Article

Late surfactant replacement therapy increases surfactant protein-B content in a randomized pilot study.

Department of Pediatrics, University of California San Francisco, San Francisco CA.
Pediatric Research (Impact Factor: 2.84). 10/2012; 72(6). DOI: 10.1038/pr.2012.136
Source: PubMed

ABSTRACT Background:
Surfactant dysfunction may contribute to the development of bronchopulmonary dysplasia (BPD) in persistently ventilated preterm infants. We conducted a multicenter randomized, blinded, pilot study to assess the safety and efficacy of late administration of doses of a surfactant protein-B (SP-B)-containing surfactant (calfactant) in combination with prolonged inhaled nitric oxide (iNO) in infants ≤1,000 g birth weight (BW).

Methods:
We randomized 85 preterm infants ventilated at 7–14 d after birth to receive either late administration of surfactant (up to 5 doses) plus prolonged iNO or iNO alone. Large aggregate surfactant was isolated from daily tracheal aspirates (TAs) for measurement of SP-B content, total protein, and phospholipid (PL).

Results:
Late administration of surfactant had minimal acute adverse effects. Clinical status as well as surfactant recovery and SP-B content in tracheal aspirate were transiently improved as compared to the controls; these effects waned after 1 d. The change in SP-B content with surfactant dosing was positively correlated with SP-B levels during treatment (r = 0.50, P = 0.02).

Conclusion:
Low SP-B values increased with calfactant administration, but the relationship of this response to SP-B levels suggests that degradation is a contributing mechanism for SP-B deficiency and surfactant dysfunction. We conclude that late therapy with surfactant in combination with iNO is safe and transiently increases surfactant SP-B content, possibly leading to improved short- and long-term respiratory outcomes.

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    • "Moreover, Beresford and Shaw described how lower bronchoalveolar lavage SP-B and SP-D concentrations in preterm infants ventilated for respiratory distress syndrome were associated with worse clinical prognoses [29]. In this context, Keller et al. [30] demonstrated recently in preterm infants that late administration of a surfactant containing SP-B surfactant transiently increases SP-B content in the lung aspirates, possibly leading to improved short- and long-term respiratory outcomes. The diagnostic value of C-proSP-B in newborns in this context is still unknown and will require additional clinical studies. "
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    ABSTRACT: Alveolar--capillary membrane leaks can increase the amount of surfactant protein B (SP-B) in the bloodstream. The purpose of this study was to measure the concentration of C-proSP-B, a SP-B precursor that includes C-terminal domains, in various body fluids of newborn infants and determine its dependence on gestational age. C-pro-SPB was measured in amniotic fluid and umbilical cord blood at birth, and in peripheral blood and urine on postnatal day 3 in 137 newborn infants with a median birth weight of 2015 g (range, 550--4475 g) and gestational age of 34 weeks (range, 23--42 weeks). C-proSP-B levels differed more than 100-fold among samples. The levels (median; interquartile range) were highest in peripheral blood (655.6 ng/mL; 419.0-1467.0 ng/mL) and lowest in urine (3.08 ng/mL; 2.96-3.35 ng/mL). C-proSP-B levels in amniotic fluid (314.9 ng/mL; 192.7--603.6 ng/mL) were approximately half of those in peripheral blood. In cord blood C-proSP-B was slightly lower (589.1 ng/mL; 181.2-1129.0 ng/mL) compared with peripheral blood. C-proSP-B levels significantly increased in all the fluids sampled except urine with decreasing gestational age (p < 0.001). This novel assay allows for the quantitative measurement of C-proSP-B in blood and amniotic fluid. The dependence of C-proSP-B on gestational age may hamper its use for the detection of alveolar leaks in preterm newborns.
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