Evidence map›Paper›PMID 34344623›Full record

ArticleThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation2021

Donor derived cell free DNA% is elevated with pathogens that are risk factors for acute and chronic lung allograft injury.

Katrina Bazemore, Michael Rohly, Nitipong Permpalung, Kai Yu, Irina Timofte, A Whitney Brown, Jonathan Orens, Aldo Iacono, Steven D Nathan, Robin K Avery and 3 more

Abstract read
In one paragraph

Article in The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
–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

18 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Utility of donor-derived cell-free DNA testing after lung transplantation in the precision medicine era.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2026
    Review
  4. Donor-derived cell-free DNA associated with increased risk of chronic lung allograft dysfunction and mortality: Are absolute levels better than percentage?The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2026
    Observational
  5. Article
  6. Article
  7. Persistent and progressive acute lung allograft dysfunction is linked to cell compositional and transcriptional changes in small airways.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Donor Fractions of Cell-Free DNA Are Elevated During CLAD But Not During Infectious Complications After Lung Transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2024
    Article
  13. Review
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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

13 authors.

Katrina BazemoreDivision of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore.
Michael RohlyColumbus State University, Columbus, Georgia.
Nitipong PermpalungDivision of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore.
Kai YuNational Cancer Institute, National Institutes of Health, Rockville, Maryland.
Irina TimofteGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Department of Medicine, University of Maryland, College Park, Maryland.
A Whitney BrownGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Advanced Lung Disease and Transplant Program, Inova Heart and Vascular Institute, Inova Fairfax Hospital, Falls Church, Virginia.
Jonathan OrensDivision of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore; Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland.
Aldo IaconoGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Department of Medicine, University of Maryland, College Park, Maryland.
Steven D NathanGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Department of Medicine, University of Maryland, College Park, Maryland.
Robin K AveryDivision of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore.
Hannah ValantineGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Sean Agbor-EnohGenomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: Sean.agbor-enoh@nih.gov.
Pali D ShahDivision of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore; Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland. Electronic address: pdedhiy2@jhmi.edu.

Funding

Cell-free DNA to detect transplant rejectionZIAHL006268 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI AGBOR-ENOH, SEAN · 2021 to 2025
$8.8M
Intramural NIH HHS Z99 HL999999
6 · The paper itself

Abstract

backgroundAcute and chronic forms of lung allograft injury are associated with specific respiratory pathogens. Donor-derived cell free DNA (ddcfDNA) has been shown to be elevated with acute lung allograft injury and predictive of long-term outcomes. We examined the %ddcfDNA values at times of microbial isolation from bronchoalveolar lavage (BAL).

methodsTwo hundred and six BAL samples from 51 Lung Transplant Recipients (LTRs) with concurrently available plasma %ddcfDNA were analyzed along with microbiology and histopathology. Microbial species were grouped into bacterial, fungal, and viral and "higher risk" and "lower risk" cohorts based on historical association with downstream allograft dysfunction. Analyses were performed to determine pathogen category association with %ddcfDNA, independent of inter-subject variability.

resultsPresence of microbial isolates in BAL was not associated with elevated %ddcfDNA compared to samples without isolates. However, "higher risk" bacterial and viral microbes showed greater %ddcfDNA values than lower risk species (1.19% vs. 0.65%, p < 0.01), independent of inter-subject variability. Histopathologic abnormalities concurrent with pathogen isolation were associated with higher %ddcfDNA compared to isolation episodes with normal histopathology (medians 1.23% and 0.66%, p = 0.05). Assessments showed no evidence of correlation between histopathology or bronchoscopy indication and presence of higher risk vs. lower risk pathogens.

conclusion%ddcfDNA is higher among cases of microbial isolation with concurrent abnormal histopathology and with isolation of higher risk pathogens known to increase risk of allograft dysfunction. Future studies should assess if %ddcfDNA can be used to stratify pathogens for risk of CLAD and identify pathogen associated injury prior to histopathology.

Indexed as

Tissue DonorsTransplant RecipientsAgedAllograftsBronchoscopyCell-Free Nucleic AcidsFemaleFollow-Up StudiesHumansLungLung InjuryLung TransplantationMaleMiddle AgedProspective StudiesRisk AssessmentCell-Free Nucleic AcidscfDNAchronic lung allograft dysfunctionlung transplantationtransplant infection

Identifiers

PMID34344623
PMCPMC8571060

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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.