title: An adult model of exclusive viral wheeze: inflammation in the upper and lower respiratory tracts.
abstract: BACKGROUND
  We have previously reported an experimental infection of young adults with a history of episodic and exclusive viral wheeze (EVW) using human coronavirus, in which 16 of 24 with EVW (15 atopic) and 11 of 19 healthy controls (seven atopic) developed a symptomatic cold with evidence of infection, but only those with EVW developed lower respiratory tract symptoms and increased airway responsiveness.
  
  
  OBJECTIVE
  The aim of this study was to compare the EVW and control groups from this study for inflammatory changes occurring in the upper and lower respiratory tracts during the experimental infection, in particular, to determine whether eosinophil-driven inflammation was associated with EVW.
  
  
  METHODS
  Nasal lavage and induced sputum were collected prior to inoculation (day 0) and 2, 4 and 17 days later. Differential cell counts were performed and supernatant was assayed for IL-8, IL-5, IFN-gamma, and eosinophilic cationic protein (ECP).
  
  
  RESULTS
  There was no difference between the two groups in any measurement at baseline. In both groups, during colds the volume of nasal secretion increased as did leucocyte counts in both upper and lower respiratory tracts. A modest increase in nasal neutrophil count was seen in both EVW and control groups with symptomatic colds on day 2 (median (quartile) difference from baseline 5.4 (0.0, 11.0) and 1.8 (-1.1, 2.2)x10(4)/mL of secretions, respectively). The change in nasal neutrophil counts in all subjects correlated with nasal symptom scores. A significant relative increase in sputum differential neutrophil count was seen on day 4 in the EVW group with a cold but not in controls (mean difference (95% confidence interval) 20.4 (9.6, 31.1)% and 3.1 (-8.2, 14.5)%, respectively, P<0.01); however, this increase did not correlate with lower respiratory tract symptom scores. IL-8 increased in both the upper and lower respiratory tracts in both EVW and control subjects with colds, the largest change being seen on day 4 in the sputum of those with EVW (mean difference from baseline (95% confidence interval) 2.5 (0.55-4.46) ng/mL). Only modest changes were seen in IFN-gamma and no changes were seen in IL-5 or ECP. None of the results was influenced by the atopic status of the subjects in either group.
  
  
  CONCLUSIONS
  EVW wheeze is characterized by neutrophilic inflammation in both the upper and lower respiratory tracts without eosinophilia (even in atopic subjects). IL-8 is likely to be an important chemokine in this process. Symptoms and airway responsiveness were correlated with change in neutrophils.
authors.affiliation: Department of Respiratory Paediatrics, Royal Victoria Infirmary, Newcastle upon Tyne, UK. Michael.Mckean@nuth.northy.nhs.uk
authors.forename: M C
authors.initials: MC
authors.lastname: Mckean
authors.forename: C
authors.initials: C
authors.lastname: Hewitt
authors.forename: P C
authors.initials: PC
authors.lastname: Lambert
authors.forename: St
authors.initials: S
authors.lastname: Myint
authors.forename: M
authors.initials: M
authors.lastname: Silverman
mesh_terms: D003139:Common Cold / Q000473:pathology / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000502:physiology; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000378:metabolism; D009297:Nasal Mucosa / Q000378:metabolism; D012135:Respiratory Sounds; D012141:Respiratory Tract Infections / Q000473:pathology* / Q000503:physiopathology; D013183:Sputum / Q000737:chemistry
chemical_list: D016209:Interleukin-8