̽��ֱ�� of Cambridge - Cystic Fibrosis Trust

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

̽��ֱ��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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Widely-used COVID-19 antiviral could be helping SARS-CoV-2 to evolve

cjb250 — Mon, 25 Sep 2023 15:00:41 +0000

̽��ֱ��drug works by disrupting the virus’s genome, causing it to develop random mutations as it replicates, weakening the virus to prevent replication, thereby enabling clearance of infection.

But in research published today in Nature, scientists have shown that in some cases, mutated forms of the virus have been able to be transmitted from patients treated with molnupiravir and spread within the community.

Dr Christopher Ruis from the Department of Medicine at the ̽��ֱ�� of Cambridge said: “Molnupiravir is one of a number of drugs being used to fight COVID-19. It belongs to a class of drugs that can cause the virus to mutate so much that it is fatally weakened. But what we’ve found is that in some patients, this process doesn’t kill all the viruses, and some mutated viruses can spread. This is important to take into account when assessing the overall benefits and risks of molnupiravir and similar drugs.”

Molnupiravir, marketed under the brand name Lagevrio, is licensed for the treatment of COVID-19 in several countries, including the UK, USA and Japan. It has been used to treat the disease since late 2021.

In the body, molnupiravir is converted into a molecule that disrupts the genome of the SARS-CoV-2 virus, introducing some nucleotide mutations in its RNA – randomly changing some Cs to Ts and some Gs to As. These changes mean that as the virus replicates, its progeny get weaker, reducing how quickly the virus is able to replicate and ridding the body of the virus.

However, concern has been expressed that in some cases, a number of mutated viruses may not be killed off quickly enough and so are able to infect other individuals, potentially allowing new mutated viruses to spread.

During the COVID-19 pandemic, a number of countries – spearheaded by the Cambridge-led COVID-19 Genomics UK Consortium – sequenced virus samples, depositing the information in databases such as the Global Initiative on Sharing All Influenza Data (GISAID) and the International Nucleotide Sequence Database Collaboration (INSDC). This allowed scientists and public health agencies to track the evolution and spread of the virus, and in particular to look out for so-called ‘variants of concern’ – versions of the virus with mutations that might make them more transmissible, more lethal, or able to evade the immune system of vaccinated individuals, such as the Delta and Omicron variants.

A team of researchers from the UK and South Africa noticed a number of viral genomes that contained a large number of mutations, particularly where Cs had changed to Ts and Gs to As. While C-to-T mutations are relatively common overall in SARS-CoV-2 evolution, G-to-A mutations occur much less frequently, and a higher proportion of G-to-A mutations is associated with molnupiravir treatment.

̽��ֱ��team then analysed a family tree of more than 15 million SARS-CoV-2 sequences in the GISAID and INSDC databases looking for which mutations had occurred at each point in the virus’s evolutionary history. They found that viruses with this signature of mutations had begun to emerge almost exclusively from 2022 onwards and in countries and age groups where molnupiravir was being widely used to treat COVID-19.

To confirm the link, the researchers examined treatment records in England and found that at least one in three of viruses showing the mutational signature involved the use of molnupiravir.

̽��ֱ��researchers also saw small clusters of patients infected with mutated viruses, which suggests that these new viruses were being passed from one person to another. However, none of the known variants of concern has so far been linked to the use of molnupiravir.

Dr Theo Sanderson from the Francis Crick Institute, said: “COVID-19 is still having a major effect on human health, and some people have difficulty clearing the virus, so it’s important we develop drugs which aim to cut short the length of infection. But our evidence shows that a specific antiviral drug, molnupiravir, also results in new mutations, increasing the genetic diversity in the surviving viral population.

“Our findings are useful for ongoing assessment of the risks and benefits of molnupiravir treatment. ̽��ֱ��possibility of persistent antiviral-induced mutations needs to be taken into account for the development of new drugs which work in a similar way.”

̽��ֱ��research was funded by Wellcome, Cancer Research UK, the Medical Research Council, National Institute for Health and Care Research, Fondation Botnar, UK Cystic Fibrosis Trust and the Oxford Martin School.

Reference
Sanderson, T et al. A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes. Nature; 25 Sept 2023: DOI: 10.1038/s41586-023-06649-6

Molnupiravir, an antiviral drug used to treat patients with COVID-19, appears to be driving SARS-CoV-2 to mutate and evolve, with some of these new viruses being transmitted onwards, a new study has shown. It is not clear, however, whether these mutated viruses pose an increased risk to patients or are able to evade the vaccine.

