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Vol. 87, No. 4, 2005
Issue release date: May 2005
Biol Neonate 2005;87:338–344

New Synthetic Surfactants: The Next Generation?

Pfister R.H. · Soll R.F.
Department of Pediatrics, University of Vermont College of Medicine, Burlington, Vt., USA

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Surfactant preparations have been proven to improve clinical outcome of infants at risk for or having respiratory distress syndrome (RDS). In clinical trials, ani mal-derived surfactant preparations reduce the risk of pneumothorax and mortality when compared to non-protein-containing synthetic surfactant preparations. In part, this is thought to be due to the presence of surfactant proteins in animal-derived surfactant preparations. Four native surfactant proteins have been identified. The hydrophobic surfactant proteins B (SP-B) and C (SP-C) are tightly bound to phospholipids. These proteins have important roles in maintaining the surface tension-lowering properties of pulmonary surfactant. Surfactant protein A (SP-A) and D (SP-D) are extremely hydrophilic and are not retained in the preparation of any commercial animal-derived surfactant products. These proteins are thought to have a role in recycling surfactant and improving host defense. There is concern that animal-derived products may have some batch-to-batch variation regarding the levels of native pulmonary surfactant proteins. In addition, there is concern regarding the hypothetical risk of transmission of viral or unconventional infectious agents from an animal source. New surfactant preparations, composed of synthetic phospholipids and essential hydrophobic surfactant protein analogs, have been developed. These surfactant protein analogs have been produced by peptide synthesis and recombinant technology to provide a new class of synthetic surfactants that may be a suitable alternative to animal-derived surfactants. Preliminary clinical studies have shown that treatment with these novel surfactant preparations can ameliorate RDS and improve clinical outcome. Clinicians will need to further understand any differences in clinical effects between available products.

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  1. Fujiwara T, Maeta H, Chida S, Morita T, Watabe Y, Abe T: Artificial surfactant therapy in hyaline membrane disease. Lancet 1980;1:55–59.
  2. Soll RF, McQueen MC: Respiratory distress syndrome; in Sinclair J, Bracken M (eds): Effective Care of the Newborn. Oxford, Oxford University Press, 1992.
  3. Horbar JD, Wright EC, Onstad L: Decreased mortality associated with the introduction of surfactant therapy: An observational study of neonates weighing 601–1300 grams at birth. Pediatrics 1993;92:191–196.
  4. Schwartz RM, Luby AM, Scanlon JW, Kellogg RJ: Effect of surfactant on morbidity, mortality and resource use in newborns weighing 500 to 1500 g. N Eng J Med 1994;330:1476–1480.
  5. King RJ: Isolation and chemical composition of pulmonary surfactant; in Robertson B, Van Golde LMG, Batenburg JJ (eds): Pulmonary Surfactant. Amsterdam, Elsevier Science, 1984, pp 1–15.
  6. Clements JA: Functions of the alveolar lining. Am Rev Respir Dis 1977;115:67–71.
  7. Whitsett JA, Nogee LM, Weaver TE, Horowitz AD: Human surfactant protein B: Structure, function, regulation, and genetic disease. Physiol Rev 1995;75:749–757.
  8. Hawgood S, Benson BJ, Hamilton RL Jr: Effects of surfactant-associated proteins and calcium ions on the structure and surface activity of lung surfactant lipids. Biochemistry 1985;24:184–190.
  9. Horbar JD, Wright LL, Soll RF, Wright EC, Fanaroff AA, Korones SB, Shankaran S, Oh W, Fletcher BD, Bauer CR, Tyson JE, Lemons JA, Donovan EF, Stoll BJ, Stevenson DD, Papile LA, Philips III J, for the National Institute of Child Health and Human Development Neonatal Research Network: A multicenter randomized trial comparing two surfactants for the treatment of neonatal respiratory distress syndrome. J Pediatr 1993;123:757–766.
  10. Vermont-Oxford Neonatal Network: A multicenter randomized trial comparing synthetic surfactant with modified bovine surfactant extract in the treatment of neonatal respiratory distress syndrome. Pediatrics 1996;97:1–6.

