Log in
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.
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.
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.
A new intervention has been developed and trialled in patient groups characterised by mucus obstruction of the airways. Outcomes for these patient groups have improved, and health service decisions have been informed by the underpinning research. A spin-out business, Ockham Biotech Ltd., was created and has generated overseas investment.
A novel mucolytic application and inhaled route of administration for heparin has provided a simple and cost-effective therapeutic means of relieving the symptoms of mucus obstruction in diseases including CF and COPD, which cost the NHS ~£600m and £1bn, pa, respectively.
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.
Ongoing research by the University of Southampton has led to significant advances in the understanding of respiratory diseases, for which the dearth of available treatments had health repercussions on a global scale for many years. The formation of a spin-out company, Synairgen, has enabled the discovery and development of new therapeutics, the filing of several major patents in the UK, the US and Asia and external collaborations with industry and government funders. These continuing developments are key to tackling conditions that affect millions of sufferers in the UK alone and which, according to some estimates, cost the NHS £2.6bn every year. The research has given rise to more than £16m in follow-on funding from the NIHR and the MRC for further studies into the treatment of respiratory illnesses.
COPD affects up to 3.5 million people in the UK and costs the NHS £700m pa. Over the last 15 years, research by Professor Calverley and colleagues at the University of Liverpool (UoL) has impacted significantly on the care of COPD patients. Specifically, this group showed that routine testing of COPD patients for the presence of bronchodilator reversibility was unreliable and did not predict clinical outcomes. This changed international guideline recommendations in 2007 and the Quality Outcomes Framework payments to GPs in 2009. They showed that oral corticosteroids accelerated recovery from exacerbations and that anti-inflammatory drugs, whether inhaled corticosteroids or PDEIV inhibitors, reduced exacerbations by 25% with a subsequent fall in the number and length of hospitalisations. This led to changed NICE guidance for corticosteroids in 2010 and drug registration with EMA and FDA for the PDEIV inhibitor treatment in 2011. Treatment in UK and Western Europe has changed as a result of this research.
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.
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.
Imperial College preclinical studies guided the desired selectivity profile for long-acting muscarinic receptor antagonists (LAMA). Binding, functional and clinical studies from Imperial laboratories were the first to demonstrate the long duration of tiotropium bromide (Spiriva®) in human tissue, and confirmed its long duration of action in patients and established it as the first-line treatment for chronic obstructive pulmonary disease (COPD). Tiotropium has had a beneficial impact on the management of COPD and is incorporated into the major international treatment guidelines. It improves symptoms, reduces exacerbations and mortality, and provides a cost-effective therapy. Imperial have also produced the first pre-clinical and clinical data for the next LAMA in development (glycopyrrolate, Seebri®), which has recently been marketed. Our profiling of tiotropium has also led to the development of several novel LAMA.