Early Postnatal Surge of Serum Clara Cell Secretory Protein in Newborn Infants

Abstract

Background: Clara cell secretory protein (CCSP) is an anti-inflammatory mediator, but its role in neonatal lung adaptation and diseases is uncertain. Objective: To characterize postnatal changes in serum CCSP in relation to gestation, respiratory disease (RDS) and bronchopulmonary dysplasia (BPD) in comparison with other anti-inflammatory cytokines (IL-4, -10 and -13). Methods: Blood was collected from 76 infants (26 of 23–29 weeks’ gestation, 33 of 30–36 weeks’ gestation and 17 term infants) at birth (preterm cord blood); on admission; at 12, 24 and 48 h; and on days 3–4 and 7 of life. CCSP was assayed by ELISA and cytokines by Bio-Plex. Results: Median serum CCSP in extremely and moderately preterm infants rose from a baseline of 13.6 and 15.9 to 33.4 ng/ml (p = 0.04) and 59.8 ng/ml (p = 0.03) at 12 h of age, respectively. CCSP levels were highest in term infants (80.7 ng/ml at 12 h). CCSP then decreased to 22.5 ng/ml on days 3–4 (p = 0.001). CCSP of 37 RDS infants fell to a lower baseline on days 4 and 7 than that of the 22 non-RDS preterms. The 8 infants who developed BPD had persistently low serum CCSP (12.7 ng/ml at 12 h). In contrast, early postnatal changes were not seen in IL-4, -10 and -13 levels, but low IL-10 and -13 levels were found on day 7 in BPD infants. Conclusions: Serum CCSP levels were characterized by an early postnatal surge. This apparent gestation-influenced surge may represent an initiation of a protective cascade against postnatal lung injury during extrauterine adaptation.

Clara Cell Protein Expression in Mechanically Ventilated Term and Preterm Infants with Respiratory Distress Syndrome and at Risk of Bronchopulmonary Dysplasia: A Pilot Study

“…This pilot study is in agreement with previous studies for preterm infants [14, 23] but provides further evidence for term infants. Furthermore, CC16 levels at birth were found to positively correlate with BPD diagnosis and negatively with severity.…”

Evaluation of Club Cell 10-kDa Protein (CC10) Levels in Full-Term Infants

“…Previous work suggested that there is a postnatal surge of [CC10] peaking 12-24 h after birth and falling thereafter [2,8]. Our study was not designed to replicate these findings since our numbers at each time point were small, and we could have missed such a finding.…”

“…We found that CC10 is detectable in all three compartments, with the least amount in the stool. Previous studies evaluating serum [CC10] in term infants primarily examined infants with respiratory illness, thus making these values harder to interpret [2,8]. Serum CC10 is known to increase when lung injury is present due to increased CC10 leakage across the bronchoalveolar/blood barrier [10].…”

“…With ongoing development of novel therapies to decrease the incidence of BPD and associated chronic respiratory morbidity, understanding baseline CC10 levels in healthy term infants is critically important. Since previous studies of CC10 in term infants examined a combined cohort of those with and without respiratory disease, limited data exist on CC10 levels in full-term infants with normal lungs [2,8]. In addition, no investigations have been done correlating CC10 levels in the blood, urine, and stool in newborn infants.…”

A Comparison of KL-6 and Clara Cell Protein as Markers for Predicting Bronchopulmonary Dysplasia in Preterm Infants

“…Ogihara et al [14] suggested that prenatal lung injury has a priming effect, increasing the susceptibility of fetal lungs to subsequent toxic agents. Loughran-Fowlds et al [23] also found that infants who developed BPD had persistently lower serum CC16 levels at 12 hours compared with those who did not develop BPD. However, Sarafidis et al [17] found significantly higher CC16 concentrations at 14 days in ventilated infants who developed BPD than in nonventilated infants who did not develop BPD.…”