04/05/2005
Studied in vivo surfactant-associated protein B (SP-B) kinetics
An Italian pilot study demonstrates that SP-B kinetics can be measured in vivo in humans using stable isotope technology, a potential valuable tool to understand SP-B in human lung disease.

Surfactant-associated proteins B and C (SP-B and SP-C, respectively) play a critical role in maintaining the biophysical function of surfactant, although they represent < 5% of surfactant by weight. In respiratory distress syndrome the amount of phospholipids and of SP-B decrease. The key role of SP-B is proved evident in congenital SP-B deficiency, which is characterized by severe respiratory failure, leading to death unless lung transplant is performed.

To date, no data on SP-B kinetics in humans is available, although there is information in adult and newborn animals, in which radioactive labels can be used.

The Italian pilot study aims to demonstrate the feasibility of measuring SP-B kinetics in vivo in newborn infants by means of stable isotopes. This study reports for the first time data on SP-B synthesis and kinetics measured by stable isotopes in vivo in humans.

The methodology of the pilot study is based on the administration of a 24-h infusion of 2 mg/kg/h 1-13C valine, dissolved in normal saline as metabolic precursor of SP-B to six newborn infants (weight 3.5 ± 0.5 kg; age 12 d, range 1-43 d). Exclusion criteria were congenital chromosomal abnormalities and exogenous surfactant given at < 48 h before study start.
Three of the study infants also received in vivo 0.4 mg/kg/h 16,16,16 2H palmitate acid to label surfactant DSPC. 13C and 2H enrichments of SP-B and DSPC were measured by gas chromatography-mass spectrometry.

SP-B kinetics was measured successfully in all six infants. The ascending part of the SP-B kinetic curve was similar to the DSPC curve, suggesting similar secretion pathways. The preliminary results indicate that SP-B has a short half-life of ~ 20h. This can be due to a rapid turnover. If this outcome were to be confirmed in a larger number of patients, it could be hypothesized that SP-B concentrations may rapidly become critically low in case of reduced synthesis or of accelerated catabolism. The findings obtained agree with existing animal data.

In a previous study an analogous method based on stable isotopes had been deployed to measure endogenous surfactant phosphatidylcholine (PC) kinetics and disaturated phosphatidylcholine (DSPC) half-life in humans.

Conclusion
The study proves that SP-B kinetics can be measured in vivo in humans using stable isotope technology and indicates that this method can be a valuable tool to better understand the role of SP-B in human lung disease.

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