Abstract / Summary
Background Asthma is characterized by different inflammatory phenotypes. We hypothesized that sputum eosinophil-derived neurotoxin (EDN), and myeloperoxidase (MPO) or interleukin-8 (IL-8) levels improves the granulocytic characterization of asthma compared to sputum granulocyte counts. Methods EDN, IL-8 and MPO were assayed in induced sputum supernatants from patients with severe and mild-to-moderate asthma, and healthy controls. Elevated cut-off values were determined using Youden Index. Asthma patients were stratified in four subgroups based on EDN and IL8 or MPO levels. Results Sputum EDN, IL-8 and MPO levels were higher in severe asthma (n=193) than in controls (n=40). Optimal cut-offs were 103.5 ng·mL −1 for EDN, 1150.7 pg·mL −1 for IL-8 and 220 ng·mL −1 for MPO. 53 patients (23%) were EDN High IL-8 Low , 16 (7%) EDN Low IL-8 High , 112 (49%) EDN High IL-8 High , and 49 (21%) EDN Low IL-8 Low or 28 (12%) were EDN High MPO Low , 24 (10%) EDN Low MPO High , 137 (60%) EDN High MPO High , and 41 (18%) EDN Low MPO Low . In each of the 4 granulocytic count classifiers, the most prevalent biomarker classifier was EDN High IL-8 High or EDN High MPO High . The EDN Low IL-8 High or EDN Low MPO High groups were in the obese range, had the highest number of exacerbations, lowest FeNO, lower sputum eosinophils and higher Hospital Anxiety and Depression Scale score. Conclusions Classification according to granulocyte activation biomarkers provides greater understanding of the inflammatory response and information on the underlying pathophysiological processes. Sputum profiling with EDN and EPO or IL-8 is useful for the application of precision medicine to severe asthma.