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Chronic obstructive pulmonary disease
Original article
Genetic mannose binding lectin deficiency is associated with airway microbiota diversity and reduced exacerbation frequency in COPD
  1. Alison J Dicker1,
  2. Megan L Crichton1,
  3. Andrew J Cassidy1,
  4. Gill Brady2,
  5. Adrian Hapca3,
  6. Roger Tavendale4,
  7. Gisli G Einarsson5,
  8. Elizabeth Furrie6,
  9. J Stuart Elborn5,7,
  10. Stuart Schembri1,
  11. Sara E Marshall1,
  12. Colin N A Palmer4,
  13. James D Chalmers1
  1. 1Scottish Centre for Respiratory Research, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
  2. 2Tayside Respiratory Research Group, Clinical Research Centre, Dundee, UK
  3. 3Dundee Epidemiology and Biostatistics Unit, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
  4. 4Pat MacPherson Centre for Pharmacogenetics and Pharmacogenomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
  5. 5School of Medicine, Centre for Experimental Medicine, Dentistry and Biomedical Sciences, Queen’s University, Belfast, UK
  6. 6Department of Immunology, NHS Tayside, Ninewells Hospital Department of Medicine, Dundee, Dundee, UK
  7. 7National Heart and Lung Institute, Imperial College London, London, UK
  1. Correspondence to Dr James D Chalmers, Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital & Medical School, Dundee DD1 9SY, UK; jchalmers{at}dundee.ac.uk

Abstract

Background In cystic fibrosis and bronchiectasis, genetic mannose binding lectin (MBL) deficiency is associated with increased exacerbations and earlier mortality; associations in COPD are less clear. Preclinical data suggest MBL interferes with phagocytosis of Haemophilus influenzae, a key COPD pathogen. We investigated whether MBL deficiency impacted on clinical outcomes or microbiota composition in COPD.

Methods Patients with COPD (n=1796) underwent MBL genotyping; linkage to health records identified exacerbations, lung function decline and mortality. A nested subcohort of 141 patients, followed for up to 6 months, was studied to test if MBL deficiency was associated with altered sputum microbiota, through 16S rRNA PCR and sequencing, or airway inflammation during stable and exacerbated COPD.

Findings Patients with MBL deficiency with COPD were significantly less likely to have severe exacerbations (incidence rate ratio (IRR) 0.66, 95% CI 0.48 to 0.90, p=0.009), or to have moderate or severe exacerbations (IRR 0.77, 95% CI 0.60 to 0.99, p=0.047). MBL deficiency did not affect rate of FEV1 decline or mortality. In the subcohort, patients with MBL deficiency had a more diverse lung microbiota (p=0.008), and were less likely to be colonised with Haemophilus spp. There were lower levels of airway inflammation in patients with MBL deficiency.

Interpretation Patients with MBL deficient genotype with COPD have a lower risk of exacerbations and a more diverse lung microbiota. This is the first study to identify a genetic association with the lung microbiota in COPD.

  • copd exacerbations
  • copd epidemiology
  • macrophage biology
  • bacterial infection
  • innate immunity

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-2016-209931

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    Footnotes

    • Contributors All authors participated in study design, data analysis and interpretation of the data. All authors were involved in writing and revising the article prior to submission.

    • Funding Chief Scientist Office, Scotland (ETM/262). JDC is supported by the GSK/British Lung Foundation Chair of Respiratory Research and a fellowship from the Wellcome Trust (099084/Z/12/Z) . GoSHARE was supported by the Wellcome Trust (099177/Z/12/Z).

    • Competing interests SEM is now an employee of the Wellcome Trust. All other authors have no competing interest to decline.

    • Patient consent Obtained.

    • Ethics approval East of Scotland Research Ethics Committee.

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

    • Data sharing statement Data are available and can be accessed through the Health Informatics Centre at the University of Dundee.

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