Prevalence and impact of eosinophilic degranulation in patients with severe asthma

<bold>Background:</bold> With the recognition of T2 inflammation in asthma as a heterogenous entity, an increasing interest has developed in functional aspects of eosinophils beyond the mere presence. Eosinophilic degranulation has been proposed as marker of treatment refractory disease however, the prevalence as well as clinical and immunological impact in severe asthma is incompletely understood. <bold>Aim:</bold> To report the prevalence of eosinophilic degranulation and the impact on clinical/immunological characteristics in an unselected population of patients with severe asthma. <bold>Method:</bold> A total of 88 patients with severe asthma from the SATS and SIGNATURE study were stratified based on the presence of free eosinophil granules in sputum. <bold>Results:</bold> Marked eosinophilic degranulation was present in one-fourth of patients (27%) and was associated with higher levels of mRNA expression of Charcot-Leyden Crystals/Galactin-10 (p<0.001). These patients were characterized by higher mean age (57 ± 14 years vs 47 ± 14 years, p=0.005), larger proportion of men (71% vs 47%, p=0.005), lower mean FEV1/FVC ratio (62.67 ± 12.90 vs 72.26 ± 19.16, p=0.017), and higher median blood- and sputum eosinophils (p<0.001 for both). Furthermore, they had higher levels of mRNA expression of the mast cell marker CPA3 (p<0.001) and elevated autoantibody titers towards EPX and/or MARCO (50% vs 6%, p<0.001). <bold>Conclusion:</bold> Eosinophilic degranulation clinically associates with late-onset asthma with impaired lung function and is characterized by eosinophilic cytolysis with formation of Charcot-Leyden Crystals, a complex local inflammatory response with autoimmunity towards eosinophils and macrophages, as well as mast cell involvement.