Multiple Respiratory Microbiota Profiles Are Associated With Lower Airway Inflammation in Children With Protracted Bacterial Bronchitis

Robyn L. Marsh, Heidi C. Smith-Vaughan, Alice C.H. Chen, Julie M. Marchant, Stephanie T. Yerkovich, Peter G. Gibson, Susan J. Pizzutto, Sandra Hodge, John W. Upham, Anne B. Chang

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background: Effective management of protracted bacterial bronchitis (PBB) is needed to prevent chronic disease (eg, bronchiectasis). Understanding the contributions of ongoing airway infection and inflammation is important to achieving optimal PBB treatments. The aim of this study was to compare BAL microbiota, bacterial biomass, and inflammatory markers in children with PBB and age-matched control patients.

    Methods: BAL was prospectively collected from 28 children with PBB (median age, 1.7 years; range, 0.6-7.4) and 8 control patients (median age, 1.9 years; range, 0.4-4.7). BAL microbiology was determined using culture, 16S ribosomal RNA gene sequencing and bacterial biomass quantification. BAL inflammatory cells, IL-8, and IL-1β were used to assess lower airway inflammation.

    Results: Bacterial biomass, neutrophil percentage, IL-8, and IL-1β levels were significantly higher in children with PBB compared with control patients. BAL microbiota in children with PBB was significantly different to that of control patients (permutational multivariate analysis of variance P =.001) and clustered into four distinct profiles that were either dominated by a respiratory pathogen or contained a more diverse microbiota including Prevotella species. Alpha diversity was unrelated to bacterial biomass, culture of recognized respiratory pathogens, or inflammatory markers.

    Conclusions: Neutrophilic inflammation in children with PBB was associated with multiple BAL microbiota profiles. Significant associations between inflammatory markers and bacterial biomass, but not alpha diversity, suggest that inflammation in children with PBB is not driven by single pathogenic species. Understanding the role of the entire respiratory microbiota in PBB pathogenesis may be important to determining whether bacteria other than the recognized pathogens contribute to disease recurrence and progression to bronchiectasis.

    Original languageEnglish
    Pages (from-to)778-786
    Number of pages9
    JournalChest
    Volume155
    Issue number4
    Early online date17 Jan 2019
    DOIs
    Publication statusPublished - Apr 2019

    Fingerprint

    Bronchitis
    Microbiota
    Dimercaprol
    Inflammation
    Biomass
    Bronchiectasis
    Interleukin-8
    Interleukin-1
    Prevotella
    16S Ribosomal RNA
    RNA Sequence Analysis
    Microbiology
    rRNA Genes
    Disease Progression
    Analysis of Variance
    Neutrophils
    Chronic Disease
    Multivariate Analysis
    Bacteria
    Recurrence

    Cite this

    Marsh, Robyn L. ; Smith-Vaughan, Heidi C. ; Chen, Alice C.H. ; Marchant, Julie M. ; Yerkovich, Stephanie T. ; Gibson, Peter G. ; Pizzutto, Susan J. ; Hodge, Sandra ; Upham, John W. ; Chang, Anne B. / Multiple Respiratory Microbiota Profiles Are Associated With Lower Airway Inflammation in Children With Protracted Bacterial Bronchitis. In: Chest. 2019 ; Vol. 155, No. 4. pp. 778-786.
    @article{1a906daf18c74ae58ab6b71c6e94657a,
    title = "Multiple Respiratory Microbiota Profiles Are Associated With Lower Airway Inflammation in Children With Protracted Bacterial Bronchitis",
    abstract = "Background: Effective management of protracted bacterial bronchitis (PBB) is needed to prevent chronic disease (eg, bronchiectasis). Understanding the contributions of ongoing airway infection and inflammation is important to achieving optimal PBB treatments. The aim of this study was to compare BAL microbiota, bacterial biomass, and inflammatory markers in children with PBB and age-matched control patients. Methods: BAL was prospectively collected from 28 children with PBB (median age, 1.7 years; range, 0.6-7.4) and 8 control patients (median age, 1.9 years; range, 0.4-4.7). BAL microbiology was determined using culture, 16S ribosomal RNA gene sequencing and bacterial biomass quantification. BAL inflammatory cells, IL-8, and IL-1β were used to assess lower airway inflammation. Results: Bacterial biomass, neutrophil percentage, IL-8, and IL-1β levels were significantly higher in children with PBB compared with control patients. BAL microbiota in children with PBB was significantly different to that of control patients (permutational multivariate analysis of variance P =.001) and clustered into four distinct profiles that were either dominated by a respiratory pathogen or contained a more diverse microbiota including Prevotella species. Alpha diversity was unrelated to bacterial biomass, culture of recognized respiratory pathogens, or inflammatory markers. Conclusions: Neutrophilic inflammation in children with PBB was associated with multiple BAL microbiota profiles. Significant associations between inflammatory markers and bacterial biomass, but not alpha diversity, suggest that inflammation in children with PBB is not driven by single pathogenic species. Understanding the role of the entire respiratory microbiota in PBB pathogenesis may be important to determining whether bacteria other than the recognized pathogens contribute to disease recurrence and progression to bronchiectasis.",
    keywords = "bronchitis, human microbiome, microbiota, pediatrics, pulmonary inflammation",
    author = "Marsh, {Robyn L.} and Smith-Vaughan, {Heidi C.} and Chen, {Alice C.H.} and Marchant, {Julie M.} and Yerkovich, {Stephanie T.} and Gibson, {Peter G.} and Pizzutto, {Susan J.} and Sandra Hodge and Upham, {John W.} and Chang, {Anne B.}",
    year = "2019",
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    doi = "10.1016/j.chest.2019.01.002",
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    Multiple Respiratory Microbiota Profiles Are Associated With Lower Airway Inflammation in Children With Protracted Bacterial Bronchitis. / Marsh, Robyn L.; Smith-Vaughan, Heidi C.; Chen, Alice C.H.; Marchant, Julie M.; Yerkovich, Stephanie T.; Gibson, Peter G.; Pizzutto, Susan J.; Hodge, Sandra; Upham, John W.; Chang, Anne B.

