title: Experimental rhinovirus infection as a human model of chronic obstructive pulmonary disease exacerbation.
abstract: BACKGROUND
  Respiratory virus infections are associated with chronic obstructive pulmonary disease (COPD) exacerbations, but a causative relationship has not been proven. Studies of naturally occurring exacerbations are difficult and the mechanisms linking virus infection to exacerbations are poorly understood. We hypothesized that experimental rhinovirus infection in subjects with COPD would reproduce the features of naturally occurring COPD exacerbations and is a valid model of COPD exacerbations.
  
  
  OBJECTIVE
  To evaluate experimental rhinovirus infection as a model of COPD exacerbation and to investigate the mechanisms of virus-induced exacerbations.
  
  
  METHODS
  We used experimental rhinovirus infection in 13 subjects with COPD and 13 nonobstructed control subjects to investigate clinical, physiologic, pathologic, and antiviral responses and relationships between virus load and these outcomes.
  
  
  RESULTS
  Clinical data; inflammatory mediators in blood, sputum, and bronchoalveolar lavage; and viral load in nasal lavage, sputum, and bronchoalveolar lavage were measured at baseline and after infection with rhinovirus 16. After rhinovirus infection subjects with COPD developed lower respiratory symptoms, airflow obstruction, and systemic and airway inflammation that were greater and more prolonged compared with the control group. Neutrophil markers in sputum related to clinical outcomes and virus load correlated with inflammatory markers. Virus load was higher and IFN production by bronchoalveolar lavage cells was impaired in the subjects with COPD.
  
  
  CONCLUSIONS
  We have developed a new model of COPD exacerbation that strongly supports a causal relationship between rhinovirus infection and COPD exacerbations. Impaired IFN production and neutrophilic inflammation may be important mechanisms in virus-induced COPD exacerbations.
authors.affiliation: Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, Norfolk Place, London W2 1PG, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mallia
authors.forename: Simon D
authors.initials: SD
authors.lastname: Message
authors.forename: Vera
authors.initials: V
authors.lastname: Gielen
authors.forename: Marco
authors.initials: M
authors.lastname: Contoli
authors.forename: Katrina
authors.initials: K
authors.lastname: Gray
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kebadze
authors.forename: Julia
authors.initials: J
authors.lastname: Aniscenko
authors.forename: Vasile
authors.initials: V
authors.lastname: Laza-Stanca
authors.forename: Michael R
authors.initials: MR
authors.lastname: Edwards
authors.forename: Louise
authors.initials: L
authors.lastname: Slater
authors.forename: Alberto
authors.initials: A
authors.lastname: Papi
authors.forename: Luminita A
authors.initials: LA
authors.lastname: Stanciu
authors.forename: Onn M
authors.initials: OM
authors.lastname: Kon
authors.forename: Malcolm
authors.initials: M
authors.lastname: Johnson
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010850:Picornaviridae Infections; D029424:Pulmonary Disease, Chronic Obstructive / Q000821:virology*; D012229:Rhinovirus; D019562:Viral Load
chemical_list: D018836:Inflammation Mediators