EFFECT OF A PLATELET-ACTIVATING-FACTOR (PAF) ANTAGONIST, SR-27417A, ON PAF-INDUCED GAS-EXCHANGE ABNORMALITIES IN MILD ASTHMA

Inhaled platelet-activating factor (PAF), both in normals and in asthm atic patients, provokes transient systemic effects, neutropenia, bronc hoconstriction and arterial oxygenation abnormalities similar to those shown in spontaneous exacerbations of asthma, To investigate the effi cacy of a new PAF-receptor antagonist, SR 27417A, on all these changes after PAF challenge, 12 nonsmoking patients (four females and eight m ales) (mean+/-SEM) age 24+/-1 yrs with mild asthma (forced expiratory volume in one second (FEV1) 93+/-3% predicted) were studied in a doubl e-blind, placebo-controlled, cross-over fashion 2 weeks apart. PAF aer osol challenge (18 mu g) was carried out 3 h after oral administration of either SR 27417A (20 mg) or placebo, Respiratory system resistance (Rrs) and arterial blood gases and neutrophil cell counts were measur ed at baseline, before compound/placebo administration, and at 5, 15 a nd 45 min after PAF, Compared to vehicle, SR 27417A brought about mode rate attenuation of PAF-induced neutropenia at 5 min (by 140%; p<0.025 ), and rebound neutrophilia at 15 and 35 min (p<0.025), increases of R rs (by 90-65%) (p<0.01) and of alveolar-arterial pressure difference f or oxygen (PA-a,O-2) at 5 min (by 68%) and 15 min (by 63%), and decrea ses of arterial oxygen tension (Pa,O-2) at 5 min (by 57%; p<0.025, eac h). Furthermore, systemic effects and platelet aggregation tests (p<0. 001) were abolished after the administration of the compound. We concl ude that SR 27417A is effective in inhibiting systemic, cellular and p ulmonary effects after platelet-activating factor challenge in patient s with mild bronchial asthma.