Surfactant-secreted phospholipase A2 interaction and respiratory outcome in preterm neonates

Secreted phospholipase A2 hydrolyses surfactant phospholipids and is crucial for the inflammatory cascade; preterm neonates are treated with exogenous surfactant but the interaction between surfactant and phospholipase is unknown. We hypothesize that this interplay is complex and the enzyme plays a relevant role in neonates needing surfactant replacement. We aimed to: 1) identify phospholipases A2 isoforms expressed in preterm lung; 2) study the enzyme role on surfactant re-treatment and function and the effect of exogenous surfactant on the enzyme system; 3) verify if phospholipase A2 is linked to respiratory outcomes. In bronchoalveolar lavages of preterm neonates, we measured enzyme activity (alone or with inhibitors), enzyme subtypes, surfactant protein-A and inflammatory mediators. Surfactant function and phospholipid profile were also tested. Urea ratio was used to obtain epithelial lining fluid concentrations. Follow-up data were prospectively collected. Subtype-IIA is the main phospholipase isoform in preterm lung, although subtype-IB may be significantly expressed. Neonates needing surfactant retreatment have higher enzyme activity (p=0.021) and inflammatory mediators (palways£0.001), and lower amounts of phospholipids (p always<0.05). Enzyme activity was inversely correlated to surfactant adsorption (r=-0.6; p=0.008;adjusted p=0.009), total phospholipids (r=-0.475; p=0.05) and phosphatidylcholine (r=-0.622;p=0.017). Exogenous surfactant significantly reduced global phospholipase activity (p<0.001), subtype -IIA (p=0.005), and increased dioleoylphosphatidylglycerol (p<0.001) and surfactant adsorption (p<0.001). Enzyme activity correlated with duration of ventilation (r=0.679, p=0.005; adjusted p=0.04), respiratory morbidity score at 12 months postnatal age (t-b=0.349, p=0.037; adjusted p=0.043), but was not associated with mortality, bronchopulmonary dysplasia or other long-term respiratory outcomes.