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Tweet for #Breathtember, PF awareness month

September is #Breathtember – Global Pulmonary Fibrosis Awareness Month

 Get out of Breath for #Breathtember

Tweet Tweet!

https://www.breathingmatters.co.uk/wp-content/uploads/2013/06/twitter.png

To help raise awareness, we ask that supporters tweet different challenges during September including the term ‘#Breathtember and 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 virtual 5K/10K run or walk
  • Singing until you are out of breath
  • Walking over the wondrous London bridges
  • Blowing bubbles … or windmills!
  • Or just simply walking up the stairs!

The important thing is that you tweet your challenge including the hashtag ‘#Breathtember’ to raise awareness of pulmonary fibrosis.  Add a photo if you like.  This September, we want as many people as possible to get to know what Pulmonary Fibrosis really means.

Follow us on Twitter @Breathingmatter 

Article in The Guardian Respiratory Health Supplement

Professor Jo Porter, our Medical Director, has had an article published in the Respiratory Health Supplement in The Guardian today (22.6.21), explaining research into the impact of COVID-19 on lung fibrosis

This is what Prof Porter had to say:

A study is underway to assess the impact of COVID-19 on lung fibrosis development.  Interstitial lung disease (ILD), or lung fibrosis, diagnosed by CT scan, causes difficulty breathing by affecting the delicate membrane separating the blood and air in the lungs.  Joanna Porter, Professor of Respiratory Medicine at University College London, says there are more than 200 causes of ILD, including asbestos, mould, feathers, underlying conditions such as rheumatoid arthritis, and infection.  COVID-19 infection may be the latest contributor to ILD development.

COVID-19 impact – Dividing her research role with clinical work as head of the national NHS centre for ILD at University College London Hospitals, Professor Porter says there are an estimated 16,000 new ILD cases per year but this could be an underestimate as some people may not know they have the disease.  Specialists agree that current evidence is limited, however there is concern regarding the impact of COVID-19 on ILD and lung fibrosis patients. What is known is that patients with the most severe form of ILD – idiopathic pulmonary fibrosis (IPF) – do less well if they catch the virus.  The UK ILD Post-COVID Study is now following up hospitalised and non-hospitalised post-COVID patients to see how many develop a new ILD as a result of SARS-CoV-2 infection.  This UKRI funded multicentre study will look at patients in the PHOSP study who had a CT scan three months after their initial infection and compare that with their 12-month follow-up scan to identify ongoing and resolved issues.  Although we do not know the final figures, unpublished preliminary data from UCLH suggest around 4% of patients may be affected.

Professor Porter is also Medical Director of Breathing Matters, a UCLH charity, dedicated to finding a cure for all forms of ILD/pulmonary fibrosis. She points out that anything we learn from post-COVID ILD will almost certainly help other patients with lung fibrosis. Breathing Matters has continued vital research throughout the pandemic to address these critical questions.

Read the full Respiratory Health Campaign to find out more about key respiratory conditions, new innovations and the importance of good air quality

You can also read more on the online campaign at healthawareness.co.uk/respiratory

 

How COVID-19 Is Helping Research Into Pulmonary Fibrosis?

The interstitial lung diseases (ILDs) are a group of over 200 different diseases that may result in lung inflammation or (in the worst case) pulmonary fibrosis (PF). There are many different aetiologies for ILD/PF and in some cases, we do not know the cause, so called ‘idiopathic’.

One of the questions that we at Breathing Matters want to answer is – can COVID-19 give you pulmonary fibrosis? There are a few clues that this might be the case. Other coronaviruses such as Severe Acute Respiratory Syndrome (SARS) or Middle East Respiratory Syndrome (MERS) have been reported to cause PF in a small percentage of patients, but of course the numbers of patients affected by SARS-CoV-2, the virus that causes COVID-19, will be much greater so, even if only a small percentage are affected, the numbers may still be very large. The diagnosis of ILD/PF is suggested by a clinical finding of breathlessness and abnormal lung function. The diagnosis is then confirmed with a CT scan of the chest.

