Sensitisation to recombinant Aspergillus fumigatus allergens and clinical outcomes in COPD

Tiew, Pei Yee and Narayana, Jayanth Kumar and Li Quek, Marilynn Swee and Ang, Yan Ying and San Ko, Fanny Wai and Poh, Mau Ern and Jaggi, Tavleen Kaur and Xu, Huiying and Thng, Kai Xian and Koh, Mariko Siyue and Tee, Augustine and Hui, David Shu Cheong and Abisheganaden, John Arputhan and Tsaneva-Atanasova, Krasimira and Chew, Fook Tim and Chotirmall, Sanjay H. (2023) Sensitisation to recombinant Aspergillus fumigatus allergens and clinical outcomes in COPD. European Respiratory Journal, 61 (1). ISSN 0903-1936, DOI https://doi.org/10.1183/13993003.00507-2022.

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Abstract

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.

Item Type: Article
Funders: UNSPECIFIED
Uncontrolled Keywords: Allergens; Aspergillus; Aspergillus fumigatus; Humans; Immunoglobulin E; Prospective Studies; Pulmonary Disease, Chronic Obstructive
Subjects: R Medicine
R Medicine > RA Public aspects of medicine
Divisions: Faculty of Medicine
Faculty of Medicine > Medicine Department
Depositing User: Ms Zaharah Ramly
Date Deposited: 01 Nov 2024 08:07
Last Modified: 01 Nov 2024 08:07
URI: http://eprints.um.edu.my/id/eprint/39123

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