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Very considerable changes worldwide, in the management of patients with chronic obstructive pulmonary disease (COPD) admitted with acute ventilatory failure, have been a major impact of the research of the King's College London (KCL) Clinical Respiratory Physiology Group. Previously, invasive ventilation to treat such COPD patients was associated with complications which could be fatal. The KCL group conducted the first randomised controlled trial in the world of treatment by non-invasive ventilation (NIV). The trial demonstrated that NIV reduces complications and death compared to invasive ventilation. The study dramatically changed the treatment of hypercapnic flare-ups (where there is too much carbon dioxide in the blood) of acute COPD worldwide. NIV has become best and routine practice, and is advocated in national and international guidelines, benefiting many thousands of COPD patients.
It is important that valid outcome measures are used to assess clinical services and interventions to demonstrate that services are effective. Additionally, outcomes of interventions need to be meaningful to the patients reporting them, as this adds value to the outcome of trials over and above the statistically significant difference derived mathematically. Singh and colleagues explored the minimum clinically important difference of the incremental shuttle walking test for individuals with chronic respiratory disease. As a result of Singh's research, this threshold is now included in international guidelines for pulmonary rehabilitation and has also been introduced into research and practice among people attending cardiac rehabilitation over the last 5 years.
Congenital myasthenic syndromes (CMS) are inherited neuromuscular disorders caused by defects at neuromuscular junctions, which are often a result of acetylcholine receptor gene mutations. A subset of CMS patients (around 14% in the US and Europe) have limb-girdle myasthenia (LGM). This disease can be highly disabling with symptoms including increasing weakness of skeletal muscles. As a result of collaborative work between Newcastle and Oxford, it was determined that many LGM patients have a mutation of the Dok-7 gene (unrelated to the acetylholine receptor), and do not, therefore, respond to standard CMS treatments. Since then, a number of additional mutations have been discovered, and genetic testing is now available for the majority of known LGM-causative genes. Crucially, Dok-7 patients, and those with other non-receptor related mutations, can now be diagnosed accurately and treated effectively, with ephedrine and salbutamol (in the US, albuterol). This significantly improves these patients' quality of life by enabling them to walk and breathe unassisted.
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.
In this case study we describe an interrelated collection of impacts on healthcare in the NHS; these are summarised in the Table below.
Poor treatment adherence and self-management are universally recognised as major problems across all illnesses. Research at Kings College London (KCL) has resulted in new ways of assessing, investigating and improving these problems. These are now achieving widespread impact through the highly successful commercial organisation Atlantic Healthcare, which provides medication adherence and patient support programmes on a global scale. These programmes, which are now reaching patients with over 50 major medical conditions in a large number of countries, are very solidly based on the findings from KCL research.
Motor neuron disease (MND) is a devastating and debilitating disease with poor prognosis; most patients die from progressive respiratory failure within three years of onset. A randomised controlled trial conducted in Newcastle provided robust evidence that non-invasive ventilation for patients with MND can significantly improve quality of life and increase survival (216 days with non-invasive ventilation compared to 11 days without). Findings from this trial underpinned recommendations concerning the use of non-invasive ventilation in MND in clinical guidelines internationally, and use in clinical practice has increased in the UK, across Europe, and in the US and Australasia. In the UK, the number of MND patients successfully established on non-invasive ventilation in 2009 had increased 3.4-fold since 2000 and since 2009 has further increased almost two-fold.
Work on better management and identification of Medically Unexplained Symptoms (MUS) has led to the introduction of new treatments in primary care in England through the Improving Access to Psychological Treatment (IAPT) programme as well as having an impact on service planning and commissioning. These approaches have also been implemented into the routine training and practice of General Practitioners (GPs) in parts of Europe. A clinical and economic evaluation of a psychosocial approach to chronic fatigue syndrome using general nurses and development of a cognitive behaviour therapy approach has changed general practice and enhanced the patient experience for those with MUS.
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 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.