Evidence map›Paper›PMID 24853585›Full record

Trial reportThe Lancet. Respiratory medicine2014

Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials.

Carolyn S Calfee, Kevin Delucchi, Polly E Parsons, B Taylor Thompson, Lorraine B Ware, Michael A Matthay, NHLBI ARDS Network

6 registry-linked trialsOpen access · greenAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Respiratory medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 6 registered trials, which are not on this map. Cited by 959 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
959citing papers in PubMed, 6 pooled it
33.3field-weighted citation impact, top 1% 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.

NCT02644798 completednot on this mapstarted 2016, after this paper: background citation

Nucleotide Polymorphism in ARDS Outcome: a Whole Exome Sequencing Association Study

TypeobservationalSponsorSoutheast University, ChinaRan2016 to 2017Enrolled105ConditionsARDSArmsBaseline-recorded data recorded
NCT05075161 phase3recruitingnot on this mapstarted 2022, after this paper: background citation

Pirfenidone to Prevent Fibrosis in ARDS. A Randomized Controlled Trial - PIONEER

TypeinterventionalSponsorUniversità Vita-Salute San RaffaeleRan2022 to 2026Enrolled130ConditionsAcute Respiratory Distress Syndrome (ARDS)ArmsPirfenidone, Placebo
NCT06123962 recruitingnot on this mapstarted 2023, after this paper: background citation

Acute Lung/ Acute Respiratory Distress Syndrome and Extra-pulmonary Organ Injury Clinical Sub-phenotyping Study

TypeobservationalSponsorChina-Japan Friendship HospitalRan2023 to 2025Enrolled1,500ConditionsAcute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)ArmsCollect peripheral blood and bronchoalveolar lavage fluid
NCT07281911 not yet recruitingnot on this mapstarted 2026, after this paper: background citation

Characterization of Early Biological and Mechanical Profiles in Sepsis-Associated ARDS for Studying Compartmentalization (Serial Bronchoalveolar Lavage and Plasma Biomarkers) to Identify Inflammatory and Hybrid Subphenotypes

TypeobservationalSponsorHospital Universitari Vall d'Hebron Research InstituteRan2026 to 2029Enrolled145ConditionsAcute Hypoxemic Respiratory Failure, Sepsis, ARDS (Acute Respiratory Distress Syndrome)ArmsSerial bronchoalveolar lavage and biological-physiological assessment
NCT07511582 phase2recruitingnot on this mapstarted 2026, after this paper: background citation

Efficacy, Safety, and Tolerability of Methylprednisolone in Critically Ill Patients With the Hyperinflammatory Phenotype: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Trial

TypeinterventionalSponsorBin DuRan2026 to 2028Enrolled150ConditionsSepsis, Acute Respiratory Distress SyndromeArmsMethylprednisolone (MP), Placebo
NCT07779642 phase2not yet recruitingnot on this mapstarted 2026, after this paper: background citation

Precision Medicine Adaptive Network Platform Trial in Hypoxemic Acute Respiratory Failure

TypeinterventionalSponsorUniversity of Colorado, DenverRan2026 to 2030Enrolled300ConditionsARDS (Acute Respiratory Distress Syndrome), Acute Hypoxic Respiratory FailureArmsSimvastatin, Baricitinib
3 · Its place in the literature

Who cites it

959 citing papers in PubMed, 6 syntheses or guidelines pooled it, 1,486 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Guideline
  5. Pooled it
  6. Pooled it
  7. Trial
  8. Trial
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Review
  14. Article
  15. Article
  16. Review
  17. Observational
  18. Article
  19. Article
  20. Article

899 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Carolyn S CalfeeDepartments of Medicine and Anesthesia, Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, CA, USA. Electronic address: carolyn.calfee@ucsf.edu.
Kevin DelucchiDepartment of Psychiatry, University of California San Francisco, San Francisco, CA, USA.
Polly E ParsonsDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, University of Vermont, Burlington, VT, USA.
B Taylor ThompsonDepartment of Medicine, Pulmonary and Critical Care Medicine Unit, Massachusetts General Hospital, Boston, MA, USA; Biostatistics Unit, Massachusetts General Hospital, Boston, MA, USA.
Lorraine B WareDepartment of Medicine, Division of Allergy, Pulmonary and Critical Care, Vanderbilt, University, Nashville, TN, USA.
Michael A MatthayDepartments of Medicine and Anesthesia, Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, CA, USA; Cardiovascular Research Institute, San Francisco, CA, USA.
NHLBI ARDS Network
University of California, San Francisco · USMassachusetts General Hospital · USUniversity of Vermont · USVanderbilt University · US

