Mitochondrial dysfunction in eosinophilic severe asthma
Research type
Research Study
Full title
Mitochondrial dysfunction of eosinophils as a driving force for its activation in eosinophilic severe asthma.
IRAS ID
293693
Contact name
Pankaj Bhavsar
Contact email
Sponsor organisation
Joint Research Compliance Office, Imperial College London and Imperial College
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Severe asthma is asthma that does not respond adequately to existing treatments including steroids and bronchodilators and is a disease with different types (phenotypes). Eosinophilic severe asthma is a well-characterised endotype of asthma that is thought to be driven by eosinophil activation and responds to anti-IL5-antibody treatment. The mechanisms by which eosinophils in severe eosinophilic asthma are activated are not known but recent studies have delineated an inflammatory eosinophil subtype that is likely to be driving asthma. Studies in man show that lung resident eosinophils (rEos) found in non-asthmatic human lungs were phenotypically distinct from the inflammatory eosinophils (iEos) isolated from the sputum of eosinophilic asthmatic patients. These data highlight the existence of distinctive circulatory and lung resident subsets of eosinophils in man. In addition, mitochondrial dysfunction may play a role in activating these cells through alteration of ATP production, metabolism and excessive oxidative stress.
In this project called MODESA, we will focus on analysing mitochondrial function by measuring these parameters on eosinophils obtained from blood of patients with severe eosinophilic asthma before and after receiving anti-IL5-antibody treatments. This data will be correlated with the single cell transcriptomic analysis of these cells that will be performed in parallel.
We will recruit 15 Healthy volunteers, 15 biologic naïve SA not on maintenance oral corticosteroid (OCS) therapy, 15 SA currently on Mepolizumab therapy with good clinical response and 20 patients with eosinophilic granulomatosis with polyangiitis (EGPA) as a further hyper-eosinophilic disease group.
At the end of this study, we will be able to determine i) mitochondrial function of subsets of eosinophils present in asthma of each patient (ii) whether mepolizumab and mitochondrial inhibitors have an impact on the activation of eosinophils (iii) inflammatory profiles of eosinophils.REC name
London - Surrey Borders Research Ethics Committee
REC reference
21/PR/1060
Date of REC Opinion
25 Nov 2021
REC opinion
Further Information Favourable Opinion