Evidence map›Paper›PMID 33941271›Full record

ArticleSkeletal muscle2021

Multi-omics reveals age-related differences in the diaphragm response to mechanical ventilation: a pilot study.

Qiong Lyu, Ya Wen, Xiang Zhang, Alex B Addinsall, Nicola Cacciani, Lars Larsson

Open access · goldAbstract readComparative Study
In one paragraph

Article in Skeletal muscle, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
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

10 citing papers in PubMed, 13 citations in OpenAlex.

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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

6 authors at 1 institution in 3 countries.

Qiong Lyu *Department of Physiology and Pharmacology, Karolinska Institutet, Bioclinicum, J8:30, SE-171 77, Stockholm, Sweden.
Ya Wen *Department of Physiology and Pharmacology, Karolinska Institutet, Bioclinicum, J8:30, SE-171 77, Stockholm, Sweden.
Xiang ZhangDepartment of Physiology and Pharmacology, Karolinska Institutet, Bioclinicum, J8:30, SE-171 77, Stockholm, Sweden.
Alex B AddinsallDepartment of Physiology and Pharmacology, Karolinska Institutet, Bioclinicum, J8:30, SE-171 77, Stockholm, Sweden.
Nicola CaccianiDepartment of Physiology and Pharmacology, Karolinska Institutet, Bioclinicum, J8:30, SE-171 77, Stockholm, Sweden.
Lars LarssonDepartment of Physiology and Pharmacology, Karolinska Institutet, Bioclinicum, J8:30, SE-171 77, Stockholm, Sweden. lars.larsson@ki.se.ORCID 0000-0003-3722-035X
Karolinska Institutet · SE

Funding

Stockholms Läns Landsting 20150423, 20170133Vetenskapsrådet 8651
6 · The paper itself

Abstract

backgroundOld age is associated with a significantly increased mortality in COVID-19 patients exposed to long-term controlled mechanical ventilation (CMV) and suggested to be due to the hyperinflammatory response associated with the viral infection. However, our understanding of age-related differences in the response to CMV in the absence of a viral infection remains insufficient.

methodsYoung (7-8 months) and old (28-32 months) F344 BN hybrid rats were exposed to the ICU condition for 5 days, i.e., complete immobilization, mechanical ventilation, and extensive monitoring. Transcriptomic (RNA-Seq) and proteomics (Proximity Extension Assay) analyses of the diaphragm and proteomics analysis of plasma were conducted to investigate the molecular differences between young and old rats exposed to the ICU condition.

resultsAccording to multi-omics analyses, significant differences were observed in the diaphragm between young and old rats in response to 5 days CMV and immobilization. In young rats, metabolic pathways were primarily downregulated in response to immobilization (post-synaptic blockade of neuromuscular transmission). In old rats, on the other hand, dramatic immune and inflammatory responses were observed, i.e., an upregulation of specific related pathways such as "IL-17 signaling pathway", along with a higher level of inflammatory factors and cytokine/chemokine in plasma.

conclusionsThe dramatically increased mortality in old ICU patients with COVID-19-associated hyperinflammation and cytokine storm need not only reflect the viral infection but may also be associated with the ventilator induced diaphragm dysfunction (VIDD) and hyperinflammatory responses induced by long-term CMV per se. Although mechanical ventilation is a life-saving intervention in COVID-19 ICU patients, CMV should be cautiously used especially in old age and other means of respiratory support may be considered, such as negative pressure ventilation.

Indexed as

ProteomeRespiration, ArtificialTranscriptomeAge FactorsAnimalsBiomarkersDiaphragmFemaleGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksInflammation MediatorsPilot ProjectsProtein Interaction MapsProteomicsRatsBiomarkersInflammation MediatorsProteomeAgeCOVID-19HyperinflammationMechanical ventilationVIDD

Identifiers

PMID33941271
PMCPMC8089133
OpenAlexW3157286292

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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.