Allergen-Induced Bronchoconstriction in Asthmatic Children (11)
As only the oral route of administration had been used in previous studies to examine the effect of PAF antagonists on PAF- and allergen-induced bronchoconstriction, we used an aerosol form in this study, hoping to achieve the maximal effect with fewer side effects. Our results showed that inhalation of five puffs of BN52021 at a concentration of 450 ng/ml was able to inhibit completely the immediate bronchoconstriction induced by PAF inhalation in both normal and asthmatic individuals and the allergen-induced immediate bronchoconstriction in some asthmatics. Moreover, no obvious adverse effects were observed. In previous studies, however, more than 100 mg of oral BN52063 was needed to suppress the PAF- and allergen-induced wheal and flare skin reaction and bronchoconstriction. The specificity of BN52021 was further confirmed by the failure of BN52021 to block methacholine-induced bronchospasm. proventil inhaler
Tachyphylaxis had been shown to occur rapidly after repeated inhalation of PAF, and this phenomenon may interfere with the interpretation of the efficacy of BN52021 in blocking PAF-induced bronchospasm. In this study, subjects were instructed to inhale twofold increasing doses of PAF every 15 minutes during PAF provocation challenge, but no clear-cut tachyphylaxis was found. The reasons for the discrepancy between this series and other studies are unknown; however, Cuss et al found that not all tested individuals showed consistent tachyphylaxis when Vp30 was measured, and Rubin et al also demonstrated a steady decrease of SGaw with increasing PAF. Furthermore, BN52021 was shown to block the PAF-induced bronchoconstriction in a dose-dependent manner (Fig 1).