Effects of experimental rhinovirus 16 infection on airway hyperresponsiveness to bradykinin in asthmatic subjects in vivo

Disturbance of the balance between excitatory and inhibitory activity of the airway sensory nerves has been implicated in asthma pathogenesis, particularly during exacerbations of the disease. The objective of this study was to examine the effect of experimental rhinovirus 1C (RV16) infection on airway responsiveness to bradykinin, a potent sensory nerve stimulus, in asthma. Thirteen atopic, mildly asthmatic subjects participated in a parallel, placebo-controlled study. A total dose of 2.6 to 5.6 x 10(4) TClD50 RV16 (n = 7) or its diluent (n = 6) was inoculated on 2 consecutive days (Days 0 and 1). Histamine and bradykinin challenges were performed before (Days -7 and -6) and after (Days 3 and 4) inoculation. The response was measured by FEV(1) and partial flow-volume curves, and it was expressed as PC(20)FEV(1) and PC40V over dot(40p), respectively (changes expressed in doubling dose: DD). Before inoculation, PC(20)FEV(1) and PC40V over dot(40p) to histamine were not significantly different between the groups (p greater than or equal to 0.22), whereas PC(20)FEV(1) and PC40V over dot(40p) to bradykinin tended to be higher in the RV16 group (p = 0.11 and p = 0.06, respectively). PC(20)FEV(1) and PC40V over dot(40p) to histamine decreased significantly in the RV16 group (mean change +/- SEM: -0.65 +/- 0.20 DD, p = 0.02 and -0.98 +/- 0.28 DD, p = 0.01, respectively), but not in the placebo group (p greater than or equal to 0.26). PC40V over dot(40p) to bradykinin increased significantly in the placebo group (+2.46 +/- 0.92 DD, p = 0.04), with a similar trend for PC(20)FEV(1) (+1.50 +/- 0.62 DD, p = 0.06), whereas there were no significant changes in the RV16 group (p greater than or equal to 0.77). These changes in PC40V over dot(40p) to histamine and bradykinin were significantly different between the groups (p = 0.02). We conclude that repeated bradykinin challenge over a 10-d interval induces tachyphylaxis in asthmatic subjects in vivo and that experimental RV16 infection abolishes such tachyphylaxis to bradykinin while it enhances airway responsiveness to histamine. These results do not favor a predominant role of airway sensory nerves in rhinovirus-induced exacerbations of asthma.