title: The inhibitory actions of azelastine hydrochloride on the early and late bronchoconstrictor responses to inhaled allergen in atopic asthma.
abstract: We have examined the effect of azelastine hydrochloride, 8.8 mg, on the early and late responses to inhaled allergen in a group of 12 atopic subjects with asthma. On two separate days, 3 weeks apart, patients were administered either oral azelastine, 8.8 mg, or matched placebo. Four hours later they inhaled via nebulizer, a dose of allergen (grass pollen or Dermatophagoides pteronyssinus) that had previously been demonstrated to produce a 25% fall in FEV1. Plasma-histamine concentrations and FEV1 levels were measured at intervals during the subsequent 8 hours. After placebo, allergen inhalation produced rapid bronchoconstriction in all subjects with a maximum mean fall in FEV1 at 30 minutes of 22.8 +/- 3.4% from the postsaline baseline value. Five subjects also developed a late bronchoconstriction response with a fall in FEV1 of greater than 15% from postsaline baseline value between 2 and 8 hours after challenge. Azelastine reduced the bronchoconstrictor response during the first 10 minutes and produced a maximum mean fall at 30 minutes of 21.2 +/- 4.4% from the postsaline baseline value. Azelastine had a marked inhibitory effect, reducing the maximum mean fall from 23.9 +/- 6.3% to 9.6 +/- 3.9% from the postsaline baseline value. Analysis of the area under the FEV1 response time-course curves revealed that azelastine reduced the early response (first 2 hours) by 32.5% (p less than 0.05) (all subjects) and reduced the late response (2 to 8 hours) by 70.2% (p less than 0.05) (n = 5). Azelastine had no significant inhibitory effect on the early increase in plasma histamine.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Immunopharmacology Group, Medicine I and Clinical Pharmacology, Southampton General Hospital, England.
authors.forename: P
authors.initials: P
authors.lastname: Rafferty
authors.forename: W H
authors.initials: WH
authors.lastname: Ng
authors.forename: G
authors.initials: G
authors.lastname: Phillips
authors.forename: J
authors.initials: J
authors.lastname: Clough
authors.forename: M K
authors.initials: MK
authors.lastname: Church
authors.forename: R
authors.initials: R
authors.lastname: Aurich
authors.forename: S
authors.initials: S
authors.lastname: Ollier
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
mesh_terms: D000328:Adult; D000485:Allergens / Q000008:administration & dosage*; D001249:Asthma / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006632:Histamine / Q000097:blood; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010793:Phthalazines / Q000627:therapeutic use*; D011724:Pyridazines / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000485:Allergens; D006634:Histamine H1 Antagonists; D010793:Phthalazines; D011724:Pyridazines; D006632:Histamine; C020976:azelastine