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

Abstract

ABSTRACT:The role of corticosteroid in severe bronchopulmonary dyplasia (BPD) is still debated. Scanty data are available on the corticosteroids effect on surfactant metabolism. Our objective was to compare surfactant kinetics in preterm infants with developing BPD, before and after dexamethasone (DEXA) treatment. Twenty-eight studies were performed in 14 preterm infants (birth weight 786 Ϯ 192 g, gestational age 26 Ϯ 1 wk) on high ventilatory setting, before (age 22 Ϯ 11 d) and after (age 33 Ϯ 11 d) DEXA.13 C-labeled dipalmitoyl-phosphatidylcholine (DPPC) was administered endotrachelly to trace pulmonary surfactant. Surfactant disaturatedphosphatidylcholine (DSPC) kinetics and pools were calculated from DSPC 13 C-enrichment curves of serial tracheal aspirates and bicompartmental analysis. Total protein and myeloperoxidase (MPO) activity in tracheal aspirates were also measured and expressed per ml of Epithelial Lining Fluid (ELF). After DEXA, DSPC alveolar pool increased significantly from 8.2 Ϯ 7.6 to 10.6 Ϯ 11.3 mg/kg (p ϭ 0.039), total proteins and MPO were reduced from 8.8 Ϯ 8.6 to 3.1 Ϯ 2.1 mg/ml ELF (p ϭ 0.046) and from 1822 Ϯ 1224 to 1261 Ϯ 987 mU/mlELF (p ϭ 0.028) respectively. In conclusion, DEXA treatment in mechanically ventilated preterm infants with severe respiratory failure and at high risk of developing BPD, significantly reduced inflammatory markers and increased alveolar surfactant DSPC pool. (Pediatr Res 63: 433-437, 2008) B ronchopulmonary dysplasia (BPD) remains the most common respiratory complication of very preterm infants. Its pathogenesis recognizes multiple factors, such as prenatal infection, lung immaturity, volutrauma and barotrauma, oxygen toxicity, lung edema and airway inflammation, which probably act additively or synergistically to promote lung injury. Primary or secondary inflammatory reaction leads to an amplification of lung insult, interferes with alveolarization and alters lung development (1,2). Reduced surfactant synthesis and/or surfactant inhibition/inactivation due to lung immaturity and to protein leak across the alveolar capillary barrier have been described in association with marked alterations of surfactant phospholipids (3-5). More recently, Ballard et al. demonstrated a reduction in surfactant specific proteins in tracheal aspirates of preterm infants with developing BPD (6).The association between lung inflammation and BPD constitutes the rationale for the use of corticosteroids as antiinflammatory drugs. Corticosteroids are potent antiinflammatory agents; they reduce polymorphonuclear cells recruitment in the lungs, inhibit the production of elastase, prostaglandins, leucotrienes, tumor necrosis factor, and interleukins, decrease vascular permeability and pulmonary edema, and increase synthesis of anti-oxidant enzymes (7). Despite the recent findings of a strong negative effect on neurodevelopment, corticosteroids are still being used for life-threatening ventilator dependent respiratory failure (8 -10). In premature rabbits, dexamethasone (DEXA) decreases p...

Pulmonary surfactant synthesis after unilateral lung injury in mice

“…To further explain these findings, we used deuterated water as metabolic precursor of DSPC to measure surfactant DSPC synthesis and secretion of the I and NI lungs, together with total lungs DSPC turnover (7,10). Below we briefly comment on the effect of DSPC metabolism on lung homogenate DSPC pools and BALF DSPC pools.…”

“…Study mice (naïve controls and HCl treated mice, n ϭ 4 per control or experimental group) received an intraperitoneal dose of 1 ml/kg 10% (v/v) of deuterated water (Cambridge Isotope Laboratories, Andover, MA) to assess DSPC-palmitate synthesis and secretion. Animals were killed at 4,8,10,12,20, and 24 h after isotope administration, corresponding to 22,26,28,30,38, and 42 h after HCl injury. The age matched naïve control animals received the intraperitoneal dose of deuterated water and were killed at 4,8,10,12,20, and 24 h after isotopes administration.…”

“…Absorbance was recorded for 4 min at 460 nm. Each sample was determined in duplicate (10). Results are expressed as units/g wet weight.…”

Surfactant protein B and A concentrations are increased in neonatal pneumonia

“…13 C-palmitate enrichment was measured by gas-chromatography-mass-spectrometry (GC-MS, 6890N-5973 inert, Agilent Technologies, Milan, Italy). Results were expressed as mole percent excess referring to a calibration curve (31,38).…”

Pathogenesis of Bronchopulmonary Dysplasia

“…However in 1998, Griese and Westerburg [95] demonstrated that the inhibition of surfactant function by proteins leaked into the airspaces did not play a major role during recovery from RDS, so they concluded that endogenous remodeling of surfactant might be of greater relevance. More recently, dexamethasone treatment not only significantly reduced inflammatory markers but also significantly increased the alveolar surfactant desaturated phosphatidylcholine pool in mechanically ventilated preterm infants with severe respiratory failure who were at high risk for developing BPD [96]. …”