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Speed of lung inflation at birth influences the initiation of lung injury in preterm lambs
David G. Tingay, … , David W. Greening, Prue M. Pereira-Fantini
David G. Tingay, … , David W. Greening, Prue M. Pereira-Fantini
Published August 6, 2024
Citation Information: JCI Insight. 2024;9(18):e181228. https://doi.org/10.1172/jci.insight.181228.
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Research Article Inflammation Pulmonology

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

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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 do not have 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 affect lung mechanics, mechanical power, or gas exchange compared with 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 in current clinical use resulted in less lung injury without compromising tidal ventilation or gas exchange.

Authors

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

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Figure 6

Proteome analysis of nondependent and dependent lung following 15- and 90-minute ventilation at different flow rates.

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Proteome analysis of nondependent and dependent lung following 15- and 9...
(A–H) Principal component analysis (PCA) of 15-minute nondependent (A), dependent (B), and 90-minute nondependent (C) and dependent (D) lung, with prediction ellipses depicted at a confidence interval of 0.95. Venn diagram of differentially expressed proteins (DEPs) identified in 15-minute nondependent (E), dependent (F), and 90-minute nondependent (G) and dependent (H) lung protein datasets. (I–R) QL F-test with multiplicity correction testing applied using Benjamin-Hochberg method; FDR < 0.05. Volcano plots of 15-minute nondependent (I–K) and dependent (L–N) and 90-minute nondependent (O and P) and dependent (Q and R) protein data sets, with DEPs that display increased abundance highlighted in red and DEPs with decreased abundance highlighted in blue. (S–U) Top 10 DEP abundance in 90-minute nondependent (S) and dependent (T) lung, represented as Log2(fold change) relative to UVC90, and their protein-protein network interaction STRING (U), with high confidence (0.700) and FDR < 0.0001.

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