̽��ֱ�� of Cambridge - Royal Papworth Hospital NHS Foundation Trust

One in 3,000 people at risk of punctured lung from faulty gene – almost 100 times higher than previous estimate

cjb250 — Mon, 07 Apr 2025 23:01:05 +0000

̽��ֱ��gene in question, FLCN, is linked to a condition known as Birt-Hogg-Dubé syndrome, symptoms of which include benign skin tumours, lung cysts, and an increased risk of kidney cancer.

In a study published today in the journal Thorax, a team from the ̽��ֱ�� of Cambridge examined data from UK Biobank, the 100,000 Genomes Project, and East London Genes & Health – three large genomic datasets encompassing more than 550,000 people.

They discovered that between one in 2,710 and one in 4,190 individuals carries the particular variant of FLCN that underlies Birt-Hogg-Dubé syndrome. But curiously, whereas patients with a diagnosis of Birt-Hogg-Dubé syndrome have a lifetime risk of punctured lung of 37%, in the wider cohort of carriers of the genetic mutation this was lower at 28%. Even more striking, while patients with Birt-Hogg-Dubé syndrome have a 32% of developing kidney cancer, in the wider cohort this was only 1%.

Punctured lung – known as pneumothorax – is caused by an air leak in the lung, resulting in painful lung deflation and shortness of breath. Not every case of punctured lung is caused by a fault in the FLCN gene, however. Around one in 200 tall, thin young men in their teens or early twenties will experience a punctured lung, and for many of them the condition will resolve itself, or doctors will remove air or fluid from their lungs while treating the individual as an outpatient; many will not even know they have the condition.

If an individual experiences a punctured lung and doesn’t fit the common characteristics – for example, if they are in their forties – doctors will look for tell-tale cysts in the lower lungs, visible on an MRI scan. If these are present, then the individual is likely to have Birt-Hogg-Dubé syndrome.

Professor Marciniak is a researcher at the ̽��ֱ�� of Cambridge and an honorary consultant at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust and Royal Papworth Hospital NHS Foundation Trust. He co-leads the UK’s first Familial Pneumothorax Rare Disease Collaborative Network, together with Professor Kevin Blyth at Queen Elizabeth ̽��ֱ�� Hospital and ̽��ֱ�� of Glasgow. ̽��ֱ��aim of the Network is to optimise the care and treatment of patients with rare, inherited forms of familial pneumothorax, and to support research into this condition.

Professor Marciniak said: “If an individual has Birt-Hogg-Dubé syndrome, then it’s very important that we’re able to diagnose it, because they and their family members may also be at risk of kidney cancer.

“ ̽��ֱ��good news is that the punctured lung usually happens 10 to 20 years before the individual shows symptoms of kidney cancer, so we can keep an eye on them, screen them every year, and if we see the tumour it should still be early enough to cure it.”

Professor Marciniak says he was surprised to discover that the risk of kidney cancer was so much lower in carriers of the faulty FLCN gene who have not been diagnosed with Birt-Hogg-Dubé syndrome.

“Even though we’ve always thought of Birt-Hogg-Dubé syndrome as being caused by a single faulty gene, there’s clearly something else going on,” Professor Marciniak said. “ ̽��ֱ��Birt-Hogg-Dubé patients that we've been caring for and studying for the past couple of decades are not representative of when this gene is broken in the wider population. There must be something else about their genetic background that’s interacting with the gene to cause the additional symptoms.”

̽��ֱ��finding raises the question of whether, if an individual is found to have a fault FLCN gene, they should be offered screening for kidney cancer. However, Professor Marciniak does not believe this will be necessary.

“With increasing use of genetic testing, we will undoubtedly find more people with these mutations,” he said, “but unless we see the other tell-tale signs of Birt-Hogg-Dubé syndrome, our study shows there's no reason to believe they’ll have the same elevated cancer risk.”

̽��ֱ��research was funded by the Myrovlytis Trust, with additional support from the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Katie Honeywood, CEO of the Myrovlytis Trust, said: " ̽��ֱ��Myrovlytis Trust are delighted to have funded such an important project. We have long believed that the prevalence of Birt-Hogg-Dubé syndrome is far higher than previously reported. It highlights the importance of genetic testing for anyone who has any of the main symptoms associated with BHD including a collapsed lung. And even more so the importance of the medical world being aware of this condition for anyone who presents at an emergency department or clinic with these symptoms. We look forward to seeing the impact this projects outcome has on the Birt-Hogg-Dubé and wider community."

