Impact of a Soluble Phospholipase A₂ Inhibitor on Inhaled Allergen Challenge in Subjects with Asthma

Abstract

The possible roles of secretory phospholipases A₂ (sPLA₂) in asthma include the release of arachidonic acid from cellular membranes, generation of lysophospholipids, sPLA₂-mediated activation of cPLA₂ with increased leukotriene production, and surfactant degradation. LY333013 is a potent inhibitor of sPLA₂. This study examined the impact of two doses of LY333013 vs. placebo on allergen-induced bronchoconstriction following inhaled allergen challenge in atopic asthmatics. Fifty subjects were randomly assigned to treatment, and 40 subjects completed the study. A double-blind, placebo-controlled, random order, crossover study design was used. LY333013 had no impact on the primary outcome variables of the areas under the FEV₁ response curve early (0–3 hours) (AUC_early) and late (3–8 hours) (AUC_late) following inhaled allergen challenge. No significant drug-related adverse effects were observed. The response to inhaled allergen challenge was reproducible and confirms the utility of this technique as a model in which to screen compounds for further testing in asthmatic patients.

• Asthma
• Bronchial provocation tests
• Phospholipases A
• Randomized controlled trials
• Spirometry