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. 2024 Nov 28;64(5):2400907.
doi: 10.1183/13993003.00907-2024. Print 2024 Nov.

Residential exposure to Aspergillus spp . is associated with exacerbations in COPD

Pei Yee Tiew  1   2   3 , Janice M Leung  4   5   3 , Micheál Mac Aogáin  6   7 , Parteek Johal  5 , Tavleen Kaur Jaggi  2 , Agnes Che Yan Yuen  5 , Fransiskus Xaverius Ivan  2 , Julia Yang  4 , Tina Afshar  5 , Augustine Tee  8 , Mariko Siyue Koh  1 , Yee Hui Lim  9 , Anthony Wong  9 , Lakshmi Chandrasekaran  9 , Justine G Dacanay  9 , Daniela I Drautz-Moses  9 , Thun How Ong  1 , John A Abisheganaden  2   10 , Fook Tim Chew  11 , Stephan C Schuster  9 , Christopher Carlsten  4   5   12 , Sanjay H Chotirmall  13   10   12
Affiliations

Residential exposure to Aspergillus spp . is associated with exacerbations in COPD

Pei Yee Tiew et al. Eur Respir J. .

Abstract

Background: Sensitisation to Aspergillus fumigatus is linked to worse outcomes in patients with COPD; however, its prevalence and clinical implications in domestic (residential) settings remains unknown.

Methods: Individuals with COPD (n=43) recruited in Singapore had their residences prospectively sampled and assessed by shotgun metagenomic sequencing including indoor air, outdoor air and touch surfaces (a total of 126 specimens). The abundance of environmental A. fumigatus and the occurrence of A. fumigatus (Asp f) allergens in the environment were determined and immunological responses to A. fumigatus allergens determined in association with clinical outcomes including exacerbation frequency. Findings were validated in 12 individuals (31 specimens) with COPD in Vancouver, Canada, a climatically different region.

Results: 157 metagenomes from 43 homes were assessed. 11 and nine separate Aspergillus spp. were identified in Singapore and Vancouver, respectively. Despite climatic, temperature and humidity variation, A. fumigatus was detectable in the environment from both locations. The relative abundance of environmental A. fumigatus was significantly associated with exacerbation frequency in both Singapore (r=0.27, p=0.003) and Vancouver (r=0.49, p=0.01) and individuals with higher Asp f 3 sensitisation responses lived in homes with a greater abundance of environmental Asp f 3 allergens (p=0.037). Patients exposed and sensitised to Asp f 3 allergens demonstrated a higher rate of COPD exacerbations at 1-year follow-up (p=0.021).

Conclusion: Environmental A. fumigatus exposure in the home environment including air and surfaces with resulting sensitisation carries pathogenic potential in individuals with COPD. Targeting domestic A. fumigatus abundance may reduce COPD exacerbations.

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Conflict of interest statement

