Beyond the Eosinophil: Understanding the Impact of Eosinophil Depletion on T2 Inflammation. (BEUTI)
Benralizumab is a relatively new treatment that is approved by NICE (National Institute for Health and Care Excellence, https://www.nice.org.uk/) for patients with severe asthma who have ongoing eosinophilic inflammation that remains poorly controlled despite high dose inhaled glucocorticosteroid medication. Eosinophils are a type of white blood cell that are linked to allergy and inflammation and are raised in people with severe asthma. Severe asthma is associated with a type-2 (T2) inflammation phenotype characterised by increased T2 cytokines (IL-13, IL-4, IL-5). Increased levels of eosinophils can cause inflammation in the lungs, increasing the risk of asthma attacks. The standard treatment for asthma involves taking inhaled glucocorticosteroid medication which primarily work by suppressing eosinophilic inflammation in the lungs. Benralizumab is a monoclonal antibody that targets a receptor on the surface of eosinophils called interleukin-5 receptor-α (IL-5Rα) leading to the rapid death of these cells and consequently a reduction in airways inflammation. In clinical trials, benralizumab has been shown to reduce both symptoms and the number of asthma attacks suffered by those with severe eosinophilic asthma. However, it remains unclear whether this clinical efficacy relates purely to the removal of the eosinophil, or additionally to the impact of this on other parts of the immune system. The BEUTI study will examine the structure and function of airway cells in patients with severe eosinophilic asthma. Particularly how the immune function of these cells changes with treatment and whether benralizumab leads to a reduction in T2 mediators and/or activation in airway cells. The aim is to take samples of cells from the airways during a bronchoscopy (a camera test looking into the lungs) before starting benralizumab and after 12 weeks of treatment. These investigations will allow us to better understand how benralizumab affects the cells within the airways and the pathways involved.
• Informed consent.
• Patients aged 18 and over with a diagnosis of severe eosinophilic asthma for at least the last 6 months
• Eligible for benralizumab based on NICE criteria
• Poorly-controlled (ACQ-6 \>1.5)
• FeNO ≥50ppb at screening despite high dose inhaled corticosteroids (at least 1000mcg BDP equivalent) +/- maintenance prednisolone
• Adult-onset (18+) asthma in a minimum of 50% of the study subjects