The need for SPeeD: can acute surfactant protein D administration reduce ventilator-induced inflammation?

Endogenous surfactant deficiency is a hallmark of preterm birth and the primary driver of respiratory distress syndrome (RDS). 1 The development of exogenous surfactants in the 1980s led to a transformational increase in survival rates for infants born preterm. However, despite exogenous surfactant therapy being effective at reducing the acute severity of RDS, rates of bronchopulmonary dysplasia (BPD), the chronic lung disease consequence of preterm RDS, remain unchanged. 2 Endogenous surfactant is comprised primarily of phospholipids and surfactant proteins (A, B, C, D). 1 No commercially available animal-derived or synthetic formulas have successfully included all four proteins in their formulations, with animal-derived products containing only surface tension-reducing hydrophobic surfactant proteins B and C due to the purification process, and synthetic formulas including combinations of recombinant surfactant proteins A, B, C, or D, but never all four. 3 Animal-derived preparations remain the most commonly used surfactants as they are considered superior to synthetic formulations containing recombinants. Despite this, they lack the host defence immune-related functions that the hydrophilic surfactant proteins A and D perform. 4 Given that rates of BPD remain persistently high, it may be time to revisit the potential of recombinant surfactant proteins in exogenous surfactant therapy as a disease-modifying approach beyond mitigating acute respiratory distress.