Phenotyping circulating and lung eosinophils in severe asthma.
Research type
Research Study
Full title
Phenotyping circulating and lung eosinophils in severe asthma.
IRAS ID
152907
Contact name
Pankaj Bhavsar
Contact email
Sponsor organisation
Joint Research Compliance Office, Imperial College London and Imperial College
Duration of Study in the UK
2 years, 11 months, 31 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). With the recent introduction of antibody treatments (also called biologics) to block proteins such as Interleukin(IL)-4, IL-5 and IL-13, a raised blood eosinophil count is used to select patients for this treatment. 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 this project called P-CLESA, we will to explore the relationship between subsets of circulating and lung resident eosinophils in severe asthma and the efficacy of Mepolizumab (anti-IL-5) therapy. We will use gene and protein expression analyses to identify subsets of eosinophils in two cohorts of severe asthmatics (SA):
Blood only- we will recruit 15 biologic naïve SA not on maintenance oral corticosteroid (OCS) therapy and 15 SA currently on Mepolizumab therapy with good clinical response.
Blood and Bronchoscopy- we will recruit 36 SA severe asthma patients appropriately characterised SA (Eos>300/ul), not on OCS maintenance therapy, to achieve paired biopsy samples from 30 patients. Following normal standard of care these patients will be prescribed Mepolizumab over a 1 yr period. Blood samples will be taken at baseline, 3 and 12 months and endobronchial lung biopsies at baseline and 1 yr post mepolizumab therapy, respectively.
At the end of this study, we will be able to (i) determine the subsets of eosinophils present in asthma of each patient (ii) how these subsets may change in response to Mepolizumab therapy (iii) for those who fail therapy with this biologic, indicate what other treatments would be more suitable.REC name
West Midlands - Black Country Research Ethics Committee
REC reference
20/WM/0206
Date of REC Opinion
30 Sep 2020
REC opinion
Further Information Favourable Opinion