̽��ֱ�� of Cambridge - Stefan Marciniak

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.

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Rare disease research at Cambridge receives major boost with launch of two new centres

cjb250 — Mon, 22 Apr 2024 23:34:17 +0000

̽��ֱ��virtual centres, supported by the charity LifeArc, will focus on areas where there are significant unmet needs. They will tackle barriers that ordinarily prevent new tests and treatments reaching patients with rare diseases and speed up the delivery of rare disease treatment trials.

̽��ֱ��centres will bring together leading scientists and rare disease clinical specialists from across the UK for the first time, encouraging new collaborations across different research disciplines and providing improved access to facilities and training.

LifeArc Centre for Rare Mitochondrial Diseases

Professor Patrick Chinnery will lead the LifeArc Centre for Rare Mitochondrial Diseases, a national partnership with the Lily Foundation and Muscular Dystrophy UK, together with key partners at UCL, Newcastle ̽��ֱ�� and three other centres (Oxford, Birmingham and Manchester).

Mitochondrial diseases are genetic disorders affecting 1 in 5,000 people. They often cause progressive damage to the brain, eyes, muscles, heart and liver, leading to severe disability and a shorter life. There is currently have no cure for most conditions, however, new opportunities to treat mitochondrial diseases have been identified in the last five years, meaning that it’s a critical time for research development. ̽��ֱ��£7.5M centre will establish a national platform that will connect patient groups, knowledge and infrastructure in order to accelerate new treatments getting to clinical trial.

Professor Chinnery said: “ ̽��ֱ��new LifeArc centre unites scientific and clinical strengths from across the UK. For the first time we will form a single team, focussed on developing new treatments for mitochondrial diseases which currently have no cure.”

Adam Harraway has Mitochondrial Disease and says he lives in constant fear of what might go wrong next with his condition. “With rare diseases such as these, it can feel like the questions always outweigh the answers. ̽��ֱ��news of this investment from LifeArc fills me with hope for the future. To know that there are so many wonderful people and organisations working towards treatments and cures makes me feel seen and heard. It gives a voice to people who often have to suffer in silence, and I'm excited to see how this project can help Mito patients in the future."

LifeArc Centre for Rare Respiratory Diseases

Professor Stefan Marciniak will co-lead the LifeArc Centre for Rare Respiratory Diseases, a UK wide collaborative centre co-created in partnership with patients and charities. This Centre is a partnership between Universities and NHS Trusts across the UK, co-led by Edinburgh with Nottingham, Dundee, Cambridge, Southampton, ̽��ֱ�� College London and supported by six other centres (Belfast, Cardiff, Leeds, Leicester, Manchester and Royal Brompton).

For the first time ever, it will provide a single ‘go to’ centre that will connect children and adults with rare respiratory disease with clinical experts, researchers, investors and industry leaders across the UK. ̽��ֱ��£9.4M centre will create a UK-wide biobank of patient samples and models of disease that will allow researchers to advance pioneering therapies and engage with industry and regulatory partners to develop innovative human clinical studies.

Professor Marciniak said: “There are many rare lung diseases, and together those affected constitute a larger underserved group of patients. ̽��ֱ��National Translational Centre for Rare Respiratory Diseases brings together expertise from across the UK to find effective treatments and train the next generation of rare disease researchers.”

Former BBC News journalist and presenter, Philippa Thomas, has the rare incurable lung disease, Lymphangioleiomyomatosis (LAM). Her condition has stabilised but for many people, the disease can be severely life-limiting. Philippa said: “There is so little research funding for rare respiratory diseases, that getting treatment - let alone an accurate diagnosis - really does feel like a lottery. It is also terrifying being diagnosed with something your GP will never have heard of.”

Globally, there are more than 300 million people living with rare diseases. However, rare disease research can be fragmented. Researchers can lack access to specialist facilities, as well as advice on regulation, trial designs, preclinical regulatory requirements, and translational project management, which are vital in getting new innovations to patients.

