Surfactant plus budesonide decreases lung and systemic inflammation in mechanically ventilated preterm sheep

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

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

BACKGROUND: Mechanical ventilation with normal tidal volumes (VT) causes lung and systemic inflammation in preterm sheep. Mechanical ventilation is associated with bronchopulmonary dysplasia (BPD) in preterm infants, and the addition of budesonide to surfactant decreases BPD in clinical trials.

HYPOTHESIS: Budesonide with surfactant will decrease the lung injury from mechanical ventilation for 24 h in preterm sheep.

METHODS: Lambs at 126 + 1 d GA were delivered and randomized to either: A) surfactant (200 mg/kg) or B) surfactant mixed with budesonide (0.25 mg/kg) prior to mechanical ventilation with VT of 7-8 mL/kg for 2, 6, or 24 h (n=6-7/group). Lung physiology and budesonide levels in the plasma and the lung were measured. Lung tissue, bronchoalveolar lavage fluid (BALF), liver, and brain tissues were evaluated for indicators of injury.

RESULTS: High initial budesonide plasma levels of 170 ng/mldecreased to 3 ng/ml at 24 h. Lung tissue budesonide levels were less than 1% of initial dose by 24 h. Although physiologic variables were generally similar, budesonide exposed lambs required lower mean airway pressures, had higher hyperoxia responses, and had more stable blood pressures. Budesonide decreased pro-inflammatory mRNA in the lung, liver, and brain. Budesonide also decreased total protein and pro-inflammatory cytokines in BALF, and decreased iNOS activation at 24 h.

CONCLUSION: In ventilated preterm lambs, most of the budesonide left the lung within 24 h. The addition of budesonide to surfactant improved physiology, decreased markers of lung injury, and decreased systemic responses in liver and brain.

Original languageEnglish
Pages (from-to)L888-L893
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume316
Issue number5
DOIs
Publication statusPublished - 1 May 2019

Fingerprint

Dive into the research topics of 'Surfactant plus budesonide decreases lung and systemic inflammation in mechanically ventilated preterm sheep'. Together they form a unique fingerprint.

Cite this