The Role of Histamine in Allergen and Adenosine-Induced Bronchoconstriction

Abstract

We have investigated the role of histamine in allergen and adenosine-5′-monophosphate (AMP)-induced bronchoconstriction in asthmatic subjects by performing inhalation challenge tests with histamine, AMP and allergen after treatment with placebo or the potent H₁ histamine receptor antagonist, terfenadine. Single concentrations of each agonist which had previously been shown to produce a 30% fall in FEV₁ were used. After placebo, AMP and histamine both produced rapid bronchoconstriction reaching a maximum within 5 min and returning to within 10% of baseline after 25 min. Terfenadine inhibited this reaction to histamine completely and to AMP by 86%. The response to allergen was slower in onset and was sustained over 45 min and was inhibited 50% by terfenadine. We interpret these results as reflecting the contribution of histamine to the various airway challenges, both histamine and the newly generated mediators comprise the response to allergen, whereas AMP selectively enhances mast cell degranulation without affecting the production of arachidonic acid derived mediators.

A study of the clinical efficacy of azelastine in patients with extrinsic asthma, and its effect on airway responsiveness.

“…The results of both Taytard et al (1987) and Rafferty et al (1987) using terfenadine accord well with our own experience with azelastine. Further work is required to elucidate whether the clinical improvement which we recorded was solely attributable to the potent Hl-receptor antagonism of azelastine or to an additional 'anti-allergic' activity.…”

Species differences in adenosine receptor‐mediated bronchoconstrictor responses

“…Moreover, the model is, by definition, unlikely to mirror accurately the mechanism of the augmented adenosine‐induced bronchoconstrictor responses seen in intrinsic asthmatics or nonatopic smokers [ 64, 65]. Furthermore, the mediator of the bronchoconstrictor response to adenosine in the Brown Norway rat is 5‐HT and not, as in the asthmatic patient, mainly histamine [ 14–16]. Finally, the relative distribution and pharmacological profile of adenosine receptor subtypes between rat and human remains largely undefined and may turn out to be a complicating factor in extrapolating data from the rat model to man.…”

“…Venous plasma histamine levels are also increased after AMP challenge [ 13]. Pharmacological analysis reveals that the bronchoconstrictor response to adenosine is inhibited (≥ 80%) by pretreatment with the selective histamine H 1 receptor antagonists, terfenadine and astemizole [ 14–16]. The selective cyclooxygenase inhibitors, indomethacin and flurbiprofen, also partly inhibit AMP‐induced bronchoconstriction [ 17, 18] indicating that products of arachidonic acid metabolism also play a role, albeit minor, in adenosine‐induced bronchoconstriction in asthmatic patients.…”

Effects of mediator antagonism on mannitol and adenosine monophosphate challenges

“…We did not include a further randomized limb with antihistamine alone, as patients were already attending for eight bronchial challenges in the present protocol. Other studies have shown antihistamines to attenuate AHR to AMP [20, 21] or mannitol [8] challenge. For example, Lee et al observed that singles doses of desloratadine 5 mg, levocetirizine 5 mg and fexofenadine 180 mg all improved the AMP PC 20 compared to placebo by approximately one doubling dilution, but prolonged the time taken to recovery [21].…”