Dr Catriona Crombie, Head of Rare Disease at LifeArc, says: “We’re extremely proud to be launching four new LifeArc Translational Centres for Rare Diseases. Each centre has been awarded funding because it holds real promise for delivering change for people living with rare diseases. These centres also have the potential to create a blueprint for accelerating improvements across other disease areas, including common diseases.”

Adapted from a press release from LifeArc

Cambridge researchers will play key roles in two new centres dedicated to developing improved tests, treatments and potentially cures for thousands of people living with rare medical conditions.

̽��ֱ��new LifeArc centre unites scientific and clinical strengths from across the UK

Patrick Chinnery

Alexander_Safonov (Getty)

Woman inhaling from a mask nebulizer

Yes

Tiny golden bullets could help tackle asbestos-related cancers

cjb250 — Tue, 27 Oct 2020 11:10:12 +0000

In a study published today in journal Small, the researchers demonstrate that once inside the cancer cells, the nanotubes absorb light, causing them to heat up, thereby killing the cells.

More than 2,600 people are diagnosed in the UK each year with mesothelioma, a malignant form of cancer caused by exposure to asbestos. Although the use of asbestos is outlawed in the UK now, the country has the world’s highest levels of mesothelioma because it imported vast amounts of asbestos in the post-war years. ̽��ֱ��global usage of asbestos remains high, particularly in low- and middle-income countries, which means mesothelioma will become a global problem.

“Mesothelioma is one of the ‘hard-to-treat’ cancers, and the best we can offer people with existing treatments is a few months of extra survival,” said Dr Arsalan Azad from the Cambridge Institute for Medical Research at the ̽��ֱ�� of Cambridge. “There’s an important unmet need for new, effective treatments.”

In 2018, the ̽��ֱ�� of Cambridge was awarded £10million from the Engineering and Physical Sciences Research Council to help develop engineering solutions, including nanotech, to find ways to address hard-to-treat cancers.

In a collaboration between the ̽��ֱ�� of Cambridge and ̽��ֱ�� of Leeds, researchers have developed a form of gold nanotubes whose physical properties are ‘tunable’ – in other words, the team can tailor the wall thickness, microstructure, composition, and ability to absorb particular wavelengths of light.

̽��ֱ��researchers added the nanotubes to mesothelioma cells cultured in the lab and found that they were absorbed by the cells, residing close to the nucleus, where the cell’s DNA lies. When the team targeted the cells with a laser, the nanotubes absorbed the light and heated up, killing the mesothelioma cell.

Professor Stefan Marciniak, also from the Cambridge Institute for Medical Research and a Fellow at St Catharine’s College, Cambridge, added: “ ̽��ֱ��mesothelioma cells ‘eat’ the nanotubes, leaving them susceptible when we shine light on them. Laser light is able to penetrate deep into tissue without causing damage to surrounding tissue. It then gets absorbed by the nanotubes, which heat up and, we hope in the future, could be used to cause localised cancer-cell killing.”

̽��ֱ��team will be developing the work further to ensure the nanotubes are targeted to cancer cells with less effect on normal tissue.

̽��ֱ��nanotubes are made in a two-step process. First, solid silver nanorods are created of the desired diameter. Gold is then deposited from solution onto the surface of the silver. As the gold builds-up at the surface, the silver dissolves from the inside to leave a hollow nanotube.

̽��ֱ��approach advanced by the Leeds team allows these nanotubes to be developed at room temperature, which should make their manufacture at scale more feasible.

Professor Stephen Evans from the School of Physics and Astronomy at the ̽��ֱ�� of Leeds said: “Having control over the size and shape of the nanotubes allows us to tune them to absorb light where the tissue is transparent and will allow them to be used for both the imaging and treatment of cancers. ̽��ֱ��next stage will be to load these nanotubes with medicines for enhanced therapies.”

̽��ֱ��research was funded by the British Lung Foundation, Victor Dahdaleh Foundation, National Institute for Health Research Cambridge Biomedical Research Centre, Royal Papworth Hospital NHS Foundation Trust, Alpha1-Foundation, Medical Research Council and the Engineering & Physical Sciences Research Council.