Initial studies from China, Italy and the UK have remarkably similar findings. Of patients with COVID-19 discharged from a hospital in China, nearly half had abnormal lung function (Mo X, et al. European Respiratory Journal 55: 2001217, 2020).  Data from Leeds of patients with COVID-19 discharged from hospital showed that the majority (75% of those admitted to intensive care, and 65% of those admitted to the regular wards) still suffered from fatigue at 6 to 8 weeks post discharge. The number suffering from continual breathlessness was also high (70% of those admitted to intensive care, and 45% of those admitted to the ward).  (Halpin S et al. Journal Medical Virology, First published: 30 July 2020, DOI: (10.1002/jmv.26368).  An Italian study from Rome found that at 60 days around 55% of patients were suffering from fatigue and 40% from breathlessness.  It is unclear what is the cause of these high levels of breathlessness, but a study from Austria is following their patients up in more detail at 6, 12 and 24 weeks after discharge. So far, they have found that at 6 weeks 47% of patients are short of breath and this falls to 39% at 12 weeks. In addition, 33% have abnormal lung function suggestive of lung fibrosis, but this falls to 22% at 12 weeks. Of course, to diagnose lung fibrosis requires at CT scan of the chest and they found that CT scans suggested an interstitial lung disease (ILD) or lung fibrosis in 88% falling to 56% at 12 weeks. However, it is also important to know how much of the lung is affected, and many of the studies do not clarify this, but just comment on whether ILD is present or not. The result is that it is hard to know whether these patients had minimal or significant ILD changes on the CT scan. Clearly, Breathing Matters will be looking out for the 24 week data.

Our own experience is that of around 800 patients seen at UCLH with COVID-19, in the first wave approximately 4-6% have persistent or slowly resolving CT changes at 12 months suggestive of interstitial lung involvement. The incidence of ILD may be less in subsequent waves because of the wider use of the steroid, dexamethasone, in patients with COVID-19 pneumonitis. Currently, our main priority is to analyse the scans of 20,000 patients who were hospitalised with COVID-19 and are taking part in the national PHOSP study, to see how common the development of ILD/ PF is in a much larger group of patients.  We will also look at 10,000 patients who had COVID-19 but were not hospitalised. This study funded by UKRI is a multicentre study that will look at the incidence of post COVID-ILD, investigate how much of the lung is affected and what the critical contributory factors are. It may be that this virus and the enormous numbers of patients that have been infected will shed some light on the pathogenesis of other ILD/PF diseases.​

We will keep you informed of any new findings.

 

Virtual London Marathon – Places Available!

The VIRTUAL Virgin Money London Marathon returns this October 2021, giving you the chance to take part in this year’s Guinness World Record-breaking attempt!

General entry is now sold out.  The only way to be a part of the world’s biggest-ever marathon is to secure a charity place, and Breathing Matters is lucky to have a few coveted places.

Whilst 50,000 runners are running the traditional London Marathon from Blackheath to The Mall, a further 50,000 runners in the virtual event will be running the same distance, just in a place of their choosing!  Last year’s Virtual Virgin Money London Marathon, which was held for the first time in 2020, was awarded an official Guinness World Records title for the Most users to run a remote marathon in 24 hours’ at 37,966 runners.  The organisers want to smash this record in the 2021 race – and if they do, every runner will have the opportunity to claim their official world record certificate.

Run 26.2 miles on your own course over 24 hours – Your Run Your Way!

  • Date:            Sunday 3rd October 2021, 00:00:00 to 23:59:59
  • Where:         Anywhere
  • Register by: 16th July 2021
  • Entry:            £20 plus £200 sponsorship

Email breathingmatters@ucl.ac.uk to sign up now.

Don’t miss your chance to become a world record holder!

 

Check out the London Marathon Training Hub

Be proud to run for Breathing Matters and wear one of our running vests or T-shirts, available from our online shop

Are NETS the link between COVID-19 and ILD?

