium can produce bronchodilation, tachycardia, and inhibition of secretion similar to that of atropine but with less inhibitory effect on mucociliary clearance relative to atropine. Hence, inhaled ipratropium and tiotropium provide useful antichohnergic therapy of chronic obstructive pulmonary disease and asthma while minimizing the increased accumulation of lower airway secretions encountered with atropine. 

More importantly, the effects of theophylline are not limited to bronchodila-tion, bnt also include immunomodulatory, anti-inflammatory, and bronchoprotec-tive activity that substantially contribute to its usefulness as a prophylactic drug in asthma and other respiratory diseases. Additional effects include an increase in mucociliary clearance, a decrease of microvascular leakage into the airways, and an improvement of respiratory mnscle fatigue, especially that of the diaphragm. Theophylline fnrthermore acts centrally, blocking the decrease in ventilation that occurs with sustained hypoxia. While some of these effects are the rationale for its use in asthma, others form the basis for its effectiveness in chronic obstructive pulmonary disease (COPD) or in the treatment of apnea in premature newborns. 

A common complication of persistent hypersecretion and mucus plugging is a less effective mucociliary clearance mechanism. Inhaled bacteria which are normally quickly cleared from the bronchial system have greater opportunity for tissue invasion. Chronically affected asthmatics are more likely to develop bacterial bronchitis. It is not unusual for CB to become superimposed on the asthma as a consequence of these infections. Interestingly asthmatics who get an acute bacterial bronchitis will often note an improvement of their asthmatic symptoms. 

Pavia D, Lopez-Vidriero MT, Clarke SW. Mediators and mucociliary clearance in asthma. Bull Eur Physiopathol Respir 1987 23(suppl 10) 89S-94S. 

The first purified and characterized drug substances were administered as aerosols as a topical treatment for asthma approximately 50 years ago. More recently, drugs have been evaluated for systemic delivery. For each category of drug the mechanism of clearance from the airways must be considered. These mechanisms may be listed as mucociliary transport, absorption, and cell-mediated translocation. The composition and residence time of the particle will influence the mechanism of clearance. 

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 goal in treatment of sinusitis is eradication of infection with clearance of the infected material from the sinuses. While the use of an appropriate antibiotic is necessary, the use of ancillary therapy is also of utmost importance. Steam and nasal saline, decongestants, topical corticosteroids, and mucoevacuants are given in an attempt to reduce nasal obstruction, increase sinus ostia size, promote improved mucociliary function, decrease mucosal inflammation, and thin secretions. In selected patients who fail to respond to aggressive medical therapy, functional endoscopic surgery can often provide relief. In patients with poorly controlled asthma, treatment of underlying sinusitis has been shown to dramatically improve the asthmatic state. 

Foster WM, Langenback EG, Bergofsky EH. Lung mucociliary function in man interdependence of bronchial and tracheal mucus transport velocities with lung clearance in bronchial asthma and healthy subjects. Ann Occup Hyg (Inhaled Particles V) 1982 26 227-244. 

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