Differences in effect of treatment with mepolizumab and benralizumab on resident and inflammatory eosinophils

• Age ≥ 18 • Diagnosis of severe refractory eosinophilic asthma • Eligible for mepolizumab or benralizumab therapy according the national recommendations for severe asthma of the Dutch society for lung diseases and tuberculosis (NVALT guideline 2013): Patients with asthma, for whom alternative diagnoses are excluded, comorbidity optimally treated, provoking factors minimized and therapy compliance optimized, but despite this still have insufficient asthma control (≥ 1.5 ACQ-7 or other questionnaire) or frequent (≥2 annually) severe exacerbations (systemic CS needed) while routinely using high-dose asthma medication (≥ 1000 mcg/day fluticasone propionate equivalent and/or daily OCS in combination with LABA or other controller medication); or patients who can achieve asthma control only with systemic CS and are therefore are risk for adverse effects or the corticosteroids. • Treated with mepolizumab or benralizumab for at least 4 months. • Before treatment with biologics a blood eosinophilia (≥ 150 eosinophils/l blood) irrespective of steroid use

• Any infection (eg. HIV, Hepatitis, STDs) • Insulin dependent diabetes • Smoking at present or in the last 12 months and/or a past history of more than 10 pack years • Proven allergic bronchopulmonary aspergillosis • Auto-immune diseases • Use of medication, excluding: o Anticonceptives o Pain killers, if used less than once a week • exuberant alcohol consumption (for males > 36 glasses per week, for females >24 glasses per week) • Drug use • History of cancer • Use of biologicals other than mepolizumab or benralizumab • daily oral steroid therapy during the three months preceding inclusion