In response to the COVID-19 pandemic, researchers are investigating how the virus causes lung damage, in order to help identify treatment strategies. There is some overlap between the mechanisms being studied in COVID-19 and Interstitial Lung Disease (ILD).  One of these is the production of structures known as ‘NETs’ in the lungs. A clinical trial currently led by Professor Porter at UCL aims to understand whether targeting these NETs improves outcomes for COVID-19 patients. This continues a line of work investigating the role of NETs in ILD.

NETs is short for Neutrophil Extracellular Traps. They contain DNA, enzymes, and proteins, and are produced by the neutrophil (a white blood cell) to fight infection.  The role of NETs in COVID-19 pneumonia is also under investigation. A study published last year showed that some of the markers of NETs used in Professor Porter’s ILD study were found in blood samples from COVID-19 patients (2). The levels of these markers correlated with other blood tests known to signify inflammation. Furthermore, adding blood samples from patients with COVID-19 to healthy neutrophils in the lab caused them to produce NETs. This could mean that NET production is related to lung damage in patients with COVID-19 pneumonia.

Further research is needed to determine whether NETs are a cause or by-product of lung damage in these diseases. However, knowing that NETs are associated with severe COVID-19, and that they are present in the lungs of patients with ILD, means that they could be used as a ‘biomarker’ – a molecular signal of lung damage. Promisingly, it could mean that reducing the activity of NETs in the lungs is a potential treatment strategy in the future.

The crossover between NETs in COVID-19 and ILD demonstrates the importance of ongoing research in this field. The team at UCL Respiratory are incredibly grateful for the support of Breathing Matters in helping to facilitate this research.

If you would like to help us continue our important work, please support us at: https://bit.ly/2HFVW5p

 

References:

  1. Khawaja AA, Chong DLW, Sahota J, Mikolasch TA, Pericleous C, Ripoll VM, Booth HL, Khan S, Rodriguez-Justo M, Giles IP, Porter JC. Identification of a Novel HIF-1α-αMβ2 Integrin-NET Axis in Fibrotic Interstitial Lung Disease. Front Immunol. 2020 Oct 15;11:2190. doi: 10.3389/fimmu.2020.02190. PMID: 33178179; PMCID: PMC7594517.
  2. Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, Blair C, Weber A, Barnes BJ, Egeblad M, Woods RJ, Kanthi Y, Knight JS. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020 Jun 4;5(11):e138999. doi: 10.1172/jci.insight.138999. PMID: 32329756; PMCID: PMC7308057.

 

Top 10 Highlights in 10 Years

1: Involving You

We have had many opportunities to meet our supporters over the years from small personal meetings to large tours; both are very special to us – you are the lifeblood, or the lungs (!), of Breathing Matters.

Our launch event on 19th January 2011 seems like only yesterday.  Professor Geoffrey Laurent, the then Director of the Centre for Respiratory Centre, was joined by his team of scientists and researchers as well as respiratory doctors.  It was attended by over 100 patients and relatives.  Speakers included Jo Porter, Malcolm Weallans and Manjiry Tamhane who spoke about topics ranging from living with respiratory disease through to the importance of patient support in shaping future scientific research and ways you could directly help us.  Our scientists were inspired by meeting our supporters and the patients whom their work helps.

Since then, you have attended our research meetings, events and our patient supporter meetings; you have helped us steer the way forward and shaped our research; you have advised on our fundraising and awareness strategies, you have attended our centre tours to see our labs and talk to our researchers about our work, and you have helped celebrate our achievements.

2: The First UK Treatments for IPF

In 2014, UCLH became an NHS-England Specialist Centre for the diagnosis and management of Interstitial Lung Disease.  This was important and timely as it enabled our doctors to prescribe idiopathic pulmonary fibrosis patients with Pirfenidone and Nintedanib – the first treatments in the UK available to IPF patients. These antifibrotic therapies slow decline in lung function and reduce the risk of acute respiratory deteriorations.

This was a game-changer.

