Dexamethasone Treatment of Infants at Risk for Chronic Lung Disease: Surfactant Components and Inflammatory Parameters in Airway Specimens

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 ventilatordependent infants, with a mean +. SD gestational age of 26 ? 2 wk and a mean birth weight of 836 4 173 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 DEXtreated 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-1P, 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 nonsedimentable protein and a decrease in the capacity of this protein to inhibit surface activity. (Pediatr Res 36: 387-393, 1994) Abbreviations AS, airway specimen CLD, chronic lung disease DEX, dexamethasone ELF, epithelial lining fluid LF, lactoferrin MPO, myeloperoxidase PC, phosphatidylcholine PL, placebo SP-A, surfactant protein-A SPC, disaturated phosphatidylcholine Despite improved survival, many preterm infants fail to recover from the acute lung injury and develop CLD. In addition to immaturity, factors contributing to the development of CLD include barotrauma, oxygen toxicity, and inflammation (1, 2). The significance of the various suggested pathogenetic mechanisms is unclear.DEX therapy decreases the requirement of respiratory support and improves pulmonary mechanics in ventilator-dependent preterm infants (3-6). In several controlled trials on ventilator-dependent very-low-birth-weight infants, DEX therapy has improved the short-term pulmonary outcome, decreasing the duration of mechanical ventilation, but not the long-term outcome (7-11). Many potential mechanisms for the acute effect of DEX have been proposed. These include an increase in surfactant synthesis (12, 13) and in activity of antioxidant enzymes (14) shown after prenatal glucocorticoid therapy in fetal animals, and reduction of pulmonary edema, lung water, and alveolar epithelial permeability shown in preterm...

Dexamethasone Therapy in Preterm Infants Developing Bronchopulmonary Dysplasia: Effect on Pulmonary Surfactant Disaturated-Phosphatidylcholine Kinetics

“…We also showed a reduced total protein content and a reduced MPO activity in tracheal aspirates, confirming previous findings in preterm infants with chronic lung disease (12)(13)(14)16,18).…”

“…In preterm newborns with BPD, Kari et al showed that DEXA significantly decreased the nonsedimentable protein in epithelial lining fluid, whereas it did not affect the concentration of surfactant phosphatidycholine, 1L-1 〉 and lactoferrin (18). No data are available on the effect of corticosteroids on surfactant kinetics in human BPD.…”

The Pulmonary Surfactant System: Biochemical and Clinical Aspects

“…The effect is a decrease of morbidity [159], in spite of a brief period of suppression of the basal corticoid concentration. Postnatal glucocorticoid therapy shows no clear evidence of long term benefits [160]. However, the combined use of corticosteroids with surfactant improved the outcome of therapy compared with the use of surfactant alone [147].…”

The Effects of Corticosteroid on Tissue Lactoferrin in Patients with Nasal Polyposis

“…14 Kari et al found no change in LF levels in ventilator-dependent infants, despite the increase in surfactant A in bronchial epithelium surface liquid as a result of dexamethasone application. 15 Although it might be considered that LF levels must be decreased by CSs, which is one of the main inhibitors of the immune system, common results of all these reported studies suggest that CSs exert no inhibitory effect on the innate immune system while 16 In this study, no effect of CS treatment was noted on tissue LF levels in patients with NP, even though there was a significant reduction in NP in response to CS treatment, as indicated by endoscopic and radiological findings. This study indicates that CS treatment may exert its beneficial clinical effect on NP by other mechanisms rather than via altering tissue LF levels.…”