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 pathogenesi s, particularly during exacerbations of the disease. The objective of this study was to examine the effect of experimental rhinovirus 1C (RV 16) 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 ino culated on 2 consecutive days (Days 0 and 1). Histamine and bradykinin challenges were performed before (Days -7 and -6) and after (Days 3 a nd 4) inoculation. The response was measured by FEV(1) and partial flo w-volume curves, and it was expressed as PC(20)FEV(1) and PC40V over d ot(40p), respectively (changes expressed in doubling dose: DD). Before inoculation, PC(20)FEV(1) and PC40V over dot(40p) to histamine were n ot 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, respecti vely). PC(20)FEV(1) and PC40V over dot(40p) to histamine decreased sig nificantly 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 th e 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 R V16 group (p greater than or equal to 0.77). These changes in PC40V ov er dot(40p) to histamine and bradykinin were significantly different b etween the groups (p = 0.02). We conclude that repeated bradykinin cha llenge over a 10-d interval induces tachyphylaxis in asthmatic subject s in vivo and that experimental RV16 infection abolishes such tachyphy laxis to bradykinin while it enhances airway responsiveness to histami ne. These results do not favor a predominant role of airway sensory ne rves in rhinovirus-induced exacerbations of asthma.