A high-risk airway mycobiome characterises frequent COPD exacerbators

Background: A lack of study on the COPD mycobiome exists. Methods: We performed the largest multicenter evaluation of the COPD mycobiome including patients from Asia (Singapore and Malaysia) and the UK (Scotland) (n=380). Non-diseased controls (n=47) were assessed and longitudinal analyses performed during and following exacerbations (n=34). COPD mycobiomes were examined based on mortality and occurrence of serum specific-IgE against selected fungi. Results: A distinct mycobiome profile in COPD evidenced by increased α-diversity (p<0.001) exists. Significant differences including greater inter-fungal interaction (by co-occurrence) characterise very frequent exacerbators (PERMANOVA, adjusted p<0.001). Longitudinal analyses during and following exacerbations reveal that antibiotics and corticosteroids do not affect mycobiome profiles. Unsupervised clustering results in 2 patient groups: one with increased symptoms (CAT score) and Saccharomyces dominance and a second with frequent exacerbations & higher mortality characterized by Aspergillus, Penicillium and Curvularia. Serum specific IgE levels were elevated against fungi characterizing the ‘high-risk’ group. Conclusion: Frequent COPD exacerbators are characterized by Aspergillus, Penicillium and Curvularia and illustrate poorer survival and systemic specific-IgE responses against these fungi allowing COPD risk stratification based on airway mycobiomes. Funding: Singapore Ministry of Health’s National Medical Research Council under its Research Training Fellowship (NMRC/Fellowship/0049/2017) (P.Y.T) and Clinician-Scientist Individual Research Grant (MOH-000141) (S.H.C). The TARDIS study is funded by Glaxosmithkline & British Lung Foundation (Fellowship to JDC).