Poster Presentation 29th Annual Lorne Proteomics Symposium 2024

Low gas flow rates reduce early preterm lung injury in preterm lambs (#120)

David G Tingay 1 2 , Monique Fatmous 1 , Kelly Kenna 1 , Jack Chapman 1 2 , Ellen Douglas 1 , Arun Sett 1 3 4 , Lovelle Poh 1 , Anna Quach 1 2 , Sophia Dahm 1 , Magdy Sourial 1 5 , Haoyun Fang 6 7 , David W Greening 6 7 8 , Prue Pereira-Fantini 1 2
  1. Neonatal Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
  2. Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
  3. Newborn Services, Joan Kirner Women's and Children's, Sunshine Hospital, Western Health , Melbourne, Victoria, Australia
  4. Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia
  5. Translation Research Unit, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
  6. Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
  7. Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, Victoria, Australia
  8. Baker Department of Cardiovascular Research, Translation and Implementation, La Trobe University, Melbourne, Victoria, Australia

Background

Many preterm infants require artificial breathing support with positive pressure ventilation (PPV) after birth.  Whilst lifesaving, short periods of PPV can initiate preterm lung injury which may lead to chronic lung disease. Within the delivery room, clinicians can control two settings during PPV; the amount of pressure used (inflating pressure) and the speed of that lung inflation – bias (gas) flow – which determines how quickly the lung takes to reach set inflating pressure. There is currently no evidence-based justification for applied gas flow settings at birth.

Objective

To determine the role of gas flow rates in initiating early lung injury pathways in the preterm lung using a lamb model of prematurity.

Design/Methods

Steroid-exposed preterm lambs (124-127d; 23-25 week human gestation equivalent) (n=44, 8-10/group) were randomly allocated to 15-min of PPV using 4, 6 or 8-10 L/min gas flow during placental circulation. Based on the lack of injury differences between 4 and 6 L/min, the study was repeated using low (4-6) or high (8-10) L/min flow rates for 90-min in steroid-exposed, surfactant-treated preterm lambs (126-129d; 27-28 week equivalent) (n=45, 15/group) to elucidate the role of gas flow on potentiation of lung injury. Unventilated controls (n=11-13) were obtained for comparative analyses.

Lung mechanics and aeration were measured throughout ventilation, and bronchoalveolar fluid and lung tissue collected for histology and proteomics. Matched lung tissue samples from gravity non-dependent and dependent regions were TMT-labelled and analysed using LC-MS/MS in data-dependent acquisition mode. EdgeR was used to identify differentially expressed proteins (DEPs, FDR<0.05) and gene set enrichment analysis performed for bioinformatic analysis. 

Results

The speed and acceleration of pressure and volume change during inflation was faster with increasing flow rates, although this did not compromise ventilation and gas exchange. Lower flow rates resulted in less bronchoalveolar fluid protein concentration and detached epithelial cells (markers of injury), and better lung morphology. 1543 (15-min) and 2588 (90-min) proteins were quantified with mass spectrometry, with high flow groups containing the greatest number of DEPs across lung regions, and greater abundance of acute inflammatory and innate immune response proteins compared to low flow at 90-min. Lower flow rates increased platelet-derived growth factor (PDGF) signalling at 90-min (decreased signalling associated with bronchopulmonary dysplasia).

Conclusion(s)

Our combination of clinical and proteomic measures highlight that supporting the preterm lung with lower gas flow rates than currently used clinically, resulted in less lung injury without compromising tidal ventilation or gas exchange.