Distinct nasal airway bacterial microbiotas differentially relate to exacerbation in pediatric patients with asthma

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

31201890

DOI Digital object identifier for electronic documents.

10.1016/j.jaci.2019.05.035

URI

Authors

McCauley K, Durack J, Valladares R, Fadrosh DW, Lin DL, Calatroni A, LeBeau PK, Tran HT, Fujimura KE, LaMere B, Merana G, Lynch K, Cohen RT, Pongracic J, Khurana Hershey GK, Kercsmar CM, Gill M, Liu AH, Kim H, Kattan M, Teach SJ, Togias A, Boushey HA, Gern JE, Jackson DJ, Lynch SV

Journal

The Journal of allergy and clinical immunology

Year

2019

Keywords:

16S rRNA, Microbiota, Moraxella species, Staphylococcus species, airway, asthma, exacerbation, rhinovirus

BACKGROUND: In infants, distinct nasopharyngeal bacterial microbiotas differentially associate with the incidence and severity of acute respiratory tract infection and childhood asthma development. OBJECTIVE: We hypothesized that distinct nasal airway microbiota structures also exist in children with asthma and relate to clinical outcomes. METHODS: Nasal secretion samples (n = 3122) collected after randomization during the fall season from children with asthma (6-17 years, n = 413) enrolled in a trial of omalizumab (anti-IgE) underwent 16S rRNA profiling. Statistical analyses with exacerbation as the primary outcome and rhinovirus infection and respiratory illnesses as secondary outcomes were performed. Using A549 epithelial cells, we assessed nasal isolates of Moraxella, Staphylococcus, and Corynebacterium species for their capacity to induce epithelial damage and inflammatory responses. RESULTS: Six nasal airway microbiota assemblages, each dominated by Moraxella, Staphylococcus, Corynebacterium, Streptococcus, Alloiococcus, or Haemophilus species, were observed. Moraxella and Staphylococcus species-dominated microbiotas were most frequently detected and exhibited temporal stability. Nasal microbiotas dominated by Moraxella species were associated with increased exacerbation risk and eosinophil activation. Staphylococcus or Corynebacterium species-dominated microbiotas were associated with reduced respiratory illness and exacerbation events, whereas Streptococcus species-dominated assemblages increased the risk of rhinovirus infection. Nasal microbiota composition remained relatively stable despite viral infection or exacerbation; only a few taxa belonging to the dominant genera exhibited relative abundance fluctuations during these events. In vitro, Moraxella catarrhalis induced significantly greater epithelial damage and inflammatory cytokine expression (IL-33 and IL-8) compared with other dominant nasal bacterial isolates tested. CONCLUSION: Distinct nasal airway microbiotas of children with asthma relate to the likelihood of exacerbation, rhinovirus infection, and respiratory illnesses during the fall season.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Claregrieve1, ChiomaBlessing, Ifeanyisam

Subjects

Location of subjects

United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.

Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology

Nasal cavity

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Group 0 name Corresponds to the control (unexposed) group for case-control studies

children who did not experience asthma exacerbation

Group 1 name Corresponds to the case (exposed) group for case-control studies

Children who experienced exacerbation

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

children who experienced exacerbation of their asthma (physician-prescribed use of systemic corticosteroids for asthma symptoms, hospitalization for asthma, or both)

Group 0 sample size Number of subjects in the control (unexposed) group

346

Group 1 sample size Number of subjects in the case (exposed) group

67

Lab analysis

Sequencing type

16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene

V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).

relative abundances

Statistical test

Zero-Inflated Beta Regression

Significance threshold p-value or FDR threshold used for differential abundance testing (if any)

0.15

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?

Yes

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment

age

Signature 1

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Curated date: 2021/01/10

Curator: Victoria Goulbourne

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Source: Table E5

Description: Differential microbial abundance between children with exacerbation and children without

Abundance in Group 1: decreased abundance in Children who experienced exacerbation

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Haemophilus

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Experiment 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Claregrieve1, ChiomaBlessing, Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Samples with no rhinovirus infection

Group 1 name Corresponds to the case (exposed) group for case-control studies

Samples with any rhinovirus infection

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Samples with rhinovirus infection assessed by using quantitative PCR and partial sequencing to identify viral strain type

Group 0 sample size Number of subjects in the control (unexposed) group

1883

Group 1 sample size Number of subjects in the case (exposed) group

1239

Lab analysis

Statistical Analysis

Signature 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

Curated date: 2021/01/10

Curator: Victoria Goulbourne

Revision editor(s): Claregrieve1, WikiWorks

Source: Table E5

Description: Differential microbial abundance between samples with rhinovirus and samples without

Abundance in Group 1: increased abundance in Samples with any rhinovirus infection

NCBI	Quality Control	Links
Streptococcus

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Signature 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

Curated date: 2021/01/10

Curator: Victoria Goulbourne

Revision editor(s): Claregrieve1, WikiWorks

Source: Table E5

Description: Differential microbial abundance between samples with rhinovirus and samples without

