EFFECT OF A PLATELET-ACTIVATING-FACTOR ANTAGONIST, WEB-2086, ON ALLERGEN-INDUCED ASTHMATIC RESPONSES

Background-Platelet activating factor (PAF) has been implicated in the pathogenesis of airway hyperresponsiveness in asthma. The purpose of this study was to evaluate the effects of a selective PAF antagonist ( WEB 2086), given in doses known to antagonise the effects of inhaled P AF in human subjects, on allergen induced early and late asthmatic res ponses and on airway hyperresponsiveness. Methods-Eight atopic, mildly asthmatic subjects were studied during a screening period and two tre atment periods. During the screening period subjects inhaled an allerg en to which they were known to be sensitised and the response was meas ured as the fall in the forced expired volume in one second (FEV1) to show the presence of early (0-1 h) and late (3-7 h) asthmatic response s. On another day the subjects inhaled allergen diluent. During the tr eatment periods subjects inhaled allergen after one week's pretreatmen t with WEB 2086 (100 mg three times a day) or placebo administered in a randomised, double blind, crossover fashion. Histamine airway respon siveness was measured 24 hours before and 24 hours after allergen and the results were expressed as the provocative concentration causing a 20% fall in FEV1 (PC20). Results-The maximal early asthmatic response after allergen with placebo treatment was 18.4% (SE 4.4%) and with WEB 2086 18.9% (4.4%). The maximal late response with placebo treatment w as 21.7% (5.3%) and with WEB 2086 21.2% (3.0%). The log difference (be fore and after allergen) in histamine PC20 was 0.35 (0.06) after place bo treatment and 0.30 (0.1) after WEB 2086. Conclusions-These results indicate that one week of treatment with an orally administered PAF an tagonist (WEB 2086) does not attenuate allergen induced early or late responses or airway hyperresponsiveness.