Refractory Asthma Stratification Programme (RASP) Bronchoscopy Study

Summary

The Investigators hypothesise that asthma is not a single disease, but a syndrome resulting from several distinct underlying disease processes known as endotypes. There are approximately 30,000 genes in humans, and each gene is responsible for the production of a particular protein. Using a technique called "whole genome expression profiling" The Investigators have undertaken a small study looking at the activity of all 30,000 genes in the airway tissue of people with asthma. This work has identified 3 mutually exclusive distinct molecular patterns (endotypes) of severe asthma and has identified other potentially important molecular targets (manuscripts in preparation). In particular,the Investigators have found that 25-50% of patients have asthma associated with the activity of proteins called Th2 cytokines (Th2-high asthma). New treatments are in development that target this pathway. However, the Investigators do not know what is driving severe asthma in patients who do not express these Th2 cytokines. The aim of this study is to investigate in more detail the molecular mechanisms driving severe asthma in patients who do not express Th2 cytokines (Th2-low asthma), so that the Investigators can identify new targets for treatment in this group. To do this the Investigators will collect airway tissue via a telescope (bronchoscope), and analyse gene and protein expression in the tissue. The Investigators will then compare the molecular activity between patients with Th2-high and Th2-low asthma, and healthy control subjects (data obtained from a parallel study).

Conditions

• Persistent Asthma

Interventions

PROCEDURE

Bronchoscopy

Flexible bronchoscopy will be performed under conscious sedation (with premedication using a mild sedative such as 1-2.5 mg IV midazolam) followed by use of topical anaesthesia (lidocaine spray) on the throat, vocal cords, and trachea in order to investigate the airways. The procedure allows sampling of the airway tissue to allow for laboratory analysis. Three brushings of a small area of the epithelial surface of an airway will be performed via a specialised channel of the bronchoscope with the use of a sterile cytology brush and up to eight 2-mm endobronchial biopsies.

Sponsors & Collaborators

• Genentech, Inc.

  collaborator INDUSTRY

• Queen's University, Belfast

  collaborator OTHER

• Medical Research Council

  collaborator OTHER_GOV

• University of Leicester

  lead OTHER

Principal Investigators

• Peter Bradding, MBBS · University of Leicester

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-09-26

Primary Completion

2024-10-31

Completion

2024-10-31

Countries

• United Kingdom

Study Locations