Molnupiravir belongs to a class of drugs that can cause the virus to mutate so much that it is fatally weakened. But what we’ve found is that in some patients, this process doesn’t kill all the viruses

Christopher Ruis

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SARS-CoV-2 viruses

̽��ֱ��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 – 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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£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.

New Heart and Lung Research Institute opens

cjb250 — Mon, 11 Jul 2022 06:31:58 +0000

A major new institute opens today, bringing together the largest concentration of scientists and clinicians in heart and lung medicine in Europe.

Effectiveness of antibiotics significantly reduced when multiple bugs present

jg533 — Sat, 19 Mar 2022 00:01:00 +0000

In the study, published today in ̽��ֱ��ISME Journal, researchers say that even a low level of one type of microbe in the airways can have a profound effect on the way other microbes respond to antibiotics.

̽��ֱ��results highlight the need to consider the interaction between different species of microbe when treating infections with antibiotics - and to adjust dosage accordingly.

“People with chronic infections often have co-infection with several pathogens, but the problem is we don’t take that into account in deciding how much of a particular antibiotic to treat them with. Our results might help explain why, in these people, the antibiotics just don’t work as well as they should,” said Thomas O’Brien, who carried out the research for his PhD in the ̽��ֱ�� of Cambridge’s Department of Biochemistry and is joint first author of the paper.

Chronic bacterial infections such as those in the human airways are very difficult to cure using antibiotics. Although these types of infection are often associated with a single pathogenic species, the infection site is frequently co-colonised by a number of other microbes, most of which are not usually pathogenic in their own right.

Treatment options usually revolve around targeting the pathogen, and take little account of the co-habiting species. However, these treatments often fail to resolve the infection. Until now scientists have had little insight into why this is.

To get their results the team developed a simplified model of the human airways, containing artificial sputum (‘phlegm‘) designed to chemically resemble the real phlegm coughed up during an infection, packed with bacteria.

̽��ֱ��model allowed them to grow a mixture of different microbes, including pathogens, in a stable way for weeks at a time. This is novel, because usually one pathogen will outgrow the others very quickly and spoil the experiment. It enabled the researchers to replicate and study infections with multiple species of microbe, called ‘poly-microbial infections’, in the laboratory.

̽��ֱ��three microbes used in the experiment were the bacteria Pseudomonas aeruginosa and Staphylococcus aureus, and the fungus Candida albicans – a combination commonly present in the airways of people with cystic fibrosis.

̽��ֱ��researchers treated this microbial mix with an antibiotic called colistin, which is very effective in killing Pseudomonas aeruginosa. But when the other pathogens were present alongside Pseudomonas aeruginosa, the antibiotic didn’t work.

“We were surprised to find that an antibiotic that we know should clear an infection of Pseudomonas effectively just didn’t work in our lab model when other bugs were present,” said Wendy Figueroa-Chavez in the ̽��ֱ�� of Cambridge’s Department of Biochemistry, joint first author of the paper.

̽��ֱ��same effect happened when the microbial mix was treated with fusidic acid – an antibiotic that specifically targets Staphylococcus aureus, and with fluconazole - an antibiotic that specifically targets Candida albicans.

̽��ֱ��researchers found that significantly higher doses of each antibiotic were needed to kill bacteria when it was part of poly-microbial infection, compared to when no other pathogens were present.

“All three species-specific antibiotics were less effective against their target when three pathogens were present together,” said Martin Welch, Professor of Microbial Physiology and Metabolism in the ̽��ֱ�� of Cambridge’s Department of Biochemistry and senior author of the paper.

At present antibiotics are usually only laboratory tested against the main pathogen they are designed to target, to determine the lowest effective dose. But when the same dose is used to treat infection in a person it often doesn’t work, and this study helps to explain why. ̽��ֱ��new model system will enable the effectiveness of potential new antibiotics to be tested against a mixture of microbe species together.

Poly-microbial infections are common in the airways of people with cystic fibrosis. Despite treatment with strong doses of antibiotics, these infections often persist long-term. Chronic infections of the airways in people with asthma and chronic obstructive pulmonary disorder (COPD) are also often poly-microbial.

By looking at the genetic code of the Pseudomonas bacteria in their lab-grown mix, the researchers were able to pinpoint specific mutations that give rise to this antibiotic resistance. ̽��ֱ��mutations were found to arise more frequently when other pathogens were also present.

