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Asthma and wheeze severity and the oropharyngeal microbiota in children and adolescents

Asthma and wheeze severity and the oropharyngeal microbiota in children and adolescents
Asthma and wheeze severity and the oropharyngeal microbiota in children and adolescents

Rationale: there is a major unmet need for improving the care of children and adolescents with severe asthma and wheeze. Identifying factors contributing to disease severity may lead to improved diagnostics, biomarkers, or therapies. The airway microbiota may be such a key factor. 

Objectives: to compare the oropharyngeal airway microbiota of children and adolescents with severe and mild/moderate asthma/wheeze. 

Methods: oropharyngeal swab samples from school-age and preschool children in the European U-BIOPRED (Unbiased BIOmarkers in the PREDiction of respiratory disease outcomes) multicenter study of severe asthma, all receiving severity-appropriate treatment, were examined using 16S ribosomal RNA gene sequencing. Bacterial taxa were defined as amplicon sequence variants. 

Results: we analyzed 241 samples from four cohorts: A) 86 school-age children with severe asthma; B) 39 school-age children with mild/moderate asthma; C) 65 preschool children with severe wheeze; and D) 51 preschool children with mild/moderate wheeze. The most common bacteria were Streptococcus (mean relative abundance, 33.5%), Veillonella (10.3%), Haemophilus (7.0%), Prevotella (5.9%), and Rothia (5.5%). Age group (school-age vs. preschool) was associated with the microbiota in β-diversity analysis (F = 3.32, P = 0.011) and in a differential abundance analysis (28 significant amplicon sequence variants). Among all children, we found no significant difference in the microbiota between children with severe and mild/moderate asthma/wheeze in univariable β-diversity analysis (F = 1.99, P = 0.08, N = 241), but a significant difference in a multivariable model (F = 2.66, P = 0.035), including the number of exacerbations in the previous year. Age was also significant when expressed as a microbial maturity score (Spearman Rho, 0.39; P = 4.6 × 10-10); however, this score was not associated with asthma/wheeze severity. 

Conclusions: there was a modest difference in the oropharyngeal airway microbiota between children with severe and mild/moderate asthma/wheeze across all children but not in individual age groups, and a strong association between the microbiota and age. This suggests the oropharyngeal airway microbiota as an interesting entity in studying asthma severity, but probably without the strength to serve as a biomarker for targeted intervention.

airway, microbiota, oropharyngeal, pediatrics, severe asthma
2329-6933
2031-2043
Thorsen, Jonathan
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Stokholm, Jakob
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Rasmussen, Morten Arendt
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Roggenbuck-Wedemeyer, Michael
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Vissing, Nadja H.
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Mortensen, Martin S.
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Brejnrod, Asker D.
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Fleming, Louise
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Bush, Andrew
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Roberts, Graham
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Singer, Florian
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Frey, Urs
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Hedlin, Gunilla
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Nordlund, Björn
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Murray, Clare S.
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Abdel-Aziz, Mahmoud I.
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Hashimoto, Simone
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van Aalderen, Wim
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Maitland-van der Zee, Anke H.
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Shaw, Dominick
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Fowler, Stephen J.
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Sousa, Ana
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Sterk, Peter J
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Chung, Kian Fan
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Adcock, Ian M.
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Djukanovic, Ratko
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Auffray, Charles
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Bansal, Aruna T.
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Wagers, Scott
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Chawes, Bo
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Bønnelykke, Klaus
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Sørensen, Søren Johannes
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Bisgaard, Hans
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Thorsen, Jonathan
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Stokholm, Jakob
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Rasmussen, Morten Arendt
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Roggenbuck-Wedemeyer, Michael
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Vissing, Nadja H.
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Mortensen, Martin S.
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Brejnrod, Asker D.
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Fleming, Louise
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Bush, Andrew
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Roberts, Graham
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Singer, Florian
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Frey, Urs
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Hedlin, Gunilla
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Nordlund, Björn
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Murray, Clare S.
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Abdel-Aziz, Mahmoud I.
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Hashimoto, Simone
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van Aalderen, Wim
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Maitland-van der Zee, Anke H.
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Shaw, Dominick
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Fowler, Stephen J.
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Sousa, Ana
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Sterk, Peter J
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Chung, Kian Fan
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Adcock, Ian M.
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Djukanovic, Ratko
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Auffray, Charles
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Bansal, Aruna T.
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Wagers, Scott
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Chawes, Bo
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Bønnelykke, Klaus
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Sørensen, Søren Johannes
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Bisgaard, Hans
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Thorsen, Jonathan, Stokholm, Jakob, Rasmussen, Morten Arendt, Roggenbuck-Wedemeyer, Michael, Vissing, Nadja H., Mortensen, Martin S., Brejnrod, Asker D., Fleming, Louise, Bush, Andrew, Roberts, Graham, Singer, Florian, Frey, Urs, Hedlin, Gunilla, Nordlund, Björn, Murray, Clare S., Abdel-Aziz, Mahmoud I., Hashimoto, Simone, van Aalderen, Wim, Maitland-van der Zee, Anke H., Shaw, Dominick, Fowler, Stephen J., Sousa, Ana, Sterk, Peter J, Chung, Kian Fan, Adcock, Ian M., Djukanovic, Ratko, Auffray, Charles, Bansal, Aruna T., Wagers, Scott, Chawes, Bo, Bønnelykke, Klaus, Sørensen, Søren Johannes and Bisgaard, Hans (2022) Asthma and wheeze severity and the oropharyngeal microbiota in children and adolescents. Annals of the American Thoracic Society, 19 (12), 2031-2043. (doi:10.1513/AnnalsATS.202110-1152OC).

