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Management and Treatment of IPF – Update

Idiopathic Pulmonary Fibrosis, or IPF, is a growing problem worldwide with increasing numbers of people being affected. There is no cure and treatment options are limited to expensive anti-fibrotic drugs that can slow down the progression of the disease, but not reverse it or stop it completely. These medications have multiple side effects, which can further impact on patients’ quality of life, and only patients with moderate lung function impairment have approved funding to receive them.

The management of patients with IPF is multifaceted and consists of patient education and support, regular outpatient surveillance, symptom relief, pulmonary rehabilitation, annual vaccinations to prevent respiratory infection, supplemental oxygen, managing of comorbidities and ultimately palliative care or, in a minority of patients, referral for lung transplantation.

Following the publication of the ASCEND (A Phase III Trial of Pirfenidone in Patients with Pulmonary Fibrosis) and IMPULSIS (Investigating the Safety and Efficacy of Nintedanib in IPF) trials, two new anti-fibrotic treatments became available for patients who meet stringent National Institute for Health and Care Excellence (NICE) criteria. Pirfenidone and Nintedanib neither cure nor reverse the fibrosis, and have little impact on symptoms, but have been shown to reduce rates of lung function decline and, in the case of Pirfenidone, improve progression-free survival.

Both Nintedanib and Pirfenidone, which are available for use in patients with moderate IPF as defined by an FVC of 50-80% predicted, are associated with side-effects that can affect a patient’s ability to tolerate treatment. Commonly reported side-effects of both are gastrointestinal including diarrhoea, nausea, abdominal pain, and vomiting as well as weight loss and liver enzyme derangement. Additionally, Pirfenidone is associated with skin photosensitivity. These side-effects can be managed with dose reduction, anti-motility agents, taking medication with meals and avoiding sun exposure, but undoubtedly further impact upon health related quality of life.

Update by Dr Emma Denneny

A Gift For Life – A Guide to Making A Will

Leaving Breathing Matters a gift in your Will can help us continue our pioneering research.

This is a guide to preparing, making or amending (adding a codicil to) your Will. It does not constitute legal advice and we advise that you seek professional advice to write or amend your Will. Legacy gifts to registered charities like Breathing Matters, UCLH Charity are exempt from tax, and a solicitor will be able to give advice as to tax planning.

For a Will to be valid, it must be in writing and:

  • Made by a person who is 18 years old or over.
  • Made voluntarily and without pressure from any other person.
  • Made by a person who is of sound mind. This means the person must be fully aware of the nature of the document being written.
  • Signed and dated by the person making the will in the presence of two witnesses, who are not beneficiaries of the will.

If you are making your Will while on the premises of any of the UCLH hospitals or UCL research centres, please note that no member of UCLH or UCL staff can witness your signature if this organisation is a beneficiary. Such an act could invalidate the Will because a witness cannot be a beneficiary.

If you wish to discuss any matters relating to leaving a Legacy to Breathing Matters, please email us at breathingmatters@ucl.ac.uk

 

STEPS TO MAKING A WILL

1: Appoint a solicitor – A list of solicitors who deal with wills and probate in your area can be found on the Law Society website: www.lawsociety.org.uk

2: Information to take to the solicitor – Taking the following information to your solicitor will save time and ensure that all the information is to hand when drafting your Will. Remember to split the value of any joint assets or liabilities.  See checklist below.

  • Your details: Full name, address and post code, telephone number.
  • Value of Your Estate: Up-to-date information as to the value of your estate would assist. Things to think about would be: house, antiques/paintings, household contents, vehicles, jewellery, savings and investments, insurance policies, pensions, endowments and any other assets you would like included.
  • Liabilities: This will include any debts, ie. mortgages, loans, credit card balances, credit agreements, overdrafts, tax bills and any other outstanding debts.
  • Executors – The names and contact details of, ideally, two executors (see below for more information on executors).

3: Your wishes and who you wish to benefit – A Will ensures your wishes are carried out and will save problems for your loved ones who are left behind. Those who benefit are your “beneficiaries”. They may include family, friends and any causes that you would like to leave a Legacy to. The solicitor will require their contact details and how your estate is to be divided.

