Reflections on the introduction of surfactant therapy for neonates with respiratory distress

When pulmonary surfactant was first detected in the 1950s by Pattle and Clements, many thousands of infants perished each year due to a respiratory illness termed hyaline membrane disease. Hyaline membranes are formed by plasma leaking through damaged endothelial barriers into the terminal bronchiolar: alveolar spaces. Since the leaking plasma lacks erythrocytes, these clots are opaque. Insightful research by Avery and Mead soon led to the suggestion that the neonatal respiratory distress syndrome (RDS) did not arise because of the presence of hyaline membranes, but rather was related to the lack of sufficient pulmonary surfactant, mainly as a result of immaturity. Unfortunately, initial attempts at treating RDS with aerosolized dipalmitoyl-phosphatidylcholine, the major single molecular component, proved unsuccessful. Almost 20 years later, it was demonstrated by Enhorning and Robertson that treating prematurely delivered rabbit pups with natural surfactant prevents respiratory failure. Initially, it appeared unlikely that animal surfactants could be used for therapy with human infants. However, in 1980, Fujiwara demonstrated that a modified bovine surfactant extract promoted gaseous exchange with infants suffering from RDS. Soon a number of bovine and porcine-modified surfactants and two wholly synthetic formulations were shown to alleviate RDS. The present review relates some of the key scientific findings and significant clinical contributions responsible for reducing the neonatal morbidity and mortality associated with RDS. It further describes some of the more recent findings on the biological, biophysical, and physiological significance of pulmonary surfactant in health and disease.