RT Journal Article
SR Electronic
T1 A high-risk airway mycobiome is associated with frequent exacerbation and mortality in COPD
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2002050
DO 10.1183/13993003.02050-2020
A1 Pei Yee Tiew
A1 Alison J. Dicker
A1 Holly R. Keir
A1 Mau Ern Poh
A1 Sze Lei Pang
A1 Micheál Mac Aogáin
A1 Branden Chua Qi Yu
A1 Jiunn Liang Tan
A1 Huiying Xu
A1 Mariko Siyue Koh
A1 Augustine Tee
A1 John Arputhan Abisheganaden
A1 Fook Tim Chew
A1 Bruce E. Miller
A1 Ruth Tal-Singer
A1 James D. Chalmers
A1 Sanjay H. Chotirmall
YR 2020
UL http://erj.ersjournals.com/content/early/2020/09/17/13993003.02050-2020.abstract
AB 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.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Tiew has nothing to disclose.Conflict of interest: Dr. Dicker has nothing to disclose.Conflict of interest: Dr. Keir has nothing to disclose.Conflict of interest: Dr. Poh has nothing to disclose.Conflict of interest: Dr. Pang has nothing to disclose.Conflict of interest: Dr. Mac Aogain has nothing to disclose.Conflict of interest: Dr. Chua has nothing to disclose.Conflict of interest: Dr. Tan has nothing to disclose.Conflict of interest: Dr. Xu has nothing to disclose.Conflict of interest: Dr. Koh has nothing to disclose.Conflict of interest: Dr. Tee has nothing to disclose.Conflict of interest: Dr. Abisheganaden has nothing to disclose.Conflict of interest: Dr. Chew reports personal fees from Sime Darby Technology Centre, personal fees from First Resources Ltd, personal fees from Genting Plantation, personal fees from Olam International, outside the submitted work.Conflict of interest: Dr. Miller is an employee and shareholder of Glaxosmithkline.Conflict of interest: Dr. Tal-Singer reports personal fees from Immunomet, personal fees from VOCALIS Health, outside the submitted work; and Former employee and current shareholder of GSK.Conflict of interest: Dr. Chalmers reports grants and personal fees from Glaxosmithkline, grants and personal fees from Boehringer-Ingelheim, grants and personal fees from Astrazeneca, grants from Gilead Sciences, grants and personal fees from Grifols, grants and personal fees from Insmed, personal fees from Chiesi, personal fees from Napp, personal fees from Novartis, personal fees from Zambon, outside the submitted work.Conflict of interest: Dr. Chotirmall has nothing to disclose.