Objective Previous efforts to aerosolize animal-derived surfactants have met with limited efficacy due to inadequate delivery and inactivation. Our objective was to assess the effect of an aerosolized precision-engineered, peptide-containing, synthetic surfactant (Aerosurf™: lucinactant for inhalation), delivered by a novel aerosol generator on lung mechanics, histomorphology and biomarkers of lung inflammation in spontaneously breathing, very continuous positive airway pressure (CPAP)-supported preterm lambs.

Design and Methods Following cesarean section, lambs (n = 14; 126–129 days gestation) were instrumented, delivered, supported with 100% oxygen, CPAP, and caffeine then quasi-randomized to receive CPAP alone or CPAP plus Aerosurf delivered for 90 min using capillary aerosol generator (CAG) technology. Cardiopulmonary parameters were monitored for 4 hrs. Lung IL-6, IL-8, myeloperoxidase (MPO) and histomorphometry were measured.

Results At 4 hrs, lambs treated with CPAP plus Aerosurf demonstrated greater PaO₂ (p<0.05), functional residual capacity (p<0.05), specific compliance (p<0.05), and tidal volume (p<0.05), and lower lung IL-6 (p<0.05), IL-8 (p<0.05) and MPO (p<0.05), than lambs treated with CPAP alone. Lung histomorphometry and gross inspection reflected greater expansion index (p<0.05), more gas exchange units expanded/field (p<0.05), more homogenous expansion and greater end-expiratory stability following CPAP plus Aerosurf.

Conclusions Relative to treatment with CPAP alone, Aerosurf delivery by CAG technology improved pulmonary mechanics, lung structure integrity, and reduced lung inflammation in very preterm lambs. These observations support the potential utility of this novel approach to treat preterm infants with respiratory distress syndrome.

Supported by Discovery Laboratories, Inc.