    External Resources

  11. Hudak ML, Farrell EE, Rosenberg AA, Jung AL, Auten RL, Durand DJ, Horgan MJ, Buckwald S, Belcastro MR, Donohue PK, Carrion V, Maniscalco WW, Balsan MJ, Torres BA, Miller RR, Jansen RD, Graeber JE, Laskay KM, Matteson EJ, Egan EA, Brody AS, Martin DJ, Riddlesberger MM, Montgomery P: A multicenter randomized, masked comparison trial of natural versus synthetic surfactant for the treatment of respiratory distress syndrome. J Pediatr 1996;128:396–406.
  12. Soll RF, Blanco F: Natural surfactant extract versus synthetic surfactant for neonatal respiratory distress syndrome. Cochrane Database Syst Rev 2001;(2):CD000144.
  13. van Eijk M, DeHaas CG, Haagsman HP: Quantitative analysis of pulmonary surfactant proteins B and C. Anal Biochem 1995;232:231–237.
  14. Seeger W, Grube C, Günther A, Schmidt R: Surfactant inhibition by plasma proteins: Differential sensitivity of various surfactant preparations. Eur Respir J 1993;6:971–977.
  15. Walther FJ, Hernandez-Juviel J, Bruni R, Waring AJ: Protein composition of synthetic surfactant affects gas exchange in surfactant-deficient rats. Pediatr Res 1998;43:666–673.
  16. Strayer DS, Hallman M, Merritt TA: Immunogenicity of surfactant. II. Porcine and bovine surfactants. Clin Exp Immunol 1991;83:41–46.
  17. Robertson B, Kobayashi T, Ganzuka M, Grossmann G, Li WZ, Suzuki Y: Experimental neonatal respiratory failure induced by a monoclonal antibody to the hydrophobic surfactant-associated protein SP-B. Pediatr Res 1991;30:239–243.
  18. Cochrane CG, Revak SD: Pulmonary surfactant protein B (SP-B): Structure-function relationships. Science 1991;254:566–568.
  19. Manalo E, Merritt TA, Kheiter A, Amirkhanian J, Cochrane C: Comparative effects of some serum components and proteolytic products of fibrinogen on surface tension-lowering abilities of beractant and a synthetic peptide containing surfactant KL4. Pediatr Res 1996;39:947–952.
  20. Merritt TA, Amirkhanian JD, Helbock H, Halliwell B, Cross CE: Reduction of the surface-tension-lowering ability of surfactant after exposure to hypochlorous acid. Biochem J 1993;295:19–22.
  21. Manalo E, Merritt TA, Amirkhanian JD, Kheiter A: Characterization of surfactant subtypes of beractant and a synthetic peptide containing surfactant KL4 following surface area cycling and addition of fibrinogen. Lung 1997;175:225–233.
  22. Ma J, Koppenol S, Yu H, Zografi G: Effects of a cationic and hydrophobic peptide, KL4, on model lung surfactant lipid monolayers. Biophys J 1998;74:1899–1907.
  23. Merritt TA, Kheiter A, Cochrane CG: Positive end-expiratory pressure during KL4 surfactant instillation enhances intrapulmonary distribution in a simian model of respiratory distress syndrome. Pediatr Res 1995;38:211–217.
  24. Revak SD, Merritt TA, Cochrane CG, Heldt GP, Alberts MS, Anderson DW, Kheiter A: Efficacy of synthetic peptide-containing surfactant in the treatment of respiratory distress syndrome in preterm infant rhesus monkeys. Pediatr Res 1996;39:715–724.
  25. Lipp MM, Lee KY, Zasadzinski JA, Waring AJ: Phase and morphology changes in lipid monolayers induced by SP-B protein and its amino-terminal peptide. Science 1996;273:1196–1199.
  26. Walther FJ, Hernandez-Juviel JM, Gordon LM, Sherman MA, Waring AJ: Dimeric surfactant protein B peptide sp-b(1–25) in neonatal and acute respiratory distress syndrome. Exp Lung Res 2002;28:623–640.
  27. Davis AJ, Jobe AH, Häfner D, Ikegami M: Lung function in premature lambs and rabbits treated with a recombinant SP-C surfactant. Am J Respir Crit Care Med 1998;157:553–559.
  28. Clark H, Palaniyar N, Hawgood S, Reid KB: A recombinant fragment of human surfactant protein D reduces alveolar macrophage apoptosis and pro-inflammatory cytokines in mice developing pulmonary emphysema. Ann NY Acad Sci 2003;1010:113–116.