Reference
Yngvadottir, B et al. Inherited predisposition to pneumothorax: Estimating the frequency of Birt-Hogg-Dubé syndrome from genomics and population cohorts. Thorax; 8 April 2025; DOI: 10.1136/thorax-2024-221738

As many as one in 3,000 people could be carrying a faulty gene that significantly increases their risk of a punctured lung, according to new estimates from Cambridge researchers. Previous estimates had put this risk closer to one in 200,000 people.

If an individual has Birt-Hogg-Dubé syndrome, then it’s very important that we’re able to diagnose it, because they and their family members may also be at risk of kidney cancer

Stefan Marciniak

wildpixel (Getty Images)

Chest pain

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Routine asthma test more reliable in the morning and has seasonal effects

cjb250 — Wed, 12 Mar 2025 00:01:06 +0000

Using real world data from 1,600 patients, available through a database created for speeding up research and innovation, the team also found that its reliability differs significantly in winter compared to autumn.

Asthma is a common lung condition that can cause wheezing and shortness of breath, occasionally severe. Around 6.5% of people over six years old in the UK are affected by the condition. Treatments include the use of inhalers or nebulisers to carry medication into the lungs.

̽��ֱ��majority of asthma attacks occur at nighttime or early in the morning. Although this may in part be due to cooler nighttime air and exposure to dust mites and allergens, it also suggests that circadian rhythms – our ‘body clocks’ – likely play a role.

Researchers at the Victor Phillip Dahdaleh Heart and Lung Research Institute, a collaboration between the ̽��ֱ�� of Cambridge and Royal Papworth Hospital NHS Foundation Trust (RPH), wanted to explore whether these circadian rhythms may also have an impact on our ability to diagnose asthma, using routinely performed clinical testing.

Typically, people with suspected asthma will be offered a spirometry test, which involves taking a deep breath in, then breathing out hard and fast for as long as possible into a tube to assess lung function. They will then be administered the drug salbutamol via an inhaler or nebuliser, and shortly afterwards retake the spirometry test.

Salbutamol works by opening up the airways, so a positive test result – that is, a difference in readings between the initial and follow-up spirometry tests – means that the airways must have been narrower or obstructed to begin with, suggesting that the patient could have asthma.

Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust (CUH) has recently set up the Electronic Patient Record Research and Innovation (ERIN) database so that researchers can access patient data in a secure environment to help in their research and speed up improvements in patient care.

Using this resource, the Cambridge team analysed data from 1,600 patients referred to CUH between 2016 and 2023, adjusted for factors such as age, sex, body mass index (BMI), smoking history, and the severity of the initial impairment in lung function.

In findings published today in Thorax, the researchers found that starting at 8.30am, with every hour that passed during the working day, the chances of a positive response to the test – in other words, the patient’s lungs responding to treatment, suggesting that they could have asthma – decreased by 8%.

Dr Ben Knox-Brown, Lead Research Respiratory Physiologist at RPH, said: “Given what we know about how the risk of an asthma attack changes between night and day, we expected to find a difference in how people responded to the lung function test, but even so, we were surprised by the size of the effect.

“This has potentially important implications. Doing the test in the morning would give a more reliable representation of a patient's response to the medication than doing it in the afternoon, which is important when confirming a diagnosis such as asthma.”

̽��ֱ��researchers also discovered that individuals were 33% less likely to have a positive result if tested during autumn when compared to those tested during winter.

Dr Akhilesh Jha, a Medical Research Council Clinician Scientist at the ̽��ֱ�� of Cambridge and Honorary Consultant in Respiratory Medicine at CUH, said that there may be a combination of factors behind this difference.

“Our bodies have natural rhythms – our body clocks,” Jha said. “Throughout the day, the levels of different hormones in our bodies go up and down and our immune systems perform differently, for example. Any of these factors might affect how people respond to the lung function test.

“ ̽��ֱ��idea that the time of day, or the season of the year, affects our health and how we respond to treatments is something we’re seeing increasing evidence of. We know, for example, that people respond differently to vaccinations depending on whether they’re administered in the morning or afternoon. ̽��ֱ��findings of our study further support this idea and may need to be taken into account when interpreting the results of these commonly performed tests.”

