Comparison of incremental and bolus dose inhaled allergen challenge in asthmatic patients

Background Attenuation of airway responses to inhaled allergen is increasingly used to evaluate anti-asthma drugs. Many studies use different allergen challenge methods and the presence of the late asthmatic response can be identified by a screening challenge with inhalation of incremental doses of allergen. Once defined, subsequent challenges are often administered as a constant dose based on the dose from the screening challenge. Previously, constant dose challenges have been employed but never validated. Objective A comparative study of two methods of delivering inhaled allergen by evaluating the responses of an incremental dose allergen challenge and the same cumulative dose administered as a bolus over a single inhalation. Methods Thirty-five male patients with mild allergic asthma underwent incremental dose challenge followed 3-6 weeks later by a bolus dose challenge. Bronchoconstrictor responses were expressed as the maximum percentage fall in FEV1 from baseline during the early (0-2 h) and late (4-10 h) asthmatic responses and area under the percentage change in FEV1-time curve (AUC). Results There were no significant differences between the challenges. The mean +/- SEM fall in FEV, following incremental and bolus dose challenge was 33.1 +/- 1.8% and 29.9 +/- 2.2% during the early response, and 36.9 +/- 2.4% and 34.0 +/- 3.1% during the late response, respectively. The mean +/- SEM AUC following incremental and bolus dose challenge was 35 +/- 3 and 33 +/- 3 Delta%FEV1/h for the AUC(0-2 h), 147 +/- 12 and 139 +/- 16 Delta%FEV1/h for the AUC(4-10 h), and 204 +/- 14 and 190 +/- 19 Delta%FEV1/h for the AUC(0-10 h) , respectively. Conclusion Bolus dose allergen challenge is a safe method to administer inhaled allergen in clinical trials with a valid response when compared with incremental dose allergen challenge.