3: Funding Clinical Fellows and Their Research

Breathing Matters has funded three celebrated Clinical Fellows:

  1. Lawrence Matz Clinical Fellow – Dr Theresia Mikolasch, who set up our Cryoscope Service and was the original soldier in our Neutrophil Army.
  2. Mark Hulme Clinical Fellow – Dr Helen Garthwaite, who worked on our important PET response studies.
  3. Christopher Whittington Clinical Fellow – Dr Emma Denneny, who is currently working on novel biomarkers to detect lung fibrosis with a blood test, earlier than standard CT imaging.

The work that our Clinical Fellows have done has enabled us to leverage a further £450,000 in grants.

4: Pioneering Diagnostics – Cryoscope

Our Lawrence Matz Clinical Fellow set up the Cryoscopic Lung Biopsy Service at UCLH, a pioneering minimally invasive diagnostic technique.  The cryoscope was part-funded by Breathing Matters.  In February 2013, UCLH diagnosed idiopathic pulmonary fibrosis from a cryoscopic lung biopsy – this was a UK first.

This was important for:

  • The Patient: who undergoes a day case procedure as opposed to a surgical lung biopsy, thereby avoiding hospital admission, an unsightly and painful scar and a chest drain.
  • The histopathologist: who said the quality of the tissue and preservation were excellent and much better than other minimally invasive biopsies due to the freezing during the procedure.
  • Our ILD research programme: We now have access to lung tissue that is removed, but is excess to that needed for clinical diagnosis.

5: Predicting and Detecting Pulmonary Fibrosis

A lot of our research is looking at better ways to detect pulmonary fibrosis even whilst the lung CT scan is normal. Our ultimate aim is to make an early diagnosis of PF with a blood test. Until then, we are looking at using very very sensitive imaging techniques, such as PET scans and MRI, to detect early changes in radiologically normal lung on CT scans. We have found that we can predict how severe PF is and how quickly it will progress from these PET scans and they may even help us guide treatment. Another exciting area is radiogenomics in which we use imaging patterns to understand the role of genes that predispose individuals to developing IPF.

6: Breakthroughs in Lung Infection

Through work partly done at UCL/H, bronchiectasis was proven to be more prevalent in the UK than previously thought – leading to better GP awareness, diagnosis and treatment.

We highlighted that bronchiectasis in those with weakened immune systems due to haematological disease develops very quickly; better awareness will make doctors much better at recognizing these patients and referring them to specialist centres, such as UCLH.

Our other work uses computers and CT scans to measure the exact degree of the dilatation of the bronchi in patients with bronchiectasis.  This is a significant breakthrough as it will allow us to follow what happens to a particular patient over time, and rapidly identify if things are getting worse.

The Bronch UK national study was the first study funded by the Medical Research Council into bronchiectasis for many years. The aim of the study was to look into the spectrum of disease caused by bronchiectasis, how severe the disease is and how it actually affects the patients’ quality of life.  Thank you to our 150 recruits!

Breathing Matters has supported the important PHOSP-COVID Urgent Public Health study looking into the long term effects of the COVID-19 virus which causes lung infection.

7: Spreading the Word

Where would the medical world be without scientists and researchers?  How would they get new treatments for their patients?  How would GPs find out about new or little known diseases and know when and how to act quickly?

Breathing Matters has reached out and spread awareness through various ways over the last 10 years.  Each September, we highlight global pulmonary fibrosis awareness month through our #Breathtember campaigns, we communicate regularly with you via our website, newsletters and social media, we have held awareness stalls in our hospital [world pneumonia day, #Breathtember, organ transplant month, bronchiectasis charity stalls] and at local institutions, including Sainsbury’s where we were Local Charity of the Year.  We even advised on the IPF storyline on Coronation Street in 2019.

