The University of Southampton
Medicine

Research Group: Respiratory and allergy Research group

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The Respiratory and Allergy Group operates at the clinical interface to dissect mechanisms of respiratory diseases, define biomarkers of disease severity and translate these findings into novel therapies.  

Group Overview

Respiratory and Allergy Research
Respiratory and Allergy Research

The Group has won multiple grants from the Medical Research Council (MRC), the Wellcome Trust, Asthma UK, the British Lung Foundation and the National Institute for Health Research. The Southampton Allergy Centre is recognised as the World Allergy Organization Center of Excellence (2014-19) for allergy research, clinical service and education. Through our NIHR-funded Respiratory Biomedical Research Centre we have strong links with the University Hospital Southampton for delivery of innovative bench-to-bedside research.

We have an international reputation for investigations of asthma, as well as a number of other airways diseases such as rhinitis, chronic obstructive pulmonary disease (COPD), primary ciliary dyskinesia (PCD) and cystic fibrosis. In the past five years, we have expanded our research into interstitial lung diseases including idiopathic pulmonary fibrosis (IPF), sarcoidosis, connective tissue disease associated ILD and tuberculosis. Chronic lung diseases are frequently characterized by the presence of persistent inflammation, which may be driven by a variety of mechanisms (e.g. allergens, environmental pollutants, occupational chemicals, or persistent infections) depending on the disease. They are also associated with alterations in tissue architecture, termed remodeling, leading to impaired lung function and a reduced quality of life. Major unmet needs in these diseases are corticosteroid-refractory inflammation, prevention of pulmonary remodeling and prevention of disease exacerbations (worsening of symptoms), which can often result in hospital admission or even death. We have made significant contributions to the development of new treatments for asthma and IPF, for contributing to guidelines for disease management and in understanding the natural history of asthma and allergic diseases.

A particular strength of the Respiratory and Allergy Group is the close links between paediatric and adult research in the lung, providing a distinctive life-course perspective of disease development and progression. Our work is recognised internationally for its translational approach ranging from epidemiology and genetics, cell and molecular biology, biochemistry, pathology, therapeutic target discovery, biomarker discovery and validation, lung imaging, early proof of pharmacological efficacy, to phase I-III clinical trials. We are experts in developing models of disease using relevant human lung-derived samples which can be used outside the body (ex-vivo) to study underlying disease mechanisms and test novel drugs. This interdisciplinary research is facilitated by collaboration in Engineering, Electronics and Computer Sciences, as well as Chemistry. A key strategic initiative since 2008 has been to expand our research into the use of biomarkers for disease stratification. This has been facilitated by the seamless interface between basic and clinical research in our NIHR-funded - Respiratory Biomedical Research Unit where we have state-of-the-art mass spectrometers for lipidomic and proteomic analyses. Analysis of these large datasets is enabled by our links with University colleagues in Mathematics and Computer Science.

Key achievements

Important recent achievements of the Respiratory and Allergy Group include:

Following initial studies, our research team became the first to demonstrate the safety and bioactivity of omalizumab therapy in man. The drug is a new monoclonal antibody that targets and depletes the asthma-inducing molecule called IgE. These trials showed that the new treatment resulted in significant improvements in symptoms of severe allergic asthma and provided evidence for the new drug’s registration.

Discovery of epithelial barrier dysfunction in asthma, including abnormal innate immune responses to viral infection. This led to formation of the spin-out company Synairgen and development of inhaled interferon beta (SNG001) for virus-induced asthma exacerbations. Following a Phase II study showing that SNG001 caused a reduction in symptoms in virus-induced exacerbations in difficult-to-treat asthma, AstraZeneca has in-licensed SNG001 from Synairgen in a deal worth up to $232m to develop this novel therapy.

Identification of the asthma susceptibility gene, ADAM33 and identification of its function as a pro-angiogenic factor that may drive airway remodelling in early life. While current approaches only seek to treat asthma symptoms, our findings may point to novel disease-modifying approaches for asthma development or progression.

Monitoring the natural history of asthma and allergies through the Isle of Wight Birth Cohort and the Allergy Prevention Study has led to the identification of other susceptibility genes for asthma in children, including ATPAF1 and a novel way of preventing the development of allergies.

Identification of novel therapeutic targets including CCR4, which was shown to play a key role in T cell recruitment in asthma; experimental use of anti TNFα therapy in severe asthma.

Demonstration that airway remodelling in asthma is a consequence of bronchoconstriction and not ongoing inflammation, which has implications for asthma management.

Developing a new focus on epigenetic mechanisms in asthma with a view to investigating transgenerational mechanisms of pathogenesis. For example MicroRNA-155 targets IL13 pathways in macrophages and the hypersensitivity site V has an important role in shaping chromatin structure in differentiating CD4+T cells.

Work with adolescents with asthma or food allergy has highlighted how our clinics poorly cater for this patient group; we are now working to improve the delivery of healthcare to adolescents.

Collaboration with Human Development and Physiology Group has demonstrated the impact of early life on the development of respiratory disease in childhood within the Southampton Women’s Survey.

Leading an international study of Nintedanib in idiopathic pulmonary fibrosis (IPF). Originally developed as a treatment for lung cancer, Nintedanib has been found to halve the annual decline in breathing capacity normally seen in patients diagnosed with IPF. These results and mean that Nintedanib has the potential to offer patients a new direction in treating this aggressive disease.

Collaborations and enterprise

The Group leads in the identification and validation of biomarkers of airways disease, having co-founded UBIOPRED, a €22m programme in severe asthma funded by the EU and several pharmaceutical companies

The Group plays a leading role in the NIHR Inflammatory Respiratory Disease Translational Research Partnership which brings together world-class investigators in 26 of UK's leading academic and NHS research centres to support collaboration with the life sciences industry.

The group is a member of the MRC/ ABPI COPD initiative, COPDMAP, to develop a stratified approach to COPD (targeting the right treatments to the right people), enabling effective clinical trials as well as identifying novel biomarkers, mechanisms and targets.

The Respiratory group provided an important cornerstone for our strategic investment in infectious disease and in Chronic Obstructive Pulmonary Disease (COPD); it has made major contributions to understanding infection-induced exacerbations which has attracted a strategic collaboration with GlaxoSmithKline (GSK) to help develop new vaccines for COPD.

The group has led important Phase III studies in IPF in collaboration with Boehringer Ingelheim.

Research Staff

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