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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.
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.
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 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.
Infantile nystagmus (IN), previously known as congenital nystagmus, is a condition that impairs vision by causing continual and involuntary oscillatory movements of the eyes. IN begins in infancy and is a lifelong disorder, affecting over 88,000 people in the UK. Leicester is the leading UK centre for research into the underlying mechanisms and treatment of IN: discovering the genetic mutations behind some of the common forms of nystagmus; pioneering early diagnosis of IN; and conducting randomised clinical trials into drug treatments and other therapies. The centre provides advanced scientific and medical knowledge, and support and advice to sufferers of this physically and psychologically debilitating condition. The work has resulted in new methods of diagnosis which are more comfortable and convenient for patients and enable cost-savings for healthcare providers; and has led to the testing and subsequent prescription of pharmacological treatments which offer patients improvements in quality of life.
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.
The Dermatology Life Quality Index (DLQI) questionnaire is a clinical and research tool, which has fundamentally shifted dermatology from being doctor-centred to patient-centred. Previously, no standard method to quantify the impact of skin disease on patients existed. The DLQI was created by interviewing people with skin disease and made clinically useful through development and validation of score bands. NICE/SIGN require UK dermatologists to use the DLQI when assessing severe psoriasis and hand eczema. DLQI is used in national psoriasis guidelines in 14 countries, is available in 91 language translations, has been used in 678 clinical research studies and generated £881,236 in royalties to Cardiff University.
Subcutaneous allergen immunotherapy is highly effective in hayfever sufferers who fail to respond to anti-allergic drugs, but carries the risk of severe allergic side-effects. Professor Durham's group at Imperial College have defined the mechanisms and shown that sublingual tablet immunotherapy is an effective, safer alternative that induces long-term disease remission. The tablet approach is now widespread in Europe and is being successfully extended to other allergies (housedust mite) and internationally (ragweed allergy in USA and Japanese Cedar pollen allergy). The work is quoted in guidelines internationally and regulatory bodies now recognise the disease-modifying potential of immunotherapy and its ability to induce long-term remission.
Measurement of hormones is essential to the understanding and diagnosis of endocrine diseases. White and her research group have developed unique antibodies that are widely used in diagnostic assays for adrenocorticotrophic hormone (ACTH) and related peptides, including the first and only kit for measuring pro-opiomelanocortin (POMC), the precursor of ACTH. These assays are used worldwide for diagnosis, decisions on treatment, monitoring for recurrence of tumours and prognosis in a number of patient groups with life-threatening endocrine disorders. Global sales of the ACTH Elecsys tests by Roche exceeded 6 million kits since 2008. AstraZeneca has used the POMC and ACTH assays in its drug discovery programmes in the cardiovascular and metabolic diseases therapy area. The antibodies therefore have had health impact in relieving suffering and in improving patient care, as well as commercial impact in worldwide sales of assays and influencing drug development strategies.
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.