8: FUNdraising and FUNdraisers

Breathing Matters has had some amazing and innovative fundraising challenges over the last 10 years.  We started our fundraising journey in 2011 with the first of our charity bike rides in Richmond Park.  After 4 years, we went bigger and moved to the Olympic Velodrome offering a myriad of biking challenges.  One of our star fundraisers, Jane Walker, with the help of many of our supporters, including the Holst Singers, has now raised £30K for bronchiectasis research through the Breathing Matters charity stalls and charity concerts-amazing!  Keeping ahead of the curve, our charity silent discos at the London Steam Museum were a big hit and 2020’s virtual fundraisers were challenging in a different but safe way. But our supporters have come up with some of the BEST ideas, including golf days, head shaves and hairdressing days, jewellery sales, bake sales, house clearance sales, swims/walks/runs/bike rides of all distances, motorbike challenges, spinathons, zumbathons, charity CD, concerts and recitals, going up mountains, falling from planes or bungying, books, boxing, dieting, giving up alcohol or smoking, charity beer, charity dinners, pancake events, husky sled trails and even a tractor run … among many many more!

9: Royal Visit

In 2016, UCL Respiratory was honoured when HRH Princess Anne paid us a visit.  The Princess Royal attended in her official capacity as Chancellor of UCL to officially open the refurbished labs.  During her visit, HRH met with the designers and architects along with our important researchers and scientists, and was treated to a tour of the labs.

The Breathing Matters team was introduced to the Princess Royal and it was a huge honour to have the opportunity to talk with her about the charity and what we’ve accomplished.  HRH asked us to “keep up the good work” and, with your help, we have done just that!

10: Your Support

You, our supporters, have helped us achieve so much.

With YOUR help, at 3 years, we had reached £250K; at 7 years, we had reached £500K; and at 9 years, we reached an incredible £750K – all because of you!

We have decided to keep our charity small so we have little overheads, enabling all your hard-earned fundraising and donations to be funnelled into our vital research.

 

If you would like to help us ‘keep up the good work’ and make a difference, you can do so via our Justgiving Page or email us on breathingmatters@ucl.ac.uk for our bank details.

 

 

ILD Clinical Trials Annual Report

Breathing Matters was established 10 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 10years, 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 also have 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 are about to start to trial a novel therapy in IPF, C21, which we began working even before Breathing Matters was conceived. 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

Main benefactors: 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

Outcomes:

  1. Novel cryobiopsy service, first in the UK including training other centres; presentations at European Respiratory Society (2015 and 2018), British Thoracic Society (2014-6);
  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. Paper submitted 2021 and once accepted will be available on BM website

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 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 (2015-9); American Thoracic Society (2017 and 2019)

Publications:

  • 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.
  • Synergistic application of pulmonary 18F-FDG PET/HRCT and computer-based CT analysis with conventional severity measures to refine current risk stratification in idiopathic pulmonary fibrosis (IPF). Fraioli F, Lyasheva M, Porter JC, Bomanji J, Shortman RI, Endozo R, Wan S, Bertoletti L, Machado M, Ganeshan B, Win T, GroveEur J Nucl Med Mol Imaging. 2019 Sep;46(10):2023-2031s AM.

Next steps:

  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 are applying to the NIHR for a £400,000 grant to carry out this study:
  2. 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 before halting for COVID work, but hope to complete the study and then publish our findings later in 2021 (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:

  • The lung in a cohort of rheumatoid arthritis patients-an overview of different types of involvement and treatment. Duarte AC, Porter JC, Leandro MJ. Rheumatology (Oxford). 2019 Nov 1;58(11):2031-2038. doi: 10.1093/rheumatology/kez177.
  • Autoimmune rheumatic disease IgG has differential effects upon neutrophil integrin activation that is modulated by the endothelium. Khawaja AA, Pericleous C, Ripoll VM, Porter JC, Giles IP. Sci Rep. 2019 Feb 4;9(1):1283. doi: 10.1038/s41598-018-37852-5.
  • Identification of a novel HIF-1α-αMβ2 Integrin-NETosis axis in fibrotic interstitial lung disease. Khawaja AK, Chong DLW, Sahota J, Pericleous C, Ripoli VM, Booth HL, Khan S, Rodriguez-Justo M, Giles IP, Porter JC. Frontiers in Immunology; 2020

Next steps:

  1. To work with a group in Cold Spring Harbour, USA to see if inhibiting NET formation prevents fibrosis.
  2. To see if the presence of NETs in the blood can predict whether patients will develop lung fibrosis.

