Bronchopulmonary dysplasia (BPD) is considered one of the major complications of preterm birth (Farstad 2011; Jobe 2001). Bronchopulmonary dysplasia develops as a consequence of impaired lung development, exacerbated by the imbalance between pro‐inflammatory stimuli and anti‐inflammatory defense mechanisms typical of the preterm infant (Jobe 2001; Speer 2006).
The definition of BPD has been evolving since its first description as 28 days of oxygen exposure with characteristic radiographic changes (NIH 1979). Subsequently, oxygen dependency at 36 weeks’ postmenstrual age was shown to better predict long‐term respiratory outcomes (Shennan 1988). The current definition of BPD stratifies infants below 32 weeks requiring supplemental oxygen for at least 28 days into three severity groups (mild, moderate, and severe), depending on the presence and the amount of supplemental oxygen and the mode of respiratory support at 36 weeks’ postmenstrual age (Ehrenkranz 2005; Jobe 2001). The ‘physiologic’ definition of BPD was proposed in an attempt to address the significant intercenter variability in oxygen administration (Lapcharoensap 2015). At 36 weeks’ postmenstrual age, infants receiving less than 30% supplemental oxygen are challenged by reducing the fraction of administered oxygen during a standardized test. Infants who are unable to maintain saturations above 90% during the test are diagnosed with BPD (Walsh 2003). The incidence of BPD varies depending on the definition, complicating the course of up to 40% of the infants born between 22 and 28 weeks’ gestation (Stoll 2010). It must be noted that, although by definition BPD cannot be diagnosed before 28 days of life, a respiratory disease defined as oxygen and/or ventilator‐dependency from 7 to 28 days of life represents the initial phase of the chronic process leading to BPD, thus classified as “evolving BPD” (Walsh 2006). Infants suffering from BPD are at increased risk of death and long‐term pulmonary and neurodevelopmental morbidities (Anderson 2006; Bhandari 2006). Several treatments have been used in an attempt to prevent or treat BPD. Unfortunately, even the most promising strategies have not been able to confirm the initial enthusiasm in robust randomised controlled trials (RCTs). A recent meta‐analysis combining all the available pharmacological options to prevent BPD found that only five out of the 21 drugs tested (vitamin A, caffeine citrate, dexamethasone, inositol, and clarithromycin) in RCTs may reduce the incidence of BPD. Among these, meta‐analysis could confirm the data only for vitamin A and dexamethasone, due to the lack of multiple trials for the other drugs (Beam 2014). Moreover, vitamin A showed only a very modest effect (Darlow 2011), while the use of dexamethasone is limited in preterm infants by its well‐known long‐ and short‐term side effects (Watterberg 2010). Despite the continuous advance of neonatal care, BPD remains a significant burden for the preterm population, lacking a safe and effective treatment.
