Severe Respiratory Syncytial Virus Bronchiolitis in Infants Is Associated with Reduced Airway Interferon Gamma and Substance P

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. Aim: to determine if factors mediating proposed mechanisms for severe bronchiolitis differ with severity of disease. METHODOLOGY/PRINCIPLE FINDINGS: 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-γ), 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-γ 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-γ and NPA SP. Nasal airway sampling appears to be a useful surrogate for distal airway sampling since concentrations of IFN-γ, 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-γ 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.