Reference
Knox-Brown, B et al. ̽��ֱ��effect of time of day and seasonal variation on bronchodilator responsiveness: ̽��ֱ��SPIRO-TIMETRY study. Thorax; 12 March 2025; DOI: 10.1136/thorax-2024-222773

A lung function test used to help diagnose asthma works better in the morning, becoming less reliable throughout the day, Cambridge researchers have found.

Throughout the day, the levels of different hormones in our bodies go up and down and our immune systems perform differently. Any of these factors might affect how people respond to the lung function test

Akhilesh Jha

Koldunov (Getty Images)

Man testing breathing function by spirometry - stock photo

Yes

Cambridge and GSK announce new five-year collaboration aiming for improved outcomes for patients with hard-to-treat kidney and respiratory diseases

skbf2 — Sun, 20 Oct 2024 23:01:00 +0000

̽��ֱ��Cambridge-GSK Translational Immunology Collaboration (CG-TIC) combines ̽��ֱ�� and GSK expertise in the science of the immune system, AI and clinical development with access to patients and their data provided by Cambridge ̽��ֱ�� Hospitals.
GSK is investing more than £50 million in CG-TIC, further strengthening Cambridge’s position as Europe’s leading life sciences cluster.

GSK plc is making this investment to establish the Cambridge-GSK Translational Immunology Collaboration (CG-TIC), a five-year collaboration with the ̽��ֱ�� of Cambridge and Cambridge ̽��ֱ�� Hospitals. ̽��ֱ��collaboration is focused on understanding the onset of a disease, its progression, how patients respond to therapies and on developing biomarkers for rapid diagnosis. Ultimately, the goal is to trial more effective, personalised medicines.

̽��ֱ��collaboration will focus on kidney and respiratory diseases, both of which affect large numbers of people worldwide. Kidney disease is estimated to affect 850 million people (roughly 10% of the world’s population) (International Society of Nephrology) and chronic respiratory diseases around 545 million ( ̽��ֱ��Lancet).

Many types of kidney disease remain poorly understood and treatments, where they exist, tend to have limited efficacy. Chronic kidney disease is particularly unpleasant and debilitating for patients, often leading to end-stage disease. Treatments such as transplant and dialysis involve complex medical regimes and frequent hospital visits, making effective prevention and treatment the aim.

To make progress in treating these challenging disease areas, CG-TIC will apply an array of new techniques, including the use of cutting-edge single cell technologies to characterise how genes are expressed in individual cells. AI and machine learning have a critical role to play in transforming how data is combined and interrogated.

Using these techniques, the ambition is to be able to initiate new studies and early phase trials of new therapies for a number of hard-to-treat diseases which affect the kidneys. ̽��ֱ��same techniques will be applied to respiratory diseases and findings will be shared across the disease areas potentially to help identify and share better treatments across these different targets.

Peter Kyle, Secretary of State for Science, Innovation and Technology, welcomed the collaboration: " ̽��ֱ��UK's life sciences industry is thriving, driving innovation and improving lives. This collaboration between GSK and the ̽��ֱ�� of Cambridge demonstrates our country's leading research and development capabilities.

“By focusing on cutting-edge research and harnessing the power of AI, this has the potential to advance the treatment of immune-related diseases, which could benefit patients both here in the UK and internationally. It's a clear example of how collaboration between industry, academia, and healthcare can deliver tangible results and strengthen the UK's position in healthcare innovation."

Tony Wood, Chief Scientific Officer, GSK, added: “Collaboration is at the heart of scientific progress and is fundamental to how we do R&D at GSK. We’re excited to build on our existing work with the ̽��ֱ�� of Cambridge to further this world-leading scientific and technological capability in the UK. By bringing together Cambridge’s expertise and our own internal capabilities, including understanding of the immune system and the use of AI to accelerate drug development, we have an opportunity to help patients struggling with complex disease.”

̽��ֱ��aim of CG-TIC is to improve outcomes for patients and Cambridge provides a unique environment in which to involve them, with Cambridge ̽��ֱ�� Hospitals playing a pivotal role in the collaboration and Royal Papworth Hospital NHS Foundation Trust, the UK’s leading heart and lung hospital, a likely future partner.

Home to the hospitals and to much of the collaboration’s research activity, the Cambridge Biomedical Campus provides a unique environment where academia, industry and healthcare can come together and where human translational research is supported by the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre.

