Surfactant
Surfactant is a complex substance produced by type II alveolar epithelial cells that has several functions, including the reduction of alveolar surface tension, which is necessary to prevent alveolar collapse during expiration, as well as having anti-inflammatory and antimicrobial properties. Because surfactant is both quantitatively and qualitatively impaired during ALI, and because neonatal patients with the related condition respiratory distress syndrome benefit from exogenous surfactant therapy, it is logical that artificial supplementation of this substance may be beneficial. Surfactant consists of phospholipids and proteins A to D, and various formulations of both recombinant human and animal preparations have been tried. Natural porcine surfactant HL 10 has been studied in two small trials of 23 and 28 ALI patients, respectively, with improved mortality in both studies. The same group of investigators then proceeded to a large international, multicenter, stratified, randomized, controlled, open, parallel-group study examining the effect of administration of this surfactant preparation in 418 patients with ALI. The study was stopped prematurely for safety concerns after a trend toward increased mortality was noted after analysis of 300 patients. Overall, HL 10 therapy was associated with hypoxia and hypotension and was without a mortality benefit at both 28 and 180 days.
Several clinical studies involving various formulations of surfactant have been undertaken. Small, preliminary studies have reported beneficial effects with this therapy, only for large-scale phase III studies to refute these findings. This has also been confirmed in a meta-analysis of five studies. Debate continues regarding possible methodological limitations explaining the results of these studies. A phase 3 randomized, controlled trial investigating the efficacy of calfactant in ARDS is currently recruiting (NCT00682500).