Bronchial hyper-reactivity: recent preclinical developments.
Airway hyper-reactivity has been recognized, if not commented upon, for many decades; however, it was the use of allergen inhalation as a clinical test that focused attention upon this aspect of asthma. In allergic asthma, an association has been drawn between inflammatory events, as manifested by the late-onset reaction to allergen, and increased reactivity of airway smooth muscle. The recognition that IgE-dependent processes determine such changes has led to extensive speculation as to pathogenic mechanism underlying the events, with the mast cell being prominent in most schemes. However, no mast cell constituent has been shown to elicit long-lasting inflammatory changes appropriate to asthma nor smooth muscle hyperplasia. Furthermore, it is now clearly evident that selective mast cell stabilising drugs do not prevent development of airway hyper-reactivity that is associated with responses to allergen. Recent pre-clinical studies have implicated platelet activating factor (PAF) as a mediator central to asthma exacerbation; with cells such as platelets, macrophages and eosinophils serving as a source of this material in IgE dependent allergic reactions. The appreciation that PAF can account for acute manifestations of airway hyper-reactivity and for persisting changes of airway function (not only in acute allergic events, but also in acute and chronic non-allergic processes) may have major therapeutic implications. Established prophylactic anti-asthma drugs (i.e. cromoglycate, ketotifen, theophylline and glucocorticosteroids) inhibit such pulmonary pathology, whereas beta-adrenoceptor agonists intensify the hyper-reactivity that follows exposure of pulmonary tissue to PAF.(ABSTRACT TRUNCATED AT 250 WORDS)
Morley
J
J
Départment de la recherche préclinique, Sandoz S.A. Bâle, Suisse.
Wiesinger
D
D
D000818:Animals; D001986:Bronchial Spasm / Q000209:etiology*; D004195:Disease Models, Animal; D006801:Humans; D012130:Respiratory Hypersensitivity / Q000209:etiology*