Search

Background: Sensitisation to Aspergillus fumigatus is linked to worse outcomes in patients with COPD; however, its prevalence and clinical implications in domestic (residential) settings remains unknown., Methods: Individuals with COPD (n=43) recruited in Singapore had their residences prospectively sampled and assessed by shotgun metagenomic sequencing including indoor air, outdoor air and touch surfaces (a total of 126 specimens). The abundance of environmental A. fumigatus and the occurrence of A. fumigatus (Asp f) allergens in the environment were determined and immunological responses to A. fumigatus allergens determined in association with clinical outcomes including exacerbation frequency. Findings were validated in 12 individuals (31 specimens) with COPD in Vancouver, Canada, a climatically different region., Results: 157 metagenomes from 43 homes were assessed. 11 and nine separate Aspergillus spp . were identified in Singapore and Vancouver, respectively. Despite climatic, temperature and humidity variation, A. fumigatus was detectable in the environment from both locations. The relative abundance of environmental A. fumigatus was significantly associated with exacerbation frequency in both Singapore (r=0.27, p=0.003) and Vancouver (r=0.49, p=0.01) and individuals with higher Asp f 3 sensitisation responses lived in homes with a greater abundance of environmental Asp f 3 allergens (p=0.037). Patients exposed and sensitised to Asp f 3 allergens demonstrated a higher rate of COPD exacerbations at 1-year follow-up (p=0.021)., Conclusion: Environmental A. fumigatus exposure in the home environment including air and surfaces with resulting sensitisation carries pathogenic potential in individuals with COPD. Targeting domestic A. fumigatus abundance may reduce COPD exacerbations., Competing Interests: Conflict of interest: P.Y. Tiew and A. Tee have served on advisory boards for GlaxoSmithKline and AstraZeneca, outside the submitted work. M.S. Koh reports grant support from AstraZeneca, and honoraria for lectures and advisory board meetings paid to her hospital (Singapore General Hospital) from GlaxoSmithKline, AstraZeneca, Novartis, Sanofi, Boehringer Ingelheim and Roche, outside the submitted work. F.T. Chew reports grants from the National University of Singapore, Singapore Ministry of Education Academic Research Fund, Singapore Immunology Network, National Medical Research Council (NMRC) (Singapore), Biomedical Research Council (BMRC) (Singapore), National Research Foundation (NRF) (Singapore), Singapore Food Agency (SFA), and the Agency for Science Technology and Research (A*STAR) (Singapore), during the conduct of the study, and consulting fees from Sime Darby Technology Centre, First Resources Ltd, Genting Plantation, Olam International, Musim Mas and Syngenta Crop Protection, outside the submitted work. P.Y. Tiew reports grants from Singapore Ministry of Health's National Medical Research Council under its Transition Award (MOH- 001275-00). S.H. Chotirmall reports support for the present study from Singapore Ministry of Health's National Medical Research Council under its Clinician-Scientist Individual Research Grant (MOH-001356), Singapore Ministry of Health's National Medical Research Council under its Clinician Scientist Award (MOH-000710), Open Fund Individual Research Grant (MOH-000955) and Singapore Ministry of Education under its AcRF Tier 1 Grant (RT1/22), consultancy fees from CSL Behring, Boehringer Ingelheim and Pneumagen Ltd, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca and Chiesi Farmaceutici, and participation on a data safety monitoring board or advisory board with Inovio Pharmaceuticals Inc. and Imam Abdulrahman Bin Faisal University. J.M. Leung and C. Carlsten report grants from Canada Research Chairs program. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Background: Variable clinical outcomes are reported with fungal sensitisation in chronic obstructive pulmonary disease (COPD), and it remains unclear which fungi and what allergens associate with the poorest outcomes. The use of recombinant as opposed to crude allergens for such assessment is unknown., Methods: A prospective multicentre assessment of stable COPD (n=614) was undertaken in five hospitals across three countries: Singapore, Malaysia and Hong Kong. Clinical and serological assessment was performed against a panel of 35 fungal allergens including crude and recombinant Aspergillus and non- Aspergillus allergens. Unsupervised clustering and topological data analysis (TDA) approaches were employed using the measured sensitisation responses to elucidate if sensitisation subgroups exist and their related clinical outcomes., Results: Aspergillus fumigatus sensitisation was associated with increased exacerbations in COPD. Unsupervised cluster analyses revealed two "fungal sensitisation" groups. The first was characterised by Aspergillus sensitisation and increased exacerbations, poorer lung function and worse prognosis. Polysensitisation in this group conferred even poorer outcome. The second group, characterised by Cladosporium sensitisation, was more symptomatic. Significant numbers of individuals demonstrated sensitisation responses to only recombinant (as opposed to crude) A. fumigatus allergens f 1, 3, 5 and 6, and exhibited increased exacerbations, poorer lung function and an overall worse prognosis. TDA validated these findings and additionally identified a subgroup within Aspergillus -sensitised COPD of patients with frequent exacerbations., Conclusion: Aspergillus sensitisation is a treatable trait in COPD. Measuring sensitisation responses to recombinant Aspergillus allergens identifies an important patient subgroup with poor COPD outcomes that remains overlooked by assessment of only crude Aspergillus allergens., Competing Interests: Conflict of interest: P.Y. Tiew received honoraria for lectures and advisory board meetings paid to her hospital (Singapore General Hospital) from AstraZeneca, GlaxoSmithKline and Boehringer Ingelheim, outside the submitted work. M.S. Koh received research grant support from AstraZeneca, and honoraria for lectures and advisory board meetings paid to her hospital (Singapore General Hospital) from GlaxoSmithKline, AstraZeneca, Novartis, Sanofi and Boehringer Ingelheim, outside the submitted work. K. Tsaneva-Atanasova reports EPSRC grant EP/T017856/1. F.T. Chew reports personal fees for consultancy from Sime Darby Technology Centre, First Resources Ltd, Genting Plantation and Olam International, outside the submitted work. S.H. Chotirmall is on advisory boards for CSL Behring, Pneumagen Ltd and Boehringer Ingelheim, serves on a data and safety monitoring board for Inovio Pharmaceuticals Inc. and Imam Abdulrahman Bin Faisal University, and has received personal fees from AstraZeneca, all outside of the submitted work. All other authors have no conflicts of interest to declare., (Copyright ©The authors 2023.)