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 journalArticle

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

Fingerprint

Budesonide
Surface-Active Agents
Ventilation
Sheep
Lung
Wounds and Injuries
Liver
Brain
Parturition
Cytokines
Messenger RNA
Tidal Volume
Lung Injury
Artificial Respiration
Pneumonia
Oxygen
Pressure

Cite this

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. / Surfactant plus budesonide decreases lung and systemic responses to injurious ventilation in preterm sheep. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2020 ; Vol. 318, No. 1. pp. L41-L48.
@article{f7a4a2001fbd4b36b85155794aee837f,
title = "Surfactant plus budesonide decreases lung and systemic responses to injurious ventilation in preterm sheep",
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.",
author = "Hillman, {Noah H} and Kothe, {T Brett} and Schmidt, {Augusto F} and Kemp, {Matthew W} and Emily Royse and Erin Fee and Fabrizio Salomone and Clarke, {Michael W} and Musk, {Gabrielle C} and Jobe, {Alan H}",
year = "2020",
month = "1",
day = "1",
doi = "10.1152/ajplung.00203.2019",
language = "English",
volume = "318",
pages = "L41--L48",
journal = "AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY",
issn = "1040-0605",
publisher = "American Physiological Society",
number = "1",

}

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 journalArticle

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 -