Comparison with the genetic code of 800 samples of Pseudomonas from around the world revealed that these mutations have also occurred in human patients who had been infected with Pseudomonas and treated with colistin.

“ ̽��ֱ��problem is that as soon as you use an antibiotic to treat a microbial infection, the microbe will start to evolve resistance to that antibiotic. That’s what has happened since colistin started to be used in the early 1990’s. This is another reminder of the vital need to find new antibiotics to treat human infections,” said Welch.

This research was funded by the British Lung Foundation, the Cystic Fibrosis Trust, and the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).

Reference

O’Brien, T et al: ‘Decreased efficacy of antimicrobial agents in a polymicrobial environment.’ ̽��ֱ��ISME Journal, March 2022. DOI: 10.1038/s41396-022-01218-7

A study has found that much higher doses of antibiotics are needed to eliminate a bacterial infection of the airways when other microbes are present. It helps explain why respiratory infections often persist in people with lung diseases such as cystic fibrosis despite treatment.

People with chronic infections often have co-infection with several pathogens, but the problem is we don’t take that into account in deciding how much of a particular antibiotic to treat them with

Thomas O’Brien

Science Photo Library

Woman coughing

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Ability of multi-drug resistant infection to evolve within cystic fibrosis patients highlights need for rapid treatment

cjb250 — Thu, 29 Apr 2021 18:00:25 +0000

Around one in 2,500 children in the UK is born with cystic fibrosis, a hereditary condition that causes the lungs to become clogged up with thick, sticky mucus. ̽��ֱ��condition tends to decrease life expectancy among patients.

In recent years, M. abscessus, a species of multi-drug resistant bacteria, has emerged as a significant global threat to individuals with cystic fibrosis and other lung diseases. It can cause a severe pneumonia leading to accelerated inflammatory damage to the lungs, and may prevent safe lung transplantation. It is also extremely difficult to treat – fewer than one in three cases is treated successfully.

In a study published today in Science, a team led by scientists at the ̽��ֱ�� of Cambridge examined whole genome data for 1,173 clinical M. abscessus samples taken from 526 patients to study how the organism has evolved – and continues to evolve. ̽��ֱ��samples were obtained from cystic fibrosis clinics in the UK, as well as centres in Europe, the USA and Australia.

̽��ֱ��team found two key processes that play an important part in the organism’s evolution. ̽��ֱ��first is known as horizontal gene transfer – a process whereby the bacteria pick up genes or sections of DNA from other bacteria in the environment. Unlike classical evolution, which is a slow, incremental process, horizontal gene transfer can lead to big jumps in the pathogen’s evolution, potentially allowing it to become suddenly much more virulent.

̽��ֱ��second process is within-host evolution. As a consequence of the shape of the lung, multiple versions of the bacteria can evolve in parallel – and the longer the infection exists, the more opportunities they have to evolve, with the fittest variants eventually winning out. Similar phenomena have been seen in the evolution of new SARS-CoV-2 variants in immunocompromised patients.

Professor Andres Floto, joint senior author from the Centre for AI in Medicine (CCAIM) and the Department of Medicine at the ̽��ֱ�� of Cambridge and the Cambridge Centre for Lung Infection at Royal Papworth Hospital, said: “What you end up with is parallel evolution in different parts of an individual’s lung. This offers bacteria the opportunity for multiple rolls of the dice until they find the most successful mutations. ̽��ֱ��net result is a very effective way of generating adaptations to the host and increasing virulence.

“This suggests that you might need to treat the infection as soon as it is identified. At the moment, because the drugs can cause unpleasant side effects and have to be administered over a long period of time – often as long as 18 months – doctors usually wait to see if the bacteria cause illness before treating the infection. But what this does is give the bug plenty of time to evolve repeatedly, potentially making it more difficult to treat.”

Professor Floto and colleagues have previously advocated routine surveillance of cystic fibrosis patients to check for asymptomatic infection. This would involve patients submitting sputum samples three or four times a year to check for the presence of M. abscessus infection. Such surveillance is carried out routinely in many centres in the UK.

Using mathematical models, the team have been able to step backwards through the organism’s evolution in a single individual and recreate its trajectory, looking for key mutations in each organism in each part of the lung. By comparing samples from multiple patients, they were then able to identify the key set of genes that enabled this organism to change into a potentially deadly pathogen.

