The Clinical Implications of Aspergillus Fumigatus Sensitization in Difficult-To-Treat Asthma Patients

J Allergy Clin Immunol Pract. 2021 Dec;9(12):4254-4267.e10. doi: 10.1016/j.jaip.2021.08.038. Epub 2021 Sep 14.

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.

Trial registration: ClinicalTrials.gov NCT03996590.

Keywords: ABPA; Aspergillus fumigatus; Difficult asthma; Fungal sensitization; Lung function; SAFS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillosis, Allergic Bronchopulmonary* / diagnosis
  • Aspergillosis, Allergic Bronchopulmonary* / epidemiology
  • Aspergillus fumigatus
  • Asthma* / diagnosis
  • Asthma* / drug therapy
  • Asthma* / epidemiology
  • Bronchiectasis*
  • Humans
  • Immunoglobulin E
  • Male

Substances

  • Immunoglobulin E

Associated data

  • ClinicalTrials.gov/NCT03996590