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The clinical implications of Aspergillus Fumigatus sensitization in difficult-to-treat asthma patients

The clinical implications of Aspergillus Fumigatus sensitization in difficult-to-treat asthma patients
The clinical implications of Aspergillus Fumigatus sensitization in difficult-to-treat asthma patients

Background: fungal sensitivity has been associated with severe asthma outcomes. However, the clinical implication of Aspergillus fumigatus sensitization in difficult-to-treat (or difficult) asthma is unclear.

Objectives: to characterize the clinical implications of A fumigatus sensitization in a large difficult asthma cohort.

Methods: participants who underwent both skin prick and specific IgE testing to A fumigatus (n = 318) from the longitudinal real-life Wessex AsThma CoHort of difficult asthma, United Kingdom, were characterized by A fumigatus sensitization (either positive skin prick test result or specific IgE) and allergic bronchopulmonary aspergillosis status using clinical/pathophysiological disease measures.

Results: a fumigatus sensitization was found in 23.9% (76 of 318) of patients with difficult asthma. Compared with A fumigatus nonsensitized subjects, those with sensitization were significantly more often male (50% vs 31%), older (58 years) with longer asthma duration (33 years), higher maintenance oral corticosteroid (39.7%) and asthma biologic use (27.6%), raised current/maximum log10 total IgE+1 (2.43/2.72 IU/L), worse prebronchodilator airflow obstruction (FEV1 62.2% predicted, FEV1/forced vital capacity 61.2%, forced expiratory flow between 25% and 75% exhalation 30.9% predicted), and frequent radiological bronchiectasis (40%), but had less psychophysiologic comorbidities. Allergic bronchopulmonary aspergillosis diagnosis was associated with higher treatment needs and stronger eosinophilic signals. Factors independently associated with A fumigatus sensitization in difficult asthma included maintenance oral corticosteroid use (odds ratio [OR], 3.34) and maximum log10 total IgE+1 (OR, 4.30), whereas for allergic bronchopulmonary aspergillosis included maintenance oral corticosteroid use (OR, 6.98), maximum log10 total IgE+1 (OR, 4.65), and radiological bronchiectasis (OR, 4.08).

Conclusions: a fumigatus sensitization in difficult asthma identifies a more severe form of airways disease associated with greater morbidity, treatment need, and airways dysfunction/damage, but fewer psychophysiologic comorbidities. Screening of A fumigatus status should be an early element in the comprehensive assessment of patients with difficult asthma.

ABPA, Aspergillus fumigatus, Difficult asthma, Fungal sensitization, Lung function, SAFS
2213-2198
4254-4267.e10
Mistry, Heena
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Ajsivinac Soberanis, Hilda Maria
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Kyyaly, Mohammad Aref
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Azim, Adnan
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Barber, Clair
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Knight, Deborah
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Newell, Colin
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Haitchi, Hans Michael
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Wilkinson, Tom
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Howarth, Peter
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Seumois, Grégory
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Vijayanand, Pandurangan
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Arshad, S Hasan
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Kurukulaaratchy, Ramesh J
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Mistry, Heena
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Ajsivinac Soberanis, Hilda Maria
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Kyyaly, Mohammad Aref
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Azim, Adnan
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Barber, Clair
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Knight, Deborah
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Newell, Colin
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Haitchi, Hans Michael
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Wilkinson, Tom
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Howarth, Peter
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Seumois, Grégory
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Vijayanand, Pandurangan
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Arshad, S Hasan
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Kurukulaaratchy, Ramesh J
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Mistry, Heena, Ajsivinac Soberanis, Hilda Maria, Kyyaly, Mohammad Aref, Azim, Adnan, Barber, Clair, Knight, Deborah, Newell, Colin, Haitchi, Hans Michael, Wilkinson, Tom, Howarth, Peter, Seumois, Grégory, Vijayanand, Pandurangan, Arshad, S Hasan and Kurukulaaratchy, Ramesh J (2021) The clinical implications of Aspergillus Fumigatus sensitization in difficult-to-treat asthma patients. Journal of Allergy and Clinical Immunology: In Practice, 9 (12), 4254-4267.e10. (doi:10.1016/j.jaip.2021.08.038).

Record type: Article

Abstract

Background: fungal sensitivity has been associated with severe asthma outcomes. However, the clinical implication of Aspergillus fumigatus sensitization in difficult-to-treat (or difficult) asthma is unclear.

Objectives: to characterize the clinical implications of A fumigatus sensitization in a large difficult asthma cohort.

Methods: participants who underwent both skin prick and specific IgE testing to A fumigatus (n = 318) from the longitudinal real-life Wessex AsThma CoHort of difficult asthma, United Kingdom, were characterized by A fumigatus sensitization (either positive skin prick test result or specific IgE) and allergic bronchopulmonary aspergillosis status using clinical/pathophysiological disease measures.

