Research endoscopy platform in NIHR Oxford Clinical Research Facility
Lead Research Organisation:
University of Oxford
Department Name: Experimental Medicine
Abstract
The endoscopy platform is a critical piece of equipment for researchers studying the immune responses of our lungs, our guts, respiratory infections or new vaccines against infections. Much previous research relied on blood samples as they are easy to obtain, but increasingly we see the complex immune systems of 'mucosal' surfaces which line the lungs, the airways and our guts are very different from the blood.
Endoscopes are flexible cameras used to explore the lungs or guts and take samples from the mucosal surfaces. Tiny 2 mm biopsies can provide immense amounts of information when analysed using traditional microscope techniques, or with a whole range of new, 'single-cell' approaches. These techniques developed rapidly over the past decade allowing measurement in a single cell of the activity of 33,000 different genes. This can be repeated for tens of thousands of different cells in each sample. It is now possible also to measure in each cell 'epigenetics' - how genes are switched off or on for long periods of time. This can give insight into how early life influences lead to development of long-term conditions later in life. In the last 5 years it has been possible to use these approaches to look at the position each cell holds within the tissue: these 'spatial' techniques provide new insights into how immune cells talk to other cells of the body which make up the lining structures of these organs.
With the sudden availability of these techniques, and two research groups in asthma and lung infection research relocating to Oxford, there is a surge in demand for research endoscopies. Since 2018 the number of research endoscopies of the lung has increased more than 6-fold in Oxford, and will further increase by >40% in 2023 alone. Previously endoscopies have been conducted in NHS facilities, but that cannot meet the growing research demand, and after the pandemic backlog cancer lists must take priority. Moreover, it is not safe to study people with active respiratory infections or new aerosol vaccines in the NHS facilities as these need to happen in a negative-pressure facility where airborne particles are safely removed from the building.
The new endoscopy platform will include a light source, a video processor, a printer, a display screen, and a set of 'bronchoscopes' to inspect the lungs. As bronchoscopes need to be cleaned between each volunteer this set will enable 3 research bronchoscopies to be performed in a single day. The equipment is compatible also with existing 'colonoscopes' which are used to inspect the gut. These will be purchased separately but will allow the facility (in a new purpose-built, negative pressure research endoscopy suite) to be used by a wide variety of researchers with expertise in the lung, infectious disease, vaccine design, and gut diseases.
The main research objectives for the first 5 years are:
1. To study the immune mechanisms which drive specific forms of asthma; how antibiotics can treat severe asthma; how obesity causes asthma.
2. To study the immune effects of experimental asthma medications.
3. To study new vaccines for TB being given by aerosol rather than injection.
4. To study immunity to viruses including SARS-CoV-2 and RSV which cause COVID-19 and bronchiolitis.
5. To study rare scarring conditions of the lung ('Interstitial lung diseases').
6. To explore how cells respond to advanced therapies in inflammatory conditions including ulcerative colitis (UC), Crohn's, rheumatoid arthritis, and Sjogren's disease.
If successful, this work will accelerate development of new vaccines for TB and other lung infections, with a major impact on preventable deaths globally. Understanding the mechanisms driving asthma is the first step in developing the next generation of treatments, or potentially even cures, for asthma. Identifying new subgroups of UC and Crohn's may lead to more effective use of new and existing medicines.
Endoscopes are flexible cameras used to explore the lungs or guts and take samples from the mucosal surfaces. Tiny 2 mm biopsies can provide immense amounts of information when analysed using traditional microscope techniques, or with a whole range of new, 'single-cell' approaches. These techniques developed rapidly over the past decade allowing measurement in a single cell of the activity of 33,000 different genes. This can be repeated for tens of thousands of different cells in each sample. It is now possible also to measure in each cell 'epigenetics' - how genes are switched off or on for long periods of time. This can give insight into how early life influences lead to development of long-term conditions later in life. In the last 5 years it has been possible to use these approaches to look at the position each cell holds within the tissue: these 'spatial' techniques provide new insights into how immune cells talk to other cells of the body which make up the lining structures of these organs.
With the sudden availability of these techniques, and two research groups in asthma and lung infection research relocating to Oxford, there is a surge in demand for research endoscopies. Since 2018 the number of research endoscopies of the lung has increased more than 6-fold in Oxford, and will further increase by >40% in 2023 alone. Previously endoscopies have been conducted in NHS facilities, but that cannot meet the growing research demand, and after the pandemic backlog cancer lists must take priority. Moreover, it is not safe to study people with active respiratory infections or new aerosol vaccines in the NHS facilities as these need to happen in a negative-pressure facility where airborne particles are safely removed from the building.
