Surfactant-secreted phospholipase A<sub>2</sub>interplay and respiratory outcome in preterm neonates
Danièle De Luca, Shivani Shankar‐Aguilera, Chiara Autilio, Roberto Raschetti, Luca Vedovelli, Catherine Fitting, Christine Payré, Louise Jeammet, Jesús Pérez‐Gil, Paola Cogo, Virgilio Carnielli, Gérard Lambeau, Lhousseine Touqui
Abstract
Secreted phospholipase A 2 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: 1) identify phospholipases A 2 isoforms expressed in preterm lung; 2) study the enzyme role on surfactant retreatment and function and the effect of exogenous surfactant on the enzyme system; and 3) verify whether phospholipase A 2 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 ( P always ≤ 0.001) and lower amounts of phospholipids ( P always < 0.05). Enzyme activity was inversely correlated to surfactant adsorption (ρ = −0.6; P = 0.008; adjusted P = 0.009), total phospholipids (ρ = −0.475; P = 0.05), and phosphatidylcholine (ρ = −0.622; P = 0.017). Exogenous surfactant significantly reduced global phospholipase activity ( P < 0.001) and subtype-IIA ( P = 0.005) and increased dioleoylphosphatidylglycerol ( P < 0.001) and surfactant adsorption ( P < 0.001). Enzyme activity correlated with duration of ventilation (ρ = 0.679, P = 0.005; adjusted P = 0.04) and respiratory morbidity score at 12 mo postnatal age (τ -b = 0.349, P = 0.037; adjusted P = 0.043) but was not associated with mortality, bronchopulmonary dysplasia, or other long-term respiratory outcomes.