Inhaled nitric oxide to prevent bronchopulmonary dysplasia in preterm neonates.
Bronchopulmonary dysplasia is a chronic lung disease that affects premature infants and contributes to their morbidity and mortality. With the advent of prenatal steroids and postnatal exogenous surfactant and less aggressive respiratory support, premature infants can develop chronic oxygen dependency without even acute respiratory distress. This 'new bronchopulmonary dysplasia' could be the result of impaired postnatal growth. Several experimental studies have suggested a possible role of the vascular endothelial growth factor/nitric oxide (VEGF/NO) pathway in restoring pulmonary angiogenesis and enhancing distal lung growth. The results of the clinical studies are, however, inconclusive, and it is currently unclear which subsets of premature infants might benefit from inhaled nitric oxide. Besides, severe intracranial haemorrhage and/or cystic periventricular leucomalacia may affect the most immature babies, many of whom are spared from severe initial respiratory disease. Recently, inhaled nitric oxide was shown to significantly decrease the incidence of these neurological events, and to improve the long-term outcome in a few clinical trials. At times neuroprotective, at times neurotoxic, nitric oxide is capable of divergent effects depending upon the extent of cerebral damage, the redox state of the cell, and the experimental model used. Recently, our group found that inhaled nitric oxide had remote effects including angiogenesis and maturation on the developing brain in rodent pups. Thus, we await the results of the recently completed randomised clinical trial of inhaled nitric oxide to prevent bronchopulmonary dysplasia (the European Nitric Oxide or 'EUNO' trial) where, besides the primary endpoint of chronic oxygen dependency reduction at 36 weeks' postconceptional age, long-term lung and brain will be followed-up until 7 years of age.
Mercier
Jean-Christophe
JC
Service d'Accueil des Urgences pédiatriques, Hôpital Robert Debré, Assistance Publique - Hôpitaux de Paris & Faculté de Médecine, Université Paris 7 Denis Diderot, Paris, France. jean-christophe.mercier@rdb.aphp.fr
Olivier
Paul
P
Loron
Gauthier
G
Fontaine
Romain
R
Maury
Laure
L
Baud
Olivier
O
D000280:Administration, Inhalation; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D001993:Bronchodilator Agents / Q000494:pharmacology*; D001997:Bronchopulmonary Dysplasia / Q000517:prevention & control*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008168:Lung / Q000378:metabolism; D023421:Models, Animal; D009569:Nitric Oxide / Q000494:pharmacology*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
D001993:Bronchodilator Agents; D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide