Exogenous surfactant administration has proven inconsistent as a therapeutic modality for patients with acute respiratory distress syndrome. This is because of the severity of the injury at the time of treatment and because of the variable surfactant preparations, dosing regimes, and delivery methods used in the different trials. Future research efforts will focus on determining the optimal timing of surfactant administration in patients at risk of developing acute respiratory distress syndrome with the aim of preventing progressive lung dysfunction and determining whether surfactant treatments need to be tailored to the specific patient in question. Moreover, with the recognition that surfactant also plays an important role in host defense, the future for surfactant therapy is exciting.

In acute lung injury, a decrease in surface-active large aggregates and an increase in the less surface-active small surfactant aggregates are observed. The objective of the current study was to determine if the increase in small aggregates interfered with the function of large aggregates, thereby independently contributing to lung dysfunction.Isolated large aggregates, small aggregates, and large aggregatezsmall aggregate combinations were analysed for in vitro surface activity utilizing a pulsating bubble surfactometer. Subsequently, large aggregates, small aggregates, and large aggregatez small aggregate combinations were administered to surfactant-deficient, adult SpragueDawley rats. Physiological parameters were measured during 1 h of ventilation. After sacrifice, the whole lung lavage was analysed for protein concentration, and surface activity of the recovered large aggregates.The minimum surface tension of the large aggregatezsmall aggregate preparations (10 mN?m -1 ) was significantly higher than large aggregates alone (1 mN?m -1 ), but lower than small aggregates alone (21 mN?m -1 ) after 100 pulsations. In vivo, rats receiving large aggregateszsmall aggregates showed immediate increases in oxygenation, similar to animals given large aggregates, whereas animals given small aggregates and control animals maintained low oxygenation values.In conclusion, small aggregates interfered with large aggregates function in vitro, but this was not observed in vivo in this experimental model.

Oxidative stress on the endogenous surfactant system may represent an important mechanism contributing to the surfactant dysfunction and abnormal surfactant metabolism associated with hyperoxia-induced lung injury.