Novel concepts of treating vascular inflammation underlying neonatal lung diseases.

Abstract

Bronchopulmonary dysplasia (BPD) is the most common sequela of prematurity. While multifactorial in aetiology, there is increasing evidence that fetal growth restriction (FGR) and antenatal exposure of the fetus to inflammation play important roles in the postnatal pathophysiology of BPD. Recent studies have focussed on disrupted angiogenesis and its influence on alveolarization. While there are multiple mechanistic links, inflammation is known to be a key driver of this disruption, affecting pulmonary arterial circulation. Although postnatal corticosteroids are commonly used in extremely premature infants to treat inflammation, aimed at obviating the need for intubation and mechanical ventilation or to facilitate extubation, the use of dexamethasone has not reduced the incidence of BPD. Here, we summarize current knowledge on alternative anti-inflammatory treatment options, which have shown promising outcomes either pre-clinically or clinically. These include supplementation with vitamin C and E (antioxidants), ω-3 poly-unsaturated fatty acids, pentoxifylline, anti-inflammatory cytokines of the IL (interleukin)-1 family, namely IL-1 receptor antagonist and IL-37, and the beneficial properties of breast milk. Evaluating these alternative treatments, either individually or as combination therapies in randomized controlled trials stands to immensely benefit the clinical outlook, particularly regarding BPD, for extremely premature infants.