TY - JOUR
T1 - Sensitisation to recombinant Aspergillus fumigatus allergens and clinical outcomes in COPD
AU - Tiew, Pei Yee
AU - Narayana, Jayanth Kumar
AU - Li Quek, Marilynn Swee
AU - Ang, Yan Ying
AU - San Ko, Fanny Wai
AU - Poh, Mau Ern
AU - Jaggi, Tavleen Kaur
AU - Xu, Huiying
AU - Thng, Kai Xian
AU - Koh, Mariko Siyue
AU - Tee, Augustine
AU - Cheong Hui, David Shu
AU - Abisheganaden, John Arputhan
AU - Tsaneva-Atanasova, Krasimira
AU - Chew, Fook Tim
AU - Chotirmall, Sanjay H.
N1 - Publisher Copyright:
Copyright © The authors 2023.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85145955224&partnerID=8YFLogxK
U2 - 10.1183/13993003.00507-2022
DO - 10.1183/13993003.00507-2022
M3 - Article
C2 - 35926878
AN - SCOPUS:85145955224
SN - 0903-1936
VL - 61
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 1
M1 - 2200507
ER -