£5 – For equipment to take blood for testing antibodies for a patient with IPF.
£50 – Allows us to grow individual fibroblasts (these are the cells that produce the scarring) in the laboratory from the lungs of patients with IPF to do further studies.
£500 – Allows us to isolate the platelets from patients with IPF so that we can examine them in the laboratory and compare them to platelets from people with normal lungs.
£1,000 – For specialised antibodies to help us develop a novel blood test for early detection of PF.
£1,500 – For accessories for our lung function equipment for one year.
£3,000 – For a study to assess whether treatments for rheumatoid arthritis help the lung disease associated with RA.
£5,000 – To provide all the equipment and running costs for a ‘Western Bot’ which allows us to look at abnormal proteins in the lungs of patients with pulmonary fibrosis.
£10,000 – For a research nurse for a year working 2 days a week to collect valuable patient data and samples for research.
£50,000 – Pump priming a blue sky research proposal: allows a senior clinician to undertake a substantial period of research (a year or more) as a named research fellow to develop an hypothesis that is then submitted for full funding (£300K+).
Interstitial Lung Diseases
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Breathing Matters has a brand new Justgiving page. We have transferring to a campaign page under the UCLH Charity Justgiving Page. The new link is: https://www.justgiving.com/campaign/breathingmatters This will save us on Justgiving fees for Breathing Matters, so more of your money goes directly to where it’s needed!
Please visit our new online donation page to donate, or to just have a look-see 🙂
Current open Justgiving pages on our old Justgiving Page will remain active, so you don’t need to do anything.
Together we can do more!
Breathing Matters was established 8 years ago with the aim of finding better treatments for interstitial lung diseases (ILD) and lung infections. Since that time, we have raised money and awareness into these often neglected conditions. Looking back over the 8 years, we have come much further than any of us would have anticipated in the beginning. We have established new theories on the development of ILD or lung fibrosis and the role of the immune system in particular the clotting cascade and neutrophils. We have also better ways of monitoring and diagnosing these conditions and our novel nuclear medicine imaging programme and relatively non-invasive lung biopsy service are the first in the UK. We could not have achieved any of this without the support of our funders and our patients, so thank you all. This review highlights our achievements to date and our future directions in ILD.
Relatively Non-Invasive Lung Cryobiopsy (2014-ongoing):
Objective: To find a less invasive and better diagnostic tool for every patient with ILD
- Teresa Timberlake and family – equipment purchase
- Lawrence Matz Memorial Fund – Clinical Fellow
Breathing Matters investment: £52,000 salary; £36,000 (total £88,000)
Leveraged funding: £347,000
1. Novel cryobiopsy service, first in the UK including training other centres; presentations at European Respiratory Society (2015), British Thoracic Society (2014-6); publications: review 2016; papers in preparation:
2. Completed Lung-INHALE study Study (2019) to assess inhaled drug deposition using CLB. This will allow drug companies to develop inhaled therapies for IPF and be sure that they are reaching the part of the lung where they are needed. The use of inhaled therapy will avoid some of the side-effects of anti-fibrotic drugs that are taken as tablets.
This project was developed in discussion with a family whose mother had had a surgical lung biopsy towards the end of her life. Her experience was such that her family felt that a less invasive alternative must be available. Dr Theresia Mikolasch, the Lawrence Matz Clinical Fellow, took this on for Breathing Matters to find out and about and train in new techniques. Dr Mikolasch then returned to UCLH and established the first and only UK cryoscopic lung biopsy (CLB) service. CLB is a new way of obtaining larger lung biopsies using a flexible bronchoscope passed into the lungs through the mouth. The patient is sedated and surgery is avoided. This is not only better for the patient than a surgical lung biopsy, but also provides a solution to the lack of biopsy samples available for scientific research. GSK were so excited by the technique that they awarded Dr Mikolasch and Dr Porter a grant of over £300,000 to carry on the service for an additional 3 years.
Novel FDG-PET Imaging to Predict Prognosis and Response to Treatment in ILD (2014-ongoing):
Objective: To find a new test (biomarker) that will enable us to predict prognosis and response to treatment in each individual patient.
