INSIGHTS
Research type
Research Study
Full title
Identifying Response Defining Mechanisms for Biological Therapies in Severe Asthma: Assessing the Role of CD4-CTLs
IRAS ID
353257
Contact name
Ramesh J Kurukulaaratchy
Contact email
Sponsor organisation
University of Southampton
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
This INSIGHTS study focuses on exploring biological mechanisms that influence how people with severe asthma respond to higher-level biological therapies. Such medications are increasingly used to treat severe asthma. However, they are costly and only 70% patients respond well to them. Working with colleagues in San Diego, we previously discovered novel immune T-cells called Cytotoxic CD4-Tissue Resident Memory cells (termed CD4-CTLs) in airway samples collected from severe asthma patients in our Wessex AsThma CoHort of difficult asthma (WATCH) study. These CD4-CTLs had harmful biological properties and were associated with asthma severity plus potential poorer responses to biologic treatments. In this INSIGHTS study we will test how CD4-CTLs impact effectiveness of a commonly used family of biologic drugs (anti-IL5/5-Receptor) in severe asthma.
We will recruit 100 clinic patients with severe asthma through our WATCH study who are starting anti-IL5/5-R biologics for their clinical management, assessing them before and 12-months after they have been on these treatments. We will also recruit 10 stable severe asthma patients not starting biologics as controls. For all patients, we will collect and analyse blood and sputum for immune T-cells at both timepoints. For 20 patients, we will also analyse deeper airway samples (bronchial lavage, biopsy, brushing) from bronchoscopy at the 12-month timepoint. We will also study biologic-responsive patients for a further 12-months to assess ongoing biologic effectiveness. 24-months after starting biologic treatment, this group of patients will be seen to collect and analyse blood and sputum plus bronchoscopy samples in 25 patients (15 sustained responders, 10 faded responders). We will apply advanced molecular analyses to pre-treatment samples to see how CD4-CTLs and their harmful properties affect biologic response. We will also establish how these CD4-CTLs and their cytotoxic properties are affected by taking biologic drugs and whether CD4-CTL activity links with longer term biologic response.REC name
South Central - Hampshire B Research Ethics Committee
REC reference
25/SC/0221
Date of REC Opinion
2 Sep 2025
REC opinion
Further Information Favourable Opinion