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IMMUNOLOGICAL COROLLARY OF THE PULMONARY MYCOBIOME IN BRONCHIECTASIS: THE CAMEB STUDY

Micheál Mac Aogáin, Ravishankar Chandrasekaran, Albert Lim Yick Hou, Low Teck Boon, Gan Liang Tan, Tidi Hassan, Ong Thun How, Amanda Hui Qi Ng, Denis Bertrand, Jia Yu Koh, Sze Lei Pang, Zi Yang Lee, Xiao Wei Gwee, Christopher Martinus, Yang Yie Sio, Sri Anusha Matta, Fook Tim Chew, Holly R. Keir, John E. Connolly, John Arputhan Abisheganaden, Mariko Siyue Koh, Niranjan Nagarajan, James D. Chalmers, Sanjay H. Chotirmall
European Respiratory Journal 2018; DOI: 10.1183/13993003.00766-2018
Micheál Mac Aogáin
1Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
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Ravishankar Chandrasekaran
1Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
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Albert Lim Yick Hou
2Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore
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Low Teck Boon
3Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore
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Gan Liang Tan
4Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore
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Tidi Hassan
5Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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Ong Thun How
4Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore
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Amanda Hui Qi Ng
6Genome Institute of Singapore, A*STAR, Singapore
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Denis Bertrand
6Genome Institute of Singapore, A*STAR, Singapore
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Jia Yu Koh
6Genome Institute of Singapore, A*STAR, Singapore
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Sze Lei Pang
7Department of Biological Sciences, National University of Singapore, Singapore
8Institute of Systems Biology, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia
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Zi Yang Lee
7Department of Biological Sciences, National University of Singapore, Singapore
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Xiao Wei Gwee
7Department of Biological Sciences, National University of Singapore, Singapore
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Christopher Martinus
7Department of Biological Sciences, National University of Singapore, Singapore
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Yang Yie Sio
7Department of Biological Sciences, National University of Singapore, Singapore
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Sri Anusha Matta
7Department of Biological Sciences, National University of Singapore, Singapore
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Fook Tim Chew
7Department of Biological Sciences, National University of Singapore, Singapore
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Holly R. Keir
9University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland
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John E. Connolly
10Institute of Molecular and Cell Biology, A*STAR, Singapore
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John Arputhan Abisheganaden
2Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore
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Mariko Siyue Koh
4Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore
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Niranjan Nagarajan
6Genome Institute of Singapore, A*STAR, Singapore
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James D. Chalmers
9University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland
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Sanjay H. Chotirmall
1Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
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  • For correspondence: schotirmall@ntu.edu.sg
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Abstract

Introduction: Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a “research priorities” consensus statement for bronchiectasis Methods: Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S-28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific qPCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus-specific IgE, IgG and Thymus and Activation Regulated Chemokine levels were measured systemically and associated to clinical outcomes. Results: The bronchiectasis mycobiome is distinct, and characterised by specific fungal genera including Aspergillus, Cryptococcus, and Clavispora. A. fumigatus (in Singapore/Kuala Lumpur) and A. terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus-associated disease including sensitization and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles and associated with more severe disease, poorer pulmonary function and increased exacerbations. Conclusion: The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus-associated disease should be considered even in apparently stable patients.

Footnotes

This 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. Lim has nothing to disclose.

Conflict of interest: Dr. Ng has nothing to disclose.

Conflict of interest: Dr. Martinus has nothing to disclose.

Conflict of interest: Dr. Bertrand has nothing to disclose.

Conflict of interest: Dr. Chew reports personal fees from Sime Darby Technology Center, personal fees from Olam International and First Resources Ltd., outside the submitted work.

Conflict of interest: Dr. Tan has nothing to disclose.

Conflict of interest: Dr. Keir has nothing to disclose.

Conflict of interest: Dr. Chalmers reports grants and personal fees from Glaxosmithkline, grants and personal fees from Boehringer-Ingelheim, grants from Astrazeneca, grants and personal fees from Pfizer, grants and personal fees from Bayer Healthcare, grants and personal fees from Grifols, personal fees from Napp, outside the submitted work.

Conflict of interest: Dr. Koh has nothing to disclose.

Conflict of interest: Dr. Abisheganaden has nothing to disclose.

Conflict of interest: Dr. Connolly has nothing to disclose.

Conflict of interest: Dr. Koh has nothing to disclose.

Conflict of interest: Dr. Mac Aogáin has nothing to disclose.

Conflict of interest: Dr. Nagarajan has nothing to disclose.

Conflict of interest: Dr. Chandrasekaran has nothing to disclose.

Conflict of interest: Dr. Chotirmall has nothing to disclose.

Conflict of interest: Dr. Matta has nothing to disclose.

Conflict of interest: Dr. Pang has nothing to disclose.

Conflict of interest: Dr. Low has nothing to disclose.

Conflict of interest: Dr. Ong has nothing to disclose.

Conflict of interest: Dr. Hassan has nothing to disclose.

Conflict of interest: Dr. Gwee has nothing to disclose.

Conflict of interest: Dr. Sio has nothing to disclose.

Conflict of interest: Dr. Lee has nothing to disclose.

This is a PDF-only article. Please click on the PDF link above to read it.

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IMMUNOLOGICAL COROLLARY OF THE PULMONARY MYCOBIOME IN BRONCHIECTASIS: THE CAMEB STUDY
Micheál Mac Aogáin, Ravishankar Chandrasekaran, Albert Lim Yick Hou, Low Teck Boon, Gan Liang Tan, Tidi Hassan, Ong Thun How, Amanda Hui Qi Ng, Denis Bertrand, Jia Yu Koh, Sze Lei Pang, Zi Yang Lee, Xiao Wei Gwee, Christopher Martinus, Yang Yie Sio, Sri Anusha Matta, Fook Tim Chew, Holly R. Keir, John E. Connolly, John Arputhan Abisheganaden, Mariko Siyue Koh, Niranjan Nagarajan, James D. Chalmers, Sanjay H. Chotirmall
European Respiratory Journal Jan 2018, 1800766; DOI: 10.1183/13993003.00766-2018

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IMMUNOLOGICAL COROLLARY OF THE PULMONARY MYCOBIOME IN BRONCHIECTASIS: THE CAMEB STUDY
Micheál Mac Aogáin, Ravishankar Chandrasekaran, Albert Lim Yick Hou, Low Teck Boon, Gan Liang Tan, Tidi Hassan, Ong Thun How, Amanda Hui Qi Ng, Denis Bertrand, Jia Yu Koh, Sze Lei Pang, Zi Yang Lee, Xiao Wei Gwee, Christopher Martinus, Yang Yie Sio, Sri Anusha Matta, Fook Tim Chew, Holly R. Keir, John E. Connolly, John Arputhan Abisheganaden, Mariko Siyue Koh, Niranjan Nagarajan, James D. Chalmers, Sanjay H. Chotirmall
European Respiratory Journal Jan 2018, 1800766; DOI: 10.1183/13993003.00766-2018
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