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Effects of experimental rhinovirus 16 infection on airway hyperresponsiveness to bradykinin in asthmatic subjects in vivo.
Am J Respir Crit Care Med 1997; 155(3):833-8AJ

Abstract

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 16 (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) TCID50 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 FEV1 and partial flow-volume curves, and it was expressed as PC20FEV1 and PC40V40p, respectively (changes expressed in doubling dose: DD). Before inoculation, PC20FEV1 and PC40V40p to histamine were not significantly different between the groups (p > or = 0.22), whereas PC20FEV1 and PC40V40p to bradykinin tended to be higher in the RV16 group (p = 0.11 and p = 0.06, respectively). PC20FEV1 and PC40V40p 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 > or = 0.26). PC40V40p to bradykinin increased significantly in the placebo group (+2.46 +/- 0.92 DD, p = 0.04), with a similar trend for PC20FEV1 (+1.50 +/- 0.62 DD, p = 0.06), whereas there were no significant changes in the RV16 group (p > or = 0.77). These changes in PC40V40p 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.

Authors+Show Affiliations

Department of Pulmonology, Leiden University Medical Centre, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Controlled Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9117013

Citation

Grünberg, K, et al. "Effects of Experimental Rhinovirus 16 Infection On Airway Hyperresponsiveness to Bradykinin in Asthmatic Subjects in Vivo." American Journal of Respiratory and Critical Care Medicine, vol. 155, no. 3, 1997, pp. 833-8.
Grünberg K, Kuijpers EA, de Klerk EP, et al. Effects of experimental rhinovirus 16 infection on airway hyperresponsiveness to bradykinin in asthmatic subjects in vivo. Am J Respir Crit Care Med. 1997;155(3):833-8.
Grünberg, K., Kuijpers, E. A., de Klerk, E. P., de Gouw, H. W., Kroes, A. C., Dick, E. C., & Sterk, P. J. (1997). Effects of experimental rhinovirus 16 infection on airway hyperresponsiveness to bradykinin in asthmatic subjects in vivo. American Journal of Respiratory and Critical Care Medicine, 155(3), pp. 833-8.
Grünberg K, et al. Effects of Experimental Rhinovirus 16 Infection On Airway Hyperresponsiveness to Bradykinin in Asthmatic Subjects in Vivo. Am J Respir Crit Care Med. 1997;155(3):833-8. PubMed PMID: 9117013.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of experimental rhinovirus 16 infection on airway hyperresponsiveness to bradykinin in asthmatic subjects in vivo. AU - Grünberg,K, AU - Kuijpers,E A, AU - de Klerk,E P, AU - de Gouw,H W, AU - Kroes,A C, AU - Dick,E C, AU - Sterk,P J, PY - 1997/3/1/pubmed PY - 1997/3/1/medline PY - 1997/3/1/entrez SP - 833 EP - 8 JF - American journal of respiratory and critical care medicine JO - Am. J. Respir. Crit. Care Med. VL - 155 IS - 3 N2 - 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 16 (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) TCID50 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 FEV1 and partial flow-volume curves, and it was expressed as PC20FEV1 and PC40V40p, respectively (changes expressed in doubling dose: DD). Before inoculation, PC20FEV1 and PC40V40p to histamine were not significantly different between the groups (p > or = 0.22), whereas PC20FEV1 and PC40V40p to bradykinin tended to be higher in the RV16 group (p = 0.11 and p = 0.06, respectively). PC20FEV1 and PC40V40p 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 > or = 0.26). PC40V40p to bradykinin increased significantly in the placebo group (+2.46 +/- 0.92 DD, p = 0.04), with a similar trend for PC20FEV1 (+1.50 +/- 0.62 DD, p = 0.06), whereas there were no significant changes in the RV16 group (p > or = 0.77). These changes in PC40V40p 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. SN - 1073-449X UR - https://www.unboundmedicine.com/medline/citation/9117013/Effects_of_experimental_rhinovirus_16_infection_on_airway_hyperresponsiveness_to_bradykinin_in_asthmatic_subjects_in_vivo_ L2 - http://www.atsjournals.org/doi/full/10.1164/ajrccm.155.3.9117013?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -