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Title:Composition and diversity analysis of the lung microbiome in patients with suspected ventilator-associated pneumonia
Authors:ID Fenn, Dominic, Department of Respiratory Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands (Author)
ID Abdel-Aziz, Mahmoud, Department of Respiratory Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands (Author)
ID van Oort, Pouline, Department of Anaesthesiology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands (Author)
ID Brinkman, Paul, Department of Respiratory Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands (Author)
ID Ahmed, Waqar, Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom (Author)
ID Felton, Timothy, Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom (Author)
ID Artigas, Antonio, Critical Care Department, CIBER Enfermedades Respiratorias, Corporación Sanitaria Universitaria Parc Taulí, Universitat Autonoma de Barcelona, Sabadell, Spain (Author)
ID Póvoa, Pedro, Hospital de São Francisco Xavier, Centro Hospitalar Lisboa Ocidental, CHRC, NOVA Medical School, New University of Lisbon, Estr. Forte do Alto Duque, Lisbon, 1449-005, Portugal (Author)
ID Martin-Loeches, Ignacio, Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James’s Hospital, James’ St, Dublin, Ireland (Author)
ID Schultz, Marcus, Department of Intensive Care, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands (Author)
ID Dark, Paul, Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom (Author)
ID Fowler, Stephen, Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom (Author)
ID White, Iain R., Laboratory for Environmental and Life Sciences, University of Nova Gorica, Vipavska cesta, 5000 Nova Gorica, Slovenia (Author), et al.
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Language:English
Work type:Not categorized
Typology:1.01 - Original Scientific Article
Organization:UNG - University of Nova Gorica
Abstract:Background: Ventilator-associated pneumonia (VAP) is associated with high morbidity and health care costs, yet diagnosis remains a challenge. Analysis of airway microbiota by amplicon sequencing provides a possible solution, as pneumonia is characterised by a disruption of the microbiome. However, studies evaluating the diagnostic capabilities of microbiome analysis are limited, with a lack of alignment on possible biomarkers. Using bronchoalveolar lavage fluid (BALF) from ventilated adult patients suspected of VAP, we aimed to explore how key characteristics of the microbiome differ between patients with positive and negative BALF cultures and whether any differences could have a clinically relevant role. Methods: BALF from patients suspected of VAP was analysed using 16s rRNA sequencing in order to: (1) differentiate between patients with and without a positive culture; (2) determine if there was any association between microbiome diversity and local inflammatory response; and (3) correctly identify pathogens detected by conventional culture. Results: Thirty-seven of 90 ICU patients with suspected VAP had positive cultures. Patients with a positive culture had significant microbiome dysbiosis with reduced alpha diversity. However, gross compositional variance was not strongly associated with culture positivity (AUROCC range 0.66–0.71). Patients with a positive culture had a significantly higher relative abundance of pathogenic bacteria compared to those without [0.45 (IQR 0.10–0.84), 0.02 (IQR 0.004–0.09), respectively], and an increased interleukin (IL)-1β was associated with reduced species evenness (rs = − 0.33, p < 0.01) and increased pathogenic bacteria presence (rs = 0.28, p = 0.013). Untargeted 16s rRNA pathogen detection was limited by false positives, while the use of pathogen-specific relative abundance thresholds showed better diagnostic accuracy (AUROCC range 0.89–0.998). Conclusion: Patients with positive BALF culture had increased dysbiosis and genus dominance. An increased caspase-1-dependent IL-1b expression was associated with a reduced species evenness and increased pathogenic bacterial presence, providing a possible causal link between microbiome dysbiosis and lung injury development in VAP. However, measures of diversity were an unreliable predictor of culture positivity and 16s sequencing used agnostically could not usefully identify pathogens; this could be overcome if pathogen-specific relative abundance thresholds are used.
Keywords:Microbiome, Next-generation sequencing, Ventilator-associated pneumonia
Publication version:Author Accepted Manuscript
Year of publishing:2022
Number of pages:12
Numbering:26, 203
PID:20.500.12556/RUNG-7685 New window
COBISS.SI-ID:127273987 New window
DOI:10.1186/s13054-022-04068-z New window
NUK URN:URN:SI:UNG:REP:IN3GSMCW
Publication date in RUNG:26.10.2022
Views:1017
Downloads:0
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Record is a part of a journal

Title:Critical Care
Publisher:Springer Nature
Year of publishing:2022
ISSN:1364-8535

Licences

License:CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Link:http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:26.10.2022

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