The relative contributions of histamine and prostanoids to bronchoconstriction provoked by isocapnic hyperventilation in asthma.
It has been proposed that exercise provokes bronchoconstriction in asthma by inducing mast cell degranulation, and that this occurs secondary to the hyperpnoea of exercise causing hypertonicity of the airway lining fluid. We investigated the contribution of the mast cell products, histamine and prostaglandins, to the bronchoconstriction induced by isocapnic hyperventilation (ISH) using single doses of terfenadine, a specific histamine H1-receptor antagonist, and flurbiprofen, a potent cyclooxygenase inhibitor. We also investigated the effect of flurbioprofen in single dose on bronchial histamine reactivity. Eleven asthmatics took part in a two phase, double-blind, randomized study. In phase 1, subjects attended on three occasions and received either terfenadine 180 mg, flurbiprofen 150 mg, or placebo, prior to 6 min of ISH. The mean maximum percentage fall in forced expiratory volume in one second (FEV1) induced by ISH was 31.5(+/- 3.2)% following placebo, 29.7(+/- 4.4)% following flurbiprofen (NS), and reduced to 16.6(+/- 3.7)% following terfenadine (p less than 0.01). In phase 2, subjects received bronchial challenge with histamine following either flurbiprofen 150 mg or placebo. No significant change in bronchial reactivity following flurbiprofen was seen. We conclude that as administered in this study, flurbiprofen has no effect on baseline bronchial reactivity to histamine. The inhibitory effect of terfenadine indicates that histamine, probably from airway mast cells, makes an important contribution to bronchoconstriction induced by isocapnic hyperventilation, whereas prostaglandin release has no significant role.
Finnerty
J P
JP
Immunopharmacology Group, Southampton General Hospital, UK.
Harvey
A
A
Holgate
S T
ST
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000209:etiology / Q000503:physiopathology*; D001985:Bronchial Provocation Tests / Q000379:methods*; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage / Q000494:pharmacology*; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006985:Hyperventilation / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016593:Terfenadine / Q000008:administration & dosage / Q000494:pharmacology*
D010919:Placebos; D005480:Flurbiprofen; D016593:Terfenadine; D006632:Histamine