These adaptations can occur very quickly, but the team found that their ability to transmit between patients was constrained: paradoxically, those mutations that allowed the organism to become a more successful pathogen within the patient also reduced its ability to survive on external surfaces and in the air – the key mechanisms by which it is thought to transmit between people.

Potentially one of the most important genetic changes witnessed by the team was one that contributed towards M. abscessus becoming resistant to nitric oxide, a compound naturally produced by the human immune system. ̽��ֱ��team will shortly begin a clinical trial aimed at boosting nitric oxide in patients’ lung by using inhaled acidified nitrite, which they hope would become a novel treatment for the devastating infection.

̽��ֱ��researchers say their findings highlight the need to treat patients with Mycobacterium abscessus infection immediately, counter to current medical practice.

Examining the DNA taken from patient samples is also important in helping understand routes of transmission. Such techniques are used routinely in Cambridge hospitals to map the spread of infections such as MRSA and C. difficile – and more recently, SARS-CoV-2. Insights into the spread of M. abscessus helped inform the design of the new Royal Papworth Hospital building, opened in 2019, which has a state-of-the-art ventilation system to prevent transmission. ̽��ֱ��team recently published a study showing that this ventilation system was highly effective at reducing the amount of bacteria in the air.

Professor Julian Parkhill, joint senior author from the Department of Veterinary Medicine at the ̽��ֱ�� of Cambridge, added: “M. abscessus can be a very challenging infection to treat and can be very dangerous to people living with cystic fibrosis, but we hope insights from our research will help us reduce the risk of transmission, stop the bug evolving further, and potentially prevent the emergence of new pathogenic variants.”

̽��ֱ��team have used their research to develop insights into the evolution of M. tuberculosis – the pathogen that causes TB about 5,000 years ago. In a similar way to M. abscessus, M. tuberculosis likely started life as an environmental organism, acquired genes by horizontal transfer that made particular clones more virulent, and then evolved through multiple rounds of within-host evolution. While M. abscessus is currently stopped at this evolutionary point, M. tuberculosis evolved further to be able to jump directly from one person to another.

Dr Lucy Allen, Director of Research at the Cystic Fibrosis Trust, said: “This exciting research brings real hope of better ways to treat lung infections that are resistant to other drugs. Our co-funded Innovation Hub with the ̽��ֱ�� of Cambridge really shows the power of bringing together world-leading expertise to tackle a health priority identified by people with cystic fibrosis. We’re expecting to see further impressive results in the future coming from our joint partnership.”

̽��ֱ��study was funded by the Wellcome Trust, Cystic Fibrosis Trust, NIHR Cambridge Biomedical Research Centre and Fondation Botnar.

Reference
Bryant, JM et al. Stepwise pathogenic evolution of Mycobacterium abscessus. Science; 30 Apr 2021

Scientists have been able to track how a multi-drug resistant organism is able to evolve and spread widely among cystic fibrosis patients – showing that it can evolve rapidly within an individual during chronic infection.

We hope insights from our research will help us reduce the risk of transmission, stop the bug evolving further, and potentially prevent the emergence of new pathogenic variants

Julian Parkhill

Jon Sneddon

Patient with cystic fibrosis

Yes

Machine learning comes of age in cystic fibrosis

Anonymous — Fri, 23 Oct 2020 09:08:11 +0000

Accurately predicting how an individual’s chronic illness is going to progress is critical to delivering better-personalised, precision medicine. Only with such insight can a clinician and patient plan optimal treatment strategies for intervention and mitigation. Yet there is an enormous challenge in accurately predicting the clinical trajectories of people for chronic health conditions such as cystic fibrosis (CF), cancer, cardiovascular disease and Alzheimer’s disease.

“Prediction problems in healthcare are fiendishly complex,” said Professor Mihaela van der Schaar, Director of the Cambridge Centre for AI in Medicine (CCAIM). “Even machine learning approaches, which deal in complexity, struggle to deliver meaningful benefits to patients and clinicians, and to medical science more broadly. Off-the-shelf machine learning solutions, so useful in many areas, simply do not cut it in predictive medicine.”

Unlock this complexity, however, and enormous healthcare gains await. That is why several teams led by Professor van der Schaar and CCAIM Co-Director Andres Floto, Professor of Respiratory Biology at the ̽��ֱ�� of Cambridge and Research Director of the Cambridge Centre for Lung Infection at Royal Papworth Hospital, have developed a rapidly evolving suite of world-class machine learning (ML) approaches and tools that have successfully overcome many of the challenges.

