Mucociliary clearance rates

Clearance in the upper, or ciliated, region is governed by the rate of mucus transport along the airways. These rates have been measured in the human nose and in dogs, rats, and other species. Asmundsson and Kilbum, Hilding, and Iravani established that mucociliary clearance rates increase from the distal bronchi toward the trachea. Because bronchial openings retard mucus flow, bifurcations receive an accumulation of mucus and associated particles. The rate of mucus production and mucus thickness and velocity vary from one person to another. Thickness increases and velocity decreases greatly when some toxic elements are present in the airway. 

Asmundsson, T., and K. H. Kilbum. Mucociliary clearance rates at various levels in dog lungs. Amer. Rev. Resp. Dis. 102 388-399, 1970. 

Aspden, T. J., Adler, I, Davis, S. S., Skaugrud, Q., and Ilium, L. 1995. Chitosan as a nasal delivery system evaluation of the effect of chitosan on mucociliary clearance rate in the frog palate model. Int. I. Pharm.,122, 69. 

Willoughby R A, Ecker G L, McKee S L et al 1991 Use of scintigraphy for the determination of mucociliary clearance rates in normal, sedated, diseased and exercised horses. Canadian Journal of Veterinary Research 55 315-320... 

Changes in the viscoelasticity of mucus gels alter the mucus clearance rate and, hence, particle transport efficiency. An increase in viscosity [148], or a decrease in elasticity [132,149] of mucus gels leads to slower mucociliary clearance rates, allowing particles a longer time to penetrate mucus. 

The mucociliary clearance rate may influence the intranasal absorption of systemically active substances. Pathological conditions and an accelerated rate of mucociliary clearance shorten the contact time between active substance and the absorbing mucosa. A delayed mucociliary clearance will have the opposite effect. Nasal hypersecretion dilutes the medicine solution and delays passive absorption. In addition it may lead to a local loss of some of the medicine due to a washout effect. A change in pH of the mucus layer may have consequences oti the ionisation of some substances, and thus on their absorption [11]. 

Asmundsson T, Kilbum KH. Mucociliary clearance rates at various lengths in dog lungs. Arch Environ Health 1970 29 290-293. 

During absorption of this particular F-PHEA (Mw = 8.6 kD, Mn = 5.3 kD), through the rat lung, transfer occurred at an apparently constant rate of 110 43 ig/h or 3.5 1% of the administered dose per hour. Because mucociliary clearance from the lower airways occurs very slowly (7) these absorption rates convert to substantial bioavailabilities when the absorption process is extrapolated over a 12 h period [(3.5% x 12) or, around 42% may be feasible]. 

Rate of mucociliary clearance - Concentration of active ingredient - Type of dosage form (liquid, aerosol, powder)... 

The disposition of insulin was shown to be susceptible to non-absorptive losses to metabolism and mucociliary clearance. Modification of the deposition profile of insulin in the lung showed that higher absorption rates were obtained for more peripheral deposition and co-administration of a metabolic inhibitor reduced losses to exopeptidase metabolism [101], It is acknowledged by the investigators that the IPL technique and the dosing technique of Byron and coworkers are not widely accessible and have therefore not been widely adopted [119], Active absorption has also been studied in this system as described in Sect. 6.2.43. 

Andersen et a/.," with a saccharine-particle method, found a weak positive association between tracheobronchial clearance and nasal clearance. A strong positive correlation would have indicated that information about the tracheobronchial clearance rate can be derived by studying clearance rates in the nose, which is more accessible. The saccharine method was shown to be a useful clinical tool for evaluating the status of the nasal mucociliary function in human subjects exposed to ambient pollutants or to controlled concentrations of specific pollutant gases or aerosols. 

Impairment of mucociliary clearance, the rate at which mucus is transported from the nose to the pharynx, was found in a study of 68 Danish hardwood furniture workers. Mucostasis (defined as a nasal transit time of 40 or more minutes) increased in direct proportion to the dust concentration at 25.5mg/m, 63% had mucostasis vs. 11% at 2.2 mg/m. ... 

Direct toxic effects such as irritation, inflammation, or increased permeability will bring about symptoms such as the sneeze reflex, nasal discomfort, and hypersecretion with the possibility of underlying pathological changes such as squamous metaplasia, cilia erosion, plasma exudation, epithelial necrosis, inflammatory remodeling, or neutrophil accumulation. Indirect adverse effects can also occur and any alteration to normal nasal homeostasis should be avoided. For example, a reduction in mucociliary clearance can cause rhinitis, sinusitis, and an increased susceptibility to airway infections, and consequently ciliary movement should not be altered by any nasal medication. In the context of absorption enhancers, the rate and extent of recovery of normal nasal epithelial function after nasal administration is a prime consideration. 

Mucociliary clearance can be studied in vivo in humans using gamma scintigraphy to follow the clearance of radiolabeled solutions from the nasal cavity or by measuring the transport rate of radiolabeled markers administered to the nasal epithelium. Simpler methods are used to monitor the appearance of a strongly colored dye (by visual inspection) or sweet tasting substance such as saccharin (by taste) at the pharyngeal cavity. 

First-order rate constant for mucociliary clearance from pool A to the... 

The length of time the drag is in contact with the absorbing tissue will influence how much drag crosses the mucosa. In the nasal cavity this is influenced by the rate at which the drag is cleared from the absorption site by mucociliary clearance and by metabolism. 

The site of deposition in the nasal cavity profoundly affects the rate of mucociliary clearance of a drag moiety ... 

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. 

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