4: Leaving a Legacy to Breathing Matters – If you wish to leave a gift to us, this is called a “Bequest”. It helps if a Bequest is not too exact as types of equipment or names of treatments may change over time. If a Bequest is too specific, it may mean that we will not be able to meet all the conditions in the future and the Legacy may not be used to help with new research projects.

There are three main types of Bequests that you can choose to leave Breathing Matters a share of your estate:

Pecuniary Bequest: This is a gift of a fixed sum of money, and we recommend the following wording: “I give the sum of £.… (amount in figures and words) to Breathing Matters, UCLH Charity (registered charity no.1165398, 5th Floor East, 250 Euston Road, London NW1 2PG) to carry out research work and I direct that the receipt of a duly authorised officer of UCLH Charity shall be a valid and appropriate form of discharge.”.

Residuary Bequest: A gift made of the remainder/residual of your estate after all other beneficiaries are provided for and any debt, tax and administration costs have been met. We recommend the following wording: “I give all (or a % share) of the residue of my estate to Breathing Matters, UCLH Charity (registered charity no 1165398, 5th Floor East, 250 Euston Road, London NW1 2PG) to carry out research work and I direct that the receipt of a duly authorised officer of UCLH Charity shall be a valid and appropriate form of discharge.”.

Specific Bequest: This is a particular item or asset left as a gift. An example would be a piece of jewellery, furniture or painting. We recommend the following wording: “I give to Breathing Matters, UCLH Charity (registered charity no 1165398, 5th Floor East, 250 Euston Road, London NW1 2PG) to carry out research work and I direct that the receipt of a duly authorised officer of UCLH Charity shall be a valid and appropriate form of discharge.”.

It is also a good idea to include the following wording at the end of the Bequest: “If, at my death, any charity named as a beneficiary in this Will or any codicil hereto has changed its name or amalgamated with or transferred its assets to another body, then my executors shall give effect to any gift made to such charity as if it had been made to the body in its changed name or to the body which results from such amalgamation or to which such transfer has been made.”.

5: Who will carry out your Will? – In your Will, you appoint “executors”. They are appointed to carry out your instructions left in your Will. It is advisable to have two executors. The solicitor will need details of your executors – who can be family, friends and/or professionals. Executors can be beneficiaries to the Will. It is usual to have someone who would understand financial matters. It may help to add a side letter, setting out your instructions to the executors.

6: Signing of a Will – Until the Will has been signed, it is not valid. It must be witnessed and those witnesses can not be beneficiaries under the Will.

 

AMENDING AND UPDATING YOUR WILL

It is always a good idea to review your Will after any major life changes for example, getting married, having a child, divorced or moving house. A change to your will is called a “codicil”.

A Codicil to an Existing Will

A codicil is a minor amendment or change to your Will.   Sample wording as follows: “I [name] of [address] DECLARE THIS to be a codicil to my last Will

  1. In addition to the provisions of my said Will, I GIVE to Breathing Matters, UCLH Charity (registered charity no 1165398, 5th Floor East, 250 Euston Road, London NW1 2PG) for its research purposes

EITHER:

  1. a) the sum of £……, or
  2. b) [all or a specified %] of the residue of my estate
  3. IN WITNESS whereof, I have hereunto set my hand this [day] day of [date] SIGNED as a codicil in the presence of: (space for the names, addresses and signatures of witnesses”.

A solicitor can assist you with the final wording.

 

If you wish to discuss any matters relating to leaving a Legacy to Breathing Matters, please email us at breathingmatters@ucl.ac.uk

You can help us make a difference!

 

 

 

Sign up for a great September challenge; deadline for registration 9.8.19

Breathing Matters has places at some amazing fun and adventurous challenges coming  up – BUT YOU NEED TO REGISTER BY FRIDAY 9th AUGUST 2019!!!

Descente London Duathlon events, Richmond Park, Sunday, 8th September 2019

This is the world’s biggest duathlon on closed roads in beautiful Richmond Park in South West London.

