Effect of Benralizumab on Airway Remodeling in Asthma

Inclusion Criteria: Healthy subjects * Written informed consent indicating that they understand the purpose and procedures required for the study and are willing to participate in the study. * Age higher than 18 years. * No prior history of any chronic respiratory disease including asthma. * No prior history of allergy, i.e. allergic rhinitis, allergic conjunctivitis, hay fever, eczema. * No clinically significant abnormalities as determined by medical history, measurement of vital signs, physical examination, hematologic assessments and ECG at visit 1. * Normal lung function with FEV1 \> 90%. Non-severe asthmatics subjects * • Written informed consent indicating that they understand the purpose and procedures required for the study and are willing to participate in the study. * Age higher than 18 years. * Diagnosis of non-severe asthma according to the Global Initiative for Asthma (GINA), i.e. GINA steps 1, 2 or 3 (18). * Documented post-bronchodilator reversibility of at least 12% and at least 200 mL in FEV1 within 12 months before enrolment, or PC20 methacholine \< 16 mg/mL documented within 12 months prior to screening. * Documented blood eosinophils ≥300 cells per μL within 12 months or blood eosinophils ≥150 cells per μL at visit 1. Severe asthmatics subjects * • Written inform consent indicating that they understand the purpose and procedures required for the study and are willing to participate in the study. * Age higher than 18 years. * Diagnosis of severe asthma according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) task force (19). * Documented post-bronchodilator reversibility of at least 12% and at least 200 mL in FEV1 within 12 months before enrolment. * Documented blood eosinophils ≥300 cells per μL within 12 months or blood eosinophils ≥150 cells per μL at visit 1. Exclusion Criteria: * Active smoker or former smoker. * Diagnosis of chronic obstructive pulmonary disease (COPD), cystic fibrosis, or other significant respiratory disorder including significant occupational or environmental exposures with ongoing respiratory symptoms. * CT scan abnormality related to any respiratory disease other than asthma. * Recent asthma exacerbation (less than 6 weeks before bronchoscopy). * Contraindications related to bronchoscopy: * coagulation disorders, * unstable cardiovascular conditions, * FEV1 lower than 1 litter, * a fasting state of less than 6 hours for food and less than 2 hours for drink. * Contraindications to general anesthesia or medications (for propofol: hypersensitivity to the active substance and to any of the excipients; for lidocaine: hypersensitivity to the active substance and to any of the excipients or to local anesthetics of the amide type, epilepsy, porphyria) used in the bronchoscopy procedure. * Contraindications related to MRI: * Pacemaker or implantable cardioverter defibrillator * Metallic foreign body in the eye * Cerebral aneurysm clips * Insulin pumps * Claustrophobia * Positive urinary pregnancy test at screening for women of child-bearing potential * Breastfeeding woman. * Previously received benralizumab. * History of any clinically significant medical illness or medical disorders including (but not limited to) cardiovascular disease, neuromuscular, hematological disease including bleeding disorders, respiratory disease, hepatic or gastrointestinal disease, neurological or psychiatric disease, ophthalmological disorders, neoplastic disease, renal or urinary tract diseases, or dermatological disease. * Recent history (within previous 6 months) of alcohol or drug abuse. * Persons placed under judicial protection. * Persons participating in another research including a period of exclusion still in course. * Severely altered physical and/or psychological health which, according to, the investigator, could affect the participant's compliance of the study.