Complement Function and the Synthesis of Lung Surfactant May Be a Regulation Which Preterm Infants Have in Common

Background: Animal-derived surfactants containing surfactant proteins B (SP-B) and C (SP-C) are used to treat respiratory distress syndrome (RDS) in preterm infants. SP-B (79 residues) plays a pivotal role in lung function and the design of synthetic lung surfactant. Super Mini-B (SMB), a 41-residue peptide based on the N- and C-domains of SP-B covalently joined with a turn and two disulfides, folds as an α-helix hairpin mimicking the properties of these domains in SP-B. Here, we studied ‘B-YL’, a 41-residue SMB variant that has its four cysteine and two methionine residues replaced by tyrosine and leucine, respectively, to test whether these hydrophobic substitutions produce a surface-active, α-helix hairpin. Methods: Structure and function of B-YL and SMB in surfactant lipids were compared with CD and FTIR spectroscopy, and surface activity with captive bubble surfactometry and in lavaged, surfactant-deficient adult rabbits. Results: CD and FTIR spectroscopy of B-YL in surfactant lipids showed secondary structures compatible with peptide folding as an α-helix hairpin, similar to SMB in lipids. B-YL in surfactant lipids demonstrated excellent in vitro surface activity and good oxygenation and dynamic compliance in lavaged, surfactant-deficient adult rabbits, suggesting that the four tyrosine substitutions are an effective replacement for the disulfide-reinforced helix-turn of SMB. Here, the B-YL fold may be stabilized by a core of clustered tyrosines linking the N- and C-helices through non-covalent interactions involving aromatic rings. Conclusions: ‘Sulfur-free’ B-YL forms an amphipathic helix-hairpin in surfactant liposomes with high surface activity and is functionally similar to SMB and native SP-B. The removal of the cysteines makes B-YL more feasible to scale up production for clinical application. B-YL’s possible resistance against free oxygen radical damage to methionines by substitutions with leucine provides an extra edge over SMB in the treatment of respiratory failure in preterm infants with RDS.

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Human Surfactant and Calf Lung Surfactant Extract: Moderation of Respiratory Distress in Preterm Infants by a Single Prophylactic Dose in a Randomized and Controlled Clinical Trial

Surfactant Replacement Therapy ◽

10.1007/978-3-642-73305-5_19 ◽

1988 ◽

pp. 150-157

Author(s):

B. T. Bloom

Keyword(s):

Clinical Trial ◽

Respiratory Distress ◽

Preterm Infants ◽

Lung Surfactant ◽

Controlled Clinical Trial ◽

Prophylactic Dose

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The Miracles of Surfactant: Less Invasive Surfactant Administration, Nebulization, and Carrier of Topical Drugs

Neonatology ◽

10.1159/000516106 ◽

2021 ◽

pp. 1-10

Author(s):

Christoph Härtel ◽

Kirsten Glaser ◽

Christian P. Speer

Keyword(s):

Replacement Therapy ◽

Preterm Infants ◽

Invasive Mechanical Ventilation ◽

Lung Surfactant ◽

Standard Of Care ◽

Less Invasive ◽

Surfactant Replacement Therapy ◽

Surfactant Administration ◽

Invasive Techniques ◽

Spontaneously Breathing

Surfactant replacement therapy (SRT) has long become the standard of care in the treatment of neonatal respiratory distress syndrome (RDS), significantly decreasing acute pulmonary morbidity and mortality in preterm infants. For decades, this beneficial replacement therapy has been administered via endotracheal tube. Despite significantly improving the outcome of RDS, however, the burden of bronchopulmonary dysplasia remains, in particular, in very immature preterm infants. Acknowledging the direct relationship between exposure to and duration of invasive mechanical ventilation and chronic lung disease, the latter has been gradually replaced by noninvasive ventilation strategies in neonatal RDS. This replacement is strongly related to the demand for similarly noninvasive modes of surfactant administration. Alternative techniques in spontaneously breathing infants have evolved, including less invasive techniques using thin catheters (less invasive surfactant administration and minimally invasive surfactant treatment) as well as nebulization of surfactant, although the latter is not ready for clinical application yet. In addition, given their therapeutic delivery to the lungs and subsequent alveolar distribution, surfactant preparations represent an attractive vehicle for pulmonary deposition of drugs in preterm infants. Further improvement of SRT and expansion of the field of application of lung surfactant may hold additional benefits, especially in the treatment of the most immature preterm infants.

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