Sensitisation to recombinant Aspergillus fumigatus allergens and clinical outcomes in COPD.

This is the author accepted manuscript. The final version is available from the European Respiratory Society via the DOI in this recordBACKGROUND: Variable clinical outcomes are reported with fungal sensitisation in COPD, and it remains unclear which fungi and what allergens associate with poorest outcomes. The use of recombinant as opposed to crude allergens for such assessment is unknown. METHODS: A prospective multicenter 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 sub-groups exist and their related clinical outcomes. RESULTS: Aspergillus fumigatus sensitisation associates with increased exacerbations in COPD. Unsupervised cluster analyses reveal two "fungal sensitisation" groups, one characterized by Aspergillus sensitisation and increased exacerbations, poorer lung function and worse prognosis. Polysensitisation in this group confers even poorer outcome. The second group, characterized by Cladosporium sensitisation is more symptomatic. Significant numbers of individuals demonstrate sensitisation responses to only recombinant (as opposed to crude) Aspergillus fumigatus allergens 1, 3, 5, and 6, and exhibit higher exacerbations, poorer lung function and an overall worse prognosis. TDA validated these findings and additionally identified a sub-group within "Aspergillus sensitised COPD" enriched for frequent exacerbators. 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 remain overlooked by assessment of only crude Aspergillus allergens.Engineering and Physical Sciences Research Council (EPSRC)Singapore General Hospital Research GrantSingapore Ministry of Health's National Medical Research CouncilSingapore Ministry of Health's National Medical Research CouncilNational University of SingaporeSingapore Ministry of Education Academic Research FundSingapore Ministry of Education Academic Research FundSingapore Ministry of Education Academic Research FundSingapore Ministry of Education Academic Research FundSingapore Ministry of Education Academic Research FundSingapore Ministry of Education Academic Research FundSingapore Ministry of Education Academic Research FundSingapore Ministry of Education Academic Research FundSingapore Ministry of Education Academic Research FundSingapore Ministry of Education Academic Research FundBiomedical Research Council (BMRC) (Singapore)Biomedical Research Council (BMRC) (Singapore)Biomedical Research Council (BMRC) (Singapore)Singapore Immunology NetworkSingapore Immunology NetworkNational Medical Research Council (NMRC) (Singapore)Agency for Science Technology and Research (A*STAR) (Singapore)Agency for Science Technology and Research (A*STAR) (Singapore