  29. Walther FJ, David-Cu R, Leung C, Bruni R, Hernandez-Juviel J, Gordon LM, Waring AJ: A synthetic segment of surfactant protein A: structure, in vitro surface activity, and in vivo efficacy. Pediatr Res 1996;39:938–946.
  30. Soll RF, Dargaville P: Surfactant for meconium aspiration syndrome in full term infants. Cochrane Database Syst Rev 2000;(2):CD002054.
  31. Cochrane CG, Revak SD, Merritt TA, Schraufstatter IU, Hoch RC, Henderson C, Andersson S, Takamori H, Oades ZG: Bronchoalveolar lavage with KL4-surfactant in models of meconium aspiration syndrome. Pediatr Res 1998;44:705–715.
  32. Wiswell TE, Knight GR, Finer NN, Donn SM, Desai H, Walsh WF, Sekar KC, Bernstein G, Keszler M, Visser VE, Merritt TA, Mannino FL, Mastrioianni L, Marcy B, Revak SD, Tsai H, Cochrane CG: A multicenter, randomized, controlled trial comparing Surfaxin (Lucinactant) lavage with standard care for treatment of meconium aspiration syndrome. Pediatrics 2002;109:1081–1087.
  33. Adhikari N, Burns K, Meade M: Pharmacologic therapies for adults with acute lung injury and acute respiratory distress syndrome. Cochrane Database Syst Rev 2004;(4):CD004477.
  34. Sood SL, Balaraman V, Finn KC, Wilkerson SY, Mundie TG, Easa D: Exogenous surfactant decreases oxygenation in Escherichia coli endotoxin-treated neonatal piglets. Pediatr Pulmonol 1996;22:376–386.
  35. Wiswell TE, Smith RM, Katz LB, Mastroianni L, Wong DY, Willms D, Heard S, Wilson M, Hite RD, Anzueto A, Revak SD, Cochrane CG: Bronchopulmonary segmental lavage with Surfaxin (KL(4)-surfactant) for acute respiratory distress syndrome. Am J Respir Crit Care Med 1999;160:1188–1195.
  36. Häfner D, Germann PG, Hauschke D: Effects of rSP-C surfactant on oxygenation and histology in a rat-lung-lavage model of acute lung injury. Am J Respir Crit Care Med 1998;158:270–278.
  37. Cochrane CG, Revak SD, Merritt TA, Heldt GP, Hallman M, Cunningham MD, Easa D, Pramanik A, Edwards DK, Alberts MS: The efficacy and safety of KL4-surfactant in preterm infants with respiratory distress syndrome. Am J Respir Crit Care Med 1996;153:404–410.
  38. Moya F, Gadzinowski J, Bancalari E, Salinas V, Kopelman B, Bancalari A, Kornacka MK, Merritt TA, Segal R, Schaber C, Tsai H, D’Agostino R: A multicenter randomized masked comparison trial of lucinactant, colfosceril palmitate, and beractant for the prevention of respiratory distress syndrome in very preterm infants. Pediatrics 2005;115:1018–1029.
  39. Sinha S, Lacaze-Masmonteil T, Valls i Soler A, Gadzinowski J, Hadju J, Bernstein G, Sanchez-Luna M, Massaro J, D’Agostino R, Segal R, Schaber C: A randomized, controlled trial of lucinactant versus poractant alfa in very premature infants at high risk for respiratory distress syndrome. Pediatrics 2005;115:1030–1038.
  40. Ramanathan R, Rasmussen MR, Gerstmann DR, Finer N, Sekar K, North American Study Group: A randomized, multicenter masked comparison trial of poractant alfa (Curosurf) versus beractant (Survanta) in the treatment of respiratory distress syndrome in preterm infants. Am J Perinatol 2004;21:109–119.
  41. Collaborative European Multicenter Study Group: Surfactant replacement therapy for severe neonatal respiratory distress syndrome: an international randomized clinical trial. Pediatrics 1988;82:683–691.

    External Resources

  42. Spragg RG, Lewis JF, Walmrath HD, Johannigman J, Bellingan G, Laterre PF, Witte MC, Richards GA, Rippin G, Rathgeb F, Häfner D, Taut FJ, Seeger W: Effect of recombinant surfactant protein C-based surfactant on the acute respiratory distress syndrome. N Engl J Med 2004;351:884–892.

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