Animal-derived surfactants: where are we?

Animal-derived surfactants, as well as synthetic surfactants, have been extensively evaluated in the treatment of respiratory distress syndrome (RDS) in preterm infants. To date, treatment with animal-derived surfactant preparations has been shown to result in better clinical response during the acute phase of RDS as evidenced by more rapid weaning of inspired oxygen, pressure and lower air leaks when compared with treatment with synthetic preparations. Moreover, it has been demonstrated that neonatal mortality is lower among infants treated with a porcine-derived surfactant when compared with those treated with synthetic preparations.
Three commonly available animal-derived surfactants include beractant (BE), calfactant (CA) and poractant alfa (PA). They differ in terms of source, method of preparation, composition, viscosity, dosing volume, phospholipids content, percentage of plasmalogens and amount of SP-B and SP-C. In particular, BE is a minced bovine lung extract that contains lower amounts of phospholipids, plasmalogen and SP-B, compared with CA, which is a lavage preparation from bovine lungs. On the other hand, PA is a minced porcine surfactant that undergoes an additional step, liquid gel chromatography. As a result, PA contains only polar lipids and is more concentrated than the other animal-derived surfactants. Moreover, PA contains the highest amount of plasmalogens. Of note, an higher plasmalogen content in the tracheal aspirates from preterm infants has been associated with a lower incidence of bronchopulmonary dysplasia.
BE, CA and PA have been compared in several comparative studies. In total, eight randomized, controlled clinical trials and two retrospective studies comparing the three natural surfactants have been reported until now. Four of the eight randomized trials compared BE with CA, while the remaining four studies compared BE with PA. There are no prospective studies published comparing CA with PA.
Overall, prospective as well as retrospective studies comparing BE and CA failed to show any significant differences in clinical outcomes or dosing requirements. On the other hand, randomized, controlled clinical trials demonstrated that treatment with PA is associated with rapid weaning of oxygen and ventilatory pressures, fewer additional doses, cost benefits and survival advantage when compared with BE or CA. Moreover, a recent study conducted on an administrative database, that included over several thousands of preterm infants, indicated a significant decrease in mortality and cost benefits in favor of PA, when compared with BE or CA. These differences in outcome may be related to the differences in composition among the three animal-derived surfactants, namely, phospholipid content, volume, viscosity, plasmalogen content and/or anti-inflammatory properties.
In conclusion, current evidence supports the use of animal-derived when compared to synthetic surfactants. Among animal surfactants, PA seems to determine further clinical and cost benefits with respect to BE and CA, possibly due to its peculiar composition.

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