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



To assess how fungal immunological biomarkers are related to fixed airflow obstruction and radiological abnormalities in moderate to severe asthma.



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.



329 (76.3%) subjects were sensitised to ≥ 1 fungi. Sensitisation to Aspergillus fumigatus and/or Penicillium chrysogenum was associated with a lower post-bronchodilator FEV1compared 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%).



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.
Institute for Lung Health/Department of Infection, Immunity and Inflammation, University of Leicester, Glenfield Hospital, Leicester, UK.
K F
KF
Woolnough
Institute for Lung Health/Department of Infection, Immunity and Inflammation, University of Leicester, Glenfield Hospital, Leicester, UK.
M
M
Richardson
Department of Health Sciences, University of Leicester, Leicester, UK.
C
C
Newby
Institute for Lung Health/Department of Infection, Immunity and Inflammation, University of Leicester, Glenfield Hospital, Leicester, UK.
M
M
Craner
Institute for Lung Health/Department of Infection, Immunity and Inflammation, University of Leicester, Glenfield Hospital, Leicester, UK.
M
M
Bourne
Institute for Lung Health/Department of Infection, Immunity and Inflammation, University of Leicester, Glenfield Hospital, Leicester, UK.
W
W
Monteiro
Institute for Lung Health/Department of Infection, Immunity and Inflammation, University of Leicester, Glenfield Hospital, Leicester, UK.
S
S
Siddiqui
Institute for Lung Health/Department of Infection, Immunity and Inflammation, University of Leicester, Glenfield Hospital, Leicester, UK.
P
P
Bradding
Institute for Lung Health/Department of Infection, Immunity and Inflammation, University of Leicester, Glenfield Hospital, Leicester, UK.
C H
CH
Pashley
Institute for Lung Health/Department of Infection, Immunity and Inflammation, University of Leicester, Glenfield Hospital, Leicester, UK.
A J
AJ
Wardlaw
D000328:Adult; D000908:Antibodies, Fungal / Q000097:blood / Q000276:immunology; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000175:diagnosis* / Q000276:immunology*; D001249:Asthma / Q000175:diagnosis* / Q000209:etiology*; D015415:Biomarkers; D003430:Cross-Sectional Studies; D004804:Eosinophils; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D014057:Tomography, X-Ray Computed
D000908:Antibodies, Fungal; D015415:Biomarkers; D007074:Immunoglobulin G; D007073:Immunoglobulin E

Aspergillus fumigatus
; allergic bronchopulmonary aspergillosis; allergic fungal airway disease; asthma; lung damage