Allergen Inhalation Challenge, Refractoriness, and the Effects of Ibuprofen

Abstract

Background: Bronchoprovocation challenges use direct and indirect acting stimuli to induce airflow obstruction. Indirect stimuli, either non-allergic/non-IgE mediated (e.g. exercise, mannitol) or allergic/IgE mediated (i.e. allergen inhalation model), trigger mast cells to release bronchoconstricting mediators (e.g. cysteinyl leukotrienes, histamine). Performing repeat challenges within a short timeframe (e.g. 3 hours) with non-allergic indirect stimuli results in a diminished refractory response to the second challenge. Cross refractoriness occurs between indirect stimuli. It follows that repeat bronchoprovocation with allergen might exhibit refractoriness that might be altered by ibuprofen. This study was designed to assess the response to a second allergen challenge performed 24 hours after an initial one to determine if the response is refractory. If refractoriness developed, the study aimed to determine whether a single dose of ibuprofen would alter the refractory response to the second allergen challenge. The study design also allowed for the assessment of the effect of ibuprofen on allergen challenge outcomes, including indices of airway inflammation. Methods: Thirteen mild atopic asthmatics were enrolled in a randomized, double-blind, placebo controlled, cross-over study. Ibuprofen (400mg) or placebo was administered one hour prior to the first of two allergen challenges performed 24 hours apart. Blood and sputum eosinophils, airway responsiveness to methacholine, and levels of fractional exhaled nitric oxide were assessed before and seven hours after each allergen challenge. All data were log transformed, and differences in geometric means were analyzed by paired t-tests. Results: After placebo, early asthmatic responses for the two challenges were not significantly different (p = 0.82). A single 400 mg dose of ibuprofen decreased both the early (p = 0.03; n = 12) and late asthmatic responses (p = 0.03; n = 3) Conclusion: Allergen challenges conducted 24 hours apart do not exhibit refractoriness. A single dose of ibuprofen inhibits early and late asthmatic responses to allergen bronchoprovocation. Ibuprofen should be withheld for at least 24 hours prior to investigations utilizing allergen bronchoprovocation.