Evidence map›Paper›PMID 22207676›Full record

Trial reportChest2012

The association between a Darc gene polymorphism and clinical outcomes in African American patients with acute lung injury.

Kirsten Neudoerffer Kangelaris, Anil Sapru, Carolyn S Calfee, Kathleen D Liu, Ludmila Pawlikowska, John S Witte, Eric Vittinghoff, Hanjing Zhuo, Andrew D Auerbach, Elad Ziv and 2 more

Open access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Chest, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
5.0field-weighted citation impact, top 5% 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

32 citing papers in PubMed, 63 citations in OpenAlex.

  1. Validation of age, PaORespiratory research · 2020
    Trial
  2. Trial
  3. Article
  4. Article
  5. Review
  6. Article
  7. The ultimate tradeoff: how red cell adaptations to malaria alter the host response during critical illness.American journal of physiology. Lung cellular and molecular physiology · 2023
    Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Pathogenesis of Acute Respiratory Distress Syndrome.Seminars in respiratory and critical care medicine · 2019
    Review
  16. The Evolving Erythrocyte: Red Blood Cells as Modulators of Innate Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2018
    Review
  17. Article
  18. Review
  19. The Duffy antigen receptor for chemokines regulates asthma pathophysiology.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2017
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Kirsten Neudoerffer KangelarisDepartment of Medicine, Division of General Internal Medicine, University of California, San Francisco, San Francisco, CA; Division of Hospital Medicine, University of California, San Francisco, San Francisco, CA. Electronic address: kkangelaris@medicine.ucsf.edu.
Anil SapruDepartment of Pediatrics, Division of Critical Care, University of California, San Francisco, San Francisco, CA.
Carolyn S CalfeeDivision of Pulmonary and Critical Care, University of California, San Francisco, San Francisco, CA; Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA.
Kathleen D LiuDivision of Nephrology, University of California, San Francisco, San Francisco, CA; Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA.
Ludmila PawlikowskaDepartment of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA.
John S WitteDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA.
Eric VittinghoffDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA.
Hanjing ZhuoDivision of Pulmonary and Critical Care, University of California, San Francisco, San Francisco, CA.
Andrew D AuerbachDivision of Hospital Medicine, University of California, San Francisco, San Francisco, CA.
Elad ZivDepartment of Medicine, Division of General Internal Medicine, University of California, San Francisco, San Francisco, CA.
Michael A MatthayDivision of Pulmonary and Critical Care, University of California, San Francisco, San Francisco, CA; Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA.
National Heart, Lung, and Blood Institute ARDS Network
University of California, San Francisco · USSan Francisco General Hospital · US

Funding

Pediatric Critical Care Scientist Development ProgramK12HD047349 · NICHD · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI HEATHER T. KEENAN, Kevin M Watt · 2004 to 2026
$17.0M
Resolution of Clinical Lung InjuryR37HL051856 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MATTHAY, MICHAEL A. · 2006 to 2015
$3.9M
Chemokine-related acute lung injury pathogenesis in African-American patientsK23HL116800 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KANGELARIS, KIRSTEN NEUDOERFFER · 2013 to 2017
$876k
Impact of Cigarette Smoke Exposure on Acute Lung InjuryK23HL090833 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CALFEE, CAROLYN · 2008 to 2012
$761k
Targeted Genomic Analysis of Coagulation Pathways in Acute Lung InjuryK23HL085526 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SAPRU, ANIL · 2007 to 2011
$756k
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 K23 HL085526NHLBI NIH HHS K23 HL090833NHLBI NIH HHS K23 HL116800NHLBI 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 R37 HL051856NHLBI NIH HHS R37HL51856NICHD NIH HHS HD047349NICHD NIH HHS K12 HD047349PHS HHS T32 HP19025
6 · The paper itself

Abstract

backgroundAcute lung injury (ALI) mortality is increased among African Americans compared with Americans of European descent, and genetic factors may be involved. A functional T-46C polymorphism (rs2814778) in the promoter region of Duffy antigen/receptor for chemokines (Darc) gene, present almost exclusively in people of African descent, results in isolated erythrocyte DARC deficiency and has been implicated in ALI pathogenesis in preclinical and murine models, possibly because of an increase in circulating Duffy-binding, proinflammatory chemokines like IL-8. We sought to determine the effect of the functional rs2814778 polymorphism, C/C genotype (Duffy null state), on clinical outcomes in African Americans with acute lung injury.

methodsClinical data and biologic specimens from African American patients with ALI who enrolled in three randomized controlled trials were analyzed. Multivariate analysis accounted for proportion of African ancestry, sex, cirrhosis, and severity of illness on presentation.

resultsAmong 132 subjects, 88 (67%) were Duffy null (C/C genotype). The Duffy null state was associated with a 17% absolute risk increase (95% CI, 1.4%-33%) in mortality at 60 days, a median of 8 fewer ventilator-free days (95% CI, 1-18.5), and 4.5 fewer organ failure-free days (95% CI, 0-18) compared with individuals with the C/T or T/T genotypes (all P values < .05). Estimates were similar on multivariate analysis. In African Americans without the null variant, clinical outcomes were similar to those in patients of European descent. A subgroup analysis suggested that plasma IL-8 levels are increased in Duffy null individuals.

conclusionsOur results provide evidence that the functional rs2814778 polymorphism in the gene encoding DARC is associated with worse clinical outcomes among African Americans with ALI, possibly via an increase in circulating IL-8.

Indexed as

AllelesAcute Lung InjuryAdultAgedBlack or African AmericanCause of DeathCohort StudiesDuffy Blood-Group SystemFemaleGene FrequencyGenotypeHospital MortalityHumansInterleukin-8Linkage DisequilibriumMaleACKR1 protein, humanDuffy Blood-Group SystemInterleukin-8Receptors, Cell Surface

Identifiers

PMID22207676
PMCPMC3342784
OpenAlexW2102840915

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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.