such as "Introduction", "Conclusion"..etc
As mentioned earlier, a number of factors may produce changes in mucociliary clearance. At threshold limit values and above, there is evidence for direct effects of pollutants on epithelium including such events as ciliary damage, cell sloughing, goblet cell discharge of secretions and probably serous cell discharge of secretions (5). In vitro studies have shown effects on mediators such as histamine (140) and prostaglandins (141) which might elicit local cellular responses including increased secretions. Lippmann et al. (86,142) have suggested that clearance is influenced primarily in the airways where H2SO4 is deposited. There is also evidence for adverse pH effects on the mucosa and ciliary activity (143).
There is considerable evidence for the alteration of the nature and volume of secretions by reflex events originating from stimulation of irritant receptors. The studies by Schultz et al. (55) clearly show that increases of tracheal mucous secretions can be observed in dogs even when SO2 exposure is isolated to the larynx and no gas reaches the trachea. Keal (18) has stated that mucus secretory changes appear to precede effects on ciliary activity in rats, and Phipps (19) has shown that in the cat reflex secretory effects can be independent of bronchomotor effects, because increased secretions were produced from ammonia vapor inhalation when no bronchoconstriction was evident. Last et al. (64) has shown significant increases in secretion beyond those produced by 03 exposure with the addition of only 14 ,ug/m3 sulfuric acid to the atmosphere. All of these results indicate the degree of sensitivity of secretion response. Effects on hydration of mucus, as evidenced by changes in ion transport (7), have not been clearly demonstrated as being produced by pollutants. However, drugs that show effects on ion transport indicating increases in watery secretion have also been shown to produce increases in mucus glycoproteins. It would not be too surprising if there were parallel effects on ion transport caused by pollutants, mediated by reflex pathways, since various pollutants have been shown to increase mucus glycoprotein production. Studies of airway permeability (144), which may be related to ion transport, have shown increases with exposures to cigarette smoke (145).
Evidence has been provided suggesting that the periciliary fluid level may be a very important determinant of particle and secretion movement. Stutts et al. (147) have suggested that increased periciliary fluid may uncouple the cilia from the overlying mucus. Proctor et al. (148) have observed cases where there was no movement of particles on the mucus layer while movement of the underlying periciliary fluid could be seen with dyes.
Most studies have shown relatively few effects of pollutants on ciliary activity at concentrations not causing a loss of ciliated cells. Cilia appear to be quite hardy and affected only when exposures are at or above threshold limit values.
The observed effects on mucociliary clearance are probably the result of some combination of all these factors. It is for this reason that mucociliary clearance studies may provide sensitive indicators of responses to irritant gases and aerosols since responses relate to a summation of effects.
The available evidence suggests that, for exposures near the current air quality limits, reflex mediated effects are most likely those that will predominate and be responsible for observed changes. Therefore, susceptible individuals would be those with the most pronounced reflex responses. Individuals such as asthmatics, with heightened bronchial reactivity, could be at greater risk to inhaled pollutants than the general population. However, clearance abnormalities may not be heightened in asthmatics because the secretary response is not directly tied to the bronchoconstrictive response (19). More studies on effects of pollutants on mucociliary clearance of asthmatics would be useful to clarify this issue.
It must be recognized that increases in secretions are probably a protective response. Nadel (7) and Phipps (19) have suggested that they could act to increase the barrier between the pollutant and the sensitive epithelium. However, it would appear that the key concern is whether a "biological backfire" phenomenon might be initiated. If there is continued stimulus, then increased secretions might well persist and eventually result in impaired clearance. Or, there may be interactions produced with other pollutants or respiratory infections which will tend to perpetuate an ongoing response and eventually lead to even greater problems. Lippmann (142) has suggested that pollutant exposures may affect clearance regulation resulting in erratic clearance behavior which is more characteristic of a bronchiticlike condition. It has to be recognized that ultimate adverse effects such as chronic bronchitis will probably occur only in a small fraction of people.
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