A high-risk airway mycobiome is associated with frequent exacerbation and mortality in COPD

Pei Yee Tiew, Alison J. Dicker, Holly R. Keir, Mau Ern Poh, Sze Lei Pang, Micheál Mac Aogáin, Branden Chua Qi Yu, Jiunn Liang Tan, Huiying Xu, Mariko Siyue Koh, Augustine Tee, John Arputhan Abisheganaden, Fook Tim Chew, Bruce E. Miller, Ruth Tal-Singer, James D. Chalmers, Sanjay H. Chotirmall (Lead / Corresponding author)

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Abstract

Introduction: The COPD bacteriome associates with disease severity, exacerbations, and mortality. While COPD patients are susceptible to fungal sensitisation, the role of the fungal mycobiome remains uncertain.

Methods: We report the largest multicenter evaluation of the COPD airway mycobiome to date including participants from Asia (Singapore and Malaysia) and the United Kingdom (Scotland) when stable (n=337) and during exacerbations (n=66) as well as non-diseased controls (n=47). Longitudinal mycobiome analyses performed during and following COPD exacerbations (n=34) were examined in terms of exacerbation frequency, two-year mortality, and the occurrence of serum specific-IgE against selected fungi.

Results: A distinct mycobiome profile is observed in COPD compared to controls evidenced by increased alpha diversity (Shannon-index) (p<0.001). Significant airway mycobiome differences including greater inter-fungal interaction (by co-occurrence) characterise very frequent COPD exacerbators (≥3 exacerbations per year) (PERMANOVA, adjusted p<0.001). Longitudinal analyses during exacerbations and following treatment with antibiotics and corticosteroids did not reveal any significant change in airway mycobiome profile. Unsupervised clustering resulted in two clinically distinct COPD groups, (1) with increased symptoms (CAT score) and Saccharomyces dominance and (2) with very frequent exacerbations and higher mortality characterised by Aspergillus, Penicillium and Curvularia with a concomitant increase in serum specific IgE levels against the same fungi. During acute exacerbations of COPD, lower fungal diversity associates with higher two-year mortality.

Conclusion: The airway mycobiome in COPD is characterised by specific fungal genera associated with exacerbations and increased mortality.

Original languageEnglish
JournalEuropean Respiratory Journal
Early online date24 Sep 2020
DOIs
Publication statusE-pub ahead of print - 24 Sep 2020

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    Tiew, P. Y., Dicker, A. J., Keir, H. R., Poh, M. E., Pang, S. L., Mac Aogáin, M., Chua Qi Yu, B., Tan, J. L., Xu, H., Koh, M. S., Tee, A., Abisheganaden, J. A., Chew, F. T., Miller, B. E., Tal-Singer, R., Chalmers, J. D., & Chotirmall, S. H. (2020). A high-risk airway mycobiome is associated with frequent exacerbation and mortality in COPD. European Respiratory Journal. https://doi.org/10.1183/13993003.02050-2020