Abstract
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 |
|---|---|
| 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 |
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Keywords
- Bacterial Infection
- COPD Epidemiology
- COPD Exacerbations
- Innate Immunity
- Macrophage Biology
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Genetic mannose binding lectin deficiency is associated with airway microbiota diversity and reduced exacerbation frequency in COPD. / Dicker, Alison J.; Crichton, Megan L.; Cassidy, Andrew J.; Brady, Gill; Hapca, Adrian; Tavendale, Roger; Einarsson, Gisli G.; Furrie, Elizabeth; Elborn, J. Stuart; Schembri, Stuart; Marshall, Sara E.; Palmer, Colin N. A.; Chalmers, James D. (Lead / Corresponding author).
In: Thorax, Vol. 73, No. 6, 06.2018, p. 510-518.Research output: Contribution to journal › Article
TY - JOUR
T1 - Genetic mannose binding lectin deficiency is associated with airway microbiota diversity and reduced exacerbation frequency in COPD
AU - Dicker, Alison J.
AU - Crichton, Megan L.
AU - Cassidy, Andrew J.
AU - Brady, Gill
AU - Hapca, Adrian
AU - Tavendale, Roger
AU - Einarsson, Gisli G.
AU - Furrie, Elizabeth
AU - Elborn, J. Stuart
AU - Schembri, Stuart
AU - Marshall, Sara E.
AU - Palmer, Colin N. A.
AU - Chalmers, James D.
N1 - 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).
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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.
KW - Bacterial Infection
KW - COPD Epidemiology
KW - COPD Exacerbations
KW - Innate Immunity
KW - Macrophage Biology
U2 - 10.1136/thoraxjnl-2016-209931
DO - 10.1136/thoraxjnl-2016-209931
M3 - Article
VL - 73
SP - 510
EP - 518
JO - Thorax
JF - Thorax
SN - 0040-6376
IS - 6
ER -