Pei Yee Tiew1,2, Alison J Dicker3, Holly R Keir3, Mau Ern Poh4, Sze Lei Pang5, Micheál Mac Aogáin1, Branden Qi Yu Chua1, Jiunn Liang Tan4, Huiying Xu6, Mariko Siyue Koh2, Augustine Tee7, John Arputhan Abisheganaden6, Fook Tim Chew5, Bruce E Miller8, Ruth Tal-Singer8, James D Chalmers3, Sanjay H Chotirmall9. 1. Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore. 2. Dept of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore. 3. Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK. 4. Dept of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. 5. Dept of Biological Sciences, National University of Singapore, Singapore. 6. Dept of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore. 7. Dept of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore. 8. Medical Innovation, GSK R&D, Collegeville, PA, USA. 9. Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore schotirmall@ntu.edu.sg.
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.
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.
Authors: Pei Yee Tiew; Micheál Mac Aogáin; Soo Kai Ter; Stefano Aliberti; James D Chalmers; Sanjay H Chotirmall Journal: Mycopathologia Date: 2021-03-11 Impact factor: 2.574
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Authors: Francesco Amati; Anna Stainer; Marco Mantero; Andrea Gramegna; Edoardo Simonetta; Giulia Suigo; Antonio Voza; Anoop M Nambiar; Umberto Cariboni; Justin Oldham; Philip L Molyneaux; Paolo Spagnolo; Francesco Blasi; Stefano Aliberti Journal: Int J Mol Sci Date: 2022-01-17 Impact factor: 5.923