D A Taylor1, J G Harris, B J 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.
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 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. 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.
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. 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.
Authors: Marek L Kowalski; Ignacio Ansotegui; Werner Aberer; Mona Al-Ahmad; Mubeccel Akdis; Barbara K Ballmer-Weber; Kirsten Beyer; Miguel Blanca; Simon Brown; Chaweewan Bunnag; Arnaldo Capriles Hulett; Mariana Castells; Hiok Hee Chng; Frederic De Blay; Motohiro Ebisawa; Stanley Fineman; David B K Golden; Tari Haahtela; Michael Kaliner; Connie Katelaris; Bee Wah Lee; Joanna Makowska; Ulrich Muller; Joaquim Mullol; John Oppenheimer; Hae-Sim Park; James Parkerson; Giovanni Passalacqua; Ruby Pawankar; Harald Renz; Franziska Rueff; Mario Sanchez-Borges; Joaquin Sastre; Glenis Scadding; Scott Sicherer; Pongsakorn Tantilipikorn; James Tracy; Vera van Kempen; Barbara Bohle; G Walter Canonica; Luis Caraballo; Maximiliano Gomez; Komei Ito; Erika Jensen-Jarolim; Mark Larche; Giovanni Melioli; Lars K Poulsen; Rudolf Valenta; Torsten Zuberbier Journal: World Allergy Organ J Date: 2016-10-12 Impact factor: 4.084
Authors: Gail M Gauvreau; Beth E Davis; Guy Scadding; Louis-Philippe Boulet; Leif Bjermer; Adam Chaker; Donald W Cockcroft; Barbro Dahlén; Wyste Fokkens; Peter Hellings; Nikolaos Lazarinis; Paul M O'Byrne; Ellen Tufvesson; Santiago Quirce; Maurits Van Maaren; Frans H de Jongh; Zuzana Diamant Journal: Eur Respir J Date: 2022-08-25 Impact factor: 33.795