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 language | English |
|---|---|
| Pages (from-to) | L41-L48 |
| Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
| Volume | 318 |
| Issue number | 1 |
| Early online date | 16 Oct 2019 |
| DOIs | |
| Publication status | Published - 1 Jan 2020 |
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Surfactant plus budesonide decreases lung and systemic responses to injurious ventilation in preterm sheep. / Hillman, Noah H; Kothe, T Brett; Schmidt, Augusto F; Kemp, Matthew W; Royse, Emily; Fee, Erin; Salomone, Fabrizio; Clarke, Michael W; Musk, Gabrielle C; Jobe, Alan H.
In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 318, No. 1, 01.01.2020, p. L41-L48.Research output: Contribution to journal › Article
TY - JOUR
T1 - Surfactant plus budesonide decreases lung and systemic responses to injurious ventilation in preterm sheep
AU - Hillman, Noah H
AU - Kothe, T Brett
AU - Schmidt, Augusto F
AU - Kemp, Matthew W
AU - Royse, Emily
AU - Fee, Erin
AU - Salomone, Fabrizio
AU - Clarke, Michael W
AU - Musk, Gabrielle C
AU - Jobe, Alan H
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85077016864&partnerID=8YFLogxK
U2 - 10.1152/ajplung.00203.2019
DO - 10.1152/ajplung.00203.2019
M3 - Article
VL - 318
SP - L41-L48
JO - AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
JF - AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
SN - 1040-0605
IS - 1
ER -