title: Deficient antiviral immune responses in childhood: distinct roles of atopy and asthma.
abstract: BACKGROUND
  Impaired immune response to viral infections in atopic asthmatic patients has been recently reported and debated. Whether this condition is present in childhood and whether it is affected by atopy per se deserves further investigation.
  
  
  OBJECTIVE
  We sought to investigate airway interferon production in response to rhinovirus infection in children who are asthmatic, atopic, or both and its correlation with the airway inflammatory profile.
  
  
  METHODS
  Bronchial biopsy specimens and epithelial cells were obtained from 47 children (mean age, 5 ± 0.5 years) undergoing bronchoscopy. The study population included asthmatic children who were either atopic or nonatopic, atopic children without asthma, and children without atopy or asthma. Rhinovirus type 16 induction of IFN-λ and IFN-β mRNA and protein levels was assessed in bronchial epithelial cell cultures. The immunoinflammatory profile was evaluated by means of immunohistochemistry in bronchial biopsy specimens.
  
  
  RESULTS
  Rhinovirus type 16-induced interferon production was significantly reduced in atopic asthmatic, nonatopic asthmatic, and atopic nonasthmatic children compared with that seen in nonatopic nonasthmatic children (all P < .05). Increased rhinovirus viral RNA levels paralleled this deficient interferon induction. Additionally, IFN-λ and IFN-β induction correlated inversely with the airway T(H)2 immunopathologic profile (eosinophilia and IL-4 positivity: P < .05 and r = -0.38 and P < .05 and r = -0.58, respectively) and with epithelial damage (P < .05 and r = -0.55). Furthermore, total serum IgE levels correlated negatively with rhinovirus-induced IFN-λ mRNA levels (P < .05 and r = -0.41) and positively with rhinovirus viral RNA levels (P < .05 and r = 0.44).
  
  
  CONCLUSIONS
  Deficient interferon responses to rhinovirus infection are present in childhood in asthmatic subjects irrespective of their atopic status and in atopic patients without asthma. These findings suggest that deficient immune responses to viral infections are not limited to patients with atopic asthma but are present in those with other T(H)2-oriented conditions.
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, Section of Respiratory Diseases, University of Padova, Padua, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Baraldo
authors.forename: Marco
authors.initials: M
authors.lastname: Contoli
authors.forename: Erica
authors.initials: E
authors.lastname: Bazzan
authors.forename: Graziella
authors.initials: G
authors.lastname: Turato
authors.forename: Anna
authors.initials: A
authors.lastname: Padovani
authors.forename: Brunilda
authors.initials: B
authors.lastname: Marku
authors.forename: Fiorella
authors.initials: F
authors.lastname: Calabrese
authors.forename: Gaetano
authors.initials: G
authors.lastname: Caramori
authors.forename: Andrea
authors.initials: A
authors.lastname: Ballarin
authors.forename: Deborah
authors.initials: D
authors.lastname: Snijders
authors.forename: Angelo
authors.initials: A
authors.lastname: Barbato
authors.forename: Marina
authors.initials: M
authors.lastname: Saetta
authors.forename: Alberto
authors.initials: A
authors.lastname: Papi
mesh_terms: D001249:Asthma / Q000150:complications / Q000276:immunology* / Q000473:pathology; D001980:Bronchi / Q000473:pathology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004804:Eosinophils / Q000276:immunology / Q000821:virology; D005260:Female; D006801:Humans; D007120:Immunochemistry; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology; D007372:Interferons; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D008297:Male; D010850:Picornaviridae Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D012229:Rhinovirus; D058408:Th1-Th2 Balance; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D016899:Interferon-beta; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda