Evidence map›Paper›PMID 35544065›Full record

ArticleThe Lancet. Microbe2022

Lower respiratory tract infections in children requiring mechanical ventilation: a multicentre prospective surveillance study incorporating airway metagenomics.

Alexandra Tsitsiklis, Christina M Osborne, Jack Kamm, Kayla Williamson, Katrina Kalantar, Gytis Dudas, Saharai Caldera, Amy Lyden, Michelle Tan, Norma Neff and 23 more

Open access · goldAbstract readMulticenter Study
In one paragraph

Article in The Lancet. Microbe, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
9.3field-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.

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

31 citing papers in PubMed, 59 citations in OpenAlex.

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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

33 authors at 12 institutions in 1 country.

Alexandra TsitsiklisDepartment of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.
Christina M OsborneSection of Critical Care Medicine, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA; Section of Infectious Diseases, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
Jack KammChan Zuckerberg Biohub, San Francisco, CA, USA.
Kayla WilliamsonDepartment of Biostatistics and Informatics, University of Colorado, Colorado School of Public Health, Aurora, CO, USA.
Katrina KalantarChan Zuckerberg Biohub, San Francisco, CA, USA.
Gytis DudasGothenburg Global Biodiversity Centre, Gothenburg, Sweden.
Saharai CalderaDepartment of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.
Amy LydenChan Zuckerberg Biohub, San Francisco, CA, USA.
Michelle TanChan Zuckerberg Biohub, San Francisco, CA, USA.
Norma NeffChan Zuckerberg Biohub, San Francisco, CA, USA.
Victoria SoesantoDepartment of Biostatistics and Informatics, University of Colorado, Colorado School of Public Health, Aurora, CO, USA.
J Kirk HarrisSection of Pulmonary Medicine, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
Lilliam AmbroggioSection of Emergency Medicine, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA; Section of Hospital Medicine, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
Aline B MadduxSection of Critical Care Medicine, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
Todd C CarpenterSection of Critical Care Medicine, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
Ron W ReederDepartment of Pediatrics, University of Utah, Salt Lake City, UT, USA.
Chris LocandroDepartment of Pediatrics, University of Utah, Salt Lake City, UT, USA.
Eric A F SimõesSection of Infectious Diseases, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
Matthew K LeroueSection of Critical Care Medicine, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
Mark W HallDepartment of Pediatrics, Division of Critical Care Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
Athena F ZuppaAnesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Joseph CarcilloDepartment of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.
Kathleen L MeertDepartment of Pediatrics, Children's Hospital of Michigan, Central Michigan University, Detroit, MI, USA.
Anil SapruDepartment of Pediatrics, University of California Los Angeles, Los Angeles, CA, USA.
Murray M PollackDepartment of Pediatrics, Children's National Hospital and George Washington School of Medicine and Health Services, Washington, DC, USA.
Patrick S McQuillenDepartment of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Daniel A NottermanDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.
J Michael DeanDepartment of Pediatrics, University of Utah, Salt Lake City, UT, USA.
Matt S ZinterDepartment of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Brandie D WagnerDepartment of Biostatistics and Informatics, University of Colorado, Colorado School of Public Health, Aurora, CO, USA.
Joseph L DeRisiDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.
Peter M MouraniSection of Critical Care Medicine, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA; Department of Pediatrics, Section of Critical Care Medicine, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR, USA.
Charles R LangelierDepartment of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA. Electronic address: chaz.langelier@ucsf.edu.
Children's Hospital Colorado · USChan Zuckerberg Initiative (United States) · USUniversity of California, San Francisco · USColorado School of Public Health · USUniversity of Utah · USCentral Michigan University · USChildren's Hospital of Philadelphia · USChildren's National · USNationwide Children's Hospital · USPrinceton University · USUniversity of California, Los Angeles · USUniversity of Pittsburgh · US

Funding

Data Coordinating Center for the Collaborative Pediatric Critical Care Research NetworkU01HD049934 · NICHD · UNIVERSITY OF UTAH · PI DEAN, JONATHAN MICHAEL · 2005 to 2020
$35.2M
CPCCRN PRECISE SupplementPL1HD105462 · NICHD · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Kevin M Watt · 2021 to 2026
$17.5M
The Microbiome, Virome and Host Responses Preceding Ventilator-Associated PneumonR01HL124103 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI MOURANI, PETER M, SONTAG, MARCI K · 2014 to 2017
$2.7M
Collaborative Pediatric Critical Care Research Network (CPCCRN) at Children's NationalUG1HD049981 · NICHD · CHILDREN'S RESEARCH INSTITUTE · PI POLLACK, MURRAY MICHAEL, WESSEL, DAVID LLOYD · 2015 to 2020
$1.8M
Pediatric Critical Care Research Network at Children's Hospital of PhiladelphiaUG1HD063108 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI BERG, ROBERT ALLEN, ZUPPA, ATHENA F. · 2015 to 2020
$1.7M
Collaborative Research to Validate Biomarkers of Pediatric ARDSUG1HD083166 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MCQUILLEN, PATRICK SEAN, SAPRU, ANIL · 2015 to 2020
$1.6M
Integrated Host/Microbe Metagenomics to Improve Lower Respiratory Tract Infection Diagnosis in Critically Ill ChildrenR01HL155418 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LANGELIER, CHARLES · 2021 to 2024
$1.6M
Renewal Application for the Childrens Hospital of Pittsburgh Collaborative Pediatric Critical Care Research Network SiteUG1HD049983 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CARCILLO, JOSEPH A · 2015 to 2020
$1.6M
Collaborative Pediatric Critical Care Research NetworkUG1HD050096 · NICHD · WAYNE STATE UNIVERSITY · PI MEERT, KATHLEEN L. · 2015 to 2020
$1.6M
Collaborative Network Study of Airway Microbiome and Host Responses in Pediatric Respiratory FailureUG1HD083171 · NICHD · UNIVERSITY OF COLORADO DENVER · PI CARPENTER, TODD C · 2015 to 2020
$1.5M
Collaborative Pediatric Critical Care Research Network (UG1)UG1HD083170 · NICHD · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI HALL, MARK W · 2015 to 2020
$1.5M
Pathobiologic Transcriptional Signatures of Pulmonary Complications in Pediatric Hematopoietic Cellular TransplantationK23HL146936 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ZINTER, MATTHEW SCOTT · 2020 to 2024
$980k
NHLBI NIH HHS K23 HL138461NHLBI NIH HHS K23 HL146936NHLBI NIH HHS R01 HL124103NHLBI NIH HHS R01 HL155418NICHD NIH HHS PL1 HD105462NICHD NIH HHS U01 HD049934NICHD NIH HHS UG1 HD034116NICHD NIH HHS UG1 HD049981NICHD NIH HHS UG1 HD049983NICHD NIH HHS UG1 HD050096NICHD NIH HHS UG1 HD063108NICHD NIH HHS UG1 HD083166NICHD NIH HHS UG1 HD083170NICHD NIH HHS UG1 HD083171
6 · The paper itself

Abstract

backgroundLower respiratory tract infections (LRTI) are a leading cause of critical illness and mortality in mechanically ventilated children; however, the pathogenic microbes frequently remain unknown. We combined traditional diagnostics with metagenomic next generation sequencing (mNGS) to evaluate the cause of LRTI in critically ill children.

methodsWe conducted a prospective, multicentre cohort study of critically ill children aged 31 days to 17 years with respiratory failure requiring mechanical ventilation (>72 h) in the USA. By combining bacterial culture and upper respiratory viral PCR testing with mNGS of tracheal aspirate collected from all patients within 24 h of intubation, we determined the prevalence, age distribution, and seasonal variation of viral and bacterial respiratory pathogens detected by either method in children with or without LRTI.

findingsBetween Feb 26, 2015, and Dec 31, 2017, of the 514 enrolled patients, 397 were eligible and included in the study (276 children with LRTI and 121 with no evidence of LRTI). A presumptive microbiological cause was identified in 255 (92%) children with LRTI, with respiratory syncytial virus (127 [46%]), Haemophilus influenzae (70 [25%]), and Moraxella catarrhalis (65 [24%]) being most prevalent. mNGS identified uncommon pathogens including Ureaplasma parvum and Bocavirus. Co-detection of viral and bacterial pathogens occurred in 144 (52%) patients. Incidental carriage of potentially pathogenic microbes occurred in 82 (68%) children without LRTI, with rhinovirus (30 [25%]) being most prevalent. Respiratory syncytial virus (p<0·0001), H influenzae (p=0·0006), and M catarrhalis (p=0·0002) were most common in children younger than 5 years. Viral and bacterial LRTI occurred predominantly during winter months.

interpretationThese findings demonstrate that respiratory syncytial virus, H influenzae, and M catarrhalis contribute disproportionately to severe paediatric LRTI, co-infections are common, and incidental carriage of potentially pathogenic microbes occurs frequently. Further, we provide a framework for future epidemiological and emerging pathogen surveillance studies, highlighting the potential for metagenomics to enhance clinical diagnosis.

fundingUS National Institutes of Health and CZ Biohub.

Indexed as

Respiratory Syncytial Virus, HumanRespiratory Tract InfectionsBacteriaChildCohort StudiesCritical IllnessHaemophilus influenzaeHumansMetagenomicsMoraxella catarrhalisProspective StudiesRespiration, ArtificialUnited States

Identifiers

PMID35544065
PMCPMC9446282
OpenAlexW4221099766

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.