Abundance in Group 1: decreased abundance in Samples with any rhinovirus infection

NCBI	Quality Control	Links
Staphylococcus

Revision editor(s): Claregrieve1, WikiWorks

Experiment 3

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Claregrieve1, ChiomaBlessing, Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Samples that were RV-A negative-

Group 1 name Corresponds to the case (exposed) group for case-control studies

Samples with rhinovirus-A (RV-A)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Samples with rhinovirus-A

Group 1 sample size Number of subjects in the case (exposed) group

386

Lab analysis

Statistical Analysis

Signature 1

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Curated date: 2021/01/10

Curator: Victoria Goulbourne

Revision editor(s): Claregrieve1, WikiWorks

Source: Table E5

Description: Differential microbial abundance between samples with rhinovirus-A and samples with no rhinovirus detected

Abundance in Group 1: increased abundance in Samples with rhinovirus-A (RV-A)

NCBI	Quality Control	Links
Haemophilus
Streptococcus

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

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Curated date: 2021/01/10

Curator: Victoria Goulbourne

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Source: Table E5

Description: Differential microbial abundance between samples with rhinovirus-A and samples with no rhinovirus detected

Abundance in Group 1: decreased abundance in Samples with rhinovirus-A (RV-A)

NCBI	Quality Control	Links
Staphylococcus

Revision editor(s): Claregrieve1, WikiWorks

Experiment 5

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Claregrieve1, ChiomaBlessing, Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

children who did not experience exacerbation

Group 1 name Corresponds to the case (exposed) group for case-control studies

Children who experienced exacerbation

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

children who experienced exacerbation of their asthma (physician-prescribed use of systemic corticosteroids for asthma symptoms, hospitalization for asthma, or both)

Group 0 sample size Number of subjects in the control (unexposed) group

346

Group 1 sample size Number of subjects in the case (exposed) group

67

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment

Not specified

Signature 1

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Curated date: 2021/01/10

Curator: Victoria Goulbourne

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Source: Table I

Description: Differential microbial abundance between children with exacerbation and children without

Abundance in Group 1: increased abundance in Children who experienced exacerbation

NCBI	Quality Control	Links
Moraxella

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Signature 2

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Source: Table I

Description: Differential microbial abundance between children with exacerbation and children without

Abundance in Group 1: decreased abundance in Children who experienced exacerbation

NCBI	Quality Control	Links
Alloiococcus
Corynebacterium
Haemophilus
Staphylococcus

Revision editor(s): Claregrieve1, WikiWorks

Experiment 7

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Claregrieve1, ChiomaBlessing, Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

samples with no rhinovirus infection

Group 1 name Corresponds to the case (exposed) group for case-control studies

samples with any rhinovirus infection

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

samples with rhinovirus infection

Group 0 sample size Number of subjects in the control (unexposed) group

1883

Group 1 sample size Number of subjects in the case (exposed) group

1239

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete

Flag for review

Your review change was submitted

Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

Curated date: 2021/01/10

Curator: Victoria Goulbourne

Revision editor(s): Claregrieve1, WikiWorks

Source: Table I

Description: Differential microbial abundance between samples with any viral infection and samples without

Abundance in Group 1: increased abundance in samples with any rhinovirus infection

NCBI	Quality Control	Links
Streptococcus

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

EditHistoryDelete

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

Curated date: 2021/01/10

Curator: Victoria Goulbourne

Revision editor(s): Claregrieve1, WikiWorks

Source: Table I

Description: Differential microbial abundance between samples with any viral infection and samples without

Abundance in Group 1: decreased abundance in samples with any rhinovirus infection

NCBI	Quality Control	Links
Staphylococcus

Revision editor(s): Claregrieve1, WikiWorks

Experiment 8

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Claregrieve1, ChiomaBlessing, Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Rhinovirus-negative samples

Group 1 name Corresponds to the case (exposed) group for case-control studies

Samples with rhinovirus A

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Samples with rhinovirus A present

Group 1 sample size Number of subjects in the case (exposed) group

386

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2021/01/10

Curator: Victoria Goulbourne

Revision editor(s): Claregrieve1, WikiWorks

Source: Table I

Description: Differential microbial abundance between samples infected with rhinovirus-A and samples with no rhinovirus detected

Abundance in Group 1: increased abundance in Samples with rhinovirus A

NCBI	Quality Control	Links
Haemophilus
Streptococcus

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2021/01/10

Curator: Victoria Goulbourne

Revision editor(s): Claregrieve1, WikiWorks

Source: Table I

Description: Differential microbial abundance between samples infected with rhinovirus-A and samples with no rhinovirus detected

Abundance in Group 1: decreased abundance in Samples with rhinovirus A

NCBI	Quality Control	Links
Staphylococcus

Revision editor(s): Claregrieve1, WikiWorks