In just two years, the researchers have developed technology that has moved from producing ML-based predictions of lung failure in CF patients using a snapshot of patient data – itself a remarkable improvement on the previous state of the art – to dynamic predictions of individual disease trajectories, predictions of competing health risks and comorbidities, ‘temporal clustering’ with past patients, and much more.

̽��ֱ��researchers are presenting three of their new ML technologies this week at the North American Cystic Fibrosis Conference 2020. In-depth details of the technologies and their potential implications are available on the CCAIM website.

̽��ֱ��tools developed by the Cambridge researchers represent astonishing progress in a very short time, and reveal the power of ML methods to tackle the remaining mysteries of common chronic illnesses and provide highly precise predictions of patient-specific health outcomes of unprecedented accuracy. What’s more, such techniques can be readily applied to other chronic diseases.

Applying new ML techniques in cystic fibrosis

“Cystic fibrosis is an excellent example of a hard-to-treat, chronic condition,” said Floto. “It is often unclear how the disease will progress in a given individual over time, and there are multiple, competing complications that need preventative or mitigating interventions.”

CF is a genetic condition that affects a number of organs, but primarily the lungs, where it leads to progressive respiratory failure and premature death. In 2019, the median age of the 114 people with CF who died in the UK was 31. Only about half of the people born in the UK with CF in 2019 are likely to live to the age of 50.

Cystic fibrosis is also a fertile ground to explore ML methods, in part because of the UK Cystic Fibrosis Registry, an extensive database that covers 99% of the UK’s CF population which is managed by the UK Cystic Fibrosis Trust. ̽��ֱ��Registry holds both static and time-series data for each CF patient, including demographic information, CFTR genotype, disease-related measures including infection data, comorbidities and complications, lung function, weight, intravenous antibiotics usage, medications, transplantations and deaths.

“Almost everyone with cystic fibrosis in the UK entrusts the Registry to hold their patient data, which is then used to ensure the best care for all people with the condition,” said Dr Janet Allen, Director of Strategic Innovation at the Cystic Fibrosis Trust. “What’s exciting is that the approaches developed by Professor van der Schaar take this to a completely new level, developing tools to harness the complexity of the CF data. Turning such data into medical understanding is a key priority for the future of personalised healthcare.”

Looking to the future

̽��ֱ��suite of new tools offers tremendous potential benefit to everyone in the CF ecosystem, from patients to clinicians and medical researchers. “Our medical ML technology has matured rapidly, and it is ready to be deployed,” said van der Schaar. “ ̽��ֱ��time has come to bring its clear benefits to the individuals who need it most – in this case, the people living with cystic fibrosis. This means collaborating further with clinicians and increasing our engagement with wider healthcare systems and with data guardians beyond the UK.”

Machine learning technologies have proven to be adept at predicting the clinical trajectories of people with long-term health conditions, and innovation will continue at pace. ̽��ֱ��patient-centred revolution in precision healthcare will enable and empower both clinicians and researchers to extract greater value from the growing availability of healthcare data.

̽��ֱ��challenge ahead is to realise the potential of these tools by making them available to clinicians and hospitals around the world, where they can help improve and save the lives of people living with chronic illness. This is one of the goals of the Cambridge Centre for AI in Medicine.

World-leading AI technology developed by the Cambridge Centre for AI in Medicine and their colleagues – some of which is being showcased this week at the North American Cystic Fibrosis Conference 2020 – offers a glimpse of the future of precision medicine, and unprecedented predictive power to clinicians caring for individuals with the life-limiting condition.

̽��ֱ��time has come to bring the clear benefits of machine learning to the individuals who need it most – in this case, the people living with cystic fibrosis

Mihaela van der Schaar

Hey Paul Studios

Blue and Brown Anatomical Lung Wall Decor

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Ground-breaking ceremony celebrates start of construction work on new Heart and Lung Research Institute in Cambridge

cjb250 — Thu, 27 Feb 2020 10:23:56 +0000

̽��ֱ��HLRI, a joint venture between the ̽��ֱ�� of Cambridge and Royal Papworth Hospital NHS Foundation Trust, aims to focus on collaboration between research and its clinical use in treating patients for chronic diseases such as heart attacks, cystic fibrosis, atrial fibrillation and pulmonary hypertension.

In the UK, one in every four deaths is caused by cardiovascular disease and 20% of deaths by respiratory disease. Despite a growing awareness of risk factors, such as smoking and poor diet, the prevalence of such diseases is increasing.

