Transport mucociliary

FIGURE 5.24 Components of ciliary movement, (a) Power and recovery phases of ciliary movement. Arrows indicate the direction of ciliary travel, (b) Net mucociliary transport. Dotted arrows show the direction of cilia while the solid arrows show mucus transport. Note that net gel movement is forward in I and III while no gel movement occurs in II during the cilia recovery phase. Modified from Ful-ford and Blake. ... 

Sulfuric acid (H1SO4) and ammonium bisulfate (NH4HSO4) contribute importantly to ambient acid aerosols, particularly in geographic locations where sulfur-rich coal is used for power plant fuel, such as the eastern United States.Studies on animals and human subjects have shown that H2SO4 and NH4HSO4 alter mucociliary transport in a dose-dependent fashion and... 

Several groups investigated the use of liposomes for the intra-pulmonary delivery. Farr et al. (1985) showed that the deposition of aerosolized liposomes in the human lung depends on the aerosol particle size. Short-term retention profiles for MLVs and SUVs deposited in the lung were indicative of clearance via the mucociliary transport mechanism. 

Allegra, L., Moavero, N.E. and Rampoldi, C. (1991). Ozone-induced impairment of mucociliary transport and its prevention with M-acetylcysteine. Am. J. Med. 91, 67S-71S. 

While the lung is the major organ exposed to airborne dusts, such agents may also be swallowed following mucociliary transport and removal from the lung. Contaminating particles contained in food and drink also gain direct access into the gut. 

P2-Agonists cause airway smooth muscle relaxation by stimulating adenyl cyclase to increase the formation of cyclic adenosine monophosphate (cAMP). Other non-bronchodilator effects have been observed, such as improvement in mucociliary transport, but their significance is uncertain.11 P2-Agonists are available in inhalation, oral, and parenteral dosage forms the inhalation route is preferred because of fewer adverse effects. 

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 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. 

Wanner, A. (1981). Alteration of tracheal mucociliary transport in airway disease. Effect of pharmacologic agents. Chest 80 (Suppl. 6) 867-870. 

If inhalant is a solid mucociliary transport from lungs to GI tract may clear it out. 

If a solid, mucociliary transport may serve to clear from lungs to GI tract. 

New techniques have been developed for the direct measurement of mucociliary transport rates in the trachea. Yeates et al. used an external gamma camera to follow a bolus of labeled microspheres deposited in the large airways by aerosol inhalation they fitted a log-normal distri-... 

Mucociliary transport in the airways that constantly drains fluid and solid particles (bacteria) in a counter-current flow to the oral cavity. A drug that is deposited in the airways can... 

The efficiency of mucociliary transport depends on the force of kinociUary motion and the viscosity of bronchial mucus. Both factors can be altered pathologically (e.g., in smoker s cough, bronchitis) or can be adversely affected by drugs (atropine, antihistamines). 

Dust particles inhaled in tobacco smoke, together with bronchial mucus, must be removed from the airways by the ciliated epithelium. Ciliary activity, however, is depressed by tobacco smoke mucociliary transport is impaired. This depression favors bacterial infection and contributes to the chronic bronchitis associated with regular smoking. Chronic injury to the bronchial mucosa could be an important causative factor in increasing the risk in smokers of death from bronchial carcinoma. 

The bronchodilation produced by the methylxanthines is the major therapeutic action in asthma. Tolerance does not develop, but adverse effects, especially in the central nervous system, may limit the dose (see below). In addition to their effect on airway smooth muscle, these agents—in sufficient concentration—inhibit antigen-induced release of histamine from lung tissue their effect on mucociliary transport is unknown. 

Pritchard K., et al., Evaluation of the bioadhesive properties of hyaluronan derivatives detachment weight and mucociliary transport rate studies, J. Pharm., 129, 137, 1996. 

The supplementary presence of viruses, bacteria, air pollutants or microparticles can further trigger or support such inflammation. Cytotoxic mediators of the late phase of inflammation are additionally responsible for disorders of the mucociliary transport system, epithelial damage and dysfunction of the immunological mucosa defense against viruses and bacteria. 

Naturally the success of this therapeutic approach depends on the correct clinical investigation and on reliable diagnostic methods. For this reason in the evaluation of the efficacy of LNIT we include nasal endoscopy (0° diameter 4mm 30° diameter 2.7 mm), active anterior rhinomanometry, mucociliary transport time, specific nasal provocation test, and nasal microbiological test. 

It is possible to study cilia beat frequency and drug interaction with mucus independently using models such as tissue explants or cultures of ciliated cells or purified mucus preparations. However, these are not able to provide information about mucociliary transport rates. For such studies, a model incorporating the integrated cilia and mucus components is required such as the frog palate. Drugs, preservatives and absorption enhancers, and bioadhesive formulations have been extensively studied in this model [9]. 

Many penetration enhancers cause irreversible ciliostasis, e.g. STDHF (0.3%), laureth 9 (0.3%), sodium deoxycholate (0.3%), or irreversibly halt mucociliary transport, e.g. STDHF (1%), laureth 9 (1%), sodium deoxycholate (1%). Others, such as sodium glycocholate, are well tolerated. However the long-term effects of even a temporary impediment to the mechanism of nasal clearance is unknown and such an approach should be used with caution. 

Mucociliary clearance reduces the retention time of drags within the lungs. Efficient drag delivery of slowly absorbed drags must overcome the ability of the lung to remove drag particles by mucociliary transport. 

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