Breathing Matters investment: £34,766
Leveraged funding: £173,850
Funding from BLF for clinical trial of FDG-PET in post transplant bronchiolitis £40,000
Outcomes: Novel FDG-PET imaging programme in ILD – first in the UK; presentations at American Nuclear Medicine Society (2015), British Thoracic Society (2015-6); American Thoracic Society (2017)
Pulmonary 18F-FDG uptake helps refine current risk stratification in idiopathic pulmonary fibrosis (IPF). Win T, Screaton NJ, Porter JC, Ganeshan B, Maher TM, Fraioli F, Endozo R, Shortman RI, Hurrell L, Holman BF, Thielemans K, Rashidnasab A, Hutton BF, Lukey PT, Flynn A, Ell PJ, Groves AM. Eur J Nucl Med Mol Imaging. 2018 May;45(5):806-815. doi: 10.1007/s00259-017-3917-8. Epub 2018 Jan 16.
1. FDG-PET will be used as a response biomarker to see if we can detect which patients benefit from anti-fibrotic therapy and which patients do not benefit. We have applied to the NIHR for a £400,000 grant to carry out this study:
2. We will use FDG-PET to see if Losmapimod is of benefit in patients with rheumatoid arthritis associated lung fibrosis (RA-ILD) (see below).
3. We and others have shown that patients with IPF are more prone to blood clots. We have some very exciting work looking at anticoagulation in IPF. We have completed 2/3rds of the study and will then publish our findings later in 2019 (see below).
Interstitial lung disease (ILD) consists of a heterogeneous group of diseases with varying amounts of interstitial inflammation and fibrosis. Survival in the most severe form of lung fibrosis, idiopathic pulmonary fibrosis or IPF, is particularly poor; however, there is heterogeneity in outcome. Some patients gradually deteriorate; some undergo stepwise progression, whilst others decline rapidly. Moreover, much of the prognostic data heralds from an era when the criteria for diagnosing IPF were less well and differently defined than at present. There is a definite need to find prognostic biomarkers to predict outcome in IPF patients
Positron emission tomography (PET) offers the ability to non-invasively investigate cellular metabolism in vivo. PET studies in animals have yielded valuable insights into the biology of IPF and ILD and there is potentially encouraging evidence that PET may aid the development of therapeutic interventions to treat these debilitating conditions. It has been recently demonstrated that 18F-Fluorodeoxyglucose (18F-FDG) PET signal is consistently raised and can be objectively measured in patients with IPF. Moreover, these PET signals are shown to be stable and reproducible.
We have shown over several years and imaging hundreds of patients with ILD that the baseline measures of pulmonary 18F-FDG PET signal to predict survival in patients with IPF compared to other more established prognostic data. We have also shown that combing PET data with our clinical scoring system based on gender, age and physiology (GAP) data (“PET modified GAP score”) refined the ability to predict mortality.
Future studies are to investigate the role of FDG-PET scanning in other ILDs, such as Rheumatoid arthritis (see below) and systemic sclerosis.
Rheumatoid Arthritis (RA) Associated ILD (2018-ongoing):
Objective: To discover why 1:5 patients with RA will develop lung fibrosis and what novel treatment can prevent disease progression
Breathing Matters investment: £34,766
Leveraged funding: £102,766
Outcomes: Novel biomarker test for neutrophils extracellular traps (NETS) in ILD in discussion with UCL business for further development; presentations at American College of Rheumatology (2014-6); British Thoracic Society (2016); British Rheumatology Society (2014-6); publications: 2 papers in preparation:
Next steps: A trial of the p38 MAPKinase inhibitor Losmapimod in RA-ILD using FDG-PET as a response biomarker
RA is a chronic debilitating disease estimated to afflict 13% of the world population. Around 10% of patients with RA will develop an ILD that is very similar to the lung fibrosis that we see with IPF. Dr Akif Khawaja was funded by Rosetrees and UCL to carry out a PhD into the aetiology of RA-ILD. His work proposed that RA is a disease that starts in the lung. That chronic lung damage caused by smoking, infection and other insults causes the immune response to recognize the lungs and joints as “foreign” and attack them causing chronic damage. His work implicated neutrophils in this process and, in particular, the p38 MAPkinase pathway. Breathing Matters and Rosetrees are now funding Akif to carry out further work to investigate the role of the p38 MAPKinase inhibitor Losmapimod in patients with RA-ILD and this will combined with our novel PET imaging work. We are also hoping to develop a new test using blood or sputum to detect early activation of neutrophils in the lungs of patients at risk of ILD. This same test may act as a biomarker for prognosis and to detect early response to novel therapies.
