BACKGROUND: Acute inflammatory responses to supplemental oxygen and mechanical 
ventilation have been implicated in the pathophysiological sequelae of 
respiratory distress syndrome (RDS). Although surfactant replacement therapy 
(SRT) has contributed to lung stability, the effect on lung inflammation is 
inconclusive. Lucinactant contains sinapultide (KL4), a novel synthetic peptide 
that functionally mimics surfactant protein B, a protein with anti-inflammatory 
properties. We tested the hypothesis that lucinactant may modulate lung 
inflammatory response to mechanical ventilation in the management of RDS and may 
confer greater protection than animal-derived surfactants.
METHODS: Preterm lambs (126.8 ± 0.2 SD d gestation) were randomized to receive 
lucinactant, poractant alfa, beractant, or no surfactant and studied for 4 h. 
Gas exchange and pulmonary function were assessed serially. Lung inflammation 
biomarkers and lung histology were assessed at termination.
RESULTS: SRT improved lung compliance relative to no SRT without significant 
difference between SRT groups. Lucinactant attenuated lung and systemic 
inflammatory response, supported oxygenation at lower ventilatory requirements, 
and preserved lung structural integrity to a greater degree than either no SRT 
or SRT with poractant alfa or beractant.
CONCLUSION: These data suggest that early intervention with lucinactant may more 
effectively mitigate pulmonary pathophysiological sequelae of RDS than the 
animal-derived surfactants poractant alfa or beractant.