Reference
Ye, S & Azad, AA et al. Exploring High Aspect Ratio Gold Nanotubes as Cytosolic Agents: Structural Engineering and Uptake into Mesothelioma Cells. Small; 25 Oct 2020: DOI: 10.1002/smll.2003793

Gold nanotubes – tiny hollow cylinders one thousandth the width of a human hair – could be used to treat mesothelioma, a type of cancer caused by exposure to asbestos, according to a team of researchers at the Universities of Cambridge and Leeds.

Mesothelioma is one of the ‘hard-to-treat’ cancers, and the best we can offer people with existing treatments is a few months of extra survival. There’s an important unmet need for new, effective treatments

Arsalan Azad

Confocal fluorescence image of gold nanotures (green) in mesothelioma cells

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 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 – as here, 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.

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Punctured lung affects almost one in a hundred hospitalised COVID-19 patients

cjb250 — Thu, 10 Sep 2020 07:52:36 +0000

Like the inner tube of bicycle or car tyre, damage to the lungs can lead to a puncture. As air leaks out, it builds up in the cavity between the lung and chest wall, causing the lung to collapse. Known as a pneumothorax, this condition typically affects very tall young men or older patients with severe underlying lung disease.

During the pandemic, a team at the ̽��ֱ�� of Cambridge and Addenbrooke’s Hospital, Cambridge ̽��ֱ�� NHS Foundation Trust, observed several patients with COVID-19 who had developed punctured lungs, even though they did not fall into either of these two categories.

“We started to see patients affected by a punctured lung, even among those who were not put on a ventilator,” says Professor Stefan Marciniak from the Cambridge Institute for Medical Research. “To see if this was a real association, I put a call out to respiratory colleagues across the UK via Twitter. ̽��ֱ��response was dramatic – this was clearly something that others in the field were seeing.”

Professor Marciniak subsequently obtained the appropriate ethical approvals and exchanged anonymised clinic information about 71 patients from around the UK. This led to a study published today in the European Respiratory Journal.

Although the team are unable to provide an accurate estimate of the incidence of punctured lung in COVID-19, admissions data from the 16 hospitals participating in the study revealed an incidence of 0.91%.

“Doctors need to be alert to the possibility of a punctured lung in patients with COVID-19, even in people who would not be thought to be typical at-risk patients,” said Professor Marciniak, who is also a Fellow at St Catharine’s College, Cambridge. “Many of the cases we reported were found incidentally – that is, their doctor had not suspected a punctured lung and the diagnosis was made by chance.”

Just under two-thirds (63%) of patients with a punctured lung survived. Individuals younger than 70 years tended to survive well, but older age was associated with a poor outcome – a 71% survival rate among under 70s patients compared with 42% among older patients.

Patients with a punctured lung were three times more likely to be male than female, though this may be accounted for by the fact that large studies of patients with COVID-19 suggest that men are more commonly affected by severe forms the disease. However, the survival rate did not differ between the sexes.

Patients who had abnormally acidic blood, a condition known as acidosis that can result from poor lung function, also had poorer outcomes in COVID-19 pneumothorax.

Dr Anthony Martinelli, a respiratory doctor at Addenbrooke’s Hospital, said: “Although a punctured lung is a very serious condition, COVID-19 patients younger than 70 tend to respond very well to treatment. Older patients or those with abnormally acidic blood are at greater risk of death and may therefore need more specialist care.”

̽��ֱ��team say there may be several ways that COVID-19 leads to a punctured lung. These include the formation of cysts in the lungs, which has previously been observed in x-rays and CT scans.

Reference
Martinelli, A, et al. COVID-19 and Pneumothorax: A Multicentre Retrospective Case Series. European Respiratory Journal; 10 Sept 2020; DOI: 10.1183/13993003.02697-2020

As many as one in 100 patients admitted to hospital with COVID-19 develop a pneumothorax – a ‘punctured lung’ – according to a study led by Cambridge researchers.

Doctors need to be alert to the possibility of a punctured lung in patients with COVID-19, even in people who would not be thought to be typical at-risk patients

Stefan Marciniak

Carol VanHook

X is for X-ray

Yes

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