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Respiratory strategy at birth initiates distinct lung injury phenotypes in the preterm lamb lung

View ORCID ProfilePrue M. Pereira-Fantini, Kristin Ferguson, Karen McCall, View ORCID ProfileRegina Oakley, Elizabeth Perkins, View ORCID ProfileSean Byars, View ORCID ProfileNicholas Williamson, View ORCID ProfileShuai Nie, View ORCID ProfileDavid G Tingay
doi: https://doi.org/10.1101/2022.09.06.506865
Prue M. Pereira-Fantini
1Neonatal Research Group, Murdoch Children’s Research Institute, Parkville, Victoria, Australia
2Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia
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  • For correspondence: prue.pereira@mcri.edu.au
Kristin Ferguson
3Neonatology, The Royal Children’s Hospital, Parkville, Victoria, Australia
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Karen McCall
1Neonatal Research Group, Murdoch Children’s Research Institute, Parkville, Victoria, Australia
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Regina Oakley
1Neonatal Research Group, Murdoch Children’s Research Institute, Parkville, Victoria, Australia
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Elizabeth Perkins
1Neonatal Research Group, Murdoch Children’s Research Institute, Parkville, Victoria, Australia
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Sean Byars
4Howard Florey Institute, Parkville, Victoria, Australia
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Nicholas Williamson
5Melbourne Mass Spectrometry and Proteomics Facility (MMSPF), The Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia
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Shuai Nie
5Melbourne Mass Spectrometry and Proteomics Facility (MMSPF), The Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia
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David G Tingay
1Neonatal Research Group, Murdoch Children’s Research Institute, Parkville, Victoria, Australia
2Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia
3Neonatology, The Royal Children’s Hospital, Parkville, Victoria, Australia
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ABSTRACT

Bronchopulmonary disease is the chronic manifestation of the acute injury that may accompany ventilation following preterm birth. A lack of clear trial evidence often hampers clinical decision-making during support of the preterm lung at birth. Protein biomarkers have been used to define acute lung injury phenotypes and improve patient selection for specific interventions in adult respiratory distress syndrome. Here we present a mass spectrometry-based approach to profile the protein phenotype associated with three different aeration strategies known to cause different pathophysiological responses when applied at birth to preterm lambs. We were able to identify pathway enrichments specific to both ventilation strategy and lung regions based upon gravity-dependency. Ventilation strategy-specific phenotypes were further delineated by applying partial least square modelling to identify associations between specific proteins and clinical, physiological and morphological outcomes. This work highlights the specificity of lung injury responses to routinely applied birth interventions such as different respiratory support approaches and identified the molecular events associated with each. Furthermore, we demonstrate the capacity to subdivide preterm infants by the direct aetiology and response to lung injury; the first step towards true precision medicine in neonatology.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • The authors have declared that no conflict of interest exists

  • https://doi.org/10.26188/19252103.v1

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 08, 2022.
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Respiratory strategy at birth initiates distinct lung injury phenotypes in the preterm lamb lung
Prue M. Pereira-Fantini, Kristin Ferguson, Karen McCall, Regina Oakley, Elizabeth Perkins, Sean Byars, Nicholas Williamson, Shuai Nie, David G Tingay
bioRxiv 2022.09.06.506865; doi: https://doi.org/10.1101/2022.09.06.506865
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Respiratory strategy at birth initiates distinct lung injury phenotypes in the preterm lamb lung
Prue M. Pereira-Fantini, Kristin Ferguson, Karen McCall, Regina Oakley, Elizabeth Perkins, Sean Byars, Nicholas Williamson, Shuai Nie, David G Tingay
bioRxiv 2022.09.06.506865; doi: https://doi.org/10.1101/2022.09.06.506865

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