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

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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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. Budesonide with surfactant will decrease the lung injury from mechanical ventilation for 24 h in preterm sheep. Lambs at 126 ± 1 day gestational age were delivered and randomized to either: 1) surfactant (200 mg/kg) or 2) surfactant mixed with budesonide (0.25 mg/kg) before mechanical ventilation with VT of 7-8 ml/kg for 2, 6, or 24 h (n = 6 or 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. High initial budesonide plasma levels of 170 ng/ml decreased to 3 ng/ml at 24 h. Lung tissue budesonide levels were less than 1% of initial dose by 24 h. Although physiological variables were generally similar, budesonide- exposed lambs required lower mean airway pressures, had higher hyperoxia responses, and had more stable blood pressures. Budesonide decreased proinflammatory mRNA in the lung, liver, and brain. Budesonide also decreased total protein and proinflammatory cytokines in BALF, and decreased inducible nitric oxide synthase activation at 24 h. 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 (US)
Pages (from-to)L888-L893
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume316
Issue number5
DOIs
StatePublished - May 2019
Externally publishedYes

Keywords

  • Bronchopulmonary dysplasia
  • Lung inflammation
  • Prematurity

ASJC Scopus subject areas

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

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