How our research makes a difference
Research is vital in the fight against lung disease. It will help us develop new treatments and cures – saving, prolonging and improving lives.
In total, we've spent over £30m on hundreds of wide-ranging research projects.
Among many other achievements, the projects listed here have made, or have the potential to make, a significant impact in our five priority disease areas:
- chronic obstructive pulmonary disease (COPD)
- lung cancer
- interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF)
- children’s lung infection and wheezing
Causes of COPD flare-ups
- Study by: Dr Jadwiga Wedzicha, London Chest Hospital
- BLF grant: £59,580
- Summary: study to identify which factors cause flare-ups of COPD, concentrating on viral factors and environmental factors such as pollution.
This study showed how important viral infections are in causing flare-ups in COPD, most frequently the common cold virus. Patients had reduced lung function in colder temperatures, making them more prone to flare-ups. Most recovered to normal within three months of a flare-up but 10.5% took longer.
The researchers found that patients with COPD during flare-ups were at considerable risk of heart disease due to raised fibrinogen levels, a marker of blood-clotting activity.
How frequently people experience flare-ups depends very much on quality of life and dampness in the home, which may help viruses and bacteria to survive.
Pulmonary rehabilitation and COPD
- Study by: Professor John Moxham, King’s College Hospital, London
- BLF grant: £106,696
- Summary: to study how pulmonary rehabilitation (exercise training) can help recovery for patients with COPD following hospital admission for a flare up of their condition.
The research found that early pulmonary rehabilitation increased muscle strength and exercise capacity, improved quality of life, reduced breathlessness and reduced readmissions to hospital.
The Cochrane Collaboration Review estimates that for every four patients treated with early pulmonary rehabilitation, one subsequent hospital admission is avoided; and for every six patients treated, one life is saved.
With 130,000 people admitted to hospital each year for a flare-up of COPD, this research has the potential to save more than 21,000 lives every year. It also has the potential to prevent as many as 32,500 people with COPD being readmitted, saving the NHS up to £52 million a year.
Thanks to this valuable research, the Department of Health guidance for commissioners states that pulmonary rehabilitation should be offered to people with COPD who have recently had a flare-up requiring hospital admission.
Gene involved in lung cancer
- Study by: Professor Tyson V Sharp, University of Nottingham
- BLF grant: £72,087
- Summary: to characterise a new gene involved in lung cancer.
Professor Sharp and his team at the University of Nottingham had previously identified a gene called ‘LIMD1’, which is damaged in lung cells by cigarette smoke. With this BLF grant, the team investigated whether damage to LIMD1 might lead to lung cancer.
They studied lung cells that lacked the LIMD1 gene, and found that these cells became cancerous. This proved that a working version of the LIMD1 gene is essential to the health of lung tissue. It also suggested that damage to LIMD1 by factors such as cigarette smoke may play a key role in the development of to lung cancer.
These findings were important for two reasons. First, detecting damage to the LIMD1 gene may be a new way to identify and treat cancer much earlier, with more chance of success. Second, finding a way to replace a missing or damaged version of the LIMD1 gene with a working one may be a way to stop the growth of lung cancer.
Understanding resistance to treatment
- Study by: Professor Tariq Sethi, London
- BLF grant: £118,962
- Summary: to investigate the role of Galectin-3 (a protein) and the local tumour environment in lung cancer tumours becoming resistant to treatment.
The aim of this research was to find out whether measuring Galectin-3 to mark tissue samples from patients with non-small cell lung cancer (NSCLC) could be used to:
- predict outcomes for patients with NSCLC;
- find out how Galectin-3 interacts with immune cells in the tissue surrounding the lung cancer that are there to prevent the cancer taking hold and spreading;
- and assess effects of Galectin-3 blocking drugs as a treatment for NSCLC.
The research found that where there were high amounts of Galectin-3 around tumour samples, outcomes for patients were worse. The findings also suggested that Galectin-3 interferes with the immune system’s ability to tackle ‘foreign’ or cancerous cells.
Crucially, this work suggests that blocking Galectin-3 could, therefore, prevent tumour growth. Further research is needed but this approach may become a new, effective treatment for lung cancer.
Most of our mesothelioma work has been funded in the past four years, so it’s too early to show true ‘impact’. Of those funded, however, the following are the most important and have the greatest potential.
Mesothelioma tissue and blood sample bank
- Study by: Dr Robert Rintoul, Papworth Hospital, Cambridge
- BLF grant: £499,908
- Summary: to establish MesoBank UK, a UK-wide mesothelioma tissue and blood sample bank, the first dedicated mesothelioma ‘tissue bank’ in Europe.
Researchers from seven UK locations, including London, Aberdeen and Belfast, donate mesothelioma tissue they have in storage. They also collect new tissue when a consenting patient undergoes surgery for mesothelioma or has a biopsy (cell sample) taken.