Our places are cheaper than those advertised on their site:

Their price Our price Fundraising
Full £88 £80 +£250
Half £82 £80 +£250
Relay £139 £100 +£250
Ultra £144.50 £100 +£250

We simply ask that you raise a further £250 for Breathing Matters per participant.

More info on the event is at https://londonduathlon.com/

 

Finsbury Park Rough Runner – a Fun Obstacle Course for all Levels, Saturday 7th September 2019 and Sunday 8th September 2019

The Rough Runner is a unique obstacle course challenge; bounce on big balls and climb your way through the extraordinarily fun course before taking on the energy sapping travelator.

You can choose from the 5K or 10K course.

What others say:

  • “Loved every second of it! The course was fun and not all the obstacles were challenging so overall was a very fun experience!”– Chelsie
    “Had a very fun time for our first even like this, even though we don’t run a lot it was a lot of fun and wasn’t too competitive.” – Brandon

Places with Breathing Matters are £40 and we ask that you raise at least £60 per runner.

If you want to register for any of these challenges, email breathingmatters@ucl.ac.uk but don’t delay registration deadline is 9th August 2019.

 

Get Out of Breath for #Breathtember

 

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 colourful or musical 5K/10K run or walk
  • Singing until you are out of breath
  • Walking over the wondrous London bridges
  • Blowing bubbles … or windmills!
  • Skydiving
  • 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 see the term ‘#Breathtember’.

Follow us on Twitter for further details: @Breathingmatter 

twitter

 

 

Fireworks – Have your say

The House of Commons Petitions Committee is currently looking at the use of fireworks following a number of petitions about fireworks over the last three years.  A recent petition signed by nearly 300,000 people calls for a ban on the sale of fireworks to the public, and for fireworks displays to be restricted to licenced venues.

If you have a respiratory condition and have been impacted by fireworks, then you might be interested in attending the Petitions Committee on Fireworks on Tuesday, 2nd July 2019 at 7pm at Westminster.

At this event, you will be asked how fireworks affects your respiratory condition.  The Committee is keen to hear about people’s experiences and thoughts on potential solutions to addressing health concerns around the use of fireworks. Your views will help shape the Committee’s thinking on this topic. 

For more information and to register your interest in attending this event, please visit https://www.eventbrite.co.uk/e/petitions-committee-fireworks-event-2-july-tickets-62221407906

 

 

 

Tips for Surviving Hay Fever

Itchy eyes, runny noses, sneezing … oh no, it’s Hay Fever season again!!! 

Fear not, this article will help you prepare.

What is Hay Fever?

Hay fever (seasonal allergic rhinitis) is an allergy to pollen. The pollen season separates into three main sections:

  1. Tree pollen – late March to mid-May.
  2. Grass pollen – mid-May to July.
  3. Weed pollen – end of June to September

To get the latest pollen forecast, view the Met Office weather map which provides a UK forecast of the pollen count and provides any hay fever sufferers with an early warning.

Who Gets Hay Fever?

Hay fever is very common. It affects about 2 in 10 people in the UK. It often first develops in school-age children and during the teenage years, but may start even later in life. Hay fever tends to run in families. You are also more likely to develop hay fever if you already have asthma or eczema. A tendency to these atopic illnesses can run in families.

Hay Fever Symptoms

  • Common symptoms include sneezing, runny or blocked nose, itchy eyes, mouth and throat. Less common are headaches and hives.
  • Asthma symptoms – such as wheeze and breathlessness, may get worse if you already have asthma. Some people have asthma symptoms only during the hay fever season.
  • The symptoms may be so bad in some people that they can affect sleep, interfere with school and examinations, or interfere with work.

