Inhalation or Instillation of Steroids for the Prevention of Bronchopulmonary Dysplasia

Abstract

Survival of extremely preterm infants has increased over recent years, but bronchopulmonary dysplasia (BPD) remains a major cause of morbidity. In the USA, BPD is the most common chronic respiratory disorder of infancy and affects the pulmonary and overall health of 10,000 preterm infants annually [1]. Preclinical and clinical studies suggest a crucial role for lung inflammation and host immune response in the pathogenesis of BPD [2]. Inflammation may result from, amongst others, chorioamnionitis, postnatal infection, ventilation, and the administration of oxygen [2]. Infants with BPD have worse long-term outcomes than those without chronic lung disease. They are more than twice as likely to be readmitted to hospital in their first year of life and, having survived their primary hospitalizations, they are more likely to die than very preterm infants without chronic lung disease [3,4]. Survivors with BPD have an increased risk of neurodevelopmental impairment [5] and their respiratory function remains compromised well into adolescence [6,7]. As the first generations of extremely low birth weight (ELBW) survivors have not yet reached retirement age, there are currently no reliable data addressing the association between BPD and pulmonary diseases of the elderly such as chronic obstructive pulmonary disease. Although BPD is quite common in ELBW infants, there are infants who do not develop BPD, which supports the argument that BPD is a preventable disease, emphasizing the need for high-quality safety and efficacy prevention studies. However, according to an Institute of Medicine statement regarding pediatric drug studies, the therapeutic area that has the fewest drugs indicated for neonates is BPD [8]. As inflammation seems to be a primary mediator of injury in the pathogenesis of BPD, anti-inflammatory agents such as steroids have long been the focus of preventive research activities. However, systemic steroids, although reducing BPD, have frequently been linked to adverse neurodevelopmental outcomes and these considerations may have contributed to the recently reported widespread use of inhaled corticosteroids in neonatal units in North America and Europe. Inhaled corticosteroids were prescribed to 25% of infants born at <29 weeks of gestation with birth weights <1,500 g in neonatal units of 35 children's hospitals in the USA [9]. According to a survey across all neonatal units in Germany, 46% administered inhaled corticosteroids to preterm infants either as prophylaxis or treatment for BPD [10]. Pediatricians and neonatologists should ask themselves whether the off-label use of inhaled corticosteroids in preterm infants is justifiable in view of the available evidence. The authors of the pertinent review from the Cochrane Collaboration, including 7 studies and 492 infants, conclude that there is currently no evidence to support the routine use of inhaled steroids for the prevention of BPD [11]. Recently, the primary outcome results of the Neonatal European Study of Inhaled Steroids (NEUROSIS), including 863 very ...

Caffeine modulates glucocorticoid-induced expression of CTGF in lung epithelial cells and fibroblasts

“…If glucocorticoids may have adverse effects on airway remodeling processes via modification of pulmonary CTGF expression in vivo has yet to be defined. Although a short-term benefit of glucocorticoid treatment in severe forms of BPD has been sufficiently documented [64], concerns regarding significant unfavorable effects, including adverse neurological outcome, remain [65, 66]. Our data may add additional concerns in terms of glucocorticoid-related long-term impairments [34].…”

Early inhaled steroid use in extremely low birthweight infants: a randomised controlled trial

“…However, steroid use is also associated with serious short-term adverse effects and may increase the risk of neurodevelopmental impairment (NDI) 2. Inhaled steroids are expected to efficiently and directly affect the lungs but to produce low rates of systematic adverse effects 3. However, no evidence has yet been published to support the efficacy of inhaled steroids with respect to preventing or decreasing the severity of BPD 4 5.…”

Update on Postnatal Steroids

“…In another recent study in piglets treatment with diluted surfactant lavage followed by intratracheal instillation of budesonide had a synergistic and beneficial effect on severe meconium-injured newborn lungs [31]. In future there may be a role for steroid/surfactant mixtures in the prevention of BPD and management of other severe neonatal lung disorders [32]. …”