Conflict of interest: P.Y. Tiew and A. Tee have served on advisory boards for GlaxoSmithKline and AstraZeneca, outside the submitted work. M.S. Koh reports grant support from AstraZeneca, and honoraria for lectures and advisory board meetings paid to her hospital (Singapore General Hospital) from GlaxoSmithKline, AstraZeneca, Novartis, Sanofi, Boehringer Ingelheim and Roche, outside the submitted work. F.T. Chew reports grants from the National University of Singapore, Singapore Ministry of Education Academic Research Fund, Singapore Immunology Network, National Medical Research Council (NMRC) (Singapore), Biomedical Research Council (BMRC) (Singapore), National Research Foundation (NRF) (Singapore), Singapore Food Agency (SFA), and the Agency for Science Technology and Research (A*STAR) (Singapore), during the conduct of the study, and consulting fees from Sime Darby Technology Centre, First Resources Ltd, Genting Plantation, Olam International, Musim Mas and Syngenta Crop Protection, outside the submitted work. P.Y. Tiew reports grants from Singapore Ministry of Health's National Medical Research Council under its Transition Award (MOH- 001275-00). S.H. Chotirmall reports support for the present study from Singapore Ministry of Health's National Medical Research Council under its Clinician-Scientist Individual Research Grant (MOH-001356), Singapore Ministry of Health's National Medical Research Council under its Clinician Scientist Award (MOH-000710), Open Fund Individual Research Grant (MOH-000955) and Singapore Ministry of Education under its AcRF Tier 1 Grant (RT1/22), consultancy fees from CSL Behring, Boehringer Ingelheim and Pneumagen Ltd, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca and Chiesi Farmaceutici, and participation on a data safety monitoring board or advisory board with Inovio Pharmaceuticals Inc. and Imam Abdulrahman Bin Faisal University. J.M. Leung and C. Carlsten report grants from Canada Research Chairs program. The remaining authors have no potential conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Diversity of Aspergillus spp. detected in the home environment of patients with COPD. UpSet plot illustrating the frequency of Aspergillus spp. isolated in outdoor (balcony) air, indoor (bedroom) air and surfaces including air-conditioner filters and/or fan swabs. Bar charts corresponding to the number of homes with detectable Aspergillus spp. in the outdoor air, indoor air and on surfaces.
FIGURE 2
FIGURE 2
Environmental detection of Aspergillus fumigatus correlates with increased temperature and particulate matter. Scatterplots illustrating correlations between the relative abundance of detectable A. fumigatus within the home environment and a) indoor temperature, b) particulate matter with aerodynamic diameter <2.5 µm (PM2.5), c) particulate matter with aerodynamic diameter <10 µm (PM10) and d) relative humidity. Black dotted lines correspond to Spearman's regression and grey shaded areas represent 95% confidence intervals. ns: nonsignificant.
FIGURE 3
FIGURE 3
Environmental Aspergillus fumigatus associates with increased exacerbation frequency in individuals with COPD. Correlations between the relative abundance of A. fumigatus detected in environmental samples (air, surfaces) and number of exacerbations a) in the year preceding study recruitment and b) at 1-year follow-up. Black dotted lines correspond to Spearman's regression and grey shaded areas represent 95% confidence intervals. Scatter boxplots illustrating number of exacerbations in c) the year preceding study recruitment and d) at 1-year follow-up in homes with moderate (i.e. <1% relative abundance) and high (≥1% relative abundance) of A. fumigatus in environmental samples (air, surfaces). Forest plots for exacerbation risk ratio in e) the year preceding study recruitment and f) at 1-year follow-up adjusted for age, body mass index (BMI), smoking status, lung function (forced expiratory volume in 1 s (FEV1) % predicted) and baseline exacerbation rate (between patients with moderate and high exposure to environmental A. fumigatus). Error bars indicate 95% confidence intervals with red dots denoting significance and grey dots representing nonsignificance. FE: frequent exacerbator status at baseline. *: p<0.05, **: p<0.01.
FIGURE 4
FIGURE 4
Specific Aspergillus fumigatus allergens in the home environment of individuals with COPD. a) Heatmap demonstrating metagenome reads of specific A. fumigatus allergens in the home environment of patients with COPD: outdoor air, indoor air and surfaces. Scatter boxplots illustrating the relative abundance of environmental b) Asp f 3, c) Asp f 5 and d) Asp f 6 allergens in the home environment of patients with COPD assessed by the presence or absence of sensitisation responses to the respective allergens. e) Lung function (as forced expiratory volume in 1 s (FEV1) % predicted), f) number of exacerbations at 1-year follow-up, g) symptoms (by COPD Assessment Test (CAT) score) and h) number of exacerbations in the year preceding study recruitment between COPD patients exposed (but not sensitised) and both exposed and sensitised to Asp f 3. E: exposed (detectable significant presence of Asp f 3 in the home environment) but not sensitised; E+S: exposed and sensitised to Asp f 3. *: p<0.05, ns: nonsignificant.
FIGURE 5
FIGURE 5
Aspergillus spp. in the home environment associates with exacerbation frequency in COPD independent of geographic origin. a) Bubble plot illustrating the metagenome reads of various Aspergillus spp. detected in indoor air and surface swabs within the homes of patients with COPD from Vancouver and Singapore, respectively. Scatterplots illustrating the correlation between the relative abundance of environmental A. fumigatus and b) number of COPD exacerbations in the year preceding study recruitment, c) symptoms (by COPD Assessment Test (CAT) score) and d) lung function (as forced expiratory volume in 1 s (FEV1) % predicted) in COPD patients from Vancouver, Canada. Black dotted lines correspond to Spearman's regression and the grey shaded area represents the 95% confidence intervals. ns: nonsignificant.
FIGURE 6
FIGURE 6
Number of specific Aspergillus fumigatus allergens detected in the home environment associates with frequent exacerbations in COPD. Scatter boxplots illustrating the number of specific A. fumigatus allergens detected in the home environment in a) Vancouver and Singapore, b) frequent and nonfrequent COPD exacerbators, c) COPD with low and high symptomatic burden (by COPD Assessment Test (CAT) score), and d) between Global Initiative for Chronic Obstructive Lung Disease (GOLD) group (forced expiratory volume in 1 s (FEV1) % predicted) groups. GOLD 1: FEV1 ≥80% pred; GOLD 2: FEV1 50–79% pred; GOLD 3: FEV1 30–49% pred; GOLD 4: FEV1 <30% pred. *: p<0.05, ***: p<0.001, ns: nonsignificant.
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