All samples will meet very high standards in terms of quality, collection methods and subsequent storage techniques, to make sure they are suitable for research purposes.
Dedicated tissue banks have previously helped research into other diseases such as breast cancer, Parkinson’s disease and multiple sclerosis. Pioneering lung researchers can use the anonymous samples from MesoBank whenever they need them, allowing them to do their experiments more quickly and economically.
Ultimately, it is hoped that this resource will speed our progress towards a better understanding of mesothelioma and, hopefully, successful treatment of this disease.
Mesothelioma and the ‘ASS1’ gene
- Study by: Dr Sarah Martin, Barts Cancer Institute, London
- BLF grant: £123,356
- Summary: to identify new drugs to treat mesothelioma with loss of the ‘ASS1’ gene, which may benefit up to 50% of patients with mesothelioma.
Arginine is a type of amino acid, a vital building block that cells – including cancer cells – need to grow. Most cells can produce their own arginine. However, in about 50 per cent of mesothelioma cases, the cancerous cells have a mutation (difference) in a gene called ‘ASS1’, which stops them producing arginine. These cells depend on a steady supply of arginine from the bloodstream in order to grow.
Cutting off the supply of arginine – ‘Arginine starvation’ – may be an effective way to slow or halt tumour growth. However, this may not be enough to fully eliminate the tumour. Other treatments that target the mutation in ASS1 could be more successful in tackling this type of mesothelioma.
During this study, Dr Martin and her team will try to identify new personalised treatments to do this. Their aim is to kill the tumour cells without harming surrounding healthy cells.
Personalised treatments mean giving people drugs designed specifically to target their particular type of mesothelioma. The hope is that this will lead to more successful treatments, help reduce the use of less effective treatments and minimise associated side effects.
Radiotherapy to treat mesothelioma
- Study by: Dr Barry Laird, University of Edinburgh Cancer Research Centre
- BLF grant: £24,631
- Summary: to investigate whether PET-CT scanning can improve our ability to use radiotherapy to treat mesothelioma.
One of the difficulties of treating people with mesothelioma with radiotherapy is that the tumour usually affects the lining of the entire lung. Targeting the entire area affected with radiotherapy can have significant side effects, possibly cancelling out any benefits in terms of pain control.
On the other hand, if a specific area of the lung is targeted but this is not the area causing pain the treatment won’t have any effect on pain relief. Deciding which parts of the tumour to target with radiotherapy, and which parts to leave alone, can be extremely difficult.
The next step would be a study in which some patients receive radiotherapy based on the standard CT scan, and others receive radiotherapy based on the PET-CT scan, to see whether adding PET-CT leads to improved pain control.
The genetic causes of mesothelioma
- Study by: Dr Peter Campbell, Wellcome Trust Sanger Institute, Cambridgeshire
- BLF grant: £145,344
- Summary: to attempt to understand the genetic causes of mesothelioma, which could, in turn, lead to new treatments.
Our understanding of the genetics of mesothelioma has lagged behind other disease areas. This research sought to address this problem by analysing the largest number of mesothelioma tumour samples ever collected, to date, for one study.
The study found that:
- a large number of genetic mutations (differences) are involved in causing mesothelioma
- the majority of patients with mesothelioma have one or more difference in the enzymes used to regulate DNA and their genes
- a small number of patients with mesothelioma have mutations in genes that potentially point the way to new treatments, and should help in the design of further studies
IPF and quality of life
- Study by: Ms Janelle Yorke, University of Salford, Greater Manchester
- BLF grant: £14,614
- Summary: to develop a questionnaire to measure quality of life for people with idiopathic pulmonary fibrosis; this will help researchers to measure the impact of new therapies and monitor progress of the disease more accurately.
The causes of IPF and how it develops are not well understood. Also, although treatments are available, it is difficult to accurately monitor how well these work and how the condition progresses.
Questionnaires on ‘quality of life’ have proved extremely valuable in monitoring progression in other diseases. Prior to this grant, no such questionnaire existed for monitoring IPF.
Janelle Yorke worked with people who have IPF to create an internationally recognised questionnaire that captures information about how IPF affects quality of life. This is a great step in helping doctors to measure the progression of IPF, which in turn will help in prescribing the right treatments and monitoring their effectiveness. This will greatly improve quality of care for this condition.
A new therapy for IPF
- Study by: Professor Donna Davies, University Hospital Southampton
- BLF grant: £119,467
- Summary: to evaluate a potential new therapy for idiopathic pulmonary fibrosis.
This project aimed to evaluate a new anti-cancer drug, called ‘FK228’, as a potential new treatment for IPF. It also aimed to develop ‘biomarkers’ to assist doctors during clinical trials, to assess whether the treatment is effective or not.
