Early Inhaled Budesonide for the Prevention of Bronchopulmonary Dysplasia

Abstract

BACKGROUND Systemic glucocorticoids reduce the incidence of bronchopulmonary dysplasia among extremely preterm infants, but they may compromise brain development. The effects of inhaled glucocorticoids on outcomes in these infants are unclear. METHODS We randomly assigned 863 infants (gestational age, 23 weeks 0 days to 27 weeks 6 days) to early (within 24 hours after birth) inhaled budesonide or placebo until they no longer required oxygen and positive-pressure support or until they reached a postmenstrual age of 32 weeks 0 days. The primary outcome was death or bronchopulmonary dysplasia, confirmed by means of standardized oxygen-saturation monitoring, at a postmenstrual age of 36 weeks. RESULTS A total of 175 of 437 infants assigned to budesonide for whom adequate data were available (40.0%), as compared with 194 of 419 infants assigned to placebo for whom adequate data were available (46.3%), died or had bronchopulmonary dysplasia (relative risk, stratified according to gestational age, 0.86; 95% confidence interval [CI], 0.75 to 1.00; P=0.05). The incidence of bronchopulmonary dysplasia was 27.8% in the budesonide group versus 38.0% in the placebo group (relative risk, stratified according to gestational age, 0.74; 95% CI, 0.60 to 0.91; P=0.004); death occurred in 16.9% and 13.6% of the patients, respectively (relative risk, stratified according to gestational age, 1.24; 95% CI, 0.91 to 1.69; P=0.17). The proportion of infants who required surgical closure of a patent ductus arteriosus was lower in the budesonide group than in the placebo group (relative risk, stratified according to gestational age, 0.55; 95% CI, 0.36 to 0.83; P=0.004), as was the proportion of infants who required reintubation (relative risk, stratified according to gestational age, 0.58; 95% CI, 0.35 to 0.96; P=0.03). Rates of other neonatal illnesses and adverse events were similar in the two groups. CONCLUSIONS Among extremely preterm infants, the incidence of bronchopulmonary dysplasia was lower among those who received early inhaled budesonide than among those who received placebo, but the advantage may have been gained at the expense of increased mortality. (Funded by the European Union and Chiesi Farmaceutici; ClinicalTrials.gov number, NCT01035190.).

Antiinflammatory Effects of Budesonide in Human Fetal Lung

“…Because of safety issues with systemic dexamethasone, lungtargeted alternatives to corticosteroid therapy have been explored. Administration of inhaled budesonide has generally been ineffective (6), likely because of inefficient delivery to the lung parenchyma, although a recent trial with prolonged treatment demonstrated reduced BPD occurrence (7). Pilot studies performed by Yeh and colleagues (8,9) used intratracheal instillation of budesonide suspended in surfactant to improve the delivery of budesonide to the lung periphery.…”

Advances in emerging treatment options to prevent bronchopulmonary dysplasia

“…Inhaled steroids did not reduce BPD and death, failure to extubate or the total duration of mechanical ventilation or oxygen dependency [17]. The Neonatal European Study of Inhaled Steroids (NEUROSIS) randomised trial compared the effects of inhaled budesonide to placebo administered in the first 24 hours in 863 infants born at 23 to 27 weeks gestation who required some form of positive-pressure support [18]. The intervention was delivered until the infants no longer required supplementary oxygen or positive pressure support or were a postmenstrual age (PMA) of 32 weeks.…”

“…The intervention was delivered until the infants no longer required supplementary oxygen or positive pressure support or were a postmenstrual age (PMA) of 32 weeks. Inhaled budesonide administration was associated with significant reductions in the rate of BPD, surgical closure of a patent ductus arteriosus (PDA) and reintubation , but there was a trend towards increased mortality (16.9% versus 13.6%) [18].…”

Bronchopulmonary Dysplasia: a Modern View on Course and Outcomes

“…В большом рандомизированном исследовании показано, что раннее (в течение 24 ч после рождения) интратрахе-альное введение будесонида снижает частоту БЛД у глубо-ко недоношенных новорожденных с гестационным возрас-том менее 28 нед -до 28 против 38% в группе плацебо [56]. Продемонстрировано увеличение частоты удачной экстубации при использовании ингаляторного будесонида без снижения частоты формирования БЛД [57].…”