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

Abstract

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. 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. 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). There were no significant differences between the challenges. The mean ± sem fall in FEV₁ 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 Δ%FEV₁/h for the AUC_0–2 h, 147 ± 12 and 139 ± 16 Δ%FEV₁/h for the AUC_4–10 h, and 204 ± 14 and 190 ± 19 Δ%FEV₁/h for the AUC_0–10 h, respectively. 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.