Professor Deborah Prentice, Vice-Chancellor of the ̽��ֱ�� of Cambridge, said: “ ̽��ֱ�� ̽��ֱ�� sits at the heart of Europe’s leading life sciences cluster, where excellent research and the NHS’s clinical resources combine with the talent generated by the many innovative bioscience companies that call Cambridge home. Through this very important collaboration with GSK, Cambridge will be able to drive economic growth for the UK while improving the health of people in this country and around the world.”

Roland Sinker, CEO of Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, also welcomed the collaboration, saying: “We are very excited to be part of this important partnership, which is another example of Cambridge experts working together to develop transformational new therapies, and use existing ones more precisely, to improve outcomes for patients with chronic and debilitating conditions.”

̽��ֱ��Cambridge-GSK Translational Immunology Collaboration will be co-led by Nicolas Wisniacki, VP, Clinical Research Head, GSK (above left) and David Thomas, Professor of Renal Medicine, ̽��ֱ�� of Cambridge and principal investigator at the Cambridge Institute for Therapeutic Immunology and Infectious Diseases.

̽��ֱ��ambition of the partnership is to treat immune-related diseases more precisely with existing therapies and to rapidly develop new ones.

̽��ֱ��UK's life sciences industry is thriving, driving innovation and improving lives. This collaboration between GSK and the ̽��ֱ�� of Cambridge demonstrates our country's leading research and development capabilities.

Peter Kyle, Secretary of State for Science, Innovation and Technology

StillVision

David Thomas, Professor of Renal Medicine, ̽��ֱ�� of Cambridge and Dr Nicolas Wisniacki, VP, Clinical Research Head, GSK

Yes

Scientists map how deadly bacteria evolved to become epidemic

cjb250 — Thu, 04 Jul 2024 18:00:53 +0000

P. aeruginosa is responsible for over 500,000 deaths per year around the world, of which over 300,000 are associated with antimicrobial resistance (AMR). People with conditions such as COPD (smoking-related lung damage), cystic fibrosis (CF), and non-CF bronchiectasis, are particularly susceptible.

How P. aeruginosa evolved from an environmental organism into a specialised human pathogen was not previously known. To investigate this, an international team led by scientists at the ̽��ֱ�� of Cambridge examined DNA data from almost 10,000 samples taken from infected individuals, animals, and environments around the world. Their results are published today in Science

By mapping the data, the team was able to create phylogenetic trees – ‘family trees’ – that show how the bacteria from the samples are related to each other. Remarkably, they found that almost seven in ten infections are caused by just 21 genetic clones, or ‘branches’ of the family tree, that have rapidly evolved (by acquiring new genes from neighbouring bacteria) and then spread globally over the last 200 years. This spread occurred most likely as a result of people beginning to live in densely-populated areas, where air pollution made our lungs more susceptible to infection and where there were more opportunities for infections to spread.

These epidemic clones have an intrinsic preference for infecting particular types of patients, with some favouring CF patients and other non-CF individuals. It turns out that the bacteria can exploit a previously unknown immune defect in people with CF, allowing them to survive within macrophages. Macrophages are cells that ‘eat’ invading organisms, breaking them down and preventing the infection from spreading. But a previously-unknown flaw in the immune systems of CF patients means that once the macrophage ‘swallows’ P. aeruginosa, it is unable to get rid of it.

Having infected the lungs, these bacteria then evolve in different ways to become even more specialised for a particular lung environment. ̽��ֱ��result is that certain clones can be transmitted within CF patients and other clones within non-CF patients, but almost never between CF and non-CF patient groups.

Professor Andres Floto, Director of the UK Cystic Fibrosis Innovation Hub at the ̽��ֱ�� of Cambridge and Royal Papworth Hospital NHS Foundation Trust, and senior author of the study said: “Our research on Pseudomonas has taught us new things about the biology of cystic fibrosis and revealed important ways we might be able to improve immunity against invading bacteria in this and potentially other conditions.

“From a clinical perspective, this study has revealed important information about Pseudomonas. ̽��ֱ��focus has always been on how easily this infection can spread between CF patients, but we’ve shown that it can spread with worrying ease between other patients, too. This has very important consequences for infection control in hospitals, where it’s not uncommon for an infected individual to be on an open ward with someone potentially very vulnerable.

“We are incredibly lucky at Royal Papworth Hospital where we have single rooms and have developed and evaluated a new air-handling system to reduce the amount of airborne bacteria and protect all patients.”

