Bronchial allergen challenge: dose versus concentration.
This study was designed to investigate if two equivalent doses of allergen administered by different dosing regimes--two breaths and 10 breaths of each concentration--would result in the same magnitude of the early and late asthmatic response. Fifteen patients with extrinsic allergic asthma were challenged twice with either two or 10 breaths of twofold increasing allergen concentrations. The challenge was continued until a 20% decrease in FEV1 had been achieved. A non-cumulative PC20FEV1 allergen was derived, and the cumulative dose of allergen given was similarly derived. In order to assess the reproducibility of the challenge, seven patients were challenged twice with two-breath regime. The mean value of allergen PC20 obtained by the two-breath regime was 4.1 fold (95% CI: 2.3-7.1 fold) greater than those obtained by the 10-breath regime (P less than 0.05), whereas the difference was 1.4 fold (95% CI: -3.3-0.5 fold) for the cumulative dose (P greater than 0.05). A statistically significant larger magnitude of the early asthmatic response, as determined by the maximum per cent fall in FEV1, and late asthmatic response determined by the maximum per cent fall in peak expiratory flow domiciliary recorded during the following 24 hr after challenge, was observed in favour of the 10-breath regime compared to the two-breath regime (mean difference 6%, 95% CI: 0.6-11%). The reproducibility of the provocation test was acceptable (+/- 1.8 two-fold concentration difference). These results confirm the 'equivalent dose hypothesis', and demonstrates that dosage rather than concentration appears to determine the early and late asthmatic response after bronchial allergen challenge.
Frølund
L
L
Allergy Unit, State University Hospital, Copenhagen, Denmark.
Madsen
F
F
Scharling
B
B
Heinig
J H
JH
Svendsen
U G
UG
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology*; D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000276:immunology*; D001985:Bronchial Provocation Tests; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D006969:Hypersensitivity, Immediate / Q000276:immunology; D008297:Male; D009994:Osmolar Concentration; D010366:Peak Expiratory Flow Rate; D012130:Respiratory Hypersensitivity / Q000276:immunology
D000485:Allergens; D006632:Histamine