Record type: Article

Abstract

Rationale: there is a major unmet need for improving the care of children and adolescents with severe asthma and wheeze. Identifying factors contributing to disease severity may lead to improved diagnostics, biomarkers, or therapies. The airway microbiota may be such a key factor. 

Objectives: to compare the oropharyngeal airway microbiota of children and adolescents with severe and mild/moderate asthma/wheeze. 

Methods: oropharyngeal swab samples from school-age and preschool children in the European U-BIOPRED (Unbiased BIOmarkers in the PREDiction of respiratory disease outcomes) multicenter study of severe asthma, all receiving severity-appropriate treatment, were examined using 16S ribosomal RNA gene sequencing. Bacterial taxa were defined as amplicon sequence variants. 

Results: we analyzed 241 samples from four cohorts: A) 86 school-age children with severe asthma; B) 39 school-age children with mild/moderate asthma; C) 65 preschool children with severe wheeze; and D) 51 preschool children with mild/moderate wheeze. The most common bacteria were Streptococcus (mean relative abundance, 33.5%), Veillonella (10.3%), Haemophilus (7.0%), Prevotella (5.9%), and Rothia (5.5%). Age group (school-age vs. preschool) was associated with the microbiota in β-diversity analysis (F = 3.32, P = 0.011) and in a differential abundance analysis (28 significant amplicon sequence variants). Among all children, we found no significant difference in the microbiota between children with severe and mild/moderate asthma/wheeze in univariable β-diversity analysis (F = 1.99, P = 0.08, N = 241), but a significant difference in a multivariable model (F = 2.66, P = 0.035), including the number of exacerbations in the previous year. Age was also significant when expressed as a microbial maturity score (Spearman Rho, 0.39; P = 4.6 × 10-10); however, this score was not associated with asthma/wheeze severity. 

Conclusions: there was a modest difference in the oropharyngeal airway microbiota between children with severe and mild/moderate asthma/wheeze across all children but not in individual age groups, and a strong association between the microbiota and age. This suggests the oropharyngeal airway microbiota as an interesting entity in studying asthma severity, but probably without the strength to serve as a biomarker for targeted intervention.

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220419_UBP_mb_manus_AATS_R2_Clean - Accepted Manuscript
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Accepted/In Press date: 29 July 2022
e-pub ahead of print date: 29 July 2022
Published date: 1 December 2022
Keywords: airway, microbiota, oropharyngeal, pediatrics, severe asthma

Identifiers

Local EPrints ID: 473841
URI: http://eprints.soton.ac.uk/id/eprint/473841
ISSN: 2329-6933
PURE UUID: 8d7e392a-ae86-4f79-aa84-191df4961faa
ORCID for Graham Roberts: ORCID iD orcid.org/0000-0003-2252-1248
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

Catalogue record

Date deposited: 01 Feb 2023 17:42
Last modified: 17 Mar 2024 07:30

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Contributors

Author: Jonathan Thorsen
Author: Jakob Stokholm
Author: Morten Arendt Rasmussen
Author: Michael Roggenbuck-Wedemeyer
Author: Nadja H. Vissing
Author: Martin S. Mortensen
Author: Asker D. Brejnrod
Author: Louise Fleming
Author: Andrew Bush
Author: Graham Roberts ORCID iD
Author: Florian Singer
Author: Urs Frey
Author: Gunilla Hedlin
Author: Björn Nordlund
Author: Clare S. Murray
Author: Mahmoud I. Abdel-Aziz
Author: Simone Hashimoto
Author: Wim van Aalderen
Author: Anke H. Maitland-van der Zee
Author: Dominick Shaw
Author: Stephen J. Fowler
Author: Ana Sousa
Author: Peter J Sterk
Author: Kian Fan Chung
Author: Ian M. Adcock
Author: Charles Auffray
Author: Aruna T. Bansal
Author: Scott Wagers
Author: Bo Chawes
Author: Klaus Bønnelykke
Author: Søren Johannes Sørensen
Author: Hans Bisgaard

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