There is insufficient evidence from randomised controlled trials to guide the use of CCSP administration in preterm infants at risk of respiratory distress syndrome.
Respiratory distress syndrome caused by a deficiency of the naturally occurring lining chemicals of the lung (surfactant) occurs mainly in infants born before term. The usual treatment includes instilling artificial surfactant directly into the newborn infant's trachea followed by mechanical ventilation. However, this process can lead to lung injury, which can affect the infant's long-term health. A potential preventative strategy is to administer CCSP. This protein has the potential to reduce the lung damage caused by mechanical ventilation and thus may prevent further complications secondary to this damage known as chronic lung disease (CLD). This review found a small randomised controlled trial of intratracheal CCSP administration in preterm infants with respiratory distress syndrome that reported CCSP is well tolerated but this study did not have sufficient subjects to detect important clinical effects. In view of the encouraging results from this trial and other animal studies, high-quality trials of intratracheal CCSP administration in preterm infants with or at risk of respiratory distress syndrome are justified.
Vollständige Zusammenfassung lesen
Clara cell secretory protein (CCSP) is an immune-modulating and anti-inflammatory agent. CCSP is available synthetically as recombinant human Clara cell protein (rhCC10). It has been shown in animal models to reduce lung injury, improve pulmonary compliance and oxygenation, decrease systemic inflammation and up-regulate surfactant protein and vascular endothelial growth factor expression. These properties makes intratracheally administered CCSP a potential agent in prevention of chronic lung disease (CLD).
Zielsetzungen
To determine the effect of intratracheal CCSP administration compared to placebo or no treatment on morbidity and mortality in preterm infants with or at risk of respiratory distress syndrome (RDS).
Suchstrategie
We searched CENTRAL (The Cochrane Library, October 2010), MEDLINE and PREMEDLINE (1950 to October 2010), EMBASE (1980 to October 2010) and CINAHL (1982 to October 2010). We searched proceedings of scientific meetings, Google Scholar and reference lists of identified studies, and contacted expert informants and surfactant manufacturers.
Auswahlkriterien
Published, unpublished and ongoing randomised controlled, cluster-randomised or quasi-randomised trials of intratracheal CCSP administration, compared to placebo or no treatment on morbidity and mortality in preterm infants at risk of RDS.
Datensammlung und ‐analyse
Two authors independently assessed studies for eligibility and quality, and extracted data.
Hauptergebnisse
One pilot study was identified and included. This study enrolled 22 preterm infants 700 to 1300g with established RDS who required ventilation for surfactant administration. Infants received one intratracheal dose of placebo (n = 7), 1.5 mg/kg (n = 8) or 5 mg/kg (n = 7) rhCC10 within four hours of surfactant treatment. At either dose of rhCC10, no significant difference was reported in CLD (36 weeks postmenstrual age or 28 days), mortality, intraventricular haemorrhage, periventricular leukomalacia, patent ductus arteriosus, necrotising enterocolitis, sepsis or days supplemental oxygen compared to placebo. A significant increase in days mechanical ventilation was reported for infants receiving rhCC10 5mg/kg (mean difference 12.00, 95% confidence interval 0.39 to 23.61) but not at the lower dose. The study reported that a single intratracheal dose of rhCC10 was well tolerated and resulted in a significant reduction in tracheal aspirate neutrophil and total cell count, and lung protein concentration. There was no significant difference reported in tracheal aspirate cytokine levels between groups.
Schlussfolgerungen der Autoren
There are insufficient data to determine the role of rhCC10 in clinical practice. Further studies are required to determine if rhCC10 reduces lung inflammation in infants at risk of CLD, and to determine dose and dosing strategy.
