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Original research
Lower airway microbiota in COPD and healthy controls
  1. Solveig Tangedal1,2,
  2. Rune Nielsen1,2,
  3. Marianne Aanerud1,2,
  4. Christine Drengenes2,
  5. Gunnar R Husebø1,
  6. Sverre Lehmann1,2,
  7. Kristel S Knudsen1,
  8. Pieter S Hiemstra3,
  9. Tomas ML Eagan1,2
  1. 1 Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway
  2. 2 Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway
  3. 3 Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Solveig Tangedal, Department of Thoracic Medicine, Haukeland University Hospital, Bergen 5021, Norway; stangedal{at}gmail.com

Abstract

Background The lower airway microbiota in patients with chronic obstructive pulmonary disease (COPD) are likely altered compared with the microbiota in healthy individuals. Information on how the microbiota is affected by smoking, use of inhaled corticosteroids (ICS) and COPD severity is still scarce.

Methods In the MicroCOPD Study, participant characteristics were obtained through standardised questionnaires and clinical measurements at a single centre from 2012 to 2015. Protected bronchoalveolar lavage samples from 97 patients with COPD and 97 controls were paired-end sequenced with the Illumina MiSeq System. Data were analysed in QIIME 2 and R.

Results Alpha-diversity was lower in patients with COPD than controls (Pielou evenness: COPD=0.76, control=0.80, p=0.004; Shannon entropy: COPD=3.98, control=4.34, p=0.01). Beta-diversity differed with smoking only in the COPD cohort (weighted UniFrac: permutational analysis of variance R2=0.04, p=0.03). Nine genera were differentially abundant between COPD and controls. Genera enriched in COPD belonged to the Firmicutes phylum. Pack years were linked to differential abundance of taxa in controls only (ANCOM-BC (Analysis of Compositions of Microbiomes with Bias Correction) log-fold difference/q-values: Haemophilus −0.05/0.048; Lachnoanaerobaculum −0.04/0.03). Oribacterium was absent in smoking patients with COPD compared with non-smoking patients (ANCOM-BC log-fold difference/q-values: −1.46/0.03). We found no associations between the microbiota and COPD severity or ICS.

Conclusion The lower airway microbiota is equal in richness in patients with COPD to controls, but less even. Genera from the Firmicutes phylum thrive particularly in COPD airways. Smoking has different effects on diversity and taxonomic abundance in patients with COPD compared with controls. COPD severity and ICS use were not linked to the lower airway microbiota.

  • COPD Pathology
  • Respiratory Infection
  • COPD epidemiology

Data availability statement

Data are available in a public, open access repository. Data are available from the time of publication and without end date at DRYAD depository: https://doi.org/10.5061/dryad.rfj6q57ff. Submitted data include de-identified participant data (metadata) in .xlsx and .txt format, ASV and representative sequences tables, phylogenetic tree (rooted), and taxonomy in .qza format from QIIME 2, QIIME 2 code and R code. The data have been generated by ST and TME. The study protocol is published and linked to in the manuscript.

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Data availability statement

Data are available in a public, open access repository. Data are available from the time of publication and without end date at DRYAD depository: https://doi.org/10.5061/dryad.rfj6q57ff. Submitted data include de-identified participant data (metadata) in .xlsx and .txt format, ASV and representative sequences tables, phylogenetic tree (rooted), and taxonomy in .qza format from QIIME 2, QIIME 2 code and R code. The data have been generated by ST and TME. The study protocol is published and linked to in the manuscript.

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Footnotes

  • Contributors ST—conceptualisation, data curation, formal analysis, investigation, methodology, visualisation, writing of original draft, editing, and directly accessed and verified the data used in the manuscript. RN—conceptualisation, data curation, investigation, methodology, project administration, supervision, reviewing original draft, and directly accessed and verified the data used in the manuscript. MA—data curation, supervision and reviewing original draft. CD—investigation, methodology and reviewing original draft. GRH—investigation and reviewing original draft. SL—investigation and reviewing original draft. KSK—investigation and reviewing original draft. PSH—conceptualisation and reviewing original draft. TMLE—responsible for the overall content as the guarantor, conceptualisation, data curation, formal analysis, funding acquisition, investigation, reviewing original draft, methodology, project administration, resources, and directly accessed and verified the data used in the manuscript. All authors reviewed, contributed to and approved the final version of the article.

  • Funding The study was funded by the Bergen Medical Research Fund and Helse-Vest (Western Norway Regional Health Authorities; no award/grant number available).

  • Competing interests TMLE—support for the present manuscript; grant from Bergen Medical Research Fund and Helse-Vest (Western Norway Regional Health Authorities; no award/grant number available); other unrelated grants: GlaxoSmithKline. RN—support for the present manuscript: Novartis, Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca and Timber Merchant Delphin’s Endowment; other grants: AstraZeneca. MA—payment for lectures and support for attending meetings: Roche, AstraZeneca and Pfizer. GH—payment for lectures: Boehringer Ingelheim; participation in advisory board for AstraZeneca. KSK—payment for lectures: AstraZeneca and Boehringer Ingelheim. PSH—other grants (paid to department): Boehringer Ingelheim; payment for lectures: AstraZeneca; licensed patent on synthetic antimicrobial peptides.

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

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