Results: a fumigatus sensitization was found in 23.9% (76 of 318) of patients with difficult asthma. Compared with A fumigatus nonsensitized subjects, those with sensitization were significantly more often male (50% vs 31%), older (58 years) with longer asthma duration (33 years), higher maintenance oral corticosteroid (39.7%) and asthma biologic use (27.6%), raised current/maximum log10 total IgE+1 (2.43/2.72 IU/L), worse prebronchodilator airflow obstruction (FEV1 62.2% predicted, FEV1/forced vital capacity 61.2%, forced expiratory flow between 25% and 75% exhalation 30.9% predicted), and frequent radiological bronchiectasis (40%), but had less psychophysiologic comorbidities. Allergic bronchopulmonary aspergillosis diagnosis was associated with higher treatment needs and stronger eosinophilic signals. Factors independently associated with A fumigatus sensitization in difficult asthma included maintenance oral corticosteroid use (odds ratio [OR], 3.34) and maximum log10 total IgE+1 (OR, 4.30), whereas for allergic bronchopulmonary aspergillosis included maintenance oral corticosteroid use (OR, 6.98), maximum log10 total IgE+1 (OR, 4.65), and radiological bronchiectasis (OR, 4.08).

Conclusions: a fumigatus sensitization in difficult asthma identifies a more severe form of airways disease associated with greater morbidity, treatment need, and airways dysfunction/damage, but fewer psychophysiologic comorbidities. Screening of A fumigatus status should be an early element in the comprehensive assessment of patients with difficult asthma.

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Accepted/In Press date: 27 August 2021
e-pub ahead of print date: 14 September 2021
Published date: December 2021
Additional Information: Funding Information: The Wessex AsThma CoHort of difficult asthma (WATCH) study has been supported by the National Institute for Health Research Southampton Biomedical Research Centre and Clinical Research Facility at University Hospital Southampton National Health Service Foundation Trust, United Kingdom. The WATCH study itself is not externally funded. Funding assistance for database support for the WATCH study was initially obtained from a nonpromotional grant from Novartis (£35,000). Funding assistance for patient costs (eg, parking) was initially provided by a charitable grant (£3500) from the Asthma, Allergy & Inflammation Research Charity . The WATCH study is registered through ClinicalTrials.gov ; Identifier: NCT03996590 . Funding Information: We thank the patients who are participating in this study. We also acknowledge the contributions of the wider WATCH study team including Matthew Harvey, Mae Felongco, Helen Wheeler, June Law, Yvette Thirlwall, Kim Bentley, Laura Presland, Frances Mitchell, Yueqing Cheng, Josune Olza Meneses, Paddy Dennison, Anna Freeman, Wei Chern Gavin Fong, Kerry Day, David Hill, and Ratko Djukanovic. We also acknowledge the support of the Southampton National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) and Clinical Research Facility . The Clinical Research Facility and BRC are funded by NIHR Southampton and are a partnership between the University of Southampton and University Hospital Southampton NHS Foundation Trust . We also acknowledge funding support from Novartis and the Asthma Allergy and Inflammation Research Charity . Publisher Copyright: © 2021 American Academy of Allergy, Asthma & Immunology Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
Keywords: ABPA, Aspergillus fumigatus, Difficult asthma, Fungal sensitization, Lung function, SAFS

Identifiers

Local EPrints ID: 451450
URI: http://eprints.soton.ac.uk/id/eprint/451450
ISSN: 2213-2198
PURE UUID: 1b2c25c9-43c3-4647-a975-7091826ffaf1
ORCID for Mohammad Aref Kyyaly: ORCID iD orcid.org/0000-0002-1684-9207
ORCID for Clair Barber: ORCID iD orcid.org/0000-0001-5335-5129
ORCID for Hans Michael Haitchi: ORCID iD orcid.org/0000-0001-8603-302X
ORCID for Pandurangan Vijayanand: ORCID iD orcid.org/0000-0001-7067-9723
ORCID for Ramesh J Kurukulaaratchy: ORCID iD orcid.org/0000-0002-1588-2400

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Date deposited: 28 Sep 2021 16:35
Last modified: 17 Mar 2024 06:51

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Contributors

Author: Heena Mistry
Author: Hilda Maria Ajsivinac Soberanis
Author: Adnan Azim
Author: Clair Barber ORCID iD
Author: Deborah Knight
Author: Colin Newell
Author: Tom Wilkinson
Author: Peter Howarth
Author: Grégory Seumois
Author: Pandurangan Vijayanand ORCID iD
Author: S Hasan Arshad

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