title: High- and low-dose allergen challenges in asthmatic patients using inhaled corticosteroids.
abstract: OBJECTIVE
  The inhaled allergen challenge model has been used previously to investigate the effects of novel anti-inflammatory drugs in inhaled corticosteroid (ICS)-naïve asthmatics. The aim of this study was to characterize high- and low-dose allergen challenges in asthmatic patients using ICS.
  
  
  METHODS
  Twenty-eight asthmatic patients taking ICS (beclomethasone equivalent <1000 μg day(-1) ) were recruited for high-dose allergen challenge, of whom 10 subsequently also had a repeat low-dose challenge comprising seven allergen challenges. Induced sputum was collected for measurements of cell counts and supernatant biomarkers.
  
  
  RESULTS
  The high-dose allergen challenge caused an early and late asthmatic response in 19 of 28 patients; the mean maximal fall in the forced expiratory volume in 1 s (FEV1 ) was 29.1% (SD 6.2%) and 25.1% (SD 9.6%), respectively. There was also an increase in sputum eosinophils of 6.2% (P = 0.0004), as well as supernatant eosinophil cationic protein levels. The low-dose allergen challenge caused an acute fall in FEV1 , but had no effect on FEV1 at 24 h after challenge or sputum measurements.
  
  
  CONCLUSIONS
  The high-dose allergen challenge in asthmatics using ICS induces a late asthmatic response associated with an increase in eosinophilic airway inflammation. This may be a suitable model for studying the effects of novel anti-inflammatory drugs added to maintenance ICS treatment.
authors.affiliation: Manchester Academic Health Science Centre, Manchester, UK; University Hospital South Manchester NHS Foundation Trust, Manchester, UK; NIHR South Manchester Respiratory and Allergy Clinical Research Facility, Medicines Evaluation Unit, The University of Manchester, Manchester, UK.
authors.forename: Wha-Yong
authors.initials: WY
authors.lastname: Lee
authors.forename: Thomas
authors.initials: T
authors.lastname: Southworth
authors.forename: Steven
authors.initials: S
authors.lastname: Booth
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000485:Allergens / Q000008:administration & dosage*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D001507:Beclomethasone / Q000008:administration & dosage / Q000627:therapeutic use; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D013147:Spirometry; D011795:Surveys and Questionnaires
chemical_list: D000485:Allergens; D018927:Anti-Asthmatic Agents; D001507:Beclomethasone
keywords: allergen challenge; asthma; induced sputum; inhaled corticosteroids