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Lung microbiome and host immune tone in subjects with idiopathic pulmonary fibrosis treated with inhaled interferon-γ

Jing Wang, Melissa Lesko, Michelle H. Badri, Bianca C. Kapoor, Benjamin G. Wu, Yonghua Li, Gerald C. Smaldone, Richard Bonneau, Zachary D. Kurtz, Rany Condos, Leopoldo N. Segal
ERJ Open Research 2017 3: 00008-2017; DOI: 10.1183/23120541.00008-2017
Jing Wang
1Division of Pulmonary and Critical Care Medicine, Beijing Chaoyang Hospital, The Capital University of Medicine, Beijing, China
2Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, NY, USA
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  • ORCID record for Jing Wang
Melissa Lesko
2Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, NY, USA
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Michelle H. Badri
3Dept of Biology, Center for Genomics and Systems Biology, New York University, New York, NY, USA
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Bianca C. Kapoor
2Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, NY, USA
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Benjamin G. Wu
2Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, NY, USA
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Yonghua Li
2Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, NY, USA
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Gerald C. Smaldone
4Division of Pulmonary, Critical Care and Sleep Medicine, State University of New York at Stony Brook, Stony Brook, NY, USA
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Richard Bonneau
3Dept of Biology, Center for Genomics and Systems Biology, New York University, New York, NY, USA
5Courant Institute of Mathematical Sciences, New York University, New York, NY, USA
6Simons Center for Data Analysis, Simons Foundation, New York, NY, USA
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Zachary D. Kurtz
7Dept of Microbiology, New York University School of Medicine, New York, NY, USA
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Rany Condos
2Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, NY, USA
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Leopoldo N. Segal
2Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, NY, USA
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  • For correspondence: Leopoldo.Segal@nyumc.org
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  • FIGURE 1
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    FIGURE 1

    Unsupervised hierarchical clustering of most abundant taxa for bronchoalveolar lavage samples. The dendrogram demonstrates two well-separated clusters: one dominated by supraglottic taxa and a second one with a lower abundance of them. Clusters were not determined by pre- or post-treatment with interferon-γ.

  • FIGURE 2
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    FIGURE 2

    Microbiomic changes during inhaled interferon (IFN)-γ. a) Comparison of α diversity (based on the Shannon Index where sequences were rarified at 1000 reads per sample) before and after treatment. b) Changes in β diversity (based on UniFrac distances) before and after IFN-γ (p-value based on PERMANOVA (permutational multivariate ANOVA)). PC: principal coordinate; ns: nonsignificant. c) β diversity distance (based on UniFrac distances) between pairs of samples comparing within subject (before–after IFN-γ) versus between subjects (p-value based on Mann–Whitney test). d) Linear discriminant analysis (LDA) effect size was calculated comparing 16S rRNA data at baseline and after IFN-γ.

  • FIGURE 3
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    FIGURE 3

    Co-occurrence network between taxa and biomarkers. Th: T-helper; IPF: idiopathic pulmonary fibrosis. compPLS was utilised to evaluate associations between the lung microbiome and local/systemic biomarkers, which were categorised as Th1, Th2, Th17 and/or IPF immunological phenotype. a) Associations between taxa and bronchoalveolar lavage (BAL) fluid cytokines. b) Associations between taxa and BAL cell supernatant cytokines. c) Associations between taxa and plasma cytokines. Negative associations are in red and positive associations are in grey; edge weight is scaled to represent the degree of confidence for the associations.

Tables

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  • TABLE 1

    Demographics, pulmonary function and bronchoalveolar lavage (BAL) cell count differential

    Subjects10
    Age years69.0 (63.7–76.0)
    Male8 (80)
    Smoking status
     Current0
     Ex5 (50)
     Never5 (50)
    Pack-years (smokers)20 (10–30)
    Clinical
     Biopsy done4 (40)
     PASP elevated6 (60)
     PAP mmHg36.8 (33.2–40.7)
    N-acetyl cysteine treatment4 (40)
    Pulmonary function
     FVC % pred73.5 (68.2–84.2)
     TLC % pred71.0 (60.0–77.0)
     DLCO % pred47.5 (39.5–56.5)
     6MWT m420 (287–490)
    BAL
     BAL cells obtained ×10619.2 (13.8–31.9)
     Macrophages %78.0 (69.0–91.2)
     Lymphocytes %5.0 (3.0–9.3)
     Neutrophils %9.0 (3.5–24.3)
     Eosinophils %0.75 (0–2.25)

    Data are presented as n, median (interquartile range) or n (%). PASP: pulmonary artery systolic pressure; PAP: pulmonary arterial pressure; FVC: forced vital capacity; TLC: total lung capacity; DLCO: diffusing capacity of the lung for carbon monoxide; 6MWT: 6-min walk test.

    Supplementary Materials

    • Figures
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    • Supplementary Material

      Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.

      Supplementary material 00008-2017_Supplementary_data

    • Supplementary Material

      M.H. Badri 00008-2017_Badri

      R. Bonneau 00008-2017_Bonneau

      R. Condos 00008-2017_Condos

      B. Kapoor 00008-2017_Kapoor

      Z.D. Kurtz 00008-2017_Kurtz

      M. Lesko 00008-2017_Lesko

      Y. Li 00008-2017_Li

      L.N. Segal 00008-2017_Segal

      G. Smaldone 00008-2017_Smaldone

      J. Wang 00008-2017_Wang

      B.G. Wu 00008-2017_Wu

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    Lung microbiome and host immune tone in subjects with idiopathic pulmonary fibrosis treated with inhaled interferon-γ
    Jing Wang, Melissa Lesko, Michelle H. Badri, Bianca C. Kapoor, Benjamin G. Wu, Yonghua Li, Gerald C. Smaldone, Richard Bonneau, Zachary D. Kurtz, Rany Condos, Leopoldo N. Segal
    ERJ Open Research Jul 2017, 3 (3) 00008-2017; DOI: 10.1183/23120541.00008-2017

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    Lung microbiome and host immune tone in subjects with idiopathic pulmonary fibrosis treated with inhaled interferon-γ
    Jing Wang, Melissa Lesko, Michelle H. Badri, Bianca C. Kapoor, Benjamin G. Wu, Yonghua Li, Gerald C. Smaldone, Richard Bonneau, Zachary D. Kurtz, Rany Condos, Leopoldo N. Segal
    ERJ Open Research Jul 2017, 3 (3) 00008-2017; DOI: 10.1183/23120541.00008-2017
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