This work had led onto the first clinical trial of a treatment in RA-ILD: in particular, we will use an established pharmacological inhibitor of p38 MAPkinase to investigate the role of this pathway in the FDG PET signal seen in the lungs of patients with RA-ILD; in particular, to demonstrate a change in FDG avidity following p38MAPkinase inhibition.
A Trial of Anticoagulation in IPF (2016-2019):
Objective: To assess the potential of anticoagulation as a treatment for IPF
Main benefactors: The Hulme Family – The Mark Hulme Clinical Fellow
Breathing Matters investment: £40,000
Leveraged funding: £100,000 from UCL/H NIHR BRC
Next steps: A trial of anticoagulation with heparin in IPF using FDG-PET as a response biomarker
At present, we do not know the exact cause of idiopathic pulmonary fibrosis (IPF), although research has identified lots of processes that are likely to be involved. Currently, we believe that microscopic injury occurs in patients with IPF and then the body responds to repair this, but does so in a way that leads to more damage and scarring. One of the processes involved in repair pathway is coagulation, which minimises blood loss when tissues are damaged. Patients with IPF are at increased risk of blood clots and this can reduce their already low life expectancy. We also think that these blood clots drive the worsening of their lung disease. Researchers have shown that clotting is over-activated in the lungs of IPF patients and we want to investigate how reducing this might improve the disease. Based on work carried out at UCL, we believe that anticoagulation with heparin is safe and may even prevent disease progression in IPF. Patients will be asked if they would be willing to take the oral anticoagulant dabigitran for 3 weeks, to reduce clotting. We will perform blood tests and FDG-PET scans before and after taking the drug to judge response. If we find that the heparin is safe and the patients report some improvement that we can confirm with questionnaires lung function and FDG-PET scans, then we will progress to leverage funding for a much bigger trial. We have completed 2/3rds of this study and are just recruiting the final patients.
A Trial of a Novel Treatment (Compound X) in IPF (2019-2022):
Objective: To assess the potential of Compound X as a treatment for IPF
Main benefactors: NIHR BRC £100,000
Breathing Matters investment: £40,000
Leveraged funding: Application to British Thoracic Society, Wellcome Trust and NIHE.
Next steps: A trial of Compound X in patients with IPF
Assessing effectiveness of treatments for IPF is difficult as often they do not make patients feel better, despite decelerating disease. Currently, we are guided by regular breathing tests and special imaging of the lungs, which are insensitive to changes and may be unpleasant for patients. We need better tests like a simple blood test to predict the prognosis for individual patients, and their responses to treatment. Causes of IPF are unknown, but we have found that specific white blood cells, called neutrophils, are increased in the lungs of patients with IPF. We also found that the more neutrophils in the lungs, the faster the decline from IPF. This suggests that neutrophils are actively worsening IPF. Neutrophils produce a substance called X that we detect in the bloodstream of patients with IPF. No-one has investigated whether X causes or worsens IPF. We plan to quantify X in the blood and lungs of patients with IPF. By comparing X levels in patients with IPF against healthy individuals, this will establish whether X is increased in patients, whether high levels of X indicate more severe IPF and whether treatment for IPF reduces X levels in patients that respond. These results will ultimately help design future clinical trials testing Compound X that is able to block X as a treatment for IPF.
