Nonventilatory strategies for prevention and treatment of BPD

Despite improvements in neonatal and perinatal medicine, the incidence of bronchopulmonary dysplasia (BPD) has not been substantially reduced. Noteworthy, even if our knowledge of BPD pathogenesis have expanded extensively in the latest years, most therapeutic strategies currently in use to prevent or treat BPD are still not based on experimental and clinical evidences.
Oxygen has been the most commonly used therapy in neonatal intensive care units for the last decades. This therapy may cause tissue injury through the formation of free radicals, thus playing an important role in the pathogenesis of BPD. However, there is no consensus about the levels of oxygen saturation at which extremely premature infants should be targeted. This gap in knowledge will hopefully be closed by a number of ongoing or prospective trials addressing this issue. Hopefully, theses studies will provide new insights about the optimal oxygen saturation range for infants at highest risk to develop BPD.
Inhaled nitric oxide (iNO) acts as a selective pulmonary vasodilator. Several clinical trials have been conducted to evaluate the possible role of iNO in the prevention of BPD. However, there are still no certain evidences, and the optimal dose and timing of iNO therapy is still unclear. Another therapeutic approach may be based on the early administration of methylxanthines, and caffeine in particular. At present, there is sufficient evidence for their efficacy in the treatment of BPD, but further results are required before providing general recommendations. Last, it has been suggested that high intramuscular doses of vitamin A could slightly reduce the incidence of BPD.
A prophylactic or early application of surfactant may also be beneficial in the treatment of BPD, as suggested by several randomized trials and by some meta-analyses. In particular, a meta-analysis of three European trials enrolling 671 preterm infants treated prophylactically with the natural porcine surfactant preparation poractant-alfa demonstrated a reduction in the severity of respiratory distress syndrome, mortality, and the incidence of BPD at 28 days in survivors. A systematic review of eight trials evaluating prophylactic versus rescue treatment with surfactant revealed that a reduction of death and BPD on day 28 was associated with prophylactic treatment. In another study, early (within the first two hours) selective surfactant treatment of respiratory distress syndrome reduced the incidence of moderate to severe BPD and mortality, when compared to late  treatment. These data advocate the prophylactic or early administration of surfactant in infants at high risk of BPD.
In conclusion, BPD is still a major challenge in modern neonatology. Most of the strategies used to prevent or ameliorate the disease are not evidence-based. Currently, only few treatments have some evidence supporting their use in the treatment of BPD. However, since BPD is a multifactorial disease, it is unlikely that one single agent could be identified as a decisive tool to prevent or treat the disease. Instead, multimodal approaches will be necessary to decrease the incidence and severity of BPD, as suggested by recently published retrospective data. Further studies are required to find an ideal combination of pre- and postnatal, evidence-based strategies to prevent or ameliorate BPD.

Top