The effect of H1-receptor blockade on the development of early- and late-phase bronchoconstriction and increased bronchial responsiveness in allergen-induced asthma.
BACKGROUND
Allergen challenge of subjects with asthma produces an early asthmatic response, late asthmatic response, and increases bronchial responsiveness. Histamine partly mediates the early asthmatic response, and may play a role in late-phase responses. Azelastine has antiallergic properties and has been proposed as a treatment for asthma. We therefore investigated the contribution of histamine to late-phase responses with the use of the potent H1-receptor antagonist azelastine.


METHODS
Ten subjects with atopic asthma were studied in a double-blind, randomized, placebo-controlled trial. Azelastine was administered over 4 days before allergen challenge. Changes in airway caliber were followed with measurements of forced expiratory volume in 1 second, and changes in bronchial responsiveness were followed by methacholine and prostaglandin D2 bronchial provocation tests.


RESULTS
Azelastine significantly inhibited the development of the early asthmatic response. Azelastine had no effect on the late asthmatic response or on the development of allergen-induced increases in bronchial responsiveness. The power of the study was sufficient to have had a high probability of detecting any important differences between placebo and azelastine during the late phase.


CONCLUSIONS
Azelastine had no significant effect on the late-phase response model of asthma. This study does not support the hypothesis that histamine is an important mediator of the late asthmatic response or allergen-induced increases in bronchial responsiveness.
Twentyman
O P
OP
Department of Medicine I, University of Southampton, London, England.
Ollier
S
S
Holgate
S T
ST
D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine / Q000502:physiology; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D010793:Phthalazines / Q000627:therapeutic use*; D015230:Prostaglandin D2
D006634:Histamine H1 Antagonists; D010793:Phthalazines; D016210:Methacholine Chloride; D006632:Histamine; D015230:Prostaglandin D2; C020976:azelastine