Gas exchange response to a PAF receptor antagonist, SR 27417A, in acute asthma: A pilot study

The pathogenic role of platelet-activating factor (PAF) in asthma has been questioned due to the limited or negative efficacy of PAF antagonists; howe ver, in acute asthma (AA), where the endogenous release of PAF may be enhan ced, the effects of PAF antagonist receptors have not been investigated. It was postulated that inhaled PAF provokes gas exchange defects in mild asth ma likely to be related to airway vascular leakage. The response to a potent, selective PAF receptor antagonist, SR 27471A, on pulmonary gas exchange was studied, more specifically ventilation-perfusion (VA'/Q') distributions, in patients with AA within 48 h of hospitalization . A randomized, double-blind, placebo-controlled, parallel group (n=6, each ) design was used. After baseline measurements, either placebo or SR 27417A (20 mg, orally) was administered and measurements were repeated 3 h later. Conventional anti-asthma medication was not interrupted. Despite a near-complete inhibition of the in vitro, platelet aggregation te sts by 40 nM PAF (mean+/-SEM from 72+/-9 to 6+/-2%) and 80 nM PAF (from 81/-7 to 6+/-3%both p<0.01) by SR 27471A indicating a good bioactivity of the compound, no significant changes in baseline forced expiratory volume in o ne second, (40+/-6%), respiratory system resistance (6.2+/-0.7 cmH(2)O.L-1. s), alveolar-arterial pressure difference for oxygen (5.2+/-0.4 kPa), arter ial oxygen tension (9.0+/-0.5 kPa) or VA'/Q' distributions, as expressed by the dispersion of pulmonary blood flow (LogSD Q, 1.07+/-0.09; normal value s <0.60), were observed. It is concluded that SR 27417A has limited value when added to the conventi onal treatment of acute asthma. These findings minimize the potential patho genic role of endogenous platelet-activating factor as a relevant mediator of airway inflammation during acute asthma.