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Sensitisation to recombinant Aspergillus fumigatus allergens and clinical outcomes in COPD
PP-PDPI, 05 Ags 2022 07:57:56

Pei Yee Tiew, Jayanth Kumar Narayana, Marilynn Swee Li Quek, Yan Ying Ang, Fanny Wai San Ko, Mau Ern Poh, Tavleen Kaur Jaggi, Huiying Xu, Kai Xian Thng, Mariko Siyue Koh, Augustine Tee, David Shu Cheong Hui, John Arputhan Abisheganaden, Krasimira Tsaneva-Atanasova, Fook Tim Chew, Sanjay H. Chotirmall
European Respiratory Journal 2022; DOI: 10.1183/13993003.00507-2022

Abstract

Background 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.

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