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Out now – our May 2021 Newsletter

May 2021 Newsletter – Top 10 Quiz Answers

Top 10 selling [physical] singles of all time:

  1. White Christmas – Bing Crosby, 1942
  2. Candle in the Wind – Elton John, 1997
  3. In the Summertime – Mungo Jerry, 1970
  4. I Will Always Love You – Whitney Houston, 1992
  5. Rock Around the Clock – Bill Haley & His Comets, 1954
  6. It’s Now or Never – Elvis Presley, 1960
  7. We Are the World – USA for Africa, 1985
  8. If I Didn’t Care – The Ink Spots, 1939
  9. Yes Sir, I Can Boogie – Baccara, 1977
  10. My Heart Will Go On – Celine Dion, 1997

Top 10 selling [digital] singles of all time:

  1. Shape of You – Ed Sheeran, 2017
  2. Despacito – Luis Fonsi featuring Daddy Yankee, 2017
  3. Spotlight – Xiao Zhan, 2020
  4. Work – Rihanna featuring Drake, 2016
  5. Something Just like This – The Chainsmokers and Coldplay, 2017
  6. Perfect – Ed Sheeran, 2017
  7. See You Again – Wiz Khalifa featuring Charlie Puth, 2015
  8. Closer – The Chainsmokers featuring Halsey, 2016
  9. Rolling in the Deep – Adele, 2011
  10. Uptown Funk – Mark Ronson featuring Bruno Mars, 2014

Highest grossing films of all time

  1. Avatar – 2009
  2. Avengers: Endgame – 2019
  3. Titanic – 1997
  4. Star Wars: The Force Awakens – 2015
  5. Avengers: Infinity War –  2018
  6. Jurassic World – 2015
  7. The Lion King – 2019
  8. The Avengers – 2012
  9. Furious 7 – 2015
  10. Frozen II – 2019

Top 10 bestselling fiction books of all time:

  1. Harry Potter and the Philosopher’s Stone, JK Rowling – 1997
  2. The Little Prince, Antoine de Saint-Exupéry – 1943
  3. Dream of the Red Chamber, Cao Xueqin – 18th century
  4. The Hobbit, JRR Tolkien – 1937
  5. And Then There Were None, Agatha Christie – 1939
  6. The Lion, the Witch and the Wardrobe, CS Lewis – 1950
  7. She: A History of Adventure, H Rider Haggard – 1887
  8. The Adventures of Pinocchio (Le avventure di Pinocchio), Carlo Collodi, Italy – 1881
  9. The Da Vinci Code, Dan Brown – 2003
  10. Harry Potter and the Chamber of Secrets, JK Rowling – 1998

Top 10 bestselling author of all time:

  1. William Shakespeare
  2. Agatha Christie
  3. Barbara Cartland
  4. Danielle Steel
  5. Harold Robbins
  6. Georges Simenon
  7. Enid Blyton
  8. Sidney Sheldon
  9. JK Rowling
  10. Gilbert Patten

[Answers taken from Wikipedia]

 

 

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.

 

Help Us Ensure Captain Tom’s Legacy Lives On

On 6 April 2020, Captain Tom Moore set out round his garden to thank our NHS heroes. One hundred laps later, he’d raised an incredible £38.9 million for the NHS Covid-19 appeal.

His simple message of hope – “Tomorrow will be a good day” – inspired millions around the world and brought comfort and joy to so many during the pandemic.

Like many other charities, Breathing Matters has been hugely impacted by the Covid-19 pandemic, with the cancellation of many fundraising events and subsequent loss of income over the last year.

Now it’s your turn to build on that legacy. Friday 30 April would have been his 101st birthday and to honour him and his amazing achievements, The Captain Tom Foundation would love everyone, of all ages and abilities, to take part in the Captain Tom 100.

Do it your way! – Everyone of all ages and abilities is invited to take on a challenge around the number 100 anytime and anywhere over Captain Tom’s birthday weekend – it’s the May Bank Holiday weekend, so you’ll have lots of time.

Here’s How It Works – It’s so simple.  

