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Environment, risk factors, and triggers of asthma attacks

Someone in the UK is having an asthma attack every 10 seconds, and three people a day will die as a result of an asthma attack.

One of our core areas of research at the Centre is understanding how aspects of our environment and other triggers cause asthma attacks, and building on that knowledge to stop them from happening.

Work in this area includes: investigating why viruses such as the common cold cause much more severe symptoms in people with asthma, and blocking these effects; better understanding how air pollution triggers asthma attacks and developing ways to reduce the risk; how the health of the immune system in your lungs could lead to asthma attacks, and how we might be able to protect against this; how allergies contribute to asthma attacks; and other research that could help us to stop asthma attacks.

 

See the Centre structure for the full list of researchers supporting each research theme.

 

Hansel is developing with Johnston novel non-invasive methods to absorb respiratory mucosal lining fluid (MLF) to measure multiple cytokines and chemokines in nasal and bronchial MLF in asthma and asthma attacks. Durham and Hansel have developed a model of nasal allergen challenge, and Hansel will further develop nasal challenge models with allergen (grass pollen, house dust mite), lipopolysaccharide and resiquimod to mimic bacterial and viral challenge; and to define the impact of corticosteroids and novel therapies, including vitamin D (with Hawrylowicz), on airway mucosal function.

Openshaw, with the 45 MOSAIC collaborators, will investigate the pathogenesis of severe outcomes in influenza infections, and the reasons for increased susceptibility in people with asthma. With Culley and Johansson he will investigate the pathogenesis of respiratory syncytial virus (RSV)-induced wheezing and later asthma development, addressing aspects of innate and acquired immunity in mouse models, and translating findings relevant to both virus types into his human challenge studies with RSV and influenza with Chiu and Johnston.

Johnston, with Solari, Edwards, Walton, Jackson, Cousins, Gould, and Lavender will study the human rhinovirus challenge model to understand mechanisms of virus-induced asthma attacks, and identify targets for development of novel therapies. This work will include next generation sequencing of brushed epithelial cells, and T and B cells, ILCs and dendritic cells purified from lung lavage before and at days 3 and 8 following virus infection in people with asthma and in healthy control subjects. Targets identified by this work can then be tested in their mouse models of asthma attacks to address functional roles and identify potential new therapies

Johnston with Custovic will investigate host defence against virus and bacterial infections, early life gene-environment interactions and risk of asthma development, working to explore these relationships across the life-course from birth to adulthood.

Edwards will investigate innate responses to rhinovirus infection, to identify potential future therapeutic interventions. He will work on suppressor of cytokine signalling-1and the molecular basis of impaired interferon in asthma and on new therapeutic targets for asthma exacerbations, focusing on drug-discovery to find small molecules that suppress inflammation without reducing beneficial anti-viral interferon responses.

Solari has identified two host target proteins required for replication of rhinoviruses and is initiating chemistry to optimise current inhibitors, with the ambition of developing potent therapeutics to treat the major cause of asthma exacerbations. He with Mousnier and Edwards, collaborating with Wakelam (Babraham Institute), will study changes in the lipid content of epithelial cells following infection with virus to identify further new targets.

Moffatt and Cookson will investigate the airway microbiome, and the effects of interventions (antibiotics, inhaled steroids) on the microbiome and clinical outcomes. They are developing methodology to enable metagenomic studies on respiratory samples. Their genome-wide methylation studies will focus on DNA samples (from the Ashford Cohort, the Busselton Health Study and centres in rural Poland) to understand the impact of environmental effects on development of asthma. They will systematically study an established air-liquid interface epithelial cell model to increase understanding of the respiratory epithelium’s response to a range of environmental stimuli.

Kelly will collaborate widely within the Asthma Centre, to advance our understanding of the role of pollution in asthma, with Griffiths to investigate traffic management schemes such as the Congestion Charging Scheme (CCS) and the Low Emission Zone (LEZ) to further assess their impact on respiratory health; with additional studies planned involving personal exposure monitoring of asthmatics, and linking this with clinical events. Kelly will work on micro-plastics, which are prevalent in the environment and can be linked with an asthma panel study. Kelly maintains a strong interest in free radical/antioxidant biochemistry and with Hawrylowicz will investigate the impact of urban particulate matter, including from primary sampling sites around London, on airway and peripheral blood dendritic cell and T cell interactions, to investigate their role in asthma exacerbations and the potential for reversal of these effects by antioxidants and vitamin D.