Understanding Mucin 5 B and Its Role in IPF (2019-2022):
Objective: To assess the role of Muc5B in IPF
Main benefactors: NIHR £100,000
Breathing Matters investment: £40,000
Leveraged funding: Application to Rosetrees
Next steps: Further investigations in patients with IPF of the effects of blocking neutrophil activation
It is unclear what causes IPF, but it is thought to be a response to damage to the lining of the airways (epithelium) following an unidentified injury. This results in the
formation of excessive scar tissue which disrupts the delicate architecture of the lung and ultimately death follows from respiratory failure. We have shown from research previously sponsored by The Rosetrees Trust that a certain type of white blood cell which is specialised in fighting infections called neutrophils may play a role in PF. We have found that neutrophils are increased in the blood and lungs of patients with PF and the more neutrophils you have, the worse the individual’s outcome. In addition, it is recognised that you are more likely to develop IPF if you have a commonly occurring genetic mutation that causes increased mucus production by the lung epithelium, and in particular a protein called Mucin or MUC5B that gives sputum its stringy quality. We propose that the overproduction of MUC5B may stress the epithelium, making it more prone to damage and scarring. In addition, the increased MUC5B will attract and activate neutrophils from the blood and these white blood cells can cause further damage. We hope that, by identifying treatments that limit the number of neutrophils moving into the lung, we can protect patients from developing PF or from PF progressing. We will use neutrophils and epithelial samples form patients and healthy volunteers to compare differences and see how the MUC5B affects neutrophil activation in the lung. Lastly, we plan to block neutrophil activation and recruitment with a specific treatment that is already being developed for other indications and has an excellent safety profile. If our results are encouraging, we can take this medication into an early clinical trial for patients with IPF.
If you are a UCLH patient and want to get involved in any of the above studies, please discuss this with your consultant.
I would like to take this opportunity to reflect on another remarkable year for Breathing Matters. As we reach our 8th year, many of the seeds that we planted in 2011 are bearing fruit.
Our cryoscopic lung biopsy service, allowing us to do relatively non-invasive lung biopsies, continues to flourish and has allowed many of our patients to have a biopsy taken, but avoid the 3 day hospital stay and side-effects of a surgical lung biopsy, by having it all done by ‘key hole’.
We have finally, after many different approaches, shown a role for platelets and blood clotting in pulmonary fibrosis and have some very exciting data that we are submitting for publication in 2019. We have gone on to show that anti-coagulation may have beneficial effects in patients with IPF and we are hoping to take this into a feasibility study in 2019. It will take some years before this has the widespread clinical impact that we hope as there are many hurdles still to negotiate, but I am confident that Breathing Matters will finally answer the question ‘should patients with pulmonary fibrosis be anti-coagulated routinely?’.
However, our major achievement in 2018 in pulmonary fibrosis was the publication of our study of FDG-PET scans in IPF patients, followed for 10 years. In this tour-de-force that over 150 of our patients took part in, we showed that FDG-PET scans can predict how well individual patients do over time and are able to refine the current scoring systems based on age and lung function. This work has led on to the major pre-occupation of the last few months which has been the submission of a funding request for £400,000 to the National Institute of Health Research to see if FDG-PET can predict which patients should be treated with the drug, nintedanib or pifenidone or neither, and whether using the information from PET scans can improve the quality and length of patients’ lives – which is our ultimate goal.
A potential new vaccine against Streptococcus pneumoniae, the commonest cause of pneumonia – Streptococcus pneumoniae is the commonest cause of pneumonia, and vaccines to prevent infections by this bacteria are very important for preventing lung infections both in infants and in adults (the elderly and those with chronic lung diseases such as asthma, bronchiectasis, COPD, and interstitial lung disease). However, there is still a need for a better vaccine that is cheaper and effective against all S. pneumoniae strains rather than just a proportion. Making the most effective S. pneumoniae vaccines is expensive as it requires multiple chemical steps that each need to be very carefully controlled to ensure they have worked properly. Professor Brown’s group, in collaboration with Professor Wren from the London School of Hygiene and Tropical Medicine, have now shown in a recent scientific paper that an effective vaccine can be made using genetically engineered bacteria, a much simpler and cheaper method. Furthermore, they also have shown that the vaccine could protect against many more strains than the existing vaccine. It is hoped that this paper will stimulate investment in the new vaccine approach and eventually lead to the introduction of cheaper but better S. pneumoniae vaccines to help prevent lung infections. Reglinski et al. ‘A recombinant conjugated pneumococcal vaccine that protects against murine infections with a similar efficacy to Prevnar-13.’ NPJ Vaccines, in press 2018
New study for bronchiectasis patients – Prof Brown’s research group has started a new study for patients with bronchiectasis, mainly for patients who have developed bronchiectasis as a consequence of a haematology disease or are receiving rituximab. The aim of the project is to investigate the effects of antibody deficiency on how the immune system is able to recognise and control Streptococcus pneumoniae infections. The study is being done by Dr Hall and Dr Jose and involves measuring antibody and white cell recognition of S. pneumoniae in volunteers before and after an injection of dead S. pneumoniae into their forearm. Dr Hall will be contacting patients with bronchiectasis who may be suitable for this study to describe in more detail what it involves.
