Understanding asthma phenotypes
Research type
Research Study
Full title
Understanding asthma phenotypes: going beyond the atopic/non-atopic paradigm
IRAS ID
206952
Contact name
Susan M Ring
Contact email
Sponsor organisation
University of Bristol
Duration of Study in the UK
4 years, 3 months, 31 days
Research summary
Research Summary:
Asthma is a variable disease that includes many different subtypes (phenotypes). It is important to understand these to develop personalised treatments for asthma and interventions designed to prevent the onset and progression of the disease. Current methods to identify phenotypes in asthma are limited by a lack of information of the biological pathways underpinning these. This study will recruit 250 people with (200) and without (50) a diagnosis of asthma that have been taking part on a longitudinal birth cohort, the ALSPAC study; thus they are well characterised and have a wealth of existing information on symptoms of disease and on factors that might have influenced their health since before birth. Therefore, the pattern of disease in those with asthma (age of onset, duration, severity of symptoms, treatments) is well documented. They will be invited to attend a research clinic for detailed respiratory investigations, including completing a questionnaire, measuring lung function and obtaining blood, sputum and nasal lavage samples for analysis. These tests are in routine clinical and research use for people with asthma. It is important to have a comparison group of people without asthma to interpret the results of these tests in the context of different asthma phenotypes. The research clinic will take place in the ALSPAC premises where previous clinical measurements have been performed and it is expected that the tests will take approximately 1.5 hours. The results of the studies in the UK will be compared with identical measurements being performed in clinics in other high income and in low income countries (New Zealnd, Ecuador, Uganda and Brazil).
Summary of results:
The World ASthma Phenotypes (WASP) study started on 1 January 2016, and was conducted in five centres: Universidade Federal da Bahia (Brazil), University of Bristol (UK), St George’s Hospital Medical School (UK/Ecuador), Medical Research Council Unit/LSHTM (Uganda), and Massey University (New Zealand).
Detailed information was collected from a total of 998 asthmatics and 356 non-asthmatics, including sputum and nasal samples, blood samples, lung function and skin prick testing. Children and adolescents were enrolled in all centres except Bristol where participants were 26-27 years old but who all have detailed information on asthma throughout their childhood.
The study protocol paper was published in ERJ Open Research in August 2018. https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fdoi.org%252F10.1183%252F23120541.00013-2018%2FNBTI%2Fb8q9AQ%2FAQ%2F39bbe5a9-48fa-4371-963e-29573f74c0ac%2F3%2F1lLjoSjpwW&data=05%7C02%7Cleedseast.rec%40hra.nhs.uk%7C54a7c419b1354f2a5b8008dda351c35f%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638846293760011188%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=qIpVfGANluy3wqPo2BOIZGSIw2%2B87cdZp7dUaZb%2FIcY%3D&reserved=0Key achievements of the study so far:
• The collection of detailed data from over 1300 participants across five centres in four continents is a significant achievement in itself. The sputum induction procedure was particularly challenging and required sourcing of specific equipment and careful training of each team to ensure the protocol was applied as consistently as possible across the five centres. Other biological samples including nasal lavage and blood sampling, and comprehensive clinical measurements (lung function, skin prick testing) along with detailed questionnaire data have created a rich resource to address the objectives of this project and other important research questions beyond this study.
• Through this project, we have established a strong, interdisciplinary network across the five centres. This has enabled sharing of expertise and insight from clinicians, epidemiologists, immunologists and others, including detailed knowledge of environmental exposures and socio-demographic factors in each centre. The project has provided excellent training opportunities for doctoral students and post-doctoral researchers in each centre, who have benefitted from being part of an international research team.
• The sputum inflammatory phenotypes paper https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fdoi.org%252F10.1093%252Fije%252Fdyac173%2FNBTI%2Fb8q9AQ%2FAQ%2F39bbe5a9-48fa-4371-963e-29573f74c0ac%2F4%2FPyVmaxPlbW&data=05%7C02%7Cleedseast.rec%40hra.nhs.uk%7C54a7c419b1354f2a5b8008dda351c35f%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638846293760024717%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=Bw23nMSchNAloKanVYeRTkMzdSeAh6W56s5ncVLqpKg%3D&reserved=0 demonstrates for the first time in a single study that non-eosinophilic asthma is common in both HIC and LMICs, and has highlighted the urgent need for a better understanding of NEA to improve prevention and treatment of asthma globally.
• Our finding of a high prevalence of neutrophilic asthma in the Uganda centre is novel and warrants further investigation, including analysis of risk factors by inflammatory phenotype which is underway.
• In an analysis which combined WASP data with U-BIOPRED and STELAR/UNICORN data, we have shown that patterns of component-specific IgE (c-sIgE) responses are reflective of geographical location and study design, highlighting the importance of accounting for geographical location when building diagnostic or predictive algorithms for asthma. Despite geographical differences in c-sIgE networks, there is a remarkably consistent shift between networks of subjects with mild/moderate and severe asthma (Journal of Allergy and Clinical Immunology, in press).• Both airway inflammation and microbiology varied geographically in young people with asthma. Associations between microbiota characteristics and neutrophilic phenotype were conserved (paper under review, Thorax).
: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fpublications.ersnet.org%252Fcontent%252Ferjor%252F4%252F3%252F00013-2018%2FNBTI%2Fb8q9AQ%2FAQ%2F39bbe5a9-48fa-4371-963e-29573f74c0ac%2F2%2FGSpI-U_73l&data=05%7C02%7Cleedseast.rec%40hra.nhs.uk%7C54a7c419b1354f2a5b8008dda351c35f%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638846293760038224%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=Op0BkILCRUqSyDedl%2Bj4%2FhdLm0X7Y1%2BWWQUM8gr7dl0%3D&reserved=0
REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
16/YH/0364
Date of REC Opinion
17 Aug 2016
REC opinion
Favourable Opinion