Pharmacology of the late response to allergen and its relevance to asthma prophylaxis.
Inhalation of allergen by sensitised asthmatics results in an acute increase of airways resistance that, in some individuals, is succeeded by a response of late-onset. Late-onset responses are associated with an increased airway reactivity to constrictor stimuli that lasts for several days and hence may be akin to exacerbation of clinical asthma. For this reason, much attention has been given to inhibition of late-onset reactions by glucocorticosteroids or by cromoglycate. Such effects have been cited as evidence of anti-asthma efficacy for these drugs and also for ketotifen, as might be anticipated from prophylactic efficacy in clinical asthma. More recently, a similar inhibitory effect has been demonstrated for theophylline, which is in marked contrast to beta-adrenoceptor agonists, which have long been known not to inhibit expression of late-onset reactions. The profile of drug sensitivity observed for late-onset reactions precludes mast cell stabilisation as an adequate explanation, since late-onset reactions are unaffected by beta-adrenoceptor agonists, notwithstanding the potency of such drugs as inhibitors of mast cell secretion; furthermore, late-onset reactions can be inhibited by nonsteroidal anti-inflammatory drugs, even though such drugs can enhance mast cell secretion. Rather, present evidence favours platelet-activating factor (PAF, Paf-acether, AGEPC) as a primary determinant of late-onset reactions, especially since responses to this material can be inhibited by cromoglycate, glucocorticosteroids, ketotifen and theophylline, and since there is substantial evidence that PAF has properties that could account for exacerbation of asthma.
D000403:Airway Resistance; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D001792:Blood Platelets / Q000502:physiology; D004205:Cromolyn Sodium / Q000627:therapeutic use; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D010972:Platelet Activating Factor / Q000276:immunology*; D011058:Pollen / Q000276:immunology; D013997:Time Factors
D000485:Allergens; D010972:Platelet Activating Factor; D007073:Immunoglobulin E; D004205:Cromolyn Sodium