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ResearchIn-Press PreviewInflammationPulmonology Open Access | 10.1172/jci.insight.181228

Speed of lung inflation at birth influences the initiation of lung injury in preterm lambs

David G. Tingay,1 Monique Fatmous,2 Kelly Kenna,1 Jack Chapman,1 Ellen Douglas,1 Arun Sett,1 Qi Hui Poh,1 Sophia I. Dahm,1 Tuyen Kim Quach,1 Magdy Sourial,1 Haoyun Fang,3 David W. Greening,3 and Prue M. Pereira-Fantini1

1Neonatal Research, Murdoch Children's Research Institute, Parkville, Australia

2Neonatal Research, Murdoch Children’s Research Institute, Parkville, Australia

3Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Australia

Find articles by Tingay, D. in: JCI | PubMed | Google Scholar |

1Neonatal Research, Murdoch Children's Research Institute, Parkville, Australia

2Neonatal Research, Murdoch Children’s Research Institute, Parkville, Australia

3Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Australia

Find articles by Fatmous, M. in: JCI | PubMed | Google Scholar

1Neonatal Research, Murdoch Children's Research Institute, Parkville, Australia

2Neonatal Research, Murdoch Children’s Research Institute, Parkville, Australia

3Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Australia

Find articles by Kenna, K. in: JCI | PubMed | Google Scholar

1Neonatal Research, Murdoch Children's Research Institute, Parkville, Australia

2Neonatal Research, Murdoch Children’s Research Institute, Parkville, Australia

3Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Australia

Find articles by Chapman, J. in: JCI | PubMed | Google Scholar

1Neonatal Research, Murdoch Children's Research Institute, Parkville, Australia

2Neonatal Research, Murdoch Children’s Research Institute, Parkville, Australia

3Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Australia

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1Neonatal Research, Murdoch Children's Research Institute, Parkville, Australia

2Neonatal Research, Murdoch Children’s Research Institute, Parkville, Australia

3Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Australia

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1Neonatal Research, Murdoch Children's Research Institute, Parkville, Australia

2Neonatal Research, Murdoch Children’s Research Institute, Parkville, Australia

3Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Australia

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1Neonatal Research, Murdoch Children's Research Institute, Parkville, Australia

2Neonatal Research, Murdoch Children’s Research Institute, Parkville, Australia

3Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Australia

Find articles by Dahm, S. in: JCI | PubMed | Google Scholar

1Neonatal Research, Murdoch Children's Research Institute, Parkville, Australia

2Neonatal Research, Murdoch Children’s Research Institute, Parkville, Australia

3Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Australia

Find articles by Quach, T. in: JCI | PubMed | Google Scholar

1Neonatal Research, Murdoch Children's Research Institute, Parkville, Australia

2Neonatal Research, Murdoch Children’s Research Institute, Parkville, Australia

3Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Australia

Find articles by Sourial, M. in: JCI | PubMed | Google Scholar

1Neonatal Research, Murdoch Children's Research Institute, Parkville, Australia

2Neonatal Research, Murdoch Children’s Research Institute, Parkville, Australia

3Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Australia

Find articles by Fang, H. in: JCI | PubMed | Google Scholar

1Neonatal Research, Murdoch Children's Research Institute, Parkville, Australia

2Neonatal Research, Murdoch Children’s Research Institute, Parkville, Australia

3Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Australia

Find articles by Greening, D. in: JCI | PubMed | Google Scholar

1Neonatal Research, Murdoch Children's Research Institute, Parkville, Australia

2Neonatal Research, Murdoch Children’s Research Institute, Parkville, Australia

3Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Australia

Find articles by Pereira-Fantini, P. in: JCI | PubMed | Google Scholar

Published August 6, 2024 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.181228.
Copyright © 2024, Tingay et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published August 6, 2024 - Version history
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Abstract

Gas flow is fundamental for driving tidal ventilation and thus the speed of lung motion, but current bias flow settings to support the preterm lung after birth are without an evidence base. We aimed to determine the role of gas bias flow rates to generate positive pressure ventilation in initiating early lung injury pathways in the preterm lamb. Using slower speeds to inflate the lung during tidal ventilation (gas flow rates 4-6 L/min) did not impact lung mechanics, mechanical power or gas exchange compared to those currently used in clinical practice (8-10 L/min). Speed of pressure and volume change during inflation were faster with higher flow rates. Lower flow rates resulted in less bronchoalveolar fluid protein, better lung morphology and fewer detached epithelial cells. Overall, relative to unventilated fetal controls, there was greater protein change using 8-10 L/min, which was associated with enrichment of acute inflammatory and innate responses. Slowing the speed of lung motion by supporting the preterm lung from birth with lower flow rates than currently used clinically resulted in less lung injury without compromising tidal ventilation or gas exchange.

Supplemental material

View Supplemental Tables 2-6 containing proteomics data

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Version history
  • Version 1 (August 6, 2024): In-Press Preview
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