Abstract
Introduction The chronic obstructive pulmonary disease (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 multicentre evaluation of the COPD airway mycobiome to date, including participants from Asia (Singapore and Malaysia) and the UK (Scotland) when stable (n=337) and during exacerbations (n=66) as well as nondiseased (healthy) controls (n=47). Longitudinal mycobiome analysis was performed during and following COPD exacerbations (n=34), and examined in terms of exacerbation frequency, 2-year mortality and occurrence of serum specific IgE (sIgE) against selected fungi.
Results A distinct mycobiome profile is observed in COPD compared with controls as evidenced by increased α-diversity (Shannon index; p<0.001). Significant airway mycobiome differences, including greater interfungal interaction (by co-occurrence), characterise very frequent COPD exacerbators (three or more exacerbations per year) (permutational multivariate ANOVA; 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: one with increased symptoms (COPD Assessment Test score) and Saccharomyces dominance, and another with very frequent exacerbations and higher mortality characterised by Aspergillus, Curvularia and Penicillium with a concomitant increase in serum sIgE levels against the same fungi. During acute exacerbations of COPD, lower fungal diversity associates with higher 2-year mortality.
Conclusion The airway mycobiome in COPD is characterised by specific fungal genera associated with exacerbations and increased mortality.
Abstract
The airway mycobiome in COPD is important, and associates with exacerbations, survival and systemic immune responses https://bit.ly/32WA5kJ
Footnotes
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Author contributions: P.Y. Tiew: study design, patient recruitment and performance of experimental work, data collection, interpretation and analysis, including writing of the final manuscript. A.J. Dicker, H.R. Keir, M.E. Poh, J.L. Tan, H. Xu, M.S. Koh, A. Tee and J.A. Abisheganaden: patient recruitment, clinical data and specimen collection. M. Mac Aogáin: performance of experimental optimisation and work. S.L. Pang and B.Q.Y. Chua: performance of experimental work and data collection. B.E. Miller and R. Tal-Singer: patient recruitment and funding. F.T. Chew: conception of experiments and interpretation of results. J.D. Chalmers and S.H. Chotirmall: study design and conception of experiments, data collection, interpretation and analysis, obtained study funding, and writing of the final manuscript.
Conflict of interest: P.Y. Tiew has nothing to disclose.
Conflict of interest: A.J. Dicker has nothing to disclose.
Conflict of interest: H.R. Keir has nothing to disclose.
Conflict of interest: M.E. Poh has nothing to disclose.
Conflict of interest: S.L. Pang has nothing to disclose.
Conflict of interest: M. Mac Aogáin has nothing to disclose.
Conflict of interest: B.Q.Y. Chua has nothing to disclose.
Conflict of interest: J.L. Tan has nothing to disclose.
Conflict of interest: H. Xu has nothing to disclose.
Conflict of interest: M.S. Koh has nothing to disclose.
Conflict of interest: A. Tee has nothing to disclose.
Conflict of interest: J.A. Abisheganaden has nothing to disclose.
Conflict of interest: F.T. Chew reports personal fees for consultancy from Sime Darby Technology Centre, First Resources Ltd, Genting Plantation and Olam International, outside the submitted work.
Conflict of interest: B.E. Miller is an employee and shareholder of GlaxoSmithKline.
Conflict of interest: R. Tal-Singer reports personal fees from Immunomet and VOCALIS Health, outside the submitted work; and is a former employee and current shareholder of GlaxoSmithKline.
Conflict of interest: J.D. Chalmers reports grants and personal fees from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, Grifols and Insmed, grants from Gilead Sciences, personal fees from Chiesi, Napp, Novartis and Zambon, outside the submitted work.
Conflict of interest: S.H. Chotirmall has nothing to disclose.
Support statement: This research is supported by the Singapore Ministry of Health's National Medical Research Council under its Research Training Fellowship (NMRC/Fellowship/0049/2017) (P.Y. Tiew), a Clinician-Scientist Individual Research Grant (MOH-000141) (S.H. Chotirmall), and NTU Integrated Medical, Biological and Environmental Life Sciences (NIMBELS), Nanyang Technological University, Singapore (NIM/03/2018) (S.H. Chotirmall). The TARDIS study is funded by GlaxoSmithKline and the British Lung Foundation (fellowship to J.D. Chalmers). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received May 28, 2020.
- Accepted September 16, 2020.
- Copyright ©ERS 2021