    In: Chest, Vol. 155, No. 4, 04.2019, p. 778-786.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Multiple Respiratory Microbiota Profiles Are Associated With Lower Airway Inflammation in Children With Protracted Bacterial Bronchitis

    AU - Marsh, Robyn L.

    AU - Smith-Vaughan, Heidi C.

    AU - Chen, Alice C.H.

    AU - Marchant, Julie M.

    AU - Yerkovich, Stephanie T.

    AU - Gibson, Peter G.

    AU - Pizzutto, Susan J.

    AU - Hodge, Sandra

    AU - Upham, John W.

    AU - Chang, Anne B.

    PY - 2019/4

    Y1 - 2019/4

    N2 - Background: Effective management of protracted bacterial bronchitis (PBB) is needed to prevent chronic disease (eg, bronchiectasis). Understanding the contributions of ongoing airway infection and inflammation is important to achieving optimal PBB treatments. The aim of this study was to compare BAL microbiota, bacterial biomass, and inflammatory markers in children with PBB and age-matched control patients. Methods: BAL was prospectively collected from 28 children with PBB (median age, 1.7 years; range, 0.6-7.4) and 8 control patients (median age, 1.9 years; range, 0.4-4.7). BAL microbiology was determined using culture, 16S ribosomal RNA gene sequencing and bacterial biomass quantification. BAL inflammatory cells, IL-8, and IL-1β were used to assess lower airway inflammation. Results: Bacterial biomass, neutrophil percentage, IL-8, and IL-1β levels were significantly higher in children with PBB compared with control patients. BAL microbiota in children with PBB was significantly different to that of control patients (permutational multivariate analysis of variance P =.001) and clustered into four distinct profiles that were either dominated by a respiratory pathogen or contained a more diverse microbiota including Prevotella species. Alpha diversity was unrelated to bacterial biomass, culture of recognized respiratory pathogens, or inflammatory markers. Conclusions: Neutrophilic inflammation in children with PBB was associated with multiple BAL microbiota profiles. Significant associations between inflammatory markers and bacterial biomass, but not alpha diversity, suggest that inflammation in children with PBB is not driven by single pathogenic species. Understanding the role of the entire respiratory microbiota in PBB pathogenesis may be important to determining whether bacteria other than the recognized pathogens contribute to disease recurrence and progression to bronchiectasis.

    AB - Background: Effective management of protracted bacterial bronchitis (PBB) is needed to prevent chronic disease (eg, bronchiectasis). Understanding the contributions of ongoing airway infection and inflammation is important to achieving optimal PBB treatments. The aim of this study was to compare BAL microbiota, bacterial biomass, and inflammatory markers in children with PBB and age-matched control patients. Methods: BAL was prospectively collected from 28 children with PBB (median age, 1.7 years; range, 0.6-7.4) and 8 control patients (median age, 1.9 years; range, 0.4-4.7). BAL microbiology was determined using culture, 16S ribosomal RNA gene sequencing and bacterial biomass quantification. BAL inflammatory cells, IL-8, and IL-1β were used to assess lower airway inflammation. Results: Bacterial biomass, neutrophil percentage, IL-8, and IL-1β levels were significantly higher in children with PBB compared with control patients. BAL microbiota in children with PBB was significantly different to that of control patients (permutational multivariate analysis of variance P =.001) and clustered into four distinct profiles that were either dominated by a respiratory pathogen or contained a more diverse microbiota including Prevotella species. Alpha diversity was unrelated to bacterial biomass, culture of recognized respiratory pathogens, or inflammatory markers. Conclusions: Neutrophilic inflammation in children with PBB was associated with multiple BAL microbiota profiles. Significant associations between inflammatory markers and bacterial biomass, but not alpha diversity, suggest that inflammation in children with PBB is not driven by single pathogenic species. Understanding the role of the entire respiratory microbiota in PBB pathogenesis may be important to determining whether bacteria other than the recognized pathogens contribute to disease recurrence and progression to bronchiectasis.

    KW - bronchitis

    KW - human microbiome

    KW - microbiota

    KW - pediatrics

    KW - pulmonary inflammation

    UR - http://www.scopus.com/inward/record.url?scp=85061929115&partnerID=8YFLogxK

    U2 - 10.1016/j.chest.2019.01.002

    DO - 10.1016/j.chest.2019.01.002

    M3 - Article

    VL - 155

    SP - 778

    EP - 786

    JO - Chest

    JF - Chest

    SN - 0012-3692

    IS - 4

    ER -