Effects of Natural versus Synthetic Surfactant with SP-B and SP-C Analogs in a Porcine Model of Meconium Aspiration Syndrome

Salvesen, Bodil; Curstedt, Tore; Mollnes, Tom Eirik; Saugstad, Ola Didrik

doi:10.1159/000356065

Cited by 22 publications

(16 citation statements)

References 28 publications

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“…Here, we did not provide data showing that two-peptide synthetic surfactants are equivalent or superior to animal-derived surfactants (Curosurf and Infasurf) because this has been addressed by previous studies and recent studies with CHF5633 (MB + SP-C33) have once more independently confirmed this observation [26, 27]. …”

Section: Discussionmentioning

confidence: 98%

Synthetic lung surfactant reduces alveolar-capillary protein leakage in surfactant-deficient rabbits

Gupta

Hernández-Juviel

Waring

et al. 2015

Experimental Lung Research

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Purpose of the study Alveolar-capillary leakage of proteinaceous fluid impairs alveolar ventilation and surfactant function and decreases lung compliance in acute lung injury. We investigated the correlation between lung function and total protein levels in bronchoalveolar lavage fluid (BALF) of ventilated, lavaged surfactant-deficient rabbits treated with various clinical and synthetic lung surfactant preparations. Materials and Methods 109 Ventilated, young adult New Zealand White rabbits underwent lung lavage to induce surfactant-deficiency (PaO2 <100 torr in 100% O2), were treated with a clinical surfactant or a synthetic surfactant preparation with surfactant protein B (SP-B) and/or surfactant protein C (SP-C) analogs, and mechanically ventilated for 120 min. Total protein levels in postmortem BALF were correlated with arterial PO2 and dynamic lung compliance values at 120 min post-surfactant treatment. Results Repeated lung lavages decreased mean PaO2 values from 540 to 58 torr and lung compliance from 0.64 to 0.33 mL/kg/cm H2O. Two hours after surfactant therapy and mechanical ventilation, mean PaO2 values had increased to 346 torr and lung compliance to 0.44 mL/kg/cm H2O. Eighty-six rabbits (79%) responded to surfactant therapy with an increase in PaO2 to values >200 torr. Fourteen non-responders received inactive surfactant preparations. BALF protein levels were inversely correlated with PaO2 and lung compliance (P<0.001). Surfactant preparations containing both SP-B and SP-C proteins or peptide analogs outperformed single protein/peptide preparations. Conclusions Clinical and synthetic surfactant therapy reduces alveolar-capillary protein leakage in surfactant-deficient rabbits. Surfactant preparations with both SP-B and SP-C (analogs) were more efficient than preparations with SP-B or SP-C alone.

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Section: Discussionmentioning

confidence: 98%

Synthetic lung surfactant reduces alveolar-capillary protein leakage in surfactant-deficient rabbits

Gupta

Hernández-Juviel

Waring

et al. 2015

Experimental Lung Research

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“…In addition, pulmonary arterial pressure was not measured and the effect of surfactant lavage plus IT budesonide instillation on the pulmonary circulation across the different therapies remains unknown. Beractant, the modified bovine surfactant we used for this study, has been reported to show less resistance to inactivation by meconium than several artificial surfactants (34,35). Further studies to evaluate the effects of using different media for the therapeutic BAL are required in order to develop future treatments for severe MAS.…”

Section: Discussionmentioning

confidence: 99%

Effects of Surfactant Lavage Combined With Intratracheal Budesonide Instillation on Meconium-Injured Piglet Lungs

Lin¹,

Jeng

Kuo

et al. 2016

Pediatric Critical Care Medicine

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“…This synthetic surfactant with the working name CHF5633 has been studied in preterm lambs [75,76] and newborn pigs [77]. The synthetic surfactant was as effective as Survanta in the treatment of extremely immature newborn animals with surfactant deficiency during a study period of 5 h [75].…”

Section: New-generation Synthetic Surfactantmentioning

confidence: 99%

“…The synthetic surfactant also seemed more resistant to inactivation, since treatment with this surfactant in combination with albumin gave a significantly higher survival rate after 48 h of ventilation than treatment with albumin and Curosurf [76]. Using newborn full-term pigs, Salvesen et al [77] showed that the synthetic surfactant was as effective as Curosurf for the treatment of experimental meconium aspiration syndrome. …”

Section: New-generation Synthetic Surfactantmentioning

confidence: 99%

A Unique Story in Neonatal Research: The Development of a Porcine Surfactant

2015

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Surfactant deficiency was identified as the cause of respiratory distress syndrome (RDS) as long ago as 1959. Trials of surfactant replacement in the 1960s were unsuccessful because the preparations used contained only phospholipids and they were administered inefficiently by nebulization. In the 1970s Bengt Robertson and Göran Enhörning showed that natural surfactant, containing both phospholipids and proteins, could ameliorate the signs of RDS in immature rabbits. In the 1980s Bengt Robertson and Tore Curstedt developed a porcine surfactant, Curosurf® (named after their surnames), which was effective in immature animals and was used in a pilot clinical trial beginning in 1983. Subsequent randomized clinical trials were planned a year later by Bengt Robertson, Tore Curstedt and Henry Halliday, and the first trial was begun in 1985. This showed that Curosurf reduced pulmonary air leaks and neonatal mortality in preterm infants with severe RDS. A second trial, coordinated by Christian Speer, demonstrated that multiple doses of Curosurf were more effective than a single dose. Subsequent trials conducted by the Collaborative European Multicenter Study Group, which included among others Guilio Bevilacqua, Janna Koppe, Ola Saugstad, Nils Svenningsen and Jean-Pierre Relier, showed that early treatment was more effective than later administration and that infants treated at birth had similar neurodevelopmental status to untreated controls at a corrected age of 2 years. Members of the Collaborative European Multicenter Study Group in Denmark and Sweden performed studies to demonstrate the benefits of a combination of surfactant treatment and early continuous positive airway pressure. Curosurf has also been compared with several synthetic and natural surfactants, and at a dose of 200 mg/kg Curosurf has been shown to be superior to either Survanta® or Curosurf used at a dose of 100 mg/kg. Recently, new-generation synthetic surfactants containing both phospholipids and proteins have been developed. After preclinical testing, CHF5633 (developed by Tore Curstedt and Jan Johansson in collaboration with Chiesi Farmaceutici) has undergone a preliminary first study in humans under the guidance of Christian Speer. If effective, this new surfactant preparation could revolutionize the treatment of preterm infants worldwide as it could be made consistently and safely in almost unlimited quantities. This story of a porcine surfactant preparation has been truly remarkable, and many thousands of preterm babies worldwide are now alive and well because of it.

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Effects of Natural versus Synthetic Surfactant with SP-B and SP-C Analogs in a Porcine Model of Meconium Aspiration Syndrome

Cited by 22 publications

References 28 publications

Synthetic lung surfactant reduces alveolar-capillary protein leakage in surfactant-deficient rabbits

Synthetic lung surfactant reduces alveolar-capillary protein leakage in surfactant-deficient rabbits

Effects of Surfactant Lavage Combined With Intratracheal Budesonide Instillation on Meconium-Injured Piglet Lungs

A Unique Story in Neonatal Research: The Development of a Porcine Surfactant

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