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Author Vissing, N.H.; Larsen, J.M.; Rasmussen, M.A.; Chawes, B.L.K.; Thysen, A.H.; Bonnelykke, K.; Brix, S.; Bisgaard, H. url  doi
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  Title Susceptibility to Lower Respiratory Infections in Childhood is Associated with Perturbation of the Cytokine Response to Pathogenic Airway Bacteria Type Journal Article
  Year (down) 2016 Publication The Pediatric Infectious Disease Journal Abbreviated Journal Pediatr Infect Dis J  
  Volume 35 Issue 5 Pages 561-566  
  Keywords  
  Abstract BACKGROUND: Neonatal colonization of the airways with respiratory pathogens is associated with increased risk of lower respiratory infections (LRI) in early childhood. Therefore, we hypothesized that children developing LRI have an aberrant immune response to pathogenic bacteria in infancy. The objective was to characterize in vitro the early life systemic immune response to pathogenic bacteria and study the possible association with incidence of LRI during the first 3 years of life. METHODS: The Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) is a clinical birth cohort study of 411 children born of mothers with asthma. LRI incidence was prospectively captured from 6-monthly planned visits and visits at acute respiratory episodes. The in vitro systemic immune response to Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was characterized by the production of TNF-alpha, IFN-gamma, IL-2, IL-5, IL-10, IL-13 and IL-17 in peripheral blood mononuclear cells isolated at age 6 months from 291 infants. Data were analyzed by Poisson regression against incidence of LRI in infancy. RESULTS: A multivariable model including all cytokine responses from the 3 different bacterial stimulations significantly identified children at risk of LRI (P = 0.006). The immune response pattern associated with LRI was characterized by perturbed production of several cytokines rather than production of one specific cytokine, and was independent of concurrent asthma. TNF-alpha and IL-5 were key drivers but did not explain the entire variation in LRI susceptibility. CONCLUSIONS: Children at risk of future LRI present a perturbed systemic immune response upon exposure to common airway pathogens in early life.  
  Address From the *Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health and Medical Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark; and daggerDepartment of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark  
  Corporate Author Thesis  
  Impact Factor 02,723 First Author Vissing, N.H. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Bisgaard, H.  
  ISSN 0891-3668 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:26910587 Approved no  
  Call Number Serial 319  
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