Inflammatory imbalance in tracheal aspirate of very preterm newborns is associated with lung function deficiencies at school-age

A low expression of club cell secretory protein (CC16), high levels of pro-inflammatory cytokines, and impaired vascularisation at preterm birth are associated with airway inflammation and more severe neonatal lung disease. The aim of the present study was to investigate if levels of CC16, proinflammatory cytokines and vascular endothelial growth factors in tracheal aspirate early after birth were associated with lung function impairment at school-age. At 12 years of age, 41 children with very preterm birth underwent a comprehensive lung function testing. Tracheal aspirate from the first day of life was available from 20 of these infants (median gestational age 25+3 weeks+days, interquartal range: 24+1 to 27+0 weeks+days). Main outcome measures were levels of CC16, cytokines, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 in tracheal aspirate in newborns in association to lung function at 12 years of age. Low levels of CC16 and high levels of the proinflammatory cytokines IL-1β and TNF-α in tracheal aspirate were associated with airway obstruction at school-age but not with other lung function parameters. Furthermore, the ratio between the respective proinflammatory cytokine and CC16 showed an even stronger correlation to airway obstruction. In addition, low levels of VEGF and CC16 were associated with impaired diffusion capacity of the lung. An imbalance in inflammatory mediators and growth factors in the lungs at birth may have consequences for airway function and vasculature at school-age in preterm born children.