BACKGROUND: Mechanical ventilation from birth with normal tidal volumes (VT) causes lung injury and systemic responses in preterm sheep. The addition of budesonide to surfactant therapy decreases these injury markers.
HYPOTHESIS: Budesonide and surfactant will decrease the injury from injurious VT ventilation in preterm sheep.
METHODS: Lambs at 126 + 1 day GA were ventilated from birth with either: 1) Normal VT (surfactant 200 mg/kg prior to ventilation, PEEP 5 cmH2O, VT 8 mL/kg) or 2) Injury VT (high pressure, 100% oxygen, no PEEP) for 15 minutes, then further randomized to surfactant + saline or surfactant + 0.25 mg/kg budesonide with normal VT for 6 hours. Lung function and lung, liver, and brain tissues were evaluated for indicators of injury.
RESULTS: Injury VT + saline caused significant injury and systemic responses, and Injury VT + budesonide improved lung physiology. Budesonide decreased lung inflammation, and decreased pro-inflammatory cytokine mRNA in the lung, liver, and brain to levels similar to Normal VT + saline. Budesonide was present in plasma within 15 minutes of treatment in both ventilation groups, and less than 5% of the budesonide remained in the lung at 6 hours. mRNA sequencing of liver and periventricular white matter demonstrated multiple pathways altered by both Injury VT and budesonide, and the combination exposure.
CONCLUSION: In lambs receiving Injury VT, the addition of budesonide to surfactant improved lung physiology, and decreased pro-inflammatory cytokine responses in the lung, liver, and brain to levels similar to lambs receiving Normal VT.
|Journal||American Journal of Physiology - Lung Cellular and Molecular Physiology|
|Early online date||16 Oct 2019|
|Publication status||Published - 1 Jan 2020|