Immunological corollary of the pulmonary mycobiome in bronchiectasis: The Cameb study

TY - JOUR

T1 - Immunological corollary of the pulmonary mycobiome in bronchiectasis

T2 - The Cameb study

AU - Mac Aogáin, Micheál

AU - Chandrasekaran, Ravishankar

AU - Lim Yick Hou, Albert

AU - Teck Boon, Low

AU - Liang Tan, Gan

AU - Hassan, Tidi

AU - Thun How, Ong

AU - Hui Qi Ng, Amanda

AU - Bertrand, Denis

AU - Yu Koh, Jia

AU - Lei Pang, Sze

AU - Yang Lee, Zi

AU - Wei Gwee, Xiao

AU - Martinus, Christopher

AU - Yie Sio, Yang

AU - Anusha Matta, Sri

AU - Tim Chew, Fook

AU - Keir, Holly R.

AU - Connolly, John E

AU - Arputhan Abisheganaden, John

AU - Siyue Koh, Mariko

AU - Nagarajan, Niranjan

AU - Chalmers, James D.

AU - Chotirmall, Sanjay H.

N1 - Changi General Hospital Research Grant CHF2016.03-P; GSK/British Lung Foundation Chair of Respiratory Research (J.D.C); Ministry of Education - Singapore 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; National Medical Research Council NMRC/1150/2008 (F.T.C.); Transition Award (NMRC/TA/0048/2016) (S.H.C); The Singapore Immunology Network SIgN-06-006; SIgN-08-020.

PY - 2018/7

Y1 - 2018/7

N2 - 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 ClavisporaA. 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.

AB - 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 ClavisporaA. 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.

KW - Fungi

KW - Aspergillus

KW - microbiome

KW - mycobiome

KW - bronchiectasis

U2 - 10.1183/13993003.00766-2018

DO - 10.1183/13993003.00766-2018

M3 - Article

C2 - 29880655

SN - 0903-1936

VL - 52

SP - 1

EP - 14

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 1

M1 - 1800766

ER -