The new endoscopy platform will include a light source, a video processor, a printer, a display screen, and a set of 'bronchoscopes' to inspect the lungs. As bronchoscopes need to be cleaned between each volunteer this set will enable 3 research bronchoscopies to be performed in a single day. The equipment is compatible also with existing 'colonoscopes' which are used to inspect the gut. These will be purchased separately but will allow the facility (in a new purpose-built, negative pressure research endoscopy suite) to be used by a wide variety of researchers with expertise in the lung, infectious disease, vaccine design, and gut diseases.
The main research objectives for the first 5 years are:
1. To study the immune mechanisms which drive specific forms of asthma; how antibiotics can treat severe asthma; how obesity causes asthma.
2. To study the immune effects of experimental asthma medications.
3. To study new vaccines for TB being given by aerosol rather than injection.
4. To study immunity to viruses including SARS-CoV-2 and RSV which cause COVID-19 and bronchiolitis.
5. To study rare scarring conditions of the lung ('Interstitial lung diseases').
6. To explore how cells respond to advanced therapies in inflammatory conditions including ulcerative colitis (UC), Crohn's, rheumatoid arthritis, and Sjogren's disease.
If successful, this work will accelerate development of new vaccines for TB and other lung infections, with a major impact on preventable deaths globally. Understanding the mechanisms driving asthma is the first step in developing the next generation of treatments, or potentially even cures, for asthma. Identifying new subgroups of UC and Crohn's may lead to more effective use of new and existing medicines.
Technical Summary
Endoscopic sampling of the airways, and upper and lower gastrointestinal (GI) tract is now a cornerstone of human mucosal immunology research.
Several factors are driving a strong and growing demand for research endoscopies at the University of Oxford: the advent of single cell (sc) sequencing and novel spatial technologies, growth in experimental respiratory challenge studies, mechanistic asthma research, controlled human challenge models and inflammatory bowel disease (IBD) research. Whilst demand grows, access to NHS facilities is increasingly limited by post-pandemic NHS waiting lists.
Oxford University has recently created a dedicated specialist, negative-pressure endoscopy room within a new Experimental Medicine Clinical Research Facility (EMCRF). This is a multi-user, multi-speciality facility for early phase clinical research involving both patients and healthy volunteers. The endoscopy suite currently has no equipment.
The endoscopy platform comprises a light and power source, display monitor, printer and trolley linked to three bronchoscopes (required to run a single list), and is fully compatible with colonoscopes to be sourced separately from ex-NHS equipment. It will provide University researchers the necessary platform to undertake tissue sampling of the respiratory and GI tracts from human volunteers.
The platform will support the following research programmes:
1. Airways diseases: applying scRNAseq, scATACseq, spatial transcriptomics/ proteomics / lipidomics to investigate mechanisms of specific asthma phenotypes; infection related asthma and obesity-related asthma
2. Asthma pharmacology: bronchoscopic biologics and inhaled intervention studies
3. TB : aerosolised BCG vaccine trials
4. Viral lung infection research into SARS-CoV-2 and pneumococcal / RSV co-infection
5. Interstitial lung disease studies understanding drivers of fibrosis
6. Exploring cellular mechanisms of response to advanced therapies in IBD and autoimmunity
Several factors are driving a strong and growing demand for research endoscopies at the University of Oxford: the advent of single cell (sc) sequencing and novel spatial technologies, growth in experimental respiratory challenge studies, mechanistic asthma research, controlled human challenge models and inflammatory bowel disease (IBD) research. Whilst demand grows, access to NHS facilities is increasingly limited by post-pandemic NHS waiting lists.
Oxford University has recently created a dedicated specialist, negative-pressure endoscopy room within a new Experimental Medicine Clinical Research Facility (EMCRF). This is a multi-user, multi-speciality facility for early phase clinical research involving both patients and healthy volunteers. The endoscopy suite currently has no equipment.
The endoscopy platform comprises a light and power source, display monitor, printer and trolley linked to three bronchoscopes (required to run a single list), and is fully compatible with colonoscopes to be sourced separately from ex-NHS equipment. It will provide University researchers the necessary platform to undertake tissue sampling of the respiratory and GI tracts from human volunteers.
The platform will support the following research programmes:
1. Airways diseases: applying scRNAseq, scATACseq, spatial transcriptomics/ proteomics / lipidomics to investigate mechanisms of specific asthma phenotypes; infection related asthma and obesity-related asthma
2. Asthma pharmacology: bronchoscopic biologics and inhaled intervention studies
3. TB : aerosolised BCG vaccine trials
4. Viral lung infection research into SARS-CoV-2 and pneumococcal / RSV co-infection
5. Interstitial lung disease studies understanding drivers of fibrosis
6. Exploring cellular mechanisms of response to advanced therapies in IBD and autoimmunity
