title: The effect of an increase in inhaled allergen dose after terfenadine on the occurrence and magnitude of the late asthmatic response.
abstract: We have attempted to use a potent and selective histamine H1-receptor antagonist terfenadine to allow a larger dose of allergen to be administered to previous single early responders to investigate if an increased dose of allergen could induce a late asthmatic response. Pre-treatment with 180 mg of terfenadine enabled a geometric mean increase in allergen dose of 4.12-fold to be inhaled by eight atopic subjects with mild asthma, who initially were classified as single early responders, with maximal fall in FEV1 3-8 hr after allergen challenge (Lmax) of less than 15% from baseline value. The magnitude of early asthmatic response was similar to that obtained on the control day when allergen challenge was performed in the absence of terfenadine. Two subjects were converted to dual responders with Lmax of 23.1 and 24.3%, which occurred with a 32- and 65-fold increase in allergen dose respectively, and a 6- and 4.9-fold decrease in non-specific airways responsiveness measured as the cumulative provocative concentration of methacholine that caused a 20% fall in FEV1 from baseline. The remaining six subjects failed to achieve an Lmax of greater than 10% even with a 1.29-2.66-fold increase in allergen dose. For the group as a whole an increase in allergen dose was associated with an increase in overall bronchoconstrictor response 3-8 hr after challenge. These results indicate that it is possible to induce a late asthmatic response in a subject who previously demonstrated only an early response by increasing the dose of allergen inhaled.
authors.affiliation: Immunopharmacology Group, Medicine 1, Southampton General Hospital.
authors.forename: C K
authors.initials: CK
authors.lastname: Lai
authors.forename: R
authors.initials: R
authors.lastname: Beasley
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D005260:Female; D005541:Forced Expiratory Volume; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed; D006969:Hypersensitivity, Immediate; D008297:Male; D008688:Methacholine Compounds; D008875:Middle Aged; D011292:Premedication; D016593:Terfenadine
chemical_list: D000485:Allergens; D001559:Benzhydryl Compounds; D006634:Histamine H1 Antagonists; D008688:Methacholine Compounds; D016593:Terfenadine