Clinical & Experimental Allergy

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

Authors

  • Taylor,

    1. Royal Brompton Clinical Studies Unit, Department of Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, UK
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  • Harris,

    1. Royal Brompton Clinical Studies Unit, Department of Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, UK
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  • O'Connor

    1. Royal Brompton Clinical Studies Unit, Department of Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, UK
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O’Connor Department of Respiratory Medicine, King’s College School of Medicine and Dentistry, Bessemer Road, London SE5 9PJ, UK.

Abstract

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 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 AUC0–2 h, 147 ± 12 and 139 ± 16 Δ%FEV1/h for the AUC4–10 h, and 204 ± 14 and 190 ± 19 Δ%FEV1/h for the AUC0–10 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.

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