Dr Aaron Weimann from the Victor Phillip Dahdaleh Heart & Lung Research Institute at the ̽��ֱ�� of Cambridge, and first author on the study, said: “It’s remarkable to see the speed with which these bacteria evolve and can become epidemic and how they can specialise for a particular lung environment. We really need systematic, pro-active screening of all at risk patient groups to detect and hopefully prevent the emergence of more epidemic clones.”

̽��ֱ��research was funded by Wellcome and the UK Cystic Fibrosis Trust.

Reference
Weimann, A et al. Evolution and host-specific adaptation of Pseudomonas aeruginosa. Science; 4 July 2024; DOI: 10.1126/science.adi0908

Pseudomonas aeruginosa – an environmental bacteria that can cause devastating multidrug-resistant infections, particularly in people with underlying lung conditions – evolved rapidly and then spread globally over the last 200 years, probably driven by changes in human behaviour, a new study has found.

It’s remarkable to see the speed with which these bacteria evolve and can become epidemic and how they can specialise for a particular lung environment

Aaron Weimann

engin akyurt

A man with a respirator on his face

Yes

Licence type:

Public Domain

Long COVID linked to persistently high levels of inflammatory protein: a potential biomarker and target for treatments

ta385 — Wed, 21 Feb 2024 18:45:00 +0000

A ̽��ֱ�� of Cambridge-led study identifies the protein interferon gamma (IFN-γ) as a potential biomarker for Long COVID fatigue and highlights an immunological mechanism underlying the disease, which could pave the way for the development of much needed therapies, and provide a head start in the event of a future coronavirus pandemic.

̽��ֱ��study, published today in Science Advances, followed a group of patients with Long COVID fatigue for over 2.5 years, to understand why some recovered and others did not.

Long COVID continues to affect millions of people globally and is placing a major burden on health services. An estimated 1.9 million people in the UK alone (2.9% of the population) were experiencing self-reported Long COVID as of March 2023, according to the ONS. Fatigue remains by far the most common and debilitating symptom and patients are still waiting for an effective treatment.

̽��ֱ��study shows that initial infection with SARS-CoV-2 triggers production of the antiviral protein IFN-γ, which is a normal reaction from the immune system. For most people, when their infection clears, COVID-19 symptoms cease and production of this protein stops, but the researchers found that high levels of IFN-γ persisted in some Long COVID patients for up to 31 months.

“We have found a potential mechanism underlying Long COVID which could represent a biomarker – that is, a tell-tale signature of the condition. We hope that this could help to pave the way to develop therapies and give some patients a firm diagnosis,” said co-author, Dr Benjamin Krishna, from the Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID).

̽��ֱ��research began in 2020 when Dr Nyarie Sithole (Hughes Hall) set up a Long COVID clinic in Cambridge’s Addenbrooke’s Hospital, where he started collecting blood samples from patients and set about studying their immunology. Sithole soon enlisted the support of Dr Benjamin Krishna and Dr Mark Wills from the ̽��ֱ�� of Cambridge’s Department of Medicine.

“When the clinic started, a lot of people didn't even believe Long COVID was real,” Dr Sithole said. “We are indebted to all the patients who volunteered for this study, without whose support and participation we would obviously not have accomplished this study”.

̽��ֱ��team studied 111 COVID-confirmed patients admitted to Addenbrooke’s Hospital CUH, Royal Papworth Hospital and Cambridge and Peterborough NHS Foundation Trusts at 28 days, 90 days and 180 days following symptom onset. Between August 2020 and July 2021, they recruited 55 Long COVID patients – all experiencing severe symptoms at least 5 months after acute COVID-19 – attending the Long COVID clinic at Addenbrooke’s.

̽��ֱ��researchers analysed blood samples for signs of cytokines, small proteins crucial to the functioning of immune system cells and blood cells. They found that the white blood cells of individuals infected with SARS-CoV-2 produced IFN-γ, a pro inflammatory molecule, and that this persisted in Long COVID patients.

Dr Krishna said: “Interferon gamma can be used to treat viral infections such as hepatitis C but it causes symptoms including fatigue, fever, headache, aching muscles and depression. These symptoms are all too familiar to Long COVID patients. For us, that was another smoking gun.”

By conducting ‘cell depletion assays’, the team managed to identify the precise cell types responsible for producing IFN-γ. They pinpointed immune cells known as CD8+ T cells but found that they required contact with another immune cell type: CD14+ monocytes.

