Letter to the editor

Consistency of sputum eosinophilia in difficult-to-treat asthma: A 5-year follow-up study

Eosinophilic inflammation has long been associated with asthma. Looking at systemic and airway eosinophilia, we have recently identified a group of patients exhibiting diffuse eosinophilic inflammation. Among the mechanisms governing eosinophilic inflammation, IgE-mediated mast cell activation is a key event leading to eosinophilia in atopic asthmatics.

We conducted a retrospective study on our asthma clinic database containing more than 1500 patients and identified 205 asthmatics with successful sputum induction and concordant eosinophilic phenotype. This phenotype was defined as a sputum eosinophil count ≥ 3% and a blood eosinophils concentration ≥ 400 cells/mm³. IgE-high atopic phenotype was characterized by the presence of at least one positive specific IgE (> 0.35 kU/L) to common aeroallergens and a raised total serum IgE (≥ 113 kU/L).

The largest group of asthmatics displaying concordant eosinophilic phenotype had a raised total serum IgE and atopy (45%). IgE-low non-atopic concordant eosinophilic asthma was a predominantly late onset disease, exhibited a more intense airway eosinophilic inflammation (P < 0.05), required more often maintenance treatment with oral corticosteroids (P < 0.05) but, surprisingly, had a reduced level of bronchial hyperresponsiveness to methacholine (P < 0.05) despite similar baseline airway calibre impairment.

The more severe airway eosinophilic inflammation in IgE-low non-atopic asthmatics despite similar treatment with ICS and a higher burden of OCS points to a certain corticosteroid resistance in this asthma phenotype.

Asthma endotypes are constantly evolving. Currently, there are no universally accepted criteria to define endotypes. The T_H2-high endotype can have either allergic or nonallergic underpinnings and is typically characterized by some degree of eosinophilic airway inflammation. Unbiased clustering analyses have led to the identification of pediatric and adult phenotypes characterized by T_H2 inflammation and associated endotypes with eosinophilic inflammation. Aspirin-exacerbated respiratory disease has also long been recognized as a unique asthma phenotype. An approach to identify these groups with biomarkers and subsequently choose a targeted therapeutic modality, particularly in severe disease requiring biologic agents, is outlined.

Eosinophil Derived Neurotoxin (EDN) is an eosinophil granule protein that is released during eosinophil activation. EDN has proven to be a promising marker for eosinophilic inflammation both in asthma and in wheezing symptoms in children.

Here we present a novel ImmunoCAP^TM automated immunofluorescence research assay for measurement of EDN and its potential use in diagnosis of asthmatic children.

We report the analytical performance of the assay in serum, heparin- and EDTA-plasma in terms of precision, linearity, sensitivity, interfering substances and specimen handling. We also compared the EDN research assay with established methods for asthma diagnosis: fraction of exhaled nitric oxide (FeNO) and blood eosinophil fraction (EOS%) to demonstrate the diagnostic value of EDN in childhood asthma.

The total precision (measured using percentage CV) was ≤5.8% for both serum and plasma. The dilution analysis yielded linear results across the dynamic range of the assay for both serum and plasma. No notable interferences of endogenous substances were observed.

The median concentration of EDN was significantly higher in the asthma group compared to the healthy controls and the EDN correlates well with EOS%.

we have shown that EDN can be measured reliably and robustly with the ImmunoCAP platform in both serum and plasma samples. EDN can be used to distinguish asthmatic from healthy children and correlates well with EOS% and could be a valuable complement to both EOS% and FeNO.