title: Effect of experimental rhinovirus 16 colds on airway hyperresponsiveness to histamine and interleukin-8 in nasal lavage in asthmatic subjects in vivo.
abstract: BACKGROUND
  Asthma exacerbations are closely associated with respiratory virus infections. However, the pathophysiological consequences of such infections in asthma are largely unclear.
  
  
  OBJECTIVE
  To examine the effect of rhinovirus 16 (RV16) infection on airway hypersensitivity to histamine, and on interleukin-8 (IL-8) in nasal lavage.
  
  
  METHODS
  Twenty-seven non-smoking atopic, mildly asthmatic subjects participated in a placebo-controlled, parallel study. A dose of 0.5-2.9 x 10(4) TCID50 RV16 or placebo was nasally administered. Cold symptoms were recorded by questionnaire throughout the study. Histamine challenges were performed at entry, and on days 4 and 11 after inoculation. Nasal lavages were obtained at entry, and on days 2 and 9. The response to histamine was measured by PC20 (changes expressed as doubling doses: DD) IL-8 levels were obtained by ELISA, and were expressed in ng/ml.
  
  
  RESULTS
  RV infection was confirmed by culture of nasal lavage and/or by antibody titre rise in each of the RV16-treated subjects. Among the 19 RV 16-treated subjects, eight developed severe cold symptoms. Baseline FEV1, did not change significantly during the study in either treatment group (P = 0.99). However, in the RV16-treated subjects there was a decrease in PC20 at day 4, which was most pronounced in those with a severe cold (mean change +/- SEM: -1.14 +/- 0.28 DD, P = 0.01). In addition, IL-8 levels increased in the RV16 group at days 2 and 9 (P < 0.001). The increase in nasal IL-8 at day 2 correlated significantly with the change in PC20 at day 4 (r = -0.48, P = 0.04).
  
  
  CONCLUSIONS
  We conclude that the severity of cold, as induced by experimental RV16 infection, is a determinant of the increase in airway hypersensitivity to histamine in patients with asthma. Our results suggest that this may be mediated by an inflammatory mechanism, involving the release of chemokines such as IL-8.
authors.affiliation: Department of Pulmonology, Leiden University Medical Centre, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Grünberg
authors.forename: M C
authors.initials: MC
authors.lastname: Timmers
authors.forename: H H
authors.initials: HH
authors.lastname: Smits
authors.forename: E P
authors.initials: EP
authors.lastname: de Klerk
authors.forename: E C
authors.initials: EC
authors.lastname: Dick
authors.forename: W J
authors.initials: WJ
authors.lastname: Spaan
authors.forename: P S
authors.initials: PS
authors.lastname: Hiemstra
authors.forename: P J
authors.initials: PJ
authors.lastname: Sterk
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000209:etiology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D003139:Common Cold / Q000209:etiology / Q000503:physiopathology*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006632:Histamine; D006801:Humans; D016209:Interleukin-8 / Q000502:physiology*; D007958:Leukocyte Count; D008168:Lung / Q000502:physiology; D008297:Male; D017817:Nasal Lavage Fluid; D012229:Rhinovirus
chemical_list: D016209:Interleukin-8; D006632:Histamine