Previous studies have identified IFN-γ signatures using different approaches and cohorts, but this study’s focus on fatigue revealed a much stronger influence. Also, while previous studies have noticed IFN-y levels rising, they have not followed patients long enough to observe when they might drop back down.

̽��ֱ��Cambridge team followed its Long COVID cohort for up to 31 months post-infection. During this follow up period, over 60% of patients experienced resolution of some, if not all, of their symptoms which coincided with a drop in IFN-γ.

Vaccination helping Long COVID patients

̽��ֱ��team measured IFN-γ release in Long COVID patients before and after vaccination and found a significant decrease in IFN-γ post vaccination in patients whose symptoms resolved.

“If SARS-CoV-2 continues to persist in people with Long COVID, triggering an IFN-γ response, then vaccination may be helping to clear this. But we still need to find effective therapies,” Dr Krishna said.

“ ̽��ֱ��number of people with Long COVID is gradually falling, and vaccination seems to be playing a significant role in that. But new cases are still cropping up, and then there is the big question of what happens when the next coronavirus pandemic comes along. We could face another wave of Long COVID. Understanding what causes Long COVID now could give us a crucial head start.”

Microclotting

Some well-publicised previous studies have proposed microclotting as a principle cause of Long COVID. While not ruling out a role of some kind, these new findings suggest that microclotting cannot be the only or the most significant cause.

Classifying Long COVID

This study argues that the presence of IFN-γ could be used to classify Long COVID into subtypes which could be used to personalise treatment.

“It’s unlikely that all the different Long COVID symptoms are caused by the same thing. We need to differentiate between people and tailor treatments. Some patients are slowly recovering and there are those who are stuck in a cycle of fatigue for years on end. We need to know why,” Dr Krishna said.

Reference

B A Krishna et al., ‘Spontaneous, persistent, T-cell dependent IFN-γ release in patients who progress to long COVID’, Science Advances (2024). DOI: 10.1126/sciadv.adi9379

SARS-CoV-2 triggers the production of the antiviral protein IFN-γ, which is associated with fatigue, muscle ache and depression. New research shows that in Long COVID patients, IFN-y production persists until symptoms improve, highlighting a potential biomarker and a target for therapies.

We hope that this could help to pave the way to develop therapies and give some patients a firm diagnosis

Benjamin Krishna

Annie Spratt via Unsplash

Woman sitting on sofa in the dark, placing a hand to her forehead

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Licence type:

Attribution

A very healthy relationship: the ̽��ֱ�� and the NHS

cjb250 — Mon, 03 Jul 2023 15:40:21 +0000

As the NHS celebrates its 75th anniversary, we look at how the close relationship between the ̽��ֱ�� and the hospitals on its doorstep is driving major improvements in how we care for patients.

£16million gift to support Europe’s largest heart and lung research centre

cjb250 — Thu, 23 Mar 2023 14:00:31 +0000

̽��ֱ��Victor Phillip Dahdaleh Heart and Lung Research Institute (HLRI) is home to the largest concentration of scientists and clinicians in heart and lung medicine in Europe. It opened in July 2022 with the ambitious goal of identifying ten new potential treatments or diagnostic tests for heart and lung diseases within five years.

̽��ֱ��HLRI is located on Cambridge’s rapidly expanding Biomedical Campus, immediately adjacent to Royal Papworth Hospital. ̽��ֱ��institute brings together population health, laboratory and clinical scientists, with NHS clinicians and patients, with the aim of improving outcomes for people with cardiovascular and lung diseases such as heart attacks, pulmonary hypertension, lung cancers, cystic fibrosis and acute respiratory distress syndrome.

Dr Dahdaleh said: “Cambridge is one of the greatest Universities in the history of civilisation and, 800 years on, it is at the cutting edge of scientific progress. Over the years in which I have been supporting education and medical research around the world, I have realised the UK is a global leader in the prevention, identification and treatment of heart and lung diseases.

“I’m supporting this new Institute because, through collaboration with Royal Papworth Hospital and other leading institutions, it will enable a concentration of expertise that will make medical advances in these fields that are of international importance.”

Dr Dahdaleh has previously supported research at the ̽��ֱ�� of Cambridge looking into COVID-19 and national research on mesothelioma, a type of lung cancer linked to asbestos exposure. Cardiovascular and lung diseases kill more than 26 million people a year and have a major impact on the quality of life of many more. Alongside the immense human cost, the economic burden of these diseases – an estimated annual global cost of £840 billion – is already overwhelming and unsustainable. Yet declining air quality and increasing rates of obesity are set to compound the scale of the challenge faced worldwide.

