title: Severe respiratory syncytial virus bronchiolitis in infants is associated with reduced airway interferon gamma and substance P.
abstract: BACKGROUND
  Severe human respiratory syncytial virus (hRSV) bronchiolitis in previously well infants may be due to differences in the innate immune response to hRSV infection.
  
  
  OBJECTIVE
  to determine if factors mediating proposed mechanisms for severe bronchiolitis differ with severity of disease.
  
  
  RESULTS
  197 infants admitted to hospital with hRSV bronchiolitis were recruited and grouped according to no oxygen requirement (n = 27), oxygen dependence (n = 114) or mechanical ventilation (n = 56). We collected clinical data, nasopharyngeal aspirate (NPA) and if ventilated bronchoalveolar lavage (BAL). Interferon-gamma (IFN-gamma), substance P (SP), interleukin 9 (IL-9), urea and hRSV load, were measured in cell free supernatant from NPA and BAL. Multivariate analysis compared independent effects of clinical, virological and immunological variables upon disease severity. IFN-gamma and SP concentrations were lower in NPA from infants who required oxygen or mechanical ventilation. Viral load and IL-9 concentrations were high but did not vary with severity of disease. Independent predictors of severe disease (in diminishing size of effect) were low weight on admission, low gestation at birth, low NPA IFN-gamma and NPA SP. Nasal airway sampling appears to be a useful surrogate for distal airway sampling since concentrations of IFN-gamma, SP, IL-9 and viral load in NPA correlate with the same in BAL.
  
  
  CONCLUSIONS
  Our data support two proposed mechanisms for severe hRSV disease; reduced local IFN-gamma response and SP mediated inflammation. We found large amounts of hRSV and IL-9 in airways secretions from the upper and lower respiratory tract but could not associate these with disease severity.
authors.affiliation: Division of Child Health, School of Reproductive & Developmental Medicine, University of Liverpool, Liverpool, United Kingdom. m.g.semple@liverpool.ac.uk
authors.forename: Malcolm G
authors.initials: MG
authors.lastname: Semple
authors.forename: Hinke M
authors.initials: HM
authors.lastname: Dankert
authors.forename: Bahram
authors.initials: B
authors.lastname: Ebrahimi
authors.forename: Jailson B
authors.initials: JB
authors.lastname: Correia
authors.forename: J Angela
authors.initials: JA
authors.lastname: Booth
authors.forename: James P
authors.initials: JP
authors.lastname: Stewart
authors.forename: Rosalind L
authors.initials: RL
authors.lastname: Smyth
authors.forename: C Anthony
authors.initials: CA
authors.lastname: Hart
mesh_terms: D001988:Bronchiolitis / Q000821:virology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism*; D016906:Interleukin-9 / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000821:virology*; D018113:Respiratory Syncytial Virus, Human / Q000378:metabolism*; D012137:Respiratory System / Q000821:virology; D013373:Substance P / Q000378:metabolism*; D014508:Urea / Q000378:metabolism
chemical_list: D016906:Interleukin-9; D013373:Substance P; D007371:Interferon-gamma; D014508:Urea; D010100:Oxygen