Funding

Resolution of Clinical Lung InjuryR37HL051856 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MATTHAY, MICHAEL A. · 2006 to 2015
$3.9M
Cigarette Smoke Exposure and Acute Lung Injury After Severe Blunt TraumaR01HL110969 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CALFEE, CAROLYN · 2012 to 2016
$1.9M
RESOLUTION OF CLINICAL LUNG INJURYR01HL051856 · NHLBI · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI MATTHAY, MICHAEL A. · 1996 to 2005
$1.7M
Midcareer Investigator Award in Patient-Oriented Research in Acute Lung InjuryK24HL103836 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WARE, LORRAINE B · 2010 to 2020
$1.6M
Impact of Cigarette Smoke Exposure on Acute Lung InjuryK23HL090833 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CALFEE, CAROLYN · 2008 to 2012
$761k
CENTER FOR CLINICAL NETWORK FOR ARDS TREATMENT-N01HR46064-268046064N01HR046064 · HR · MASSACHUSETTS GENERAL HOSPITAL · 1994 to 2005
$706k
CCTG CLINICAL NETWORK FOR ARDS TREATMENT--CRITICAL CAREN01HR046059 · HR · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI MATTHAY, MICHAEL A. · 1994 to 2000
$682k
CLINICAL CENTERS--A NETWORK FOR THE TREATMENT OF ARDN01HR046063 · HR · UNIVERSITY OF MARYLAND BALTIMORE · PI SILVERMAN, HENRY J · 1994 to 2000
$649k
CLINICAL CENTERS--A NETWORK FOR THE TREAMENT OF ARDN01HR046062 · HR · LDS HOSPITAL · PI MORRIS, ALAN H · 1994 to 2000
$645k
CLINICAL CENTERS--A NETWORK FOR THE TREATMENT OF ARDN01HR046061 · HR · UNIVERSITY OF COLORADO DENVER · PI ABRAHAM, EDWARD · 1994 to 2000
$577k
CCTG CLINICAL NETWORK FOR ARDS TREATMENT--CRITICAL CAREN01HR046055 · HR · UNIVERSITY OF WASHINGTON · PI HUDSON, LEONARD D · 1994 to 2000
$468k
CCTG CLINICAL NETWORK FOR ARDS TREATMENT--CRITICAL CAREN01HR046054 · HR · VANDERBILT UNIVERSITY · PI WHEELER, ARTHUR P · 1994 to 2000
$464k
NHLBI NIH HHS HL090833NHLBI NIH HHS HL103836NHLBI NIH HHS HL112656NHLBI NIH HHS HL 51856NHLBI NIH HHS K23 HL090833NHLBI NIH HHS K24 HL103836NHLBI NIH HHS N01 HR046054NHLBI NIH HHS N01-HR 46054NHLBI NIH HHS N01-HR 46055NHLBI NIH HHS N01-HR 46056NHLBI NIH HHS N01-HR 46057NHLBI NIH HHS N01-HR 46058NHLBI NIH HHS N01-HR 46059NHLBI NIH HHS N01-HR 46060NHLBI NIH HHS N01-HR 46061NHLBI NIH HHS N01-HR 46062NHLBI NIH HHS N01-HR 46063NHLBI NIH HHS N01-HR 46064NHLBI NIH HHS R01 HL051856NHLBI NIH HHS R01 HL110969NHLBI NIH HHS R21 HL112656NHLBI NIH HHS R37 HL051856PHS HHS 110969
6 · The paper itself

Abstract

backgroundSubphenotypes have been identified within heterogeneous diseases such as asthma and breast cancer, with important therapeutic implications. We assessed whether subphenotypes exist within acute respiratory distress syndrome (ARDS), another heterogeneous disorder.

methodsWe used data from two ARDS randomised controlled trials (ARMA trial and ALVEOLI trial), sponsored by the National Heart, Lung, and Blood Institute. We applied latent class modelling to identify subphenotypes using clinical and biological data. We modelled data from both studies independently. We then tested the association of subphenotypes with clinical outcomes in both cohorts and with the response to positive end-expiratory pressure (PEEP) in the ALVEOLI cohort.

findingsWe analysed data for 1022 patients: 473 in the ARMA cohort and 549 in the ALVEOLI cohort. Independent latent class models indicated that a two-class (ie, two subphenotype) model was the best fit for both cohorts. In both cohorts, we identified a hyperinflammatory subphenotype (phenotype 2) that was characterised by higher plasma concentrations of inflammatory biomarkers, a higher prevalence of vasopressor use, lower serum bicarbonate concentrations, and a higher prevalence of sepsis than phenotype 1. Participants in phenotype 2 had higher mortality and fewer ventilator-free days and organ failure-free days in both cohorts than did those in phenotype 1 (p<0·007 for all). In the ALVEOLI cohort, the effects of ventilation strategy (high PEEP vs low PEEP) on mortality, ventilator-free days and organ failure-free days differed by phenotype (p=0·049 for mortality, p=0·018 for ventilator-free days, p=0·003 for organ-failure-free days).

interpretationWe have identified two subphenotypes within ARDS, one of which is categorised by more severe inflammation, shock, and metabolic acidosis and by worse clinical outcomes. Response to treatment in a randomised trial of PEEP strategies differed on the basis of subphenotype. Identification of ARDS subphenotypes might be useful in selecting patients for future clinical trials.

fundingNational Institutes of Health.

Indexed as

Models, StatisticalPhenotypeAdultAgedAPACHEBicarbonatesBiomarkersFemaleHumansInflammationInflammation MediatorsMaleMiddle AgedRespiration, ArtificialRespiratory Distress SyndromeSepsisBicarbonatesBiomarkersInflammation MediatorsVasoconstrictor Agents

Identifiers

PMID24853585
PMCPMC4154544
OpenAlexW2124519382

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.