In addition, in phase 1 and phase 2 clinical trials in 47 preterm infants in 6 centers in the United States, KL 4 -Surfactant induced a rapid and sustained increase in pulmonary function. Normal levels were reached within 12 hours after instillation of the surfactant. Chest radiographs revealed increasing expansion of the lungs during the 12-hour period. Phase 3 trials in human preterm infants are in preparation. Meconium aspiration syndrome in newborn infants is perhaps the most severe disease in newborns to treat, and no approved therapeutic agent is available.
Meconium degrades intrinsic surfactant and induces a marked inflammatory response in the lungs.
Lavage of the lungs with KL 4 -Surfactant partially removed meconium and provided expansion of otherwise collapsed lungs in both species. Lavage with saline removed meconium but did not result in expansion of the lungs. The inflammatory response in rabbits was diminished in the lungs lavaged with KL 4 -Surfactant but not in the lungs lavaged with saline. In the acute respiratory distress syndrome and acute lung injury in humans, the inflammation that develops in the lungs inactivates intrinsic surfactant. The lungs undergo atelectatic changes and fill with inflammatory exudate.