Improving the diagnosis and treatment of CF lung infections and maintaining lung health

CF lung infections need to be detected and diagnosed as quickly and accurately as possible. This is important for new infections and for flare ups of long-term infections (exacerbations). Sputum samples are commonly used to detect lung infections. However, improved lung health from the use of CFTR modulators such as Kaftrio mean that sputum is much harder to produce. We are supporting research to find different ways of diagnosing infections and managing exacerbations. 

Can we detect lung infections from saliva samples?

We are co-funding a PhD student in the lab of Dr Rian Griffiths at the University of Nottingham through our Venture and Innovation Award (VIA) scheme. The aim of the project is to develop a rapid and highly sensitive method for detecting infections from saliva. This will mean infections can be found earlier and treated more effectively. 

Lung infections caused by Pseudomonas aeruginosa (P. aeruginosa) are common in people with CF and can be difficult to treat due to antimicrobial resistance. Researchers will focus on detecting P. aeruginosa infections by measuring signalling chemicals the bacteria produce. 

Other bacteria and fungi grow alongside the bacteria P. aeruginosa in the lungs of people with CF. These other bugs also produce signalling chemicals. So, it is important to check the methods for detecting P. aeruginosa infection still work in the presence of other infections and are unique for this bacteria.

Diagnostic Target Product Profiles

We are a managing partner in the CF Antimicrobial Resistance Syndicate (CF AMR Syndicate for short) alongside Medicines Discovery Catapult and LifeArc. The Syndicate is a cross-sector initiative that brings together leading experts in CF or antimicrobial resistance (AMR) from industry, academia, and the clinic, as well as people with CF, to accelerate the translation of CF antimicrobials to the clinic to bring new and effective treatment options to people with CF. The Syndicate’s patient focussed Target Product Profile on developing new diagnostics is an important guidance document to support industry-based researchers.

Read more about the Diagnostic TPPs

Understanding exacerbations (flare ups of poor lung health)

Understanding more about flare ups of long term infections (known as exacerbations) is a focus of several of the Innovation Hubs within our Translational Innovation Hub Network on lung health and lung infection in CF. Known as the CF Lung Health Network for short, this network is funded in partnership with LifeArc. Programmes of work include finding triggers that cause flare ups, working out how to predict early signs of a flare up, and understanding how individuals with CF experience them. 

Find out more about our CF Lung Health Network 

Bugs that cause CF lung infections change over time and can become resistant to antimicrobial medicines, meaning that medicines such as antibiotics don’t work as well or no longer work at all. This is known as antimicrobial resistance (AMR). AMR is a problem for treating many different infections around the world. We are funding research to find new medicines that are so urgently needed to treat CF lung infections.

Testing promising new antimicrobial medicines in the lab

After researchers have found that a chemical or compound could have potential benefits as a treatment for lung infections, the next step is converting that promising chemical into a new medicine. This is done by doing lots of rigorous tests, known as the ‘pre-clinical phase’ of development. If the results of the testing are positive, the medicine will then be tested in clