The Clinical Implications of Aspergillus Fumigatus Sensitization in Difficult-To-Treat Asthma Patients
Heena Mistry1, Hilda Maria Ajsivinac Soberanis2, Mohammad Aref Kyyaly3
1Clinical and Experimental Sciences Department, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre at University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; Asthma, Allergy and Clinical Immunology Department, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; La Jolla Institute of Immunology, La Jolla, Calif; The David Hide Asthma & Allergy Research Centre, St Mary's Hospital, Newport, Isle of Wight, United Kingdom.
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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