This study compared intratracheal surfactant and budesonide to surfactant alone for prevention of BPD in extreme preterm infants admitted to a tertiary level neonatal ICU. This is the first prospective, randomized, controlled superiority pilot trial conducted in an Indian population. Although there was a trend towards fewer deaths, combined death and BPD in the intervention group, there was no statistically significant difference between the two groups.
The use of intratracheal budesonide with surfactant provides direct anti-inflammatory actions at the target location, avoiding the inflammatory cascade and BPD. The use of intratracheal steroids to prevent BPD has been studied by Yeh et al., Pan et al., and Minji Heo et al. [8,15-17]. Previous studies by Yeh et al and pan et al used bovine surfactants [8,15,16] and calf surfactant was used by Minji et al.  This study used a porcine surfactant (Curosurf) because it is feasible, requires less volume than other surfactants, is mixable (after mixing with budesonide, the mixture looks like a surfactant alone with no crystallization or discoloration), and has not been studied previously. Previous studies [8,15-17] studied VLBW babies. In this study we included only ELBW infants, the most vulnerable group with high incidence of BPD.
Unlike previous studies, which found that the intervention group had a lower incidence of BPD than the control group, in the current study, intervention group had a slightly greater incidence of BPD. One explanation is that the control group had more deaths, including neonates who may have had BPD if they had survived. The other two primary outcomes death and combined death or BPD were fewer in intervention group. However, these differences was not statistically significant. Heo et al.  reported similar results, however Yeh et al. [8,15] and Pan et al  found that the intervention group had a lower composite outcome of mortality or BPD than the control group.
One important observation in this study is that the combined outcome of death or severe BPD is significantly lower in the intervention group compared to the control group (RR 0.57(0.33-0.97); p=0.040), indicating that, severe morbidity and mortality related to BPD have been shown to decrease significantly with the intervention used. Yeh et al.  observed similar findings (RR 0.61[0.41-0.91]; p=0.016), however another study  found non-significant decreasing trend (RR 0.18(0.02-1.39); p=0.102). If comparable findings can be replicated in larger, multicentric trials, this easily accessible and low-cost intervention might be put into common clinical practice. This technique has the potential to change lung damage and result in considerable respiratory and overall health benefits.
The current study's total incidence of BPD, combined death or BPD were higher as compared to previous studies because our study population was more premature and smaller ( <28 weeks and ELBW) than previously studied ( <32 weeks and VLBW ) neonates. [8,15-17] Despite the high prevalence of BPD in the current study population, only two newborns in the control group were discharged with home oxygen, and the prevalence of ROP ³ stage 2 was minimal (10%).
The mechanism of action of budesonide is probably anti-inflammatory. Intratracheal surfactant and budesonide instillation showed immediate improvement in pulmonary status compared to systemic dexamethasone injections.  The direct local anti-inflammatory effect and the larger volume of instillation (3.5 ml/kg) in the intervention group compared to the control group may have enhanced surfactant and budesonide distribution. A prolonged effect on the lungs is implied by the fact that the intervention group required less FiO2 at 24 hours of birth, weaned to 21% FiO2 earlier, and spent less time on respiratory support (invasive and non-invasive).Our findings suggested that budesonide was effective early in therapy, which may have translated to less oxygen and respiratory support, resulting in an earlier hospital discharge in intervention group (76.5 ± 10.2 days vs 84.1 ± 12.9 days).
Corticosteroids are known to induce hyperglycemia, hypertension, and an increased risk of infection, as well as long-term effects on physical development, neuromotor, and cognitive function.  In this study, we only examined the short-term side effects of steroids and observed no differences in serum glucose, blood pressure, or culture-positive sepsis among both groups.
The intervention group had less inotrope requirement than the control group in the current study (18/54 [33.3 %] vs. 26/55 [47.2 %], p =0.172). Similar to dexamethasone, budesonide can increase cardiac stroke volume while stabilizing blood pressure. In the study of Yeh et al, the blood pressure of the intervention group was significantly higher than that of the control group on days 3–5. The later effect of budesonide on blood pressure stability may benefit newborns.
The intervention group had a lower incidence of IVH (any grade) and high-grade IVH (grade 3 &4) than the control group (12/54 [22.2%] versus 24/55 [43.6%], p = 0.24; 5/54 [9.2%] vs. 14/55 [25.4%], p = 0.041). A lower IVH may be due to fewer ventilation days, less ionotropic requirement, and less hsPDA, all contributing to a stable course during the stay. However, the present study was not powered to look for these outcomes, and other variables were not examined. A larger study population is needed to evaluate these outcomes.