1. Dream up your 100 challenge. It can be anything you like – here’s some examples:

  • Walk 100 laps of your garden, just like Captain Tom.
  • Run for 100 miles over the weekend, or 100 minutes … or 100 seconds!
  • Bake 100 cakes.
  • Dance/cycle for 100 minutes (1 hour, 40 minutes).
  • Write 100 letters.
  • Swim 100 lengths of the pool.
  • Do 100 keepy-uppies.
  • Walk 100 steps on your hands or do a handstand for 100 seconds.
  • Tell 100 jokes.
  • Do 100 burpies, press-ups or sit-ups.
  • Climb your stairs 100 times.

But the best challenges are the ones you think up yourselves!

2. Take on your Captain Tom 100 challenge any time between Friday 30 April and Monday 3 May 2021.

3. We would humbly ask that you raise funds for Breathing Matters.

Encourage your family and friends to take up the challenge and together we’ll all ensure Captain Tom’s legacy lives on.

Help inspire the next generation of Captain Toms by sharing your pictures and videos on social media, using the official hashtag #CaptainTom100

Captain Tom merchandise – https://www.captaintom.net/captain-tom-shop/

Thank you for keeping Captain Sir Tom’s legacy alive and for helping Breathing Matters.

 

 

 

Our Three Forefathers

There are 3 important gentlemen that were instrumental in creating our charity.  Without them, simply put, there would be no Breathing Matters.

1. Mr Balwant Tamhane

Balwant’s daughter is Manjiry Tamhane – Patron and co-founder of Breathing Matters.

Balwant died from idiopathic pulmonary fibrosis in 2008.  Manjiry says of her father, “He was the life and soul of any party. He was laid back, carefree, open-minded and adventurous. He came from a humble background, but worked and studied hard to provide a better life for his children and went on to become a Partner in a top London architectural firm.”

In the first 72 years of his life, Balwant was rarely ill. He hardly ever went to see a doctor and had never been admitted to hospital. He was fit, active and generally in good shape.

In the summer of 2008, Balwant started to have flu like symptoms, which was unusual for him.  These persisted and his breathing became laboured and wheezy. He was admitted to hospital and placed on oxygen. He was diagnosed with idiopathic pulmonary fibrosis; 5 weeks later he had died.

When the doctors diagnosed IPF, Manjiry went straight to the internet to search for information. Back in 2008, there was very little information available apart from a few obscure research papers from Japan and the US describing various theories and inconclusive results. Manjiry did find a US website called the Pulmonary Fibrosis Foundation, but information in the UK was sorely lacking. She knew at the time something needed to be done about this and went straight to meet with Professor Geoffrey Laurent to see if she could help change this.

2. Professor Geoff Laurent

Professor Laurent was a founding member of Breathing Matters while he was Medical Director of the Centre for Respiratory Research.

Geoff Laurent was an acclaimed scientist and a globally renowned world class researcher on every aspect of respiratory health.  A lover of life, he was blessed with an ability to bring people together in the spirit of collaboration and innovation. His curiosity and intellect were infectious.

Having completed his Bachelor of Science degree with first class honours at the University of Western Australia where he was born, Geoff was driven to seek out the best scientific outcomes from across the world. He studied at the National Heart and Lung Institute/Royal Brompton Hospital London and eventually became Professor and Director of the Centre for Respiratory Research at UCL. Geoff published over 200 articles in international journals of biomedical research and was awarded the European Respiratory Society Presidential Award for his contribution to lung science. In 2006, he was elected Fellow of the Academy of Medical Sciences and President of the British Association for Lung Research.  At UCL, Geoff established himself as one of the world leaders in chronic lung disease research, focusing primarily on lung fibrosis.

When Manjiry Tamhane came to see him in 2009 to talk about how she could help the world of pulmonary fibrosis, Geoff used his collaborative skills and was inspirational in getting together a team to create the first UK based charity that focussed on lung fibrosis and infection research – which was to become Breathing Matters.

We are sad to report that Professor Laurent passed away in 2018, but he is fondly remembered at Breathing Matters and his spirit thrives within us all.

3. Lawrence Matz

Lawrence Matz was an inaugural supporter of Breathing Matters.