Hay Fever PreventionHay Fever Fact

Although it is very difficult to avoid exposure to pollen, there are a number of measures you can take that will help you to minimise exposure and ease the severity of your hay fever symptoms. Following these steps may help provide some relief from your symptoms:

  • Keep windows closed when at home and overnight. Most pollen is released in the early morning and falls to ground level in the evenings when the air cools.
  • When outdoors, wear wrap-around sunglasses to keep pollen out of your eyes. For any outdoor tasks, such as gardening, hay fever sufferers should wear a mask.
  • Some people find smearing your nostrils with vaseline to capture the pollen helps.
  • Avoid drying clothes outside when pollen counts are high. If you do, shake items before bringing them inside.
  • Keep car windows closed when driving and fit a pollen filter to reduce the impact of pollen spores. Ensure your air conditioning is set to recirculate the air inside.
  • When indoors: vacuum regularly and clean surfaces with a damp cloth. The British Allergy Foundation have a list of ‘approved’ anti-allergen vacuums that help to filter out pollen on their website, allergyuk.org.
  • Avoid bringing fresh flowers indoors.
  • Don’t allow smoking in the house as this will irritate the lining of your nose, eyes, throat and airways, making your hay fever symptoms worse.
  • After being outside, shower and wash your hair to remove pollen.
  • Grooming and washing pets more frequently at this time of year, to remove trapped pollen from their coats, can be helpful too. Pollen levels tend to be higher on warm, dry days.
  • The Metereological office offers a useful five day pollen forecast (metoffice.gov.uk), so you can prepare for high pollen count days.

Hay fever sufferers can benefit from a wide range of non-drowsy medication which can be prescribed by your GP, or alternatively purchased over the counter from your local pharmacy.  Starting this medication two weeks before the season can prepare your body.

Your GP or hospital consultant can help you find the most appropriate treatment for you especially if you also have asthma and other allergies. Treatments include antihistamine tablets or nasal sprays, corticosteroid nasal sprays and drops, nasal decongestants, eye drops, immunotherapy, and alternative therapies.

Treatment for Severe Symptoms

Rarely, a short course of steroid tablets is prescribed for a week or so. For example, for students sitting examinations,   A short course is usually safe.   However, you should not take steroid tablets for long periods to treat hay fever, as serious side-effects may develop.

Dr Harsha Kariyawasam, Consultant Allergist at the Royal ENT Hospital says, “‘The most important step that an individual with allergic rhinitis should do is to have an accurate diagnosis. The exact allergen provoking symptoms should be identified. Where possible, allergen avoidance measures should be instigated. Treatment with medication, introduced in a step wise manner should also be undertaken. We are getting very good treating allergic rhinitis and there are several effective new treatments available. Allergy desentisation by a trained allergist is possible and there are several exciting vaccines either in practice or in development. Everyone deserves to enjoy spring and summer!”.

Visit our new Justgiving page

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!

 

Answers to Lung ‘True or False’ Winter 2019 Newsletter Quiz

 

Q: True or False: The left lung has three lobes and the right lung has two lobes?

A: The answer is FALSE. The right lung has THREE lobes and the left lung has TWO lobes

 

Q: True or False: As you age, your lungs hold less air?

A: The answer is TRUE. Your lungs are at their peak with you’re in your 20s to mid-30s.  After that, your diaphragm gets weaker and your lung tissue can’t stretch as well.

 

Q: True or False: At the time of birth, a baby’s lungs are filled with fluid?

A: The answer is TRUE.  At the time of birth, a baby’s lungs are not inflated and are actually filled with a fluid that is secreted by the lungs. When the baby moves out of the birth canal, a sudden change in environment and temperature triggers the first breath which usually takes place 10 seconds after the baby is delivered from the birth canal.

 

Q: True or False: Our lungs can never fully deflate?

A: The answer is TRUE. No matter how hard we exhale, our lungs will always retain one litre of air in the airways. This makes the lungs only human organs that can float on water.

 

Q: True or False: The rib cage helps the lungs to breathe?

A: The answer is FALSE. The diaphragm helps the lungs to breathe.  The diaphragm, located below the lungs, is the major muscle of respiration. It is a large, dome-shaped muscle that contracts rhythmically and continually, and most of the time, involuntarily. Upon inhalation, the diaphragm contracts and flattens and the chest cavity enlarges. This contraction creates a vacuum, which pulls air into the lungs. Upon exhalation, the diaphragm relaxes and returns to its domelike shape, and air is forced out of the lungs.

 

 

Winter 2019 Newsletter

ILD Clinical Trials to Date – Updated Report

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

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), 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)

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.

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 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.