15 Oct Study Evaluates Inhaled Steroids To Prevent Lung Dysplasia in Preterm Infants
Medical Research: What is the background for this study? What are the main findings?
Response: The lungs of preterm infants are very vulnerable and these infants frequently develop chronic lung disease, also called bronchopulmonary dysplasia (BPD). BPD is not only a problem of the lungs, it is also a major cause of early death in these infants and if they survive, their risks of respiratory problems in later life and neurodevelopmental impairment are increased when compared to infants without bronchopulmonary dysplasia. Few drugs are available to prevent or to treat BPD and up to this date, no licensed drug for this indication is on the market, neither in Europe nor the USA. Hence additional preventive strategies are needed to reduce the risk of BPD and inhaled glucocorticoids seemed to have a favorable benefit-risk ratio.
Medical Research: What are the main findings?
Response: A total of 863 preterm infants with a gestational age of less than 28 weeks from 40 study centers in 9 countries (8 European countries and Israel) participated in the Neonatal European Study of Inhaled Steroids (NEUROSIS). The study investigated whether inhaled budesonide, an anti-inflammatory glucocorticoid, would decrease the incidence of bronchopulmonary dysplasia and death in preterm infants. The results show for the first time that inhaled budesonide reduces the incidence of BPD in preterm infants, a finding that is statistically significant. However, in absolute numbers, more infants died during the study period in the budesonide group compared to the placebo group. This difference is not statistically significant and could be caused by chance. Budesonide had a statistically significant positive effect on two more prespecified secondary outcomes: it reduced the rate of infants requiring intubation after completion of study treatment and the frequency of surgery required to close a patent ductus arteriosus, a blood vessel connecting the pulmonary artery to the aorta. The rate of side effects was similar in the budesonide and in the placebo group.
Medical Research: What should clinicians and patients take away from your report?
Response: The results of NEUROSIS are important when considering the widespread routine use of inhaled glucocorticoids in clinical practice in neonatal units in Europe and North America (up to 46%) and the fact that little was known about the benefits and risks of this intervention before. The mortality findings are unexpected and make the interpretation of the statistically significant study results, which are all in favor of budesonide, more complicated. At this juncture, inhaled budesonide should probably not be used routinely for the prevention of bronchopulmonary dysplasia. Whether inhaled budesonide should become part of the clinical routine for the prevention of BPD in preterm infants at a later date is unclear and depends among other things on long-term follow-up data.
Medical Research: What recommendations do you have for future research as a result of this study?
Response: Pooling of all appropriate study data in systematic reviews and meta-analyses will offer the likelihood of useful practical information for practitioners considering the role of inhaled steroids for preterm infants at risk for BPD and will reveal important information about the association between budesonide and mortality. Information on short-term outcomes is insufficient to assess the overall efficacy of inhaled glucocorticoids and its associated risks and therefore long-term neurodevelopmental outcomes need to be addressed. According to the NEUROSIS protocol, study infants will be seen again for follow-up at 18-22 months corrected age.
October 15, 2015DOI: 10.1056/NEJMoa1501917
Prof. Dr. Dirk Bassler, MSc (2015). Study Evaluates Inhaled Steroids To Prevent Lung Dysplasia in Preterm Infants