Lung airways mucociliary clearance

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]. 

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. 

Mucociliary Clearance Mucociliary clearance operates by the coordinated movements of cilia, which sweep mucus out of the lungs towards the pharynx where it is swallowed. There is an inverse relationship between mucus velocity and airway generation, which relates to the lower percentage of ciliated cells, shorter cilia, lower ciliary beat frequency and lower number of secretory cells in the peripheral airways [121]. The reported tracheal mucociliary clearance... 

We have already discussed the impact of inspiratory flow rate on deposition the faster the subject inhales, the more material is deposited at bends and bifurcations in the upper and central airways, and the less material reaches the deep lung. Inspiratory flow rate may also affect the performance of inhalation systems this is particularly important in passive dry powder inhalers in which the energy of breathing is utilized to deagglomerate the formulation. Thus, for such systems, there is a contradictory requirement for the need to use high inspiratory flow rate to achieve fine particle size for deep lung delivery and yet to have sufficiently low inspiratory flow rate to avoid impaction before the drug entry to the absorptive surfaces devoid of mucociliary clearance. 

Assessment of aerosols and aerosol delivery devices requires accurate estimations of not only was the activity deposited in the limgs, but also in other regions such as oropharynx and stomach. For clearance measurements, such as mucociliary clearance, absolute estimates of activity are not required. Instead, the method should be able to confirm initial deposition of the aerosol to, primarily, the ciliated airways and provide good differentiation between central and peripheral regions to allow their respective clearances to be determined. Acquisition frame has to be sufficiently fast to allow clearance to be accurately followed, particularly during the fast initial clearance of aerosols from the lungs. 

Mucociliary clearance (MCC) Ciliary dysfunction, airway caliber, mucus production >2 p,m Primary ciliary dyskinesia, bronchial disorders, lung transplantation... 

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. 

Hasani A, Pavia D, Toms N et al (2003) Effect of aromatics on lung mucociliary clearance in patients with chronic airways obstruction. J Altem Complement Med 9 243-249 Higenbottam T (2002) Chronic cough and the cough reflex in common lung diseases. Pulm Pharmacol Ther 15 241-248... 

The mucociliary clearance mechanism is generally recognised as a defence against infectious agents and a means to remove inhaled particulate matter. Inhaled particles reach different locations in the lung depending on their size. Above 5 [an, the conducting airways filter dusts, where ciliated and mucous cells cooperate and waft the particles upwards. 

In a randomized, double-blind, placebo-controlled study of 51 patients with COPD, 1,8 cineole (3 X 200 mg/day) was given for 8 weeks. For the objective lung functions of airway resistance and speci c airway resistance, there was a clinically signi cant reduction of 21% and 26%, respec tively. The improvement was attributed to a positive in uence on disturbed breathing patterns, mucociliary clearance, and anti-in ammatory effects (Habich and Repges, 1994). 

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