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.  We are 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.

A TRIAL OF ANTICOAGULATION IN IPF (2016-ONGOING):

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.  Unfortunately, the study had to be put on hold with the COVID pandemic – we have completed 2/3rds of this study and have analysed the results. We have found a small effect and the suggestion is that we look in a few more patients that we will recruit early in the New Year.

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 21 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 5B AND ITS ROLE IN IPF (2019-2022):

Objective: To assess the role of Muc5B in IPF

Main benefactors: NIHR £300,000

Breathing Matters investment: £40,000

Next steps: Further investigations in patients with IPF of the effects of blocking neutrophil activation

Publications:

  • Mucins and their receptors in chronic lung disease. Denneny E, Sahota J, Beatson R, Thornton D, Burchell J, Porter JC. Clinical and Translational Immunology 2020

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.

We have also shown that we can detect very early changes in the CT scans of patients that make too much Muc5B and this might be a very early sign, even before the scan looks abnormal, that these patients are at risk of lung disease.

REMOTE MONITORING OF PATIENTS WITH CHRONIC LUNG DISEASE INCLUDING IPF (2021-2024):

Objective: To assess how feasible it is to monitor patients with chronic lung disease remotely to pick up deterioration in a more timely fashion

Main benefactors: NIHR and overseas PhD sponsor ~£120,000

Breathing Matters investment: £20,000

Next steps: We hope to start the study in early 2021

Mr Malik Althobiani, a respiratory therapist, has been sponsored to undertake a PhD with Professor Jo Porter to investigate the potential of remote monitoring or patients with lung diseases including IPF.  As outpatient appointments have been disrupted because of COVID-19 and access to breathing tests is limited due to the risk of spreading the virus, it is increasingly important to be able to monitor people with lung problems at home.  For people who have developed COVID, monitoring their recovery at home is also important.  Our research is designed to understand if remote monitoring of lung health and disease using wearable sensors, spirometers and pulse oximeters is possible. If so, such wearable sensors could be used to detect worsening of an underlying condition without putting patients in situations with a high risk of exposure to COVID.

Our research will evaluate whether remote monitoring of signs (such as heart rate and oxygen saturation) and symptoms (such as shortness of breath or reduced exercise tolerance) and lung function (such as walk tests and spirometry using wearable sensors and questionnaires is feasible.

If you are a UCLH patient and want to get involved in any of the above studies, please discuss this with your consultant.

 

[Updated, January 2021, J Porter]

 

 

Regular Donors Rock

Did you know, the average person in the UK will give nearly £30,000 to charitable causes throughout their lifetime.  The UK is in the Top 10 most generous countries of the world – almost 70% gave to charity in 2018!

We are so lucky at Breathing Matters to have some amazing supporters who give regular monthly donations to help our vital research.  A small donation goes a very long way at Breathing Matters as we have little overheads which enables your donations to go straight to where it counts – the research itself!  Regular giving provides us with much needed funds that we can rely on and this can help us plan our research projects for the future.

 

We would like to say a MASSIVE THANK YOU to our regular givers – you know who you are!  We depend on your regular gifts – you really do make a difference!

 

At a time when our lungs need help more than ever, if any of our community is interested in supporting Breathing Matters on a regular basis and don’t currently do so, we hope that you will consider pledging a monthly gift to support our research.

To set up a regular gift, all you need to do is:

  1. Download and complete the Standing Order Form here
  2. Hand this in to your bank so they can set up the Standing Order.
  3. Return a copy to Breathing Matters at breathingmatters@ucl.co.uk 

Have a look at our updated pulmonary fibrosis wish list:

£5 – For equipment to take blood from a patient with pulmonary fibrosis/IPF for research.

