The bronchial epithelium has a number of mechanical functions including mucociliary clearance and protection against noxious agents. However, there is increasing evidence that it is a metabolically active tissue that may modulate the function of the underlying smooth muscle by metabolism and regulation of mediators and the production of relaxant, constrictor, or chemotactic factors. It is therefore possible that the epithelial abnormalities observed in asthmatics may lead, via several different mechanisms, to increased bronchial hyperresponsiveness (figure 2), which is a fundamental feature of asthma. However, it may not be necessary to invoke structural damage to explain derangement of epithelial function. It is possible that functional biochemical abnormalities may be present in epithelial cells, thereby producing bronchial hyperresponsiveness in the absence of histologic abnormalities. Further studies with bronchial epithelium, similar to those with vascular endothelium, are needed to clarify its role in the pathogenesis of asthma.
Many antihistamines exhibit inhibition of mediator release from mast cells and basophils, in in vitro studies in addition to H1 antagonism. The underlying mechanism is unclear but is unrelated to H1-receptor antagonism. Clinical studies of antihistamins in antigen challenge and seasonal allergy demonstrate reduction of mast cell mediators in nasal lavage. It is not known what mechanism(s) underly these observations, although the concentrations required in in vitro studies suggests that a direct effect on mast cells is unlikely. Furthermore, the therapeutic contribution of this effect is difficult to assess because of concomitant clinically significant H1 antagonism. This and other potential anti-allergic effects may enhance the therapeutic benefit of antihistamines and long-term studies are underway to explore this possibility.
Platelet-activating factor (PAF) is a newly discovered lipid mediator of inflammation. When inhaled by normal volunteers, it induces bronchoconstriction associated with facial flushing and with a transient fall in circulating neutrophils. Of greater interest is its ability to induce prolonged increases inbronchial responsiveness to methacholine. These observations support an important rolefor PAF in asthama; the availability of specific PAF antagonists will allow us to test this hypothesis.
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