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.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Pei Yee Tiew received honoraria for lectures and advisory board meetings paid to her hospital (Singapore General Hospital) from GlaxoSmithKline and Boehringer Ingelheim, outside the submitted work.
Conflict of interest: Jayanth Kumar Narayana has nothing to disclose.
Conflict of interest: Marilynn Swee Li Quek has nothing to disclose.
Conflict of interest: Yan Ying Ang has nothing to disclose.
Conflict of interest: Fanny Wai San Ko has nothing to disclose.
Conflict of interest: Mau Ern Poh has nothing to disclose.
Conflict of interest: Tavleen Kaur Jaggi has nothing to disclose.
Conflict of interest: Huiying Xu has nothing to disclose.
Conflict of interest: Kai Xian Thng has nothing to disclose.
Conflict of interest: Mariko Siyue Koh received research grant support from Astra-Zeneca, honoraria for lectures and advisory board meetings paid to her hospital (Singapore General Hospital) and from GlaxoSmithKline, Astra-Zeneca, Novartis, Sanofi and Boehringer Ingelheim, outside the submitted work.
Conflict of interest: Augustine Tee has nothing to disclose.
Conflict of interest: David Shu Cheong Hui has nothing to disclose.
Conflict of interest: John Arputhan Abisheganaden has nothing to disclose.
Conflict of interest: Krasimira Tsaneva-Atanasova has nothing to disclose.
Conflict of interest: Fook Tim Chew reports personal fees for consultancy from Sime Darby Technology Centre, First Resources Ltd, Genting Plantation and Olam International, outside the submitted work.
Conflict of interest: Sanjay H. Chotirmall is on advisory boards for CSL Behring, Pneumagen Ltd and Boehringer Ingelheim, serves on a data and safety monitoring board (DSMB) for Inovio Pharmaceuticals Inc. and Imam Abdulrahman Bin Faisal University, and has received personal fees from Astra-Zeneca, all outside of the submitted work.
- Received March 9, 2022.
- Accepted July 24, 2022.
- Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org
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