Dr Anthony Freeling, Acting Vice-Chancellor of the ̽��ֱ�� of Cambridge, said: “We are truly grateful to Victor for his generous donation. There has never been a more pressing need to develop new approaches and treatments to help us tackle the heart and lung diseases that affect many millions of people worldwide. ̽��ֱ��Victor Phillip Dahdaleh Heart and Lung Research Institute is in a strong position to make a major difference to people’s lives.”

Professor John Wallwork, Chair of Royal Papworth Hospital NHS Foundation Trust, said: “When we moved our hospital to the Cambridge Biomedical Campus in 2019, one of our ambitions was to collaborate with partners to create a research and education institute on this scale. Victor’s kind donation will support all the teams working in HLRI to develop new treatments in cardiovascular and respiratory diseases, improving the lives of people in the UK and around the globe.”

̽��ֱ��HLRI includes state-of-the-art research facilities, space for collaboration between academia, healthcare providers and industry, conference and education facilities. It also includes a special 10-bed clinical research facility where the first-in-patient studies of new treatments are being conducted.

Professor Charlotte Summers, Interim Director of the HLRI, said: “We have set ourselves ambitious goals because of the urgent need to improve cardiovascular and lung health across the world. Victor’s generous gift will help us realise our ambitions. Collaboration is at the heart of our approach, with our researchers and clinicians working with patient, academic, charity and industry partners within the Cambridge Cluster, nationally and internationally.”

Dr Dahdaleh is also a significant supporter of the Duke of Edinburgh awards, York and McGill universities in his homeland of Canada, and the British Lung Foundation. Dr Dahdaleh and his wife Mona, via the Victor Dahdaleh Foundation, have a commitment to supporting scholarships for disadvantaged students pursuing higher education in addition to their extensive philanthropic support for research into cancer, lung and heart disease.

̽��ֱ��HLRI has already raised £30 million from the UK Research Partnership Investment Fund and £10 million from the British Heart Foundation, with additional funding from the Wolfson Foundation, Royal Papworth Hospital Charity and the ̽��ֱ�� of Cambridge. Additional support has been provided by the Cystic Fibrosis Trust for a Cystic Fibrosis Trust Innovation Hub within the institute.

Maintaining heart function in donors declared ‘dead by circulatory criteria’ could improve access to heart transplantation

cjb250 — Thu, 16 Mar 2023 00:55:17 +0000

̽��ֱ��organs are kept functioning by restarting local circulation to the heart, lungs and abdominal organs – but, crucially, not to the brain – of patients whose hearts have stopped beating for five minutes or longer and have been declared dead by circulatory criteria (donation after circulatory death, or DCD).

It is hoped that this technique could increase the number of usable donated hearts by as much as 30% in the future, helping address the shortage of transplant organs. In 2021, 8,409 heart transplants were reported to the Global Observatory on Donation and Transplantation (GODT) by 54 countries. This activity is in contrast with the 21,935 patients who were on a heart waiting list during the year 2021, of whom 1,511 died while waiting and many others became too sick to receive a transplant.

John Louca, a final year medical student at Gonville & Caius College, ̽��ֱ�� of Cambridge, and the study’s first author, said: “Heart transplants are the last bastion for patients with end-stage heart failure. They are successful – patients who receive a transplant live on average a further 13 to 16 years. ̽��ֱ��biggest problem they face is actually getting access to a donated heart: many patients will die before an organ becomes available. That’s why we urgently need to find ways to increase the suitability of donor organs.”

Though the first heart transplant performed at the Groote Schuur Hospital in Cape Town (South Africa) in 1967 was obtained from a DCD donor, this technique was abandoned and replaced by heart transplants obtained from donors confirmed dead using neurological criteria (donation after brain death, or DBD) – in other words, their brain has stopped functioning entirely.

Until recently, heart transplants worldwide were still performed only with organs obtained from DBD donors. However, in recent years, heart transplants from DCD donors have become a clinical reality worldwide thanks to years of research carried out in Cambridge.

DCD is the donation of organs by patients who tragically have a non-survivable illness. These patients are typically unconscious in intensive care in hospital and dependent on ventilation. Detailed discussions between doctors, specialist nurses and the patient’s family take place and if the family agree to organ donation, the process starts.

