Abstract
Background: We have demonstrated effectiveness of an aerosolized, peptide-containing, synthetic surfactant (KL4 surfactant), in spontaneously breathing CPAP-supported preterm lambs. Dose-ranging studies are required to define the dose that produces optimal physiologic and biomarker responses.
Aims: To evaluate dose-responses to aerosolized KL4 surfactant using lung mechanics, histomorphology and lung inflammation biomarkers in spontaneously breathing, CPAP-supported preterm lambs.
Methods: Following Cesarean section, lambs (n = 20; 130-132 days gestation) were anesthetized, instrumented, delivered, supported with 100% oxygen, CPAP, and caffeine then quasi-randomized to receive CPAP alone (controls) or CPAP plus aerosolized KL4 surfactant for up to 10, 20, 30 or 90 min. exposure at 1.2 mL/min. Cardiopulmonary parameters were monitored for 4 hrs. Lung IL-8 and histomorphometry were also measured.
Results: Compliance increased and lung IL-8 decreased in an aerosolized KL4 surfactant dose-dependent manner relative to CPAP treatment alone. Marked differences occurred with the 20 min dose vs. CPAP alone with little differences between the 20, 30 and 90 min. doses. PaO2 was greater than in controls following the 10, 20 and 30 min. doses and trended towards control values with the 90 min. dose. Gross and histomorphometry lung assessment demonstrated greater and more homogenous expansion compared to controls, independent of treatment duration.
Conclusions: Aerosolized KL4 surfactant improved gas exchange, pulmonary mechanics, lung structure integrity, and reduced lung inflammation in a dose-dependent manner relative to treatment with CPAP alone. These observations provide preliminary guidance for titrating dosing strategies for optimal management of RDS.(Discovery Laboratories, Inc; DURIP-ONR; NIH P20 RR 020173).
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Wolfson, M., Wu, J., Hubert, T. et al. Dose-Response to Aerosolized KL4 Surfactant in the Spontaneously Breathing CPAP-Supported Preterm Lamb. Pediatr Res 70 (Suppl 5), 751 (2011). https://doi.org/10.1038/pr.2011.976
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DOI: https://doi.org/10.1038/pr.2011.976
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