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Dexamethasone treatment of infants at risk for chronic lung disease: surfactant components and inflammatory
M A Kari1, K O Raivio, P Venge
1Children's Hospital, University of Helsinki, Finland.
Insights
Dexamethasone (DEX) treatment in preterm infants reduced airway nonsedimentable proteins, improving surfactant function. This may explain DEX
Area of Science:
- Neonatal Medicine
- Pulmonology
- Biochemistry
Background:
- Mechanisms of glucocorticoid benefits in ventilator-dependent preterm infants remain unclear.
- Preterm infants are at risk for chronic lung disease, impacting surfactant system development.
- Dexamethasone (DEX) is used to treat these infants, but its precise effects on the surfactant system are not fully understood.
Purpose of the Study:
- To investigate the hypothesis that dexamethasone (DEX) treatment favorably affects the surfactant system in preterm infants.
- To evaluate the impact of DEX on surfactant components, surface activity, and inhibitors in ventilator-dependent infants.
Main Methods:
- Randomized trial involving 23 ventilator-dependent preterm infants (gestational age 26 +/- 2 wk).
- Infants received either DEX (0.5 mg/kg/d) or placebo for 1 week, starting at 2 weeks of age.
- Airway specimens analyzed for surfactant components, surface activity, and inflammatory mediators using the urea method.
Main Results:
- DEX treatment significantly decreased nonsedimentable protein in epithelial lining fluid within 3 days (p < 0.05).
- Nonsedimentable protein from placebo-treated infants inhibited surfactant surface activity more than that from DEX-treated infants (p < 0.05).
- DEX transiently increased surfactant protein-A but did not affect other measured parameters.
Conclusions:
- Acute beneficial effects of DEX in preterm infants may be partly due to reduced nonsedimentable protein concentration.
- DEX treatment appears to decrease the inhibitory capacity of airway proteins on surfactant surface activity.
- Further research is needed to fully elucidate the long-term effects and mechanisms.
Abstract:
The mechanisms explaining the beneficial effects of glucocorticoid in ventilator-dependent preterm infants are not known. In the present randomized trial, we evaluated the hypothesis that dexamethasone (DEX) treatment of small, preterm infants at risk for chronic lung disease favorably affects the surfactant system. Twenty-three ventilator-dependent infants, with a mean +/- SD gestational age of 26 +/- 2 wk and a mean birth weight of 836 +/- 173 g, received 1 wk of treatment with either DEX (dose 0.5 mg/kg/d) or placebo beginning at 2 wk of age. The airway specimens were analyzed for surfactant components, surface activity, surfactant inhibitors, and inflammatory mediators. The concentrations of these parameters in epithelial lining fluid were calculated using the urea method. DEX treatment decreased the concentration of nonsedimentable protein in epithelial lining fluid within 3 d (p < 0.05). The nonsedimentable fraction of airway specimens decreased the surface activity of surfactant as a function of protein concentration. At a constant protein concentration, the protein from placebo-treated infants inhibited the surface activity of human surfactant in vitro more than protein from DEX-treated infants (p < 0.05). DEX transiently increased the concentration of surfactant protein-A in epithelial lining fluid but had no effect on surface activity of the sedimentable surfactant complex or on concentrations of phosphatidylcholine, IL-1 beta, lactoferrin, or myeloperoxidase. We conclude that the acute beneficial effect of DEX treatment in preterm ventilator-dependent infants may in part be mediated through a decrease in the concentration of non-sedimentable protein and a decrease in the capacity of this protein to inhibit surface activity.