Evidence map›Paper›PMID 35183181›Full record

ArticleRespiratory research2022

The association between regional transcriptome profiles and lung volumes in response to mechanical ventilation and lung injury.

Yong Song, Seiha Yen, Melissa Preissner, Ellen Bennett, Stephen Dubsky, Andreas Fouras, Peter A Dargaville, Graeme R Zosky

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In one paragraph

Article in Respiratory research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Yong SongMenzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia.
Seiha YenMenzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia.
Melissa PreissnerDepartment of Mechanical and Aerospace Engineering, Monash University, Melbourne, VIC, Australia.
Ellen BennettMenzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia.
Stephen DubskyDepartment of Mechanical and Aerospace Engineering, Monash University, Melbourne, VIC, Australia.
Andreas Fouras4Dx Limited, Melbourne, VIC, Australia.
Peter A DargavilleMenzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia.
Graeme R ZoskyMenzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia. Graeme.Zosky@utas.edu.au.ORCID http://orcid.org/0000-0001-9039-0302

Funding

Australian Research Council DE180101133National Health and Medical Research Council 1160774Royal Hobart Hospital Research Foundation 19-206the Multi-modal Australian Sciences Imaging and Visualization Environment eu92
6 · The paper itself

Abstract

backgroundLung inhomogeneity plays a pivotal role in the development of ventilator-induced lung injury (VILI), particularly in the context of pre-existing lung injury. The mechanisms that underlie this interaction are poorly understood. We aimed to elucidate the regional transcriptomic response to mechanical ventilation (MV), with or without pre-existing lung injury, and link this to the regional lung volume response to MV.

methodsAdult female BALB/c mice were randomly assigned into one of four groups: Saline, MV, lipopolysaccharide (LPS) or LPS/MV. Lung volumes (tidal volume, Vt; end-expiratory volume, EEV) were measured at baseline or after 2 h of ventilation using four-dimensional computed tomography (4DCT). Regional lung tissue samples corresponding to specific imaging regions were analysed for the transcriptome response by RNA-Seq. Bioinformatics analyses were conducted and the regional expression of dysregulated gene clusters was then correlated with the lung volume response.

resultsMV in the absence of pre-existing lung injury was associated with regional variations in tidal stretch. The addition of LPS also caused regional increases in EEV. We identified 345, 141 and 184 region-specific differentially expressed genes in response to MV, LPS and LPS/MV, respectively. Amongst these candidate genes, up-regulation of genes related to immune responses were positively correlated with increased regional tidal stretch in the MV group, while dysregulation of genes associated with endothelial barrier related pathways were associated with increased regional EEV and Vt when MV was combined with LPS. Further protein-protein interaction analysis led to the identification of two protein clusters representing the PI3K/Akt and MEK/ERK signalling hubs which may explain the interaction between MV and LPS exposure.

conclusionThe biological pathways associated with lung volume inhomogeneity during MV, and MV in the presence of pre-existing inflammation, differed. MV related tidal stretch induced up-regulation of immune response genes, while LPS combined with MV disrupted PI3K/Akt and MEK/ERK signalling.

Indexed as

AnimalsDisease Models, AnimalFemaleLung InjuryLung Volume MeasurementsMiceMice, Inbred BALB CRespiration, ArtificialSignal TransductionTidal VolumeTranscriptomeLung inhomogeneitiesMechanical ventilationRNA sequencingSepsisTranscriptomeVentilator-induced lung injury

Identifiers

PMID35183181
PMCPMC8857787

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.