Pro-inflammatory mediator responses from neonatal airway epithelial cells and early childhood wheeze

Background. Airway epithelial cell (AEC) function differs between children with and without asthma. Here we associated neonatal AEC function with asthma symptoms at four years of age.Methods. Nasal AEC were collected from neonates within 48 hours of birth. Cells were cultured and stimulated with tumour necrosis factor alpha/interleukin-1 beta (TNFα/IL-1β), lipopolysaccharide (LPS) or house dust mite (HDM). Absolute concentrations of proinflammatory mediators in the culture supernatant were quantified and expressed as median [interquartile range] in pg/mg protein. A parent-completed respiratory questionnaire was returned when the child was four years old.Results. AEC were successfully cultured in 139 neonates, of whom 120 were contacted at four years and 91 (76%) questionnaires were returned. Sixteen children had wheezed ever and 11 had recent wheeze. At birth, when compared to those with no recent wheeze, supernatants from cultured neonatal AEC from the children with recent wheeze had reduced median IL-8 (CXCL8) release after treatment with culture medium alone (p=0.049), with TNFα/IL-1β (p<0.001) and LPS (p=0.004). Additionally, and when compared to those with no recent wheeze, four year olds with recent wheeze had reduced neonatal AEC release of IL-6 (p=0.013), GMCSF (p=0.012) and ICAM-1 (p=0.017) after treatment withTNFα/IL-1β and reduced release of ICAM-1 (p=0.038) and RANTES (p=0.042) after treatment with HDM.Conclusions. Abnormalities in AEC function are present at birth before the onset of childhood wheeze. The relationship between reduced AEC function at birth and wheeze at four years was not exclusive, suggesting that post-natal factors are required for the AEC abnormality to translate into symptoms.