Evidence for the roles of histamine and prostaglandins as mediators in exercise-induced asthma: the inhibitory effect of terfenadine and flurbiprofen alone and in combination.
We investigated the effects of terfenadine, a histamine H1-receptor antagonist, and flurbiprofen, a cyclooxygenase inhibitor, on exercise-induced bronchoconstriction to assess the contribution of the mast cell products histamine and prostaglandins. Eight asthmatics were studied on 4 occasions with treadmill exercise tests. Terfenadine or placebo was administered 3 h prior to exercise, and flurbiprofen or placebo was administered 2 h prior to exercise, in a double-blind randomized trial. Airway calibre was determined by measurement of the forced expiratory volume in one second (FEV1) immediately prior to exercise challenge, and over 30 min post-exercise. Following placebo, the mean maximum percentage fall in FEV1 was 39%. This fell to 25% after terfenadine (p less than 0.05), 27% after flurbiprofen (p less than 0.05), and 30% after the active combination (NS). Analysis of the areas under curves of percentage falls in FEV1 over 30 min showed significant inhibition on all 3 active drug days (p less than 0.05). We conclude that histamine release and prostaglandin generation contribute to exercise-induced bronchoconstriction, although the interaction between these mediators appears complex.
Finnerty
J P
JP
Immunopharmacology Group, Southampton General Hospital, UK.
Holgate
S T
ST
D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D001250:Asthma, Exercise-Induced / Q000188:drug therapy* / Q000209:etiology; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D005480:Flurbiprofen / Q000627:therapeutic use*; D005541:Forced Expiratory Volume; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006636:Histamine Release / Q000502:physiology*; D006801:Humans; D008297:Male; D011453:Prostaglandins / Q000502:physiology*; D016032:Randomized Controlled Trials as Topic; D016593:Terfenadine
D001559:Benzhydryl Compounds; D006634:Histamine H1 Antagonists; D011453:Prostaglandins; D005480:Flurbiprofen; D016593:Terfenadine