Early use of Inhaled Budesonide for the Prevention of Bronchopulmonary Dysplasia

Aaron Nethercott, Mercer University College of Pharmacy

Improvements in neonatal mechanical ventilation and the use of surfactants are considered to be factors that have led to decreased rates in respiratory distress syndrome and an increase in the rates of bronchopulmonary dysplasia (BPD). It is suggested that BPD is most common among neonates that are born before gestational week 32. The last weeks of fetal development are considered critical for lung development, and therefore it is theorized that in extremely low birth weight infants, there is a complex interaction between lung development, lung injury, and lung repair which may cause BPD. [1]

It has been shown that infants with BPD are at a greater risk of alternated lung function in adulthood and that BPD causes a decrease in alveolar counts and enlarged alveoli. These defects are speculated to increase the rates of asthma and chronic obstructive pulmonary disease in all stages of life. [2]

Table 1

Early Inhaled Budesonide for the Prevention of Bronchopulmonary Dysplasia [3]
Design Multinational randomized trial (N = 863)
Objective To test the hypothesis that in preterm infants born before 28 weeks of gestation and inhaled budesonide within 24 hours after birth would decrease the incidence of bronchopulmonary dysplasia and death at 36 weeks of postmenstrual age
Study Groups There were 441 infants randomized into the budesonide group and 422 infants randomized into the placebo group.
Methods Infants received either inhaled budesonide or placebo. Inhalation of two puffs were administered every 12 hours for the first 14 days and then once daily until the last dose was given. This was done until death, oxygen supply no longer needed, or until the infant reached a postmenstrual age of 32 weeks.
Duration Unknown
Primary Outcome Measure The primary outcome was death or bronchopulmonary dysplasia at 36 weeks.

Bronchopulmonary dysplasia was defined as the need for positive pressure supplemental oxygen exceeding a fraction of 0.3 inspired oxygen.

Baseline Characteristics Budesonide group Placebo group
Gestational Age (wk) 26.1±1.3 26.1±1.2
Birth weight (g) 798±193 803±1.2
Supplemental oxygen 212 (48.5%) 193 (46.15)
Results In the budesonide group tree patients did not receive the study drug and four patients were lost to follow up (n = 437). In the placebo group, three patients were lost to follow up (n = 419).
Outcome Budesonide Placebo P value
Composite primary 175/437 (40%) 194/419 (46%) 0.05
Death 74/437 (16.9%) 57/419 (13.6%) 0.17
Survival with bronchopulmonary dysplasia 101/363 (27.8%) 138/363 (38.0%) 0.004
Adverse Events Common Adverse Events:
Budesonide Placebo P value
Brain injury 91/428 (21.3%) 70/410 (17.1%) 0.12
Necrotizing enterocolitis or intestinal perforation 51 (11.7%) 44 (10.5%) 0.58
Sepsis 148 (33.9%) 125 (29.8%) 0.20
Serious Adverse Events: Patients in the placebo group where at a higher risk for surgical ligation of patient ductus arteriosus at 12.9% (n = 54) compared to the budesonide group at 7.1% (n = 31) (p = 0.004)
Percentage that Discontinued due to Adverse Events: not applicable
Study Author Conclusions A beneficial effect of budesonide on the risk of bronchopulmonary dysplasia, as well as a possible increase in mortality associated with its use.

The study found mixed results with its primary endpoints. Budesonide did not have any effect on mortality, but did have a significant reduction of BPD when compared to placebo. Because the mortality rates where not statistically significant, it is difficult to tell if the early use of budesonide was effective in the treatment of BDP. A follow up study is planned to find any long term effects of BDP between the budesonide group and the placebo group.


  1. Jobe AH. What is BPD in 2012 and what will BPD become?. Early Hum Dev. 2012;88 Suppl 2:S27-8.
  2. Islam JY, Keller RL, Aschner JL, Hartert TV, Moore PE. Understanding the Short- and Long-Term Respiratory Outcomes of Prematurity and Bronchopulmonary Dysplasia. Am J Respir Crit Care Med. 2015;192(2):134-56.
  3. Bassler D, Plavka R, Shinwell ES, et al. Early Inhaled Budesonide for the Prevention of Bronchopulmonary Dysplasia. N Engl J Med. 2015;373(16):1497-506.

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