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

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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. Budesonide and surfactant will decrease the injury from injurious VT ventilation in preterm sheep. Lambs at 126 ± 1 day gestational age were ventilated from birth with either: 1) Normal VT [surfactant 200 mg/kg before ventilation, positive end expiratory pressure (PEEP) 5 cmH2O, VT 8 mL/kg] or 2) Injury VT (high pressure, 100% oxygen, no PEEP) for 15 min, then further randomized to surfactant + saline or surfactant + 0.25 mg/kg budesonide with Normal VT for 6 h. Lung function and lung, liver, and brain tissues were evaluated for indicators of injury. 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 min of treatment in both ventilation groups, and less than 5% of the budesonide remained in the lung at 6 h. mRNA sequencing of liver and periventricular white matter demonstrated multiple pathways altered by both Injury VT and budesonide and the combination exposure. 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 (US)
Pages (from-to)L41-L48
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume318
Issue number1
DOIs
StatePublished - 2020
Externally publishedYes

Keywords

  • Brain
  • Bronchopulmonary dysplasia
  • Liver
  • Premature
  • mRNA sequencing

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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