Surfactants: past, present and future

The history of surfactant treatment could be dated back to 1929, when Kurt von Neergaard performed the first experiments suggesting the presence of pulmonary surfactant and its relevance to the newborn's first breath. Thirty years later, it was demonstrated that preterm neonates dying of respiratory distress syndrome (RDS) had a deficiency of pulmonary surfactant.
The first trials on the use of nebulized synthetic (protein-free) surfactant to prevent RDS were published soon after Patrick Bouvier Kennedy - the son of John F Kennedy - died of RDS. The results of these preliminarily trials were largely negative; however, in the early 1970s, Goran Enhorning and Bengt Robertson demonstrated that natural surfactants, containing proteins, were effective in animal models.
In 1980, Tetsuro Fujiwara published the seminal article reporting the responses of 10 preterm infants with RDS to a bolus of modified bovine surfactant, demonstrating the acute beneficial effects of natural surfactant in the treatment of RDS. Starting from this piece of evidence, during the 1980s there were numerous randomized controlled trials of many different natural and synthetic surfactants, overall demonstrating reductions in pulmonary air leaks and neonatal mortality. Moreover, several Cochrane reviews indicated the benefits of multiple doses over a single dose, early versus late rescue-treatment and prophylaxis versus late rescue. Furthermore, natural surfactants were shown to be superior to the protein-free synthetic products.
Recently, there have been a number of randomized trials comparing different natural surfactant preparations. Commercially available bovine surfactants may have similar efficacy, but there is some evidence that a porcine surfactant used to treat RDS with an initial dose of 200 mg/kg is more effective than a bovine surfactant used with an initial dose of 100 mg/kg.
Very recently a new synthetic surfactant with a surfactant protein mimic has been compared with other commercially available natural and synthetic surfactants in two trials. The results show that the new surfactant may be superior to one of the older protein-free synthetic surfactants but there is no evidence of its superiority over established natural products. Therefore, this surfactant is currently not approved for clinical use. A number of other new synthetic surfactants have been tested in animal models or in treatment of adults with acute RDS, but so far there have been no reports of treatment of neonatal RDS.
As for the methods of administration, natural surfactants work best if given by a rapid bolus into the lungs, but less invasive methods such as a laryngeal mask, pharyngeal deposition or rapid extubation to continuos positive air pressure (CPAP) have showed promising results.
Overall, surfactant therapy has been a major advance in neonatology during the past 25 years, allowing for a reduction in mortality and pulmonary air leaks of about 50%.

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