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

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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.

Original languageEnglish
JournalThorax
Early online date03 Nov 2017
DOIs
Publication statusEarly online date - 03 Nov 2017

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    Dicker, A. J., Crichton, M. L., Cassidy, A. J., Brady, G., Hapca, A., Tavendale, R., Einarsson, G. G., Furrie, E., Elborn, J. S., Schembri, S., Marshall, S. E., Palmer, C. N. A., & Chalmers, J. D. (2017). Genetic mannose binding lectin deficiency is associated with airway microbiota diversity and reduced exacerbation frequency in COPD. Thorax. https://doi.org/10.1136/thoraxjnl-2016-209931