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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 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.
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.
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.
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.
Research by the University of Huddersfield's School of Applied Sciences has played a major role in addressing the difficulties experienced by people who use inhalers. The work has adapted existing methodologies so they can mimic how patients use nebulisers and dry powder inhalers, thereby enhancing understanding of a problem that affects millions globally. Findings and insights have been incorporated in "gold standard" guidelines that are influencing practice and policy around the world, while lead researcher Professor Henry Chrystyn's methods and techniques have become central to academic, practitioner and industry efforts to tackle the issue at national and international level.
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 the University of Nottingham has defined the clinical phenotype and management of lymphangioleiomyomatosis, a rare and often fatal multisystem disease affecting 1 in 200,000 women worldwide. The group has led the development and evaluation of new therapies and diagnostic strategies which are now part of routine clinical care. The research has underpinned the transformation of this previously under recognised and untreatable disease into a condition recognised by respiratory physicians, with international clinical guidelines, patient registries, clinical trials, specific treatments and a UK specialist clinical service.
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.