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Asthma and Chronic Obstructive Pulmonary Disease (COPD) are common, global diseases which cause considerable morbidity and mortality. Worldwide, around 235 million people suffer from asthma, while COPD accounts for 3 million, or 5% of all, global deaths, according to the World Health Organization (WHO). The relationship between inflammation and airway dysfunction is central to an understanding of their pathogenesis and treatment. The respiratory medicine group in the Department of Infection, Immunity and Inflammation has shown that optimal management of these conditions requires measurement of airway inflammation to stratify treatment regimes, an approach incorporated into national guidelines in 2012. In the late 1990s the group characterised a new clinical syndrome: `eosinophilic bronchitis', which is one of the commonest causes of chronic cough. The group's work has helped to launch a new class of drugs for asthma and to change the conceptual framework by which anti-inflammatory drugs for asthma are being developed.
Improved approaches to the management of asthma treatment in children, new NHS and BUPA healthcare guidance and changes in UK media attitudes have arisen from fundamental and clinical research at Brighton into the effects of genotype variation on responses to asthma medicines in children. Direct clinical benefits in quality of life resulted from the first-ever randomised clinical trial on genotype specific treatments for asthma. The subsequent worldwide media debate led to wider professional and public understanding of genetically-directed treatment choices and personalised medicines, with particular impact on parents of children with asthma.
Southampton research has been central to the development and international licensing of one of only two novel asthma therapies in the last 30 years, transforming asthma control and survival for severe allergic asthmatics.
Key studies by the Southampton Group have underpinned the development of immunoglobulin (Ig)-E as a key therapeutic target for controlling allergic asthma, with the Southampton-led first-in- man safety and efficacy trials critical to the registration of the anti-IgE therapy, omalizumab.
This contribution also generated significant inward investment in UK R&D and opened up wider investigation of anti-IgE therapy in a broad range of atopic and inflammatory indications.
Research at the University of Manchester (UoM) has led a step-change in respiratory care for airway disease from oral to novel inhaled therapies targeted at asthma and chronic obstructive pulmonary disease (COPD) patients worldwide. UoM researchers carried out >250 studies, partnered industry to deliver >15 new inhaled drug formulations to market and were the first to test novel CFC-free inhalers. UoM led the development of global guidelines that influence better diagnosis and management of airways diseases. Through leadership within the Montreal Protocol since 1995, UoM researchers coordinated the safe global transition to CFC-free inhalers for ~200m patients with asthma and COPD, whilst protecting the ozone layer and climate.
Heaney's research at Queen's University Belfast on difficult-to-treat asthma (or simply "difficult asthma"— DA) patients has led to changes in clinical management guidelines and a drive to co-ordinate and commission specialist services nationally for DA patients. It has also led to the establishment of a UK Multi-centre National Clinical Network and Patient Registry (Centres listed in Section 5). DA patients have persistent symptoms and frequent exacerbations despite being on high dose asthma therapy. DA patients (10% of the asthmatic population) have significant morbidity and carry a high risk of asthma death. Their clinical assessment has been optimised to ensure proper management of both their asthma and non-asthma related conditions.
In 1994, Professor Barnes and colleagues at Imperial College showed that nitric oxide (NO) concentrations were increased in the breath of asthmatic patients compared to non-asthmatic controls and were reduced after treatment with inhaled steroids. They subsequently demonstrated that exhaled NO (FENO) could be reliably measured in the clinic, was correlated with eosinophilic airway inflammation in asthma, was increased with airway inflammation and decreased when asthma was controlled. Exhaled NO has subsequently been shown by many investigators to be a useful non-invasive biomarker of airway inflammation in asthma and to improve clinical management in selected patients. They demonstrated that nasal NO is very low in patients with primary ciliary dyskinesia and is now recommended worldwide as a diagnostic test for this disease as it is a much easier method than previously available tests.
Research undertaken within Imperial College showed that corticosteroid resistance in inflammatory diseases, such as chronic obstructive pulmonary disease (COPD) and severe asthma, is explained by reduced histone deacetylase-2 and that reversal of this resistance is possible with theophylline (in low clinical doses) and PI3Kδ inhibitors, which restore HDAC2 function. This led to the founding of a spin-out company RespiVert to develop potent inhaled inhibitors of PI3Kδ. The company has been very successful in finding such new molecules, which have proven to be safe in Phase I studies. RespiVert was acquired by Johnson & Johnson in 2010 and Phase II studies are now in progress in COPD and severe asthma.
The Leicester Cilia Group (LCG) established methods to study ciliary damage and dysfunction, transforming the diagnosis and management of Primary Ciliary Dyskinesia (PCD), a genetic disorder that causes severe permanent lung damage in children. The group developed diagnostic methods, adopted in the UK and internationally, that increased the accuracy and speed of diagnosis, uncovering a number of previously unrecognised phenotypes. The group was instrumental in the establishment of the first nationally funded diagnostic service (three centres, including Leicester) in the world. This has resulted in the group jointly leading a successful bid (2012) to set up the first nationally funded management service for children with PCD.
Research at Hull into hypersensitivity of the airways has provided novel insights into the epidemiology and causes of cough, and its burden on patients. This was achieved by the development of novel methodologies that allow the rigorous and objective testing of new and existing drugs. Patients benefit through the online provision of a diagnostic tool, and Proctor & Gamble have successfully exploited the cloned cell receptors in their drug development programme resulting in a new range of pharmaceuticals for cough. The work has underpinned the standardisation of cough challenge methodology through incorporation in national and international healthcare guidelines leading to a widespread improvement in patient treatment.
Imperial College researchers demonstrated that the risk of occupational asthma is related directly to the level of exposure in the workplace and not, as previously thought, to host susceptibility. These findings directly informed UK government and industry policy with a consequent reduction in disease incidence.