Abstract
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 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%). 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.
Highlights
Allergy to fungi is associated with asthma, in its more severe manifestations [1]
A number of case series in the 1970s described the clinical and immunological features of the condition [4]. These included a diagnosis of asthma or cystic fibrosis, evidence of fleeting lung shadows on chest x-rays, a raised specific serum IgE and IgG to A. fumigatus, a high total IgE (>1000ng/ml or 417 IU/ml), proximal bronchiectasis and a blood eosinophilia
The term severe asthma with fungal sensitization (SAFS) was defined to capture patients with asthma and fungal allergy who did not meet the criteria for allergic bronchopulmonary aspergillosis (ABPA) mainly because they had a total IgE
Summary
Allergy to fungi is associated with asthma, in its more severe manifestations [1]. A number of case series in the 1970s described the clinical and immunological features of the condition [4] These included a diagnosis of asthma or cystic fibrosis, evidence of fleeting lung shadows on chest x-rays, a raised specific serum IgE (sIgE) and IgG to A. fumigatus, a high total IgE (>1000ng/ml or 417 IU/ml), proximal bronchiectasis and a blood eosinophilia. In addition other radiological abnormalities including fleeting shadows, high attenuation mucus and lung fibrosis are a consistent feature of the clinical descriptions of fungal allergy in asthma [13,14,15] It remains unclear how the immunological biomarkers that are used to diagnose ABPA relate to specific disease outcomes, in terms of lung damage, and whether they clearly identify those with fungal allergy that are at risk of disease progression. Immunological biomarkers are key to the diagnosis of allergic bronchopulmonary aspergillosis (ABPA) and fungal sensitisation, but how these relate to clinically relevant outcomes is unclear
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