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In 1959 Avery and Mead discovered that the lungs of infants who died of hyaline membrane disease (HMD) were deficient in surfactant.1 Surfactant reduces surface tension and stabilises alveoli at low lung volumes and may act as an "anti-stick" or lubricant allowing the alveolar walls to remain open.2" HMD is characterised by progressive atelectasis and respiratory failure in premature infants and is a major cause of morbidity and mortality in the neonatal period.56 Numerous studies of the development of the pulmonary surfactant system have led to the clinical use of phospholipid composition ofhuman amniotic fluid to predict lung maturity and to the use of antenatal hormones to accelerate lung maturation. Recently, this research has culminated in successful attempts to treat HMD in premature infants with surfactant replacement therapy (SRT).We will begin this article with a brief review of the pulmonary surfactant system and the various types ofsurfactants used in replacement therapy. This will be followed by a review of the animal and clinical studies investigating SRT 10-15% protein.278 The major phospholipid in surfactant is phosphatidylcholine of which approximately 70-75% is present as dipalmitoyl phosphatidylcholine (DPPC), the major surface active component in surfactant. The second most abundant phospholipid is phosphatidylglycerol (PG) which comprises 7-10% of total surfactant. These lipids are important in the formation of the monolayer on the alveolar-air interface, and PG is important in the spreadability over a large surface area. (Curosurf) has been used in Europe. In addition to containing the phospholipids of surfactant, these modified natural surfactants also contain the hydrophobic surfactant proteins SP-B and SP-C, but they do not contain the hydrophilic proteins, SP-A and SP-D. Synthetic surfactants have been designed and one preparation contains surface active phospholipids as well as agents which improve spreadability and stability of the preparation. The first synthetic surfactant preparation that was approved for use by the FDA in 1990 was Exosurf which contains DPPC, PG, and the stabilisers tyloxapol and hexadecanol. Another synthetic surfactant that has been used in both animal research and clinical trials is called artificial lung expanding compound (ALEC) which is a mixture of DPPC and phosphatidylglycerol in a ratio of 7:3 by weight.65 The synthetic preparations do not contain the surfactant proteins. There are efforts currently underway, however, to develop engineered surfactants which contain synthetic phospholipids and recombinantly synthesised human surfactant proteins. The advantages of these surfactants are that they would not be from animal sources and they would contain the human surfactant proteins which may have important physiological roles in the function and metabolism of exogenously administered surfactant without the potential for antigenic stimulation of proteins derived from animal sources.Animal studies of surfactant replacement therapy Studies of SRT in anima...

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Increased activities of phospholipase A₂ and C (PLC) have been observed in the bronchoalveolar lavages of patients with adult respiratory distress syndrome (ARDS). DL-α-Di-O-hexadecylphosphonocholine [(R)(S)-DEPN-8], a surfactant analog of superior surface activity to the major lung surfactant phospholipid, dipalmitoylphosphatidylcholine (DPPC), is not a substrate for phospholipases A₁, A₂ and D, but is a substrate for PLC. (R)(S)-DEPN-8 was found in vitro to undergo significantly less PLC-catalyzed degradation as compared to DPPC. The results suggest that (R)(S)-DEPN-8 and structurally related analogs may be useful as components of exogenous replacement surfactant formulations for the treatment of ARDS-related lung injuries.

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