Clinical Relevance of the Pulmonary Mycobiome in Non- Cystic Fibrosis Bronchiectasis: The CAMEB Study

M. Mac Aogáin1, R. Chandrasekaran1, A. Lim2, T. Low3, G. Tan3, T. Hassan4, T. Ong5, C. K. Leong5, A. H. Q. Ng6, D. Bertrand6, J. Y. Koh6, S. Pang7, Z. Lee7, X. Gwee7, C. Martinus7, Y. Sio7, S. Matta7, F. Chew7, H. R. Keir8, M. Koh5, J. A. Abisheganaden2, N. Nagarajan6, J. D. Chalmers8, S. H. Chotirmall1;

Author address: 

1Lee Kong Chian School of Medicine, Singapore, Singapore, 2Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore, Singapore, 3Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore, Singapore, 4Department of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia, 5Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore, 6Genome Institute of Singapore, A*STAR, Singapore, Singapore, 7Department of Biological Sciences, National University of Singapore, Singapore, Singapore, 8Department of Respiratory Medicine, University of Dundee, Dundee, United Kingdom.

Abstract: 

Clinical Relevance of the Pulmonary Mycobiome in Non-Cystic Fibrosis Bronchiectasis: The CAMEB Study 
Introduction: 
The role for fungi in chronic pulmonary diseases such as asthma and cystic fibrosis is emerging however no investigation to date has addressed this in non-CF bronchiectasis. We performed, to our knowledge, the largest investigation of the pulmonary mycobiome across three countries (Singapore, Malaysia and Scotland) and two populations (Asian and European). Recruited patients were part of the CAMEB study: a cross-sectional Cohort of Asian and Matched European Bronchiectasis patients.
Methods:
Stable bronchiectasis patients (N = 238) from Singapore (N=124), Malaysia (N=14) and Scotland (N=100) were recruited as participants of the CAMEB study. Non-diseased controls (N=10) were also recruited in Singapore. We performed mycobiome analysis in representative patient sputum in addition to specific qPCR for detection of various Aspergillus species. Sputum galactomannan (GM), Aspergillus-specific IgE (sIgE) measurements for A. fumigatus and A. terreus, Thymus and Activation Regulated Chemokine (TARC) levels and Anti-Aspergillus IgG levels were measured in patient serum and associated clinical data was collated.
Results:
Analysis of the bronchiectasis mycobiome revealed the presence of distinct fungal genera including: Aspergillus, Issatchenkia, Wickerhamomyces,Simplicillium, Cryptococcus, Clavispora, Botrytis, Alternaria, Trametes and Phlebia. Speciation by qPCR revealed the presence of A. fumigatus and A. terreus only. While both Asian and European populations had patients with either or both fungi, A. fumigatus was more common in Asians whilst A. terreus dominated in Europeans. The presence of A. terreus was associated with increased exacerbations. High occurrence of Aspergillus sensitization and serologic allergic bronchopulmonary aspergillosis (sABPA) were found in both cohorts and associated with poorer lung function, increased exacerbations and greater disease severity.
Conclusion:
We demonstrate for the first time that the pulmonary mycobiome in bronchiectasis is distinct and has clinical relevance. Screening for Aspergillus-associated clinical disease should be considered even in bronchiectasis patients who appear stable.
Funding: This research is supported by the Singapore Ministry of Health’s National Medical Research Council under its Transition Award (NMRC/TA/0048/2016) (S.H.C) and the Changi General Hospital Research Grant (CHF2016.03-P) (T.B.L). C.F.T. has received research support from the Singapore Ministry of Education Academic Research Fund, the Singapore Immunology Network, and the Biomedical Research Council (BMRC) (N-154-000-038-001, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, SIgN-06-006, SIgN-08-020, BMRC/01/1/21/18/077, BMRC/04/1/21/19/315).‬

2018

abstract No: 

A6205

Full conference title: 

The American Thoracic Society Conference 2018
    • ATS 2018