title: Repeated high-dose inhalation allergen challenge in asthma.
abstract: BACKGROUND
  Inhalation allergen challenge in humans is used to investigate lung pathophysiology and responses to novel therapies. However, the single high-dose allergen challenges that are commonly performed do not mimic repeated symptomatic environmental allergen exposure.
  
  
  OBJECTIVE
  To develop and evaluate the safety of a repeated high-dose symptomatic inhalation allergen challenge model.
  
  
  METHODS
  Sixteen subjects with atopic asthma were recruited. Each underwent three inhalation allergen challenges using house dust mite (Dermatophagoides pteronyssinus) antigen at 48-h intervals with a target of symptom induction and an early asthmatic reaction fall in forced expiratory volume in 1 s (FEV(1) ) of 15% from baseline.
  
  
  RESULTS
  All of the subjects completed the three-challenge protocol and the target immediate airway bronchoconstrictor response was achieved in all the subjects at all challenges. There were no adverse events recorded. The early asthmatic reaction was similar for the three challenges whether measured as mean maximal fall in FEV(1) or mean area under the curve. The late asthmatic reaction was also similar over the three challenges with no evidence of priming or desensitisation. Symptom scores and reliever medication use significantly increased over the time of the challenges. Baseline lung function and reversibility was unchanged 4 days after the last challenge.
  
  
  CONCLUSIONS
  We demonstrate that repeated high-dose inhaled house dust mite allergen challenge in human volunteers with mild asthma is safe, repeatable and acceptable. This allows the use of this model in further studies focused on understanding the pathophysiology of allergen induced asthma and the impact of therapeutic interventions.
authors.affiliation: University of Southampton School of Medicine, Infection, Inflammation and Immunology Division, Southampton General Hospital, Southampton, UK. c.l.grainge@soton.ac.uk
authors.forename: Christopher
authors.initials: C
authors.lastname: Grainge
authors.forename: Peter Hugo
authors.initials: PH
authors.lastname: Howarth
mesh_terms: D000328:Adult; D000485:Allergens / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D000818:Animals; D019540:Area Under Curve; D001249:Asthma / Q000175:diagnosis* / Q000503:physiopathology; 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; D008168:Lung / Q000503:physiopathology; D008297:Male; D039981:Pyroglyphidae / Q000276:immunology; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000485:Allergens