After treatment is withdrawn, the heart stops beating and it begins to sustain damage to its tissues. After 30 minutes, it is thought that this damage becomes irreversible and the heart unusable. To prevent this damage, at the time of death these non-beating hearts are transferred to a portable machine known as the Organ Care System (OCS) where the organ is perfused with oxygenated blood and assessed to see whether it is suitable for transplantation.

This technique was pioneered by Royal Papworth Hospital NHS Foundation Trust in Cambridge, whose transplant team carried out the first DCD heart transplant in Europe in 2015. Royal Papworth has since become the largest and most experienced DCD heart transplant centre in the world.

DCD heart transplantation started simultaneously in Australia, followed by Belgium, ̽��ֱ��Netherlands, Spain and USA. According to the GODT, 295 DCD heart transplants were performed in these six countries in 2021.

Organ Care Systems are expensive, costing around US$400,000 per machine plus an additional $75,000 for consumables for each perfused organ. An alternative, and much more cost-effective approach, is known as thoraco-abdominal normothermic reperfusion (taNRP). This involves perfusing the organ in situ in the donor’s body and is estimated to cost around $3,000. Its use was first reported in 2016 by a team at Royal Papworth Hospital.

In a study published in eClinical Medicine, an international team of clinical scientists and heart specialists from 15 major transplant centres worldwide, including the UK, Spain, the USA and Belgium, looked at clinical outcomes of 157 DCD donor hearts recovered and transplanted from donors undergoing taNRP. They compared these with the outcomes from 673 DBD heart transplants, which represents the ‘gold-standard’.

̽��ֱ��team found that overall, the use of taNRP increased the donor pool significantly, increasing the number of heart transplantations performed by 23%.

Mr Stephen Large, Consultant Cardiothoracic Surgeon at Royal Papworth Hospital and chief investigator, said: “Withdrawing life support from a patient is a difficult decision for both the families and medical staff involved and we have a duty to honour the wishes of the donor as best we can. At present, one in ten retrieved hearts is turned down, but restoring function of the heart in situ could help us ensure more donor hearts find a recipient.”

Survival rates were comparable between DCD and DBD heart transplantation, with 97% of patients surviving for more than 30 days following taNRP DCD heart transplant, 93% for more than a year and 84% of patients still alive after five years.

Professor Filip Rega, Head of Clinic at the Department of Cardiac Surgery, UZ Leuven, Belgium, said: “This promising new approach will allow us to offer heart transplantation, a last resort treatment, to many more patients in need of a new heart.”

̽��ֱ��researchers say that some of the benefits from taNRP are likely thanks to the reduced amount of time the heart was not receiving oxygenated blood, known as its warm ischaemic time, when compared to direct procurement (that is, when the heart is removed immediately for transplant, and perfused outside the body). ̽��ֱ��median average time was 16.7 minutes, significantly less than the 30 minutes associated with permanent damage to the heart cells.

An added benefit to this approach is that it allows medical teams to simultaneously preserve several organs, such as the liver, pancreas and kidneys, without the need of several organ-specific external machine perfusion devices. This decreases complexity and costs.

Professor Ashish Shah, Head of the Department of Cardiac Surgery at Vanderbilt ̽��ֱ�� Hospitals, Nashville, USA, said: “Heart transplantation has been and always will be a uniquely international effort. ̽��ֱ��current study is another example of effective international collaboration and opens a new frontier, not just in transplantation, but in our basic understanding of how all hearts can be rescued.”

Dr Beatriz Domínguez-Gil, Director General of the National Organisation of Transplantation in Spain, said: “ ̽��ֱ��results of this collaborative study bring hope to thousands of patients in need for a heart transplant every year throughout the world. Its findings reveal that DCD heart transplantation based on taNRP can lead to results at least similar to the gold standard and increase hearts available for transplantation in a manner that contributes to the sustainability of health-care systems.”

Reference
Louca, J et al. ̽��ֱ��international experience of in-situ recovery of the DCD heart: A multicentre retrospective observational study. eClin Med; published online 2 March 2023; DOI: 10.1016/j.eclinm.2023.101887

More donated hearts could be suitable for transplantation if they are kept functioning within the body for a short time following the death of the donor, new research has concluded.

Patients who receive a transplant live on average a further 13 to 16 years. ̽��ֱ��biggest problem they face is actually getting access to a donated heart

John Louca

Sewcream (Getty Images)

Hands holding an image of a heart

Yes