Evidence map›Paper›PMID 30239621›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2019

Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children.

Matt S Zinter, Christopher C Dvorak, Madeline Y Mayday, Kensho Iwanaga, Ngoc P Ly, Meghan E McGarry, Gwynne D Church, Lauren E Faricy, Courtney M Rowan, Janet R Hume and 11 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed, 1 pooled it
13.1field-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.

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

91 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.

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

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

21 authors at 6 institutions in 1 country.

Matt S ZinterDivision of Critical Care, University of California, San Francisco School of Medicine.
Christopher C DvorakDivision of Allergy, Immunology, and Blood & Marrow Transplantation, University of California, San Francisco School of Medicine.
Madeline Y MaydayDivision of Critical Care, University of California, San Francisco School of Medicine.
Kensho IwanagaDivision of Pulmonology, Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco School of Medicine.
Ngoc P LyDivision of Pulmonology, Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco School of Medicine.
Meghan E McGarryDivision of Pulmonology, Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco School of Medicine.
Gwynne D ChurchDivision of Pulmonology, Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco School of Medicine.
Lauren E FaricyDivision of Pulmonology, Department of Pediatrics, University of Vermont School of Medicine, Burlington.
Courtney M RowanDivision of Critical Care, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis.
Janet R HumeDivision of Critical Care, University of Minnesota School of Medicine, Minneapolis.
Marie E SteinerDivision of Critical Care, University of Minnesota School of Medicine, Minneapolis.
Emily D CrawfordChan Zuckerberg Biohub, University of California-San Francisco School of Medicine.
Charles LangelierDivision of Infectious Diseases, Department of Internal Medicine, University of California-San Francisco School of Medicine.
Katrina KalantarDepartment of Biochemistry & Biophysics, University of California-San Francisco School of Medicine.
Eric D ChowDepartment of Biochemistry & Biophysics, University of California-San Francisco School of Medicine.
Steve MillerDepartment of Laboratory Medicine, University of California-San Francisco School of Medicine.
Kristen ShimanoDivision of Allergy, Immunology, and Blood & Marrow Transplantation, University of California, San Francisco School of Medicine.
Alexis MeltonDivision of Allergy, Immunology, and Blood & Marrow Transplantation, University of California, San Francisco School of Medicine.
Gregory A YanikDivision of Oncology, Department of Pediatrics, Motts Children's Hospital, University of Michigan School of Medicine, Ann Arbor.
Anil SapruDivision of Critical Care, University of California, San Francisco School of Medicine.
Joseph L DeRisiChan Zuckerberg Biohub, University of California-San Francisco School of Medicine.
University of California, San Francisco · USUniversity of Minnesota · USRiley Hospital for Children · USUniversity of California, Los Angeles · USUniversity of Michigan · USUniversity of Vermont · US

Funding

Pediatric Scientist Development Program (PSDP) [K12]K12HD000850 · NICHD · YALE UNIVERSITY · PI Sallie R. Permar · 1987 to 2026
$44.1M
Indiana Pediatric Scientist Award(IPSA)K12HD068371 · NICHD · INDIANA UNIVERSITY INDIANAPOLIS · PI CLAPP, DAVID W · 2013 to 2017
$1.9M
Risk Factors For Worse Lung Function In Latinos With Cystic FibrosisK23HL133437 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MCGARRY, MEGHAN ELIZABETH · 2018 to 2023
$1.0M
Profiling the Lung Transcriptome for Precision Diagnosis of Respiratory Infections using Host/Pathogen Metagenomic SequencingK23HL138461 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LANGELIER, CHARLES · 2018 to 2021
$718k
NHLBI NIH HHS K23 HL133437NHLBI NIH HHS K23 HL138461NICHD NIH HHS K12 HD000850NICHD NIH HHS K12 HD068371NIMHD NIH HHS L60 MD010865
6 · The paper itself

Abstract

backgroundDespite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children.

methodsWe collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children's hospitals from 2014-2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort.

resultsWe identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range [IQR], 0.33-0.72 vs median, 0.96; IQR, 0.94-0.96; P < .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P < .001).

conclusionsAn optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease.

Indexed as

Immunocompromised HostMetagenomeAdolescentBacteriaChildChild, PreschoolFemaleFungiHigh-Throughput Nucleotide SequencingHumansLungLung DiseasesMaleMetagenomicsMicrobiotaMissed Diagnosisimmunocompromised hostintensive care unitsmetagenomicsmicrobiotapediatricrespiratory tract infections

Identifiers

PMID30239621
PMCPMC6784263
OpenAlexW2952498933

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.