Sensitisation to recombinant Aspergillus fumigatus allergens and clinical outcomes in COPD

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.Ministry of Education (MOE)Ministry of Health (MOH)National Medical Research Council (NMRC)Published versionThis research is supported by the Singapore General Hospital Research Grant (SRG-OPN-06-2021) (P.Y. Tiew) and the Singapore Ministry of Health's National Medical Research Council under its Clinician-Scientist Individual Research Grant (MOH-000141) (S.H. Chotirmall) and Clinician-Scientist Award (MOH-000710) (S.H. Chotirmall). K. Tsaneva-Atanasova gratefully acknowledges the financial support of the EPSRC via grant EP/T017856/1. F.T. Chew (Singapore) received grants from the National University of Singapore (N-154-000-038-001), Singapore Ministry of Education Academic Research Fund (R-154-000-191-112, 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, R-154-000-A91-592, R-154-000-A95-592, R154-000-B99-114), Biomedical Research Council (Singapore) (BMRC/01/1/21/18/077, BMRC/04/1/21/19/315, BMRC/APG2013/108), Singapore Immunology Network (SIgN-06-006, SIgN-08-020), National Medical Research Council (Singapore) (NMRC/1150/2008), and the Agency for Science Technology and Research (Singapore) (H17/01/a0/008 and APG2013/108). Funding information for this article has been deposited with the Crossref Funder Registry

VIDEOGRAPHY Maisarah Abu Samah

republic polytechni

"High-Risk" Clinical and Inflammatory Clusters in COPD of Chinese Descent

COPD is a heterogeneous disease demonstrating inter-individual variation. A high COPD prevalence in Chinese populations is described, but little is known about disease clusters and prognostic outcomes in the Chinese population across Southeast Asia. We aim to determine if clusters of Chinese patients with COPD exist and their association with systemic inflammation and clinical outcomes.Ministry of Education (MOE)Nanyang Technological UniversityNational Medical Research Council (NMRC)This research is supported by the Singapore Ministry of Health’s National Medical Research Council under its Research Training Fellowship [NMRC/Fellowship/0049/2017 to P. Y. T.] and a Clinician-Scientist Individual Research Grant [MOH-000141 to S. H. C.]; the Singapore Ministry of Education under its Singapore Ministry of Education Academic Research Fund Tier 1 [2016-T1-001-050 to S. H. C.]; the NTU Integrated Medical, Biological and Environmental Life Sciences (NIMBELS), Nanyang Technological University , Singapore [NIM/03/2018 to S. H. C.]; the Ageing Research Institute for Society and Education (ARISE), Nanyang Technological University , Singapore [ARISE/2017/6 to S. H. C.]; and Engineering and Physical Sciences Research Council (EPSRC) grant, United Kingdom [EP/N014391/1] to K. T. A