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The relationship between biomarkers of fungal allergy and lung damage in asthma.

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posted on 2017-03-23, 15:54 authored by K. F. Woolnough, M. Richardson, C. Newby, M. Craner, M. Bourne, W. Monteiro, S. Siddiqui, P. Bradding, C. H. Pashley, A. J. Wardlaw
BACKGROUND: Immunological biomarkers are the key to the diagnosis of allergic bronchopulmonary aspergillosis (ABPA) and fungal sensitisation, but how these relate to clinically relevant outcomes is unclear. OBJECTIVES: To assess how fungal immunological biomarkers are related to fixed airflow obstruction and radiological abnormalities in moderate to severe asthma. METHODS: Cross-sectional study of 431 asthmatics. Inflammatory biomarkers, lung function and an IgE fungal panel to colonising filamentous fungi, yeasts and fungal aeroallergens were measured. CT scans were scored for the presence of radiological abnormalities. Factor analysis informed the variables used in a k-means cluster analysis. Fixed airflow obstruction and radiological abnormalities were then mapped to these immunological variables in the cluster analysis. RESULTS: 329 (76.3%) subjects were sensitised to ≥ 1 fungi. Sensitisation to Aspergillus fumigatus and/or Penicillium chrysogenum was associated with a lower post-bronchodilator FEV1 compared with those not sensitised to fungi ((73.0 (95% CI 70.2-76) vs. 82.8 (95% CI 78.5-87.2)% predicted, P < 0.001), independent of atopic status (P = 0.005)), and an increased frequency of bronchiectasis (54.5%, P < 0.001), tree-in-bud (18.7%, P < 0.001) and collapse/consolidation (37.5%, P = 0.002). Cluster analysis identified three clusters: (i) hypereosinophilic (n = 71, 16.5%), (ii) high immunological biomarker load and high frequency of radiological abnormalities (n = 34, 7.9%) and (iii) low levels of fungal immunological biomarkers (n = 326, 75.6%). CONCLUSIONS AND CLINICAL RELEVANCE: IgE sensitisation to thermotolerant filamentous fungi, in particular A. fumigatus but not total IgE, is associated with fixed airflow obstruction and a number of radiological abnormalities in moderate to severe asthma. All patients with IgE sensitisation to A. fumigatus are at risk of lung damage irrespective of whether they meet the criteria for ABPA.

Funding

Supported by the National Institute for Health Research (NIHR) Leicester Respiratory Biomedical Research Unit.

History

Citation

Clinical and Experimental Allergy, 2017, 47 (1), pp. 48-56

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation

Version

  • AM (Accepted Manuscript)

Published in

Clinical and Experimental Allergy

Publisher

Wiley

issn

0954-7894

eissn

1365-2222

Acceptance date

2016-10-29

Copyright date

2016

Available date

2018-11-02

Publisher version

http://onlinelibrary.wiley.com/doi/10.1111/cea.12848/abstract

Notes

The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.

Language

en

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