According to the World Health Organization, cardiovascular disease causes nearly 18 million deaths per year, mostly due to heart attacks and stroke, with respiratory disease just behind. ̽��ֱ��combined worldwide cost of this is more than £840billion each year.

“ ̽��ֱ��Heart and Lung Research Institute is an incredible opportunity to bring together the ̽��ֱ��’s expertise in cardiovascular and respiratory science and Royal Papworth Hospital’s expertise in treating heart and lung disease,” said Professor Nick Morrell from the ̽��ֱ�� of Cambridge, who is Interim Director of the Institute.

“Heart and lung diseases affect many millions of people worldwide and the numbers are growing. Institutes such as ours, focused on these big health challenges, are urgently needed. ̽��ֱ��discoveries made by our researchers will deliver major benefits to the public through improvements in public health, new approaches to diagnosing and treating disease, and new medicines.”

Features of the Institute include: a new laboratory space; a clinical research facility; a collaboration space for link-ups between academia, healthcare providers and industry; and education facilities such as seminar rooms and a lecture theatre. It will also include a special 10-bed facility where the first-in-patient studies of new treatments can be conducted.

Professor John Wallwork, Chairman of Royal Papworth, added: “ ̽��ֱ��Heart and Lung Research Institute will mean new treatments will be created, tested and delivered to tackle the biggest causes of premature death in the world all on one site. It will also allow us to provide much more education and training to clinicians tackling heart and lung disease worldwide.

“This will be a huge step forward and demonstrates one of the reasons Royal Papworth Hospital moved to the Cambridge Biomedical Campus – to collaborate with the best researchers in the world to help to save lives. Through the Heart and Lung Research Institute, we will be able to make even quicker progress in bringing tomorrow’s treatments to today’s patients.”

Funding for HLRI is being provided by the UK Research Partnership Investment Fund, which has contributed £30m, the ̽��ֱ�� of Cambridge and the Wolfson Foundation. ̽��ֱ��British Heart Foundation has donated £10m towards the project and Royal Papworth Hospital Charity has launched its largest ever appeal to raise £5m.

Professor Wallwork added: “Every day at Royal Papworth Hospital we see the positive impact that research can have for patients with heart and lung disease, both in terms of improving life expectancy and quality of life. We have already received a number of generous donations from Royal Papworth Hospital patients and their families in support of the Heart and Lung Research Institute and will be working hard to raise additional funds over the next few years.”

Professor Sir Nilesh Samani, Medical Director of the British Heart Foundation said: “Through this funding we will help create a fantastic centre that will have a key role in driving forward our ambitious programme of heart and circulatory research. By bringing together world-leading scientists it will enable exciting opportunities for collaboration between researchers from different disciplines. And it will also accelerate the transformation of discoveries in the laboratory to treatments available at patients’ bedside.

“This grant is one of the largest the BHF has ever made and we have only been able to make this investment because of the incredible generosity of the public.”

̽��ֱ��Cystic Fibrosis Trust has also committed to raise up to £5million to fund the Cystic Fibrosis Innovation Hub, which launched last year and will transfer to the new building once it has been completed. AstraZeneca will pursue integrated research programmes with the Institute to maximise translational impact.

Groundwork began back in October 2019 with construction starting in January 2020. Piling work for the 22m deep foundations is currently underway, including the formation of a tunnel, which will link the HLRI to neighbouring Royal Papworth Hospital.

There are currently 35 people working on the site with that number due to reach more than 150 at the peak of construction, which is set for completion in early 2022.

Press release from Royal Papworth Hospital.

̽��ֱ�� ̽��ֱ�� of Cambridge and Royal Papworth Hospital held an official ground-breaking ceremony at the new Heart and Lung Research Institute (HLRI) in Cambridge earlier today. ̽��ֱ��Institute is based on the Cambridge Biomedical Campus and will create the largest cardiothoracic centre for research, education, industry collaboration, and clinical care in Europe.

̽��ֱ��Heart and Lung Research Institute is an incredible opportunity to bring together the ̽��ֱ��’s expertise in cardiovascular and respiratory science and Royal Papworth Hospital’s expertise in treating heart and lung disease

Nick Morrell

Royal Papworth Hospital

Groundbreaking for the new Heart and Lung Research Institute

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̽��ֱ�� of Cambridge - Cystic Fibrosis Trust

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