Clara cell secretory protein and inflammatory mediators in newborn infants at risk of bronchopulmonary dysplasia

The incidence of bronchopulmonary dysplasia (BPD) remains unchanged despite improved perinatal care. Measuring lung fluid inflammatory markers is a widely-used technique, but is invasive and difficult to collect in non-intubated newborn infants. Examining serum concentrations of inflammatory mediators is a less invasive investigation of lung inflammation. The primary aim was to determine early post-natal serum concentrations of anti-inflammatory Clara Cell Secretory Protein (CCSP) in relationship to newborn lung diseases and development of BPD. This included comparison of serum ([CCSP](serum)) and tracheal CCSP ([CCSP](TAF)), serum surfactant proteins A (SP-A) and B (SP-B), pro- and anti-inflammatory cytokines and S100A12; additionally whether measuring [CCSP](serum) and other markers is useful in predicting later BPD development, and finally whether CCSP can suppress inflammation in vitro. Blood was collected from infants during the first week and analysed for [CCSP](serum), surfactant proteins, S100A12 and cytokines using ‘in-house’ and commercial assays, plus tracheal aspirates for CCSP. Recombinant CCSP (rhCC10) was used to assess suppression of lipopolysaccharide (LPS) and hyperoxia-induced inflammation in BEAS-2B cells in vitro. This unique research has confirmed a gestationally-influenced increase of [CCSP](serum) in the first day of life, correlating to [CCSP](TAF). The pattern of [CCSP](serum) differed to SP-A and -B which increased over the first week, and cytokines which showed no clear pattern. Full term infants had the highest day 1 [CCSP](serum) concentrations whilst BPD-prone preterm infants had the lowest concentrations of [CCSP](serum), and low anti-inflammatory interleukin-10 and -13 on day 7. Mechanical ventilation caused increased [CCSP](serum) in moderately preterm infants. In contrast, serum pro-inflammatory cytokine concentrations were not good predictors of later BPD development. Recombinant CCSP minimally suppressed LPS-induced inflammation but not with additional hyperoxia. A novel finding was that S100A12 was supressed in preterm infants with respiratory distress syndrome (a precursor of BPD), either due to altered neutrophil response or antenatal corticosteroid exposure. These findings suggest that an early increase in CCSP production is under gestational influence and may confer more pulmonary protection to term infants. Measuring [CCSP](serum) and other markers in the early post-natal period can provide a less-invasive and adjunctive measurement in monitoring BPD.