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  • Longitudinal profiling of the lung microbiome in the AERIS study demonstrates repeatability of bacterial and eosinophilic COPD exacerbations

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Chronic obstructive pulmonary disease
Original article
Longitudinal profiling of the lung microbiome in the AERIS study demonstrates repeatability of bacterial and eosinophilic COPD exacerbations
  1. David Mayhew1,
  2. Nathalie Devos2,
  3. Christophe Lambert2,
  4. James R Brown1,
  5. Stuart C Clarke3,4,
  6. Viktoriya L Kim4,
  7. Michal Magid-Slav1,
  8. Bruce E Miller5,
  9. Kristoffer K Ostridge4,
  10. Ruchi Patel6,
  11. Ganesh Sathe6,
  12. Daniel F Simola1,
  13. Karl J Staples3,4,7,
  14. Ruby Sung5,
  15. Ruth Tal-Singer5,
  16. Andrew C Tuck3,
  17. Stephanie Van Horn6,
  18. Vincent Weynants2,
  19. Nicholas P Williams4,
  20. Jeanne-Marie Devaster2,
  21. Tom M A Wilkinson3,4,7
  22. on behalf of the AERIS Study Group
    1. 1 Computational Biology, Target Sciences, GSK R&D, King of Prussia, Pennsylvania, USA
    2. 2 GSK Vaccines, Rixensart, Belgium
    3. 3 Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK
    4. 4 Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, UK
    5. 5 Respiratory Therapy Area Unit, GSK R&D, King of Prussia, Pennsylvania, USA
    6. 6 Target and Pathway Validation, Target Sciences, GSK R&D, King of Prussia, Pennsylvania, USA
    7. 7 Wessex Investigational Sciences Hub, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK
    1. Correspondence to Professor Tom M A Wilkinson, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK; t.wilkinson{at}soton.ac.uk

    Abstract

    Background Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.

    Objective To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.

    Methods We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene. We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.

    Results The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies. Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated. We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis.

    Conclusions Subtypes of COPD have distinct bacterial compositions and stabilities over time. Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future. This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.

    Trial registration number Results, NCT01360398.

    • Copd ÀÜ mechanisms
    • Copd exacerbations
    • respiratory infection

    This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

    https://doi.org/10.1136/thoraxjnl-2017-210408

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      Footnotes

      • DM and ND contributed equally.

      • Contributors Conceived and designed the experiments: ND, JRB, GS, J-MD, TMW. Subject recruitment and sample processing: SC, VK, KO, KJS, ACT, NW. Performed the experiments: ND, RP, SVH. Data analysis: DM, ND, CL, MM-S, DFS, VW, J-MD. Data interpretation and writing: DM, ND, CL, JRB, MM-S, BEM, DFS, KJS, RT-S, VW, J-MD, TMW. The investigators obtained data and cared for the study participants. The authors had full access to all data in the study, contributed to the writing of the report and had final responsibility for the decision to submit for publication. All members of the AERIS Study Group were involved in the planning, conduct and/or reporting of the work described in the article.

      • Funding The study funder, GlaxoSmithKline Biologicals SA, designed the study in collaboration with the investigators, and coordinated collection, analysis and interpretation of data.

      • Competing interests TMW has received reimbursement for travel and meeting attendance from Boehringer Ingelheim and AstraZeneca, outside of the submitted work. SC received a grant from Pfizer, outside of the submitted work. KJS received grants from Asthma UK (08/026) and BMA HC Roscoe Award, outside of the submitted work, and he has a patent PCT/GB2010/050821 ’Ex Vivo Modelling of Therapeutic Interventions' pending. BEM, CL, DFS, DM, GS, J-MD, JRB, ND, MM-S, RS, RT-S, SVH and VW are employees of the GSK group of companies. RP was an employee of the GSK group of companies at the time the study was conducted. BEM, JRB, J-MD, ND, RT-S and VW own shares/restricted shares in the GSK group of companies. KJS, VK, KO, ACT, SC and TMW received an institutional grant from the GSK group of companies to conduct this study.

      • Ethics approval Southampton and South West Hampshire Research Ethics Committee.

      • Provenance and peer review Not commissioned; externally peer reviewed.

      • Collaborators AERIS Study Group: J Alnajar, R Anderson, E Aris, WR Ballou, A Barton, S Bourne, M Caubet, SC Clarke, D Cleary, C Cohet, N Coombs, K Cox, J-M Devaster, V Devine, N Devos, E Dineen, T Elliott, R Gladstone, S Harden, J Jefferies, V Kim, S Mesia Vela, P Moris, K Ostridge, TG Pascal, M Peeters, S Schoonbroodt, KJ Staples, A Tuck, L Welch, V Weynants, TMA Wilkinson, AP Williams, N Williams, C Woelk, M Wojtas, S Wootton.

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