£10 – For a specialised test to look at novel biomarkers in the blood of IPF patients.

£20 – For staining 4 slides of lung tissue from IPF patients to study novel molecules and link these with molecular imaging scans.

£30 – For growing individual fibroblasts (cells that produce the scarring) in the lab from the lungs of patients with IPF.

£40 – For an hour of a clinical fellow.

£50 – For analysis of a novel molecular imaging (PET) scan in an IPF patient.

£100 – For a spirometer to use at home to track patients without needing them to come into hospital – our remote monitoring project.

£500 – For isolating 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.

£5,000 – For equipment and running costs for a ‘Western Bot’ which allows us to look at abnormal proteins in the lungs of IPF patients.

£50,000 – For 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+) from a medical research charity.

 

Autumn 2020 Newsletter – Out Now

 

For the Autumn 2020 newsletter, please click here

 

 

 

 

Can COVID-19 cause lung fibrosis?

The interstitial lung diseases (ILDs) are a group of over 200 different diseases that may result in lung inflammation or (in the worst case) pulmonary fibrosis (PF). There are many different aetiologies for ILD/PF and in some cases,  we do not know the cause, so called ‘idiopathic’. One of the questions that we at Breathing Matters want to answer is can COVID-19 give you pulmonary fibrosis? There are a few clues that this might be the case. Other coronaviruses such as Severe Acute Respiratory Syndrome (SARS) or Middle East Respiratory Syndrome (MERS) have been reported to cause PF in a small percentage of patients, but of course the numbers of patients affected by SARS-CoV-2, the virus that causes COVID-19, will be much greater so, even if only a small percentage are affected, the numbers may still be very large. The diagnosis of ILD/PF is suggested by a clinical finding of breathlessness and abnormal lung function. The diagnosis is then confirmed with a CT scan of the chest.

Initial studies from China, Italy and the UK have remarkably similar findings. Of patients with COVID-19 discharged from a hospital in China, nearly half had abnormal lung function (Mo X, et al. European Respiratory Journal 55: 2001217, 2020).  Data from Leeds of patients with COVID-19 discharged from hospital showed that the majority (75% of those admitted to intensive care, and 65% of those admitted to the regular wards) still suffered from fatigue at 6 to 8 weeks post discharge. The number suffering from continual breathlessness was also high (70% of those admitted to intensive care, and 45% of those admitted to the ward).  (Halpin S et al. Journal Medical Virology, First published: 30 July 2020, DOI: (10.1002/jmv.26368).  An Italian study from Rome found that at 60 days around 55% of patients were suffering from fatigue and 40% from breathlessness.  It is unclear what is the cause of these high levels of breathlessness, but a study from Austria is following their patients up in more detail at 6, 12 and 24 weeks after discharge. So far, they have found that at 6 weeks 47% of patients are short of breath and this falls to 39% at 12 weeks. In addition, 33% have abnormal lung function suggestive of lung fibrosis, but this falls to 22% at 12 weeks. Of course, to diagnose lung fibrosis requires at CT scan of the chest and they found that CT scans suggested an interstitial lung disease (ILD) or lung fibrosis in 88% falling to 56% at 12 weeks. However, it is also important to know how much of the lung is affected, and many of the studies do not clarify this, but just comment on whether ILD is present or not. The result is that it is hard to know whether these patients had minimal or significant ILD changes on the CT scan. Clearly, Breathing Matters will be looking out for the 24 week data.

Our own experience is that of around 800 patients seen at UCLH with COVID-19, around 8% have persistent or slowly resolving CT changes at 5 months suggestive of interstitial lung involvement. Our main priority at the moment is to analyse our data from the ‘first wave’ to see how common the development of ILD/ PF is in these patients, how much of the lung is affected and what the critical contributory factors are. It may be that this virus and the enormous numbers of patients that have been infected will shed some light on the pathogenesis of other ILD/PF diseases.

We will let you know as soon as we have reviewed all these patients and their scans.