Clinical Bronchopulmonary Dysplasia Research Articles

Deregulation of the lysyl hydroxylase matrix cross-linking system in experimental and clinical bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a common and serious complication of premature birth, characterized by a pronounced arrest of alveolar development. The underlying pathophysiological mechanisms are poorly understood although perturbations to the maturation and remodeling of the extracellular matrix (ECM) are emerging as candidate disease pathomechanisms. In this study, the expression and regulation of three members of the lysyl hydroxylase family of ECM remodeling enzymes (Plod1, Plod2, and Plod3) in clinical BPD, as well as in an experimental animal model of BPD, were addressed. All three enzymes were localized to the septal walls in developing mouse lungs, with Plod1 also expressed in the vessel walls of the developing lung and Plod3 expressed uniquely at the base of developing septa. The expression of plod1, plod2, and plod3 was upregulated in the lungs of mouse pups exposed to 85% O2, an experimental animal model of BPD. Transforming growth factor (TGF)-β increased plod2 mRNA levels and activated the plod2 promoter in vitro in lung epithelial cells and in lung fibroblasts. Using in vivo neutralization of TGF-β signaling in the experimental animal model of BPD, TGF-β was identified as the regulator of aberrant plod2 expression. PLOD2 mRNA expression was also elevated in human neonates who died with BPD or at risk for BPD, compared with neonates matched for gestational age at birth or chronological age at death. These data point to potential roles for lysyl hydroxylases in normal lung development, as well as in perturbed late lung development associated with BPD.

Nasal intermittent positive pressure ventilation after surfactant treatment for respiratory distress syndrome in preterm infants <30 weeks’ gestation: a randomized, controlled trial

To compare the effect of early extubation to nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) on the need for mechanical ventilation via endotracheal tube (MVET) at 7 days of age in preterm infants <30 weeks' gestation requiring intubation and surfactant for respiratory distress syndrome (RDS) within 60 min of delivery. Multicenter, randomized, controlled trial. A total of 57 infants were randomized within 120 min of birth to NCPAP (BW 1099 g and GA 27.8 weeks) and 53 infants to NIPPV (BW 1052 g, and GA 27.8 weeks). Infants were stabilized on NCPAP at birth and were given poractant alfa combined with MVET within 60 min of age. When stabilized on MVET, they were extubated within the next hours or days to NCPAP or NIPPV. A total of 42% [corrected] of infants needed MVET at 7 days of age in the NCPAP group compared with 17% in the NIPPV group (OR: 3.6; 95% CI: 1.5, 8.7). Days on MVET were 12 ± 11 days in NCPAP group compared with 7.5 ± 12 days in the NIPPV group (median 1 vs 7 days; P=0.006). Clinical bronchopulmonary dysplasia (BPD) was 39% in the NCPAP group compared to 21% in the NIPPV group (OR: 2.4; 95% CI: 1.02, 5.6). Physiological BPD was 46% in the NCPAP group compared with 11% in the NIPPV group (OR: 6.6, 95% CI: 2.4, 17.8; P=0.001). There were no differences in any other outcomes between the two groups. NIPPV compared with NCPAP reduced the need for MVET in the first week, duration of MVET, and clinical as well as physiological BPD in preterm infants receiving early surfactant for RDS.

1677 USE OF HIGH FREQUENCY POSITIVE PRESSURE VENTILATION (HFPPV) IN CHRONIC VENTILATORY FAILURE IN NEONATES

HFPPV (ventilator rates 100-150/minute; I.E. ratio 1:2) was used in 4 infants of gestational ages 26-29 weeks, birth weight 700-1000 gms. Age at commencing HFPPV was 25-90 days. All were on mechanical ventilation with radiological and clinical broncho-pulmonary dysplasia. The Baby Bird ventilator was used. Duration of HFPPV 3-4 weeks.3 infants were successfully weaned off ventilators. The fourth infant who had mechanical ventilation discontinued had no evidence of pulmonary barotrauma on autopsy. HFPPV can be used with success in chronic ventilatory failure in neonates.