The inhibitory actions of azelastine hydrochloride on the early and late bronchoconstrictor responses to inhaled allergen in atopic asthma.
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)
Rafferty
P
P
Immunopharmacology Group, Medicine I and Clinical Pharmacology, Southampton General Hospital, England.
Ng
W H
WH
Phillips
G
G
Clough
J
J
Church
M K
MK
Aurich
R
R
Ollier
S
S
Holgate
S T
ST
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
D000485:Allergens; D006634:Histamine H1 Antagonists; D010793:Phthalazines; D011724:Pyridazines; D006632:Histamine; C020976:azelastine