The researchers investigated how FK228 affected cells called ‘fibroblasts’, which are responsible for creating scar tissue in the lungs of IPF patients. They also used cells from healthy lung tissue, especially the delicate cells involved in the exchange of oxygen and carbon dioxide, to check that the drug does not damage these cells.
The results showed that FK228 did have a strong effect on the cells responsible for scar formation without harming healthy lung cells.
The experiments also allowed the researchers to identify the required ‘biomarkers’, whose levels changed in response to the drug treatment.
Most importantly, they were able to detect these biomarkers in blood and lung secretions from IPF patients. This means that they could potentially be used to monitor each patient’s response to the drug.
Finding a biomarker that shows that the drug is having a positive effect on how scar tissue forms in IPF should boost confidence in the drug’s usefulness. It may also lead to it being fully evaluated more quickly as a potential treatment for this devastating disease. Longer term, the biomarkers will help doctors to assess individual patients and their response to a treatment.
Understanding the cause of abnormal lung scarring
- Study by: Dr Nik Hirani, Medical Research Council/University of Edinburgh
- BLF grant: £149,845
- Summary: to attempt to identify the cause of the switch from normal lung healing to abnormal lung scarring, and see if it can be modified.
Usually, the lung is able to repair itself without leaving any trace of damage through the process of regulated inflammation. In chronic lung diseases like IPF, these healthy healing processes are disrupted, leading to the creation of excess scar tissue.
We don’t currently know what causes this change from normal lung healing to abnormal lung scarring. It’s thought, though, that macrophages (large cell types that form an important part of the immune system) may play a crucial role. It is believed, too, that macrophages can switch from being helpful cells to harmful scar-promoting (or ‘fibrotic’) ones.
Dr Hirani and his team believe that molecules that respond to changes in oxygen levels may control this switch. These molecules are hypoxia-inducible factors (HIF) and prolyl hydroxylases (PHD).
To test this theory, the researchers used macrophages (from humans and mice) in which the HIF or PHD molecules were either removed entirely or overactivated through drugs or genetic manipulation.
The results showed that manipulating the HIF or PHD, either genetically or with drugs, caused these macrophages to behave differently to normal macrophages.
In mice, if inflammation was active, the altered macrophages would help the lung repair without leading to fibrosis. By contrast, if the macrophages were altered after inflammation had started to settle down, the fibrosis worsened.
The researchers are currently investigating whether there is an imbalance in HIF and PHD in macrophages in the lungs of patients with lung fibrosis that might explain why scarring develops.
Drugs that target HIF and PHD are already available for other diseases. By revealing the role of macrophages in lung fibrosis, and showing how these existing drugs can change the behaviour of macrophages, the hope is that these drugs can be tested in future trials in lung fibrosis.
Assessing lung function in pre-school children with lung disease
- Study by: Professor Janet Stocks, Institute of Child Health, London
- BLF grant: £79,444
- Summary: to investigate new ways of assessing lung function in pre-school children with lung disease.
As part of a European Respiratory Society and American Thoracic Society task force, Professor Stocks and her team achieved a high success rate of testing lung function in awake children, aged three to five, using the ‘multiple breath washout’ technique.
This work, funded by the BLF, was the first time that this technique had been used on children in this age group. The results showed that it was possible to detect lung problems in children from a much younger age than was previously possible. This allowed treatment to start earlier, with potentially much greater impact.
This method of testing lung function in young children has now become an international standard.
Treatment of childhood pneumonia
- Study by: Professor Terence Stephenson, Queen's Medical Centre, Nottingham
- BLF grant: £84,834
- Summary: a study comparing the treatment of childhood pneumonia in hospital and at home.
In this study, 246 children with pneumonia, aged between six months and 18 years, were divided into two groups: one to receive oral antibiotics for seven days, and the other to receive intravenous antibiotics.
The results showed that the oral antibiotic and intravenous antibiotic treatments were equally effective. Children in both groups took, on average, 1.3 days to show an improvement in symptoms and nine days to recover fully. From these findings, it was concluded that oral antibiotics were an effective treatment for children admitted to hospital with pneumonia, except for the most severe cases
Additional benefits to oral antibiotic treatment for pneumonia include: oral treatment allowed children to go home sooner and avoided painful injections; hospital beds are freed up for other patients; and reduced cost to the health service as the cost of treating children with pneumonia is lower in those treated with oral antibiotics.
The evidence arising from this study appears in the British Thoracic Society’s guidelines for the management of acquired pneumonia in children: update 2011, which states: “Antibiotics administered orally are safe and effective for children presenting with even severe CAP [community-acquired pneumonia] and are recommended.”
The BLF helped me present my research
John Lowe says support helps scientists to research lung disease.