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.
- Bacterial Infection
- COPD Epidemiology
- COPD Exacerbations
- Innate Immunity
- Macrophage Biology