Bronch UK update – we have now recruited 110 patients into the Medical Research Council funded Bronch UK study; well done to Dr Hall and Joel Solis (research nurse) for reaching this target, and thank you for all the patients who have volunteered to take part. The data from this study will be essential in designing future trials of new therapies or ways of managing bronchiectasis.
I would like to thank you all for your support over the year in what has been an uncertain and challenging time for many of you. With your support, Breathing Matters has continued to excel by focusing on our core mission.
Professor Jo Porter, Medical Director of Breathing Matters.
If you haven’t been to a silent disco before, you don’t know what you’re missing. This concept is straight out of the festivals and sweeping across the UK and is becoming more and more popular. This is your chance to experience a silent disco in an awesome setting. And for a fantastic cause too!
DJs do battle over separate wireless channels, playing the best in disco, 80’s and guilty pleasure classics. Don a headset and choose your favourite tune. No distraction – just dance!
The silent disco is on Friday, 9th November 2018 at 7.30pm till late at the London Museum of Water and Steam.
This museum, based right beside Kew Bridge, is an iconic and historic building, housing fabulous working engines from times gone by.
This is a unique opportunity to explore the museum after hours.
Why not make it extra special and be a VIP for the evening – VIP guests will enjoy:
– Complimentary prosecco [half bottle].
– Exclusive raised gallery with a fantastic view of the steam hall.
– Private seating area.
– Unfortunately, no wheelchair access for VIP guests.
Need to know:
– Print out tickets or show on mobile. No ticket: no entry.
– Cash only bar.
– Bring change for the cloakroom (£2.50).
– Bring cash for a chance to win big money in our Money Share game.
– Nearest station: Kew Bridge (few mins’ walk), South Western Railway.
– Directions: www.waterandsteam.org.uk/plan-your-visit
– Free car parking for 20 cars; first come first served. There is one dedicated parking space for orange or blue badge holders.
– Wheelchair access for standard tickets only.
– Free WiFi
Don’t delay, buy your tickets here
[Donations gratefully received from Bates Group and Sainsbury’s Warren Street towards the cost of this event.]
September is #Breathtember – Global Pulmonary Fibrosis Awareness Month
Get out of Breath for #Breathtember
To help raise awareness, we would ask that supporters tweet different challenges each day in September including the term ‘#Breathtember’ and to ask their followers to retweet and share this information as widely as possible.
Think outside the box for your challenges – getting out of breath for you could mean:
- Cycling around your local park
- Doing a colourful or musical 5K/10K run or walk
- Singing until you are out of breath
- Walking over the wonderous London bridges
- Blow bubbles!
- Or just simply walking up the stairs!
The important thing is that you tweet your challenge every day including the term ‘#Breathtember’ to raise awareness of pulmonary fibrosis. Add a photo if you like. This September, we want as many people as possible to see the term ‘#Breathtember’. To make the biggest impact, the aim is to get the term ‘#Breathtember’ to trend.
Follow us on Twitter for further details: @Breathingmatter
Ride London really is a true gem of an event starting at the iconic Olympic VeloPark in Lee Valley, cycling 100 miles of closed roads past London landmarks and through the stunning Surrey countryside (and hills!) and finishing in champion-style at the Mall outside Buckingham Palace! It’s the UK’s largest world-class festival of cycling.
You don’t have to be an elite cyclist, however, and can choose a start time based at your level – you just need to be able to finish the course in under 9 hours and be over 18. More info for riders can be found here.
Breathing Matters has a limited number of guaranteed places for this year’s event. Registration is £50 and we ask that you raise £450 for Breathing Matters. To sign up, email us at email@example.com
The deadline for sign ups is Tuesday, 22nd May 2018, so don’t delay.
We are delighted to announce the publication of our collaboration with the Insititute of Nuclear Medicine and our most important lung fibrosis paper to date. This work investigates the use of molecular imaging to more accurately determine disease severity in patients with pulmonary fibrosis.
