Projects per year
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.
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 language | English |
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Pages (from-to) | 510-518 |
Number of pages | 9 |
Journal | Thorax |
Volume | 73 |
Issue number | 6 |
Early online date | 3 Nov 2017 |
DOIs | |
Publication status | Published - Jun 2018 |
Keywords
- Bacterial Infection
- COPD Epidemiology
- COPD Exacerbations
- Innate Immunity
- Macrophage Biology
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Projects
- 3 Finished
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Mannose Binding Lectin Deficiency, Bacterial Infection and Disease Severity in Chronic Obstructive Pulmonary Disease: Towards Personalised Medicine for COPD
Chalmers, J., Marshall, S., Palmer, C. & Schembri, S.
1/07/13 → 30/06/15
Project: Research
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The Tayside Bioresource: Leveraging Electronic Medical Records to Deliver Personalised Medicine (Biomedical Resource Grant)
Colhoun, H., Connell, J., Doney, A., Dow, E., Morris, A., Palmer, C., Pearson, E., Sullivan, F. & Treweek, S.
1/02/13 → 31/10/15
Project: Research
Profiles
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Chalmers, James
- Molecular and Clinical Medicine - Clinical Professor (Teaching and Research) & Respiratory Research
Person: Academic