Effect of orally administered cimetidine on histamine- and antigen-induced bronchospasm in subjects with asthma.
Previous studies concerning the effect of cimetidine, a histamine H2 receptor antagonist, on histamine- or antigen-induced bronchoconstriction have yielded conflicting results. Therefore, we examined the effects of cimetidine on sensitivity to both histamine- and antigen-induced bronchospasm in 12 subjects with mild asthma (baseline FEV1 greater than 70% predicted). Bronchial challenges with inhaled histamine or antigen were performed 2 h after a single dose of 300 mg cimetidine or placebo orally administered in a random, double-blind manner on separate days. The provocative concentration of antigen or histamine that produced a 20% decline in FEV1 from the postdiluent control value (PC20) was determined and log transformed. Plasma cimetidine concentrations 2 h after oral administration (mean, 1.5 microgram/ml; range, 0.9 to 2.4 mirograms/ml) were above the minimal concentration required for suppression of gastric acid secretion. No difference was noted in FEV1, specific airway conductance, or partial expiratory flow rates after cimetidine compared with that after placebo, indicating the lack of any bronchospastic effect of cimetidine in the absence of histamine or antigen challenge. However, mean log PC20 of histamine (but not of antigen) was significantly less after cimetidine than after placebo (p less than 0.05), indicating that cimetidine augmented histamine-(but not antigen-) induced bronchospasm. Four of 12 subjects exhibited a significant (greater than or equal to fourfold) decline in PC20 for histamine after cimetidine compared with that after placebo but no subject demonstrated a significant (greater than or equal to tenfold) decline in PC20 of antigen. No relationship was apparent between baseline sensitivity to histamine and cimetidine effect on histamine sensitivity in individual subjects. We conclude that in subjects with mild asthma, cimetidine in the usual recommended orally administered dose can increase sensitivity to bronchospasm induced by histamine but not by antigen. These findings suggest that cimetidine in this dose has a blocking effect on H2 receptors in airway smooth muscle but that this effect is not sufficient to alter the net impact of immunologic release of mediators on the airways.
D000328:Adult; D000403:Airway Resistance; D000941:Antigens; D001249:Asthma / Q000097:blood / Q000503:physiopathology*; D001980:Bronchi / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D002927:Cimetidine / Q000009:adverse effects* / Q000097:blood; D005260:Female; D005541:Forced Expiratory Volume; D006146:Guanidines / Q000009:adverse effects*; D006632:Histamine; D006801:Humans; D008297:Male; D008448:Maximal Expiratory Flow Rate; D014797:Vital Capacity
D000941:Antigens; D006146:Guanidines; D002927:Cimetidine; D006632:Histamine