0618. Current thoughts on aetiology and prevention of bronchopulmonary dysplasia (BPD)

In a recent seminar on BPD there is an excellent outline of the important role of inflammatory mediators in the pathogenesis of this condition. Oxygen toxicity, barotrauma or volutrauma induce an inflammatory reaction which persists in infants who develop BPD. Pro-inflammatory cytokines (interleukins IL-1beta, IL-6 and soluble ICAM-1) are present in lung lavage fluid from day 1 in premature infants with respiratory distress and reach a peak in the second week. IL-1beta induces the release of inflammatory mediators, activating inflammatory cells and upregulating adhesion molecules on endothelial cells. ICAM-1 is a glycoprotein, promoting cell-to-cell contact. Direct contact between activated cells leads to further production of proinflammatory cytokines and other mediators. Alpha chemokine IL-8 is released, inducing neutrophil chemotaxis; the activated neutrophils mediate endothelial cytotoxicity, inhibit surfactant synthesis and release elastase. The levels of collagenase and phospholipase A2 are also raised and oxidative modification results in inactivation of alpha-1-antiprotease, further compromising the protease-antiprotease imbalance. The inflammatory infiltration is associated with loss of endothelial basement membrane and interstitial sulphated glycoaminoglycans, which are important in inhibiting fibrosis. TNF-activity increases late, peak levels are between 14 and 28 days. TNF-alpha and IL-6 induce fibroblast and collagen production. Leukotrienes are present in high levels in the lungs of infants developing BPD, and remain raised in BPD infants even at 6 months of age. Leukotrienes cause broncho-constriction, vasoconstriction, oedema, neutrophil chemotaxis, and mucus production. Given this inflammatory background it is perhaps a little surprising that the section on emerging preventive treatments focuses on prophylactic use of anti-oxidants (recombinant human CuZn superoxide dismutase) and inhaled nitric oxide. Also worthy of note is a comment that prenatal anti-oxidants via maternal administration of vitamins C and E should be beneficial. In fact a recent large scale study has shown a higher rate of LBW infants in supplemented mothers, and the authors advise against such supplementation.

Read more:
Lancet 2006; 367: 1421-31
Lancet 2006; 367: 1145-54
J Appl Physiol 1993; 74: 2234-41
Pediatrics 2003; 111: 469-76