Genetic mannose binding lectin deficiency is associated with airway microbiota diversity and reduced exacerbation frequency in COPD

Alison J. Dicker, Megan L. Crichton, Andrew J. Cassidy, Gill Brady, Adrian Hapca, Roger Tavendale, Gisli G. Einarsson, Elizabeth Furrie, J. Stuart Elborn, Stuart Schembri, Sara E. Marshall, Colin N. A. Palmer, James D. Chalmers (Lead / Corresponding author)

Research output: Contribution to journalArticle

12 Citations (Scopus)
146 Downloads (Pure)

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 suggests 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: COPD patients (n=1796) underwent MBL genotyping; linkage to health records identified exacerbations, lung function decline and mortality. A nested sub-cohort 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 sequencing, or airway inflammation during stable and exacerbated COPD.

Findings: MBL deficient COPD patients were significantly less likely to have severe exacerbations (Incidence Rate Ratio (I.R.R) 0.66, 95%CI 0.48-0.90, P=0.009), or to have a moderate or severe exacerbation (I.R.R 0.77, 95%CI 0.60-0.99, P=0.047). MBL deficiency did not affect rate of FEV1 decline or mortality. In the sub-cohort MBL deficient patients 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: MBL deficient genotype COPD patients 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.
Original languageEnglish
Pages (from-to)510-518
Number of pages9
JournalThorax
Volume73
Issue number6
Early online date3 Nov 2017
DOIs
Publication statusPublished - Jun 2018

    Fingerprint

Keywords

  • Bacterial Infection
  • COPD Epidemiology
  • COPD Exacerbations
  • Innate Immunity
  • Macrophage Biology

Cite this