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 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 Delta%FEV1/h for the AUC0-2 h, 147 +/- 12 and 139 +/- 16 Delta%FEV1/h for the AUC4-10 h, and 204 +/- 14 and 190 +/- 19 Delta%FEV1/h for the AUC0-10 h, respectively.


CONCLUSIONS
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.
Taylor
D A
DA
Royal Brompton Clinical Studies Unit, Department of Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, UK.
Harris
J G
JG
O'Connor
B J
BJ
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology*; D001985:Bronchial Provocation Tests / Q000379:methods; D002000:Bronchospirometry; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007428:Intradermal Tests; D008297:Male; D009330:Nebulizers and Vaporizers; D013997:Time Factors
D000336:Aerosols; D000485:Allergens