Surfactant plus budesonide decreases lung and systemic responses to injurious ventilation in preterm sheep

Noah H Hillman, T Brett Kothe, Augusto F Schmidt, Matthew W Kemp, Emily Royse, Erin Fee, Fabrizio Salomone, Michael W Clarke, Gabrielle C Musk, Alan H Jobe

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Abstract

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.

Original languageEnglish
Pages (from-to)L41-L48
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume318
Issue number1
Early online date16 Oct 2019
DOIs
Publication statusPublished - 1 Jan 2020

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