Surfactant-secreted phospholipase A interplay and respiratory outcome in preterm neonates.

Secreted phospholipase A hydrolyzes 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: ) identify phospholipases A isoforms expressed in preterm lung; ) study the enzyme role on surfactant retreatment and function and the effect of exogenous surfactant on the enzyme system; and ) verify whether phospholipase A 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 ( = 0.021) and inflammatory mediators ( always ≤ 0.001) and lower amounts of phospholipids ( always < 0.05). Enzyme activity was inversely correlated to surfactant adsorption (ρ = -0.6; = 0.008; adjusted = 0.009), total phospholipids (ρ = -0.475; = 0.05), and phosphatidylcholine (ρ = -0.622; = 0.017). Exogenous surfactant significantly reduced global phospholipase activity ( < 0.001) and subtype-IIA ( = 0.005) and increased dioleoylphosphatidylglycerol ( < 0.001) and surfactant adsorption ( < 0.001). Enzyme activity correlated with duration of ventilation (ρ = 0.679, = 0.005; adjusted = 0.04) and respiratory morbidity score at 12 mo postnatal age (τ = 0.349, = 0.037; adjusted = 0.043) but was not associated with mortality, bronchopulmonary dysplasia, or other long-term respiratory outcomes.