Win T, Screaton NJ, Porter JC, Ganeshan B, Maher TM, Fraioli F, Endozo R, Shortman RI, Hurrell L, Holman BF, Thielemans K, Rashidnasab A, Hutton BF, Lukey PT, Flynn A, Ell PJ, Groves AM. Pulmonary 18F-FDG uptake helps refine current risk stratification in idiopathic pulmonary fibrosis (IPF). Eur J Nucl Med Mol Imaging. 2018 Jan 16. [Epub ahead of print].
For the last 5 years, Breathing Matters has collaborated on a programme investigating the ability of PET scanning to more accurately predict prognosis in individual patients with IPF and other forms of lung fibrosis.
[Combined high resolution CT image (Left) and PET image (Right) in a patient with IPF. The CT images (A) show honey comb lung (arrow) and PET images show high signal in the honey comb area (black, at site of broken arrow). Groves et al J. Nucl Med. 2009;50:538-45.]
The newly published paper in the European Journal of Nuclear Medicine, consisted of a unique 10-year prospective study of 113 IPF patients (the largest PET study in IPF) and the first of its kind to evaluate the use of FDG (glucose metabolism) PET scanning to predict prognosis and disease progression against the current standard, Gender Age Physiology (GAP) scoring system.
The findings demonstrate that FDG (glucose metabolism) PET scanning can help identify patients with IPF who are at increased risk of death and might therefore benefit from early treatment.
The figure below shows, for the first time, that patients with IPF who have a higher lung glucose metabolism are significantly ( p<0.003) more likely to deteriorate rapidly, despite having features that would conventionally place them in a good prognostic group. This data suggests that current treatment guidelines may need to be reviewed, as currently patients placed in a conventionally favourable group are not recommended for treatment. This novel imaging biomarker may allow us to evaluate new treatments more quickly by looking for changes in PET signal in individual patients. This will mean that smaller cohorts of patients will be needed for clinical efficacy trials, with a reduction in time to bring new medicines to patients.
Dr Porter reports, “This is a potential game changer in the stratification of patients with pulmonary fibrosis, giving additional information that complements the current GAP score and allows us to more accurately predict outcomes for individual patients. This means that we can reassure patients with a low glucose uptake on the scan; but intensify follow-up, treatment and early transplant referral in those patients with high glucose uptake. This is better for patients and allows us to provide a more effective and efficient ILD service”.
Lung disease will contribute to the death of 1 in 5 people. Many people suffer from chronic lung disease that impacts on their ability to function on a daily basis. Many chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and bronchiectasis are characterised by the presence of excessive numbers of white blood cells or leukocytes that are recruited to the lung from the blood stream.
In particular, the white blood cells, called neutrophils, are recruited at the earliest signs of lung damage. In small numbers, these neutrophils are essential to fight infection, but in larger numbers, or in more activated forms, they may cause damage to the lung, especially if they deploy their anti-microbial activity before they cross into the airspace.
Before reaching the airspace in which inhaled pathogens are encountered, the neutrophils must pass across the airway epithelium and then they come into contact with the layer of airway mucus that protects the airway from infection. We propose that the epithelial-mucus barrier acts as a checkpoint to prime neutrophil function in health, so that neutrophils are only fully activated once they have passed across the epithelium, thereby limiting collateral damage.
However, patients with IPF have higher numbers of neutrophils in their broncho-alveolar lavage (BAL) fluid and this also correlates with severity of disease. Furthermore, a genetic mutation that increases the amount of Muc5B, one of the airway mucins, has been identified as a risk factor for developing IPF (either sporadic or familial). Muc5B has been implicated in inducing neutrophils to expel fibres of DNA called neutrophil extracellular traps (NETs) and in our preliminary data, is a strong chemoattractant for neutrophils.
Dr Jagdeep Sahota has applied to the Medical Research Council to carry out a project will allow us to identify factors that alter the behaviour of neutrophils as they migrate through the lungs to eradicate infection and the role of MUC5B and TGF beta (a profibrotic cytokine implicated in the development of IPF). Dr Sahota has been able to develop preliminary data using funding from Breathing Matters. Her ultimate aim is to develop novel targeted therapies to reduce neutrophil mediated lung damage whilst maintaining effectiveness against infection. These therapies may be applicable to other chronic lung diseases.