GSE131195
Surfactant plus budesonide decreases lung and systemic responses to injurious ventilation in preterm sheep
Background: Intratracheal budesonide mixed with surfactant has been investigated as an alternative to decrease lung injury and prevent bronchopulmonary dysplasia in preterm infants. However, possible systemic effects are not known. Our goal was identify systemic effects of intra-tracheal instilled budesonide by transcriptome analysis of the brain and lung in a preterm lamb model of mechanical ventilation. Methods: We performed RNA-sequencing of the fetal periventricular white matter and liver from preterm sheep after treatment with intratracheal budesonide mixed with surfactant or surfactant alone followed by mechanical ventilation. Unventilated animals were used as controls. mRNA profiles were generated from polyA selected RNA using Illumina platform. Read sequences were aligned to the sheep genome (Oar 4.0) using Bowtie2 followed read counts using featureCounts. We performed differential expression analysis  using EdgeR. Results: We identified large and significant gene expression genes both in the liver and in the priventricular white matter in animals treated with budesonide+surfactant compared to surfactant alone and unventilated animals. There were complexes synergies and antagonism of effect of ventilation and budesonide on gene expression. Ventilation induced inflammatory signaling in the periventricular white matter and liver which was partially antagonized by budesonide. Budesonide also suppressed developmental pathways in the periventricular white matter. Conclusions: Intratracheal budesonide had systemic effects including suppression of developmental pathways in the brain. These effects could have clinical implication in affecting the neurodevelopmental outcomes of preterm newborns. Overall design: mRNA profiles from periventricular white matter and liver from preterm lambs treated with surfactant + budesonide vs surfactant alone vs unventilated lambs was generated by RNA-sequencing using Illumina platform.