Effect o of iinhaled b bradykinin o on iindices o of a airway responsiveness iin a asthmatic s subjects

Asthma is characterized by airway hyperresponsiveness, a phys- iopathological abnormality which may result from the complex interplay between inflammatory cells and proinflammatory mediators. Although kinins are thought to play a role in the pathogenesis of bronchial asthma, it is not known whether bradykinin is able to induce airway hyperresponsiveness. We have, therefore, investigated the effect of inhaled bradykinin on the changes in airway calibre and in airway hyperresponsiveness to histamine, in a double-blind, randomized study of nine asthmatic subjects. Subjects were studied on two study periods, separated by at least 15 days. On the first day of each study period, sub- jects inhaled either a single dose of bradykinin or methacholine (placebo) with changes in airway calibre being followed as forced expiratory volume in one sec- ond (FEV1) and as the maximum expiratory flow rate measured at 70% of the vital capacity below total lung capacity (TLC) from a partial forced expiratory manoeu- vre (Vp30) at 3, 5, 10, 15, 30, 45 and 60 min, and then every hour for 7 h. Airway responsiveness to histamine, expressed as the provocative concentrations producing a 20% fall in FEV1 and 40% fall in Vp30 (PC20FEV1 and PC40Vp30), was measured at 3 and 7 h after inhaling the agonists, then on days 1, 3, 7 and 14. Inhalation of bradykinin caused rapid bronchoconstriction that peaked at 3-5 min. When compared to placebo, no significant difference in histamine respon- siveness was seen after bradykinin in terms of changes in PC20FEV1 values. However, when airway hyperresponsiveness was measured as PC40Vp30, we were able to show a significant increase in airway reactivity after bradykinin at 3 and 7 h, the geo- metric mean PC40Vp30 histamine value decreasing 3.2 and 1.9 fold, respectively. The results of the present study indicate that bradykinin elicits a transient increase of airway hyperresponsiveness in asthmatic subjects, but this was evident only using a sensitive indicator of the changes in airway reactivity, which suggests an effect at the level of the more peripheral airways. These data suggest that bradykinin may play a role in the pathogenesis of airway hyperresponsiveness in human asthma.