Evidence map›Paper›PMID 31982041›Full record

ArticleThe Lancet. Respiratory medicine2020

Sepsis-associated acute respiratory distress syndrome in individuals of European ancestry: a genome-wide association study.

Beatriz Guillen-Guio, Jose M Lorenzo-Salazar, Shwu-Fan Ma, Pei-Chi Hou, Tamara Hernandez-Beeftink, Almudena Corrales, M Isabel García-Laorden, Jonathan Jou, Elena Espinosa, Arturo Muriel and 22 more

Open access · greenAbstract read
In one paragraph

Article in The Lancet. Respiratory medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 5 pooled it
5.3field-weighted citation impact, top 3% 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

48 citing papers in PubMed, 5 syntheses or guidelines pooled it, 71 citations in OpenAlex.

  1. Pooled it
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  6. Article
  7. Ninjurin2 Promotes Pulmonary Endothelial Barrier Dysfunction Through VEGF/VEGFR2 Signaling Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  14. Genetic associations in sepsis and ARDS.Frontiers in pharmacology · 2026
    Review
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  18. PD-L1Respiratory research · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

32 authors at 14 institutions in 4 countries.

Beatriz Guillen-GuioResearch Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
Jose M Lorenzo-SalazarGenomics Division, Instituto Tecnológico y de Energías Renovables, Santa Cruz de Tenerife, Spain.
Shwu-Fan MaDivision of Pulmonary & Critical Care Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
Pei-Chi HouDivision of Pulmonary & Critical Care Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
Tamara Hernandez-BeeftinkResearch Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain; Research Unit, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de Gran Canaria, Spain.
Almudena CorralesResearch Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
M Isabel García-LaordenResearch Unit, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de Gran Canaria, Spain; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
Jonathan JouUniversity of Illinois College of Medicine at Peoria, Peoria, IL, USA.
Elena EspinosaDepartment of Anesthesiology, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
Arturo MurielIntensive Care Unit, Hospital Universitario Rio Hortega, Valladolid, Spain.
David DomínguezDepartment of Anesthesiology, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
Leonardo LorenteIntensive Care Unit, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain.
María M MartínIntensive Care Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
Carlos Rodríguez-GallegoDepartment of Immunology, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de Gran Canaria, Spain.
Jordi Solé-ViolánIntensive Care Unit, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de Gran Canaria, Spain; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
Alfonso AmbrósIntensive Care Unit, Hospital General de Ciudad Real, Ciudad Real, Spain.
Demetrio CarriedoIntensive Care Unit, Complejo Hospitalario Universitario de León, León, Spain.
Jesús BlancoCIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Intensive Care Unit, Hospital Universitario Rio Hortega, Valladolid, Spain.
José M AñónCIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Intensive Care Unit, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
John P ReillyDivision of Pulmonary, Allergy, and Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA.
Tiffanie K JonesDivision of Pulmonary, Allergy, and Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA.
Caroline Ag IttnerDivision of Pulmonary, Allergy, and Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA.
Rui FengDepartment of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia PA, USA.
Franziska SchöneweckIntegrated Research and Treatment Center, Jena University Hospital, Jena, Germany.
Michael KiehntopfCenter for Sepsis Control and Care, Institute of Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, Jena, Germany; Integrated Biobank Jena, Jena University Hospital, Jena, Germany.
Imre NothDivision of Pulmonary & Critical Care Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
Markus ScholzInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Frank M BrunkhorstCenter for Clinical Studies, Jena University Hospital, Jena, Germany; Paul-Martini-Clinical Sepsis Research Unit, Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
André ScheragIntegrated Research and Treatment Center, Jena University Hospital, Jena, Germany; Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital, Jena, Germany.
Nuala J MeyerDivision of Pulmonary, Allergy, and Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA.
Jesús VillarResearch Unit, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de Gran Canaria, Spain; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Keenan Research Center for Biomedical Sciences at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
Carlos FloresResearch Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain; Genomics Division, Instituto Tecnológico y de Energías Renovables, Santa Cruz de Tenerife, Spain; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Tecnologías Biomédicas, Universidad de La Laguna, Santa Cruz de Tenerife, Spain. Electronic address: cflores@ull.edu.es.
Hospital Universitario Nuestra Señora de Candelaria · ESUniversity of Pennsylvania · USInstituto de Salud Carlos III · ESJena University Hospital · DEUniversity of Virginia · USHospital Universitario de Gran Canaria Doctor Negrín · ESHospital de León · ESHospital General Universitario de Ciudad Real · ESHospital Universitario de Canarias · ESHospital Universitario La Paz · ESHospital Universitario Río Hortega · ESIllinois College · USInstituto Tecnológico y de Energías Renovables · ESLeipzig University · DE

Funding

Architectural structure and regulation of TOLLIP in IPFR01HL130796 · NHLBI · UNIVERSITY OF VIRGINIA · PI NOTH, IMRE · 2016 to 2019
$3.1M
Targeting Angiopoietin-2 in ARDSR01HL137006 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MEYER, NUALA JENNINGS · 2017 to 2021
$2.5M
Reconsidering the IL-1 axis in sepsis-associated ARDSR01HL137915 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MEYER, NUALA JENNINGS · 2017 to 2020
$2.1M
NHLBI NIH HHS R01 HL130796NHLBI NIH HHS R01 HL137006NHLBI NIH HHS R01 HL137915
6 · The paper itself

Abstract

backgroundAcute respiratory distress syndrome (ARDS) is a lung inflammatory process caused mainly by sepsis. Most previous studies that identified genetic risks for ARDS focused on candidates with biological relevance. We aimed to identify novel genetic variants associated with ARDS susceptibility and to provide complementary functional evidence of their effect in gene regulation.

methodsWe did a case-control genome-wide association study (GWAS) of 1935 European individuals, using patients with sepsis-associated ARDS as cases and patients with sepsis without ARDS as controls. The discovery stage included 672 patients admitted into a network of Spanish intensive care units between January, 2002, and January, 2017. The replication stage comprised 1345 individuals from two independent datasets from the MESSI cohort study (Sep 22, 2008-Nov 30, 2017; USA) and the VISEP (April 1, 2003-June 30, 2005) and MAXSEP (Oct 1, 2007-March 31, 2010) trials of the SepNet study (Germany). Results from discovery and replication stages were meta-analysed to identify association signals. We then used RNA sequencing data from lung biopsies, in-silico analyses, and luciferase reporter assays to assess the functionallity of associated variants.

findingsWe identified a novel genome-wide significant association with sepsis-associated ARDS susceptibility (rs9508032, odds ratio [OR] 0·61, 95% CI 0·41-0·91, p=5·18 × 10

interpretationA common variant within the FLT1 gene is associated with sepsis-associated ARDS. Our findings support a role for the vascular endothelial growth factor signalling pathway in ARDS pathogenesis and identify VEGFR-1 as a potential therapeutic target.

fundingInstituto de Salud Carlos III, European Regional Development Funds, Instituto Tecnológico y de Energías Renovables.

Indexed as

Case-Control StudiesGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansRespiratory Distress SyndromeSepsisVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1White PeopleFLT1 protein, humanVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1

Identifiers

PMID31982041
PMCPMC7772505
OpenAlexW3003044105

What OpenQuestion holds

Textmetadata
LicenceTDM
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Registered trials

None linked

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.