Lawrence had a unique gift of being able to make everyone feel as though they were the special one. The life and soul of any party, he would always stand out in the crowd. Nothing was too much for him and for his wife Gloria, his two boys Mark and Adam, family and friends – he would do just about anything for them. He lived every day like it was his last, cramming more into his all too brief time than most of us can expect to achieve in a lifetime. He enriched so many lives with his vibrancy, charm and love.

In 2009, Lawrence was diagnosed with pulmonary fibrosis.  He built up a strong bond of mutual respect with his consultant Jo Porter and wanted to help with her passion of creating a charity for research into pulmonary fibrosis.  During 2010, he regularly met with the Breathing Matters strategy and build team to give his help and advice, and he and his wife Gloria attended our launch in February 2011.

Unfortunately, having been relatively stable for nearly 2 years, Lawrence started to decline very quickly and it was clear that his own lungs would not keep going for much long despite treatment. In July 2011, Lawrence was needing oxygen for 24 hours a day. He was accepted on to the urgent transplant list, but very sadly, a transplant did not become available in time – 6 weeks later he died.  Jo and the team promised to fight on towards a cure for this cruel disease.

As engraved on his memorial stone, Lawrence taught us all the true meaning of courage.  Over the next few years, Lawrence’s loving family and friends raised £45K for Breathing Matters in his memory, and this initiated our fundraising effort towards that promised cure.

 

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.

 

 

Valentine’s 10K – care and share

Join our fun Virtual Valentine’s 10K with your loved one, be it a friend, brother/sister, mum/dad, partner or all your family bubble – a great excuse to get out (legally). Do it in your own way and in your own time.

All you need to do is register – here’s how:

  1. Register here – you will receive a confirmation email to log in to the Secure Charity Portal where you can pay your registration fee [£25 covers the cost of the place and medal only and does not go to the charity].
  2. Breathing Matters will get notification that you have signed up for your challenge and will contact you – or you can contact us directly at breathingmatters@ucl.ac.uk
  3. Set up a Breathing Matters personal fundraising page.  It is up to you how much you want to raise for Breathing Matters; there is no minimum sponsorship limit.
  4. Choose your partner and start training!!!

For more details, click here: https://bit.ly/3rDpJjd

Virtual Valentine's Day Run

Pay half now half later on amazing challenges

We know from talking to our amazing supporters that, no matter how motivated you are, it’s as tough a time as ever to commit to paying a challenge registration fee in one lump sum. To help those supporters that have a charity challenge in mind but who are struggling to get their registration fee together, the new scheme from our partners Global Adventure Challenges is here to help! 

The brand new Challenge Booster Scheme allows adventurers to secure their space on selected treks, cycles and sleds with a payment of just 50% of the registration fee. The remaining 50% will be due by the end of April 2021 – giving you a guaranteed dose of excitement, and something incredible to look forward to – and we all need that at the moment!

This offer ends at midnight on Sunday, 31 January 2021, so now’s the time to take the plunge and secure your space.

There are some truly dream challenges available for 2021 and 2022, including the stunning Northern Lights Trek, the beautiful Cycle Thailand/China/Mallorca, the historically scenic Inca Trail Trek and the woofable Husky Trail Dog Sled.

For a full list of the challenges included in this offer, please click here – please note, most UK & European cycling and trekking challenges are excluded.

 

 

 

 

 

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]

 

 

An Ode to 2020

To mark the end of this difficult year, one of our lovely supporters has written this poem:

 

Wishing all our family and friends a very Happy New Year!!

Goodbye 2020: farewell, adieu,

We’re so glad to see the back of you!

You’ve brought so much hardship, sorrow and pain,

We hope never to see your like again.

You ruined our Holidays and plans this year,

And caused our nation to live mostly in fear.

Tight restrictions and lockdowns made us all see

How important it is just to be free.

We will look back at you in years to come

As a time when we all had to stay at home.

At midnight tonight, when you depart,

Your legacy will be many a broken heart.

And so we rejoice this New Year’s Eve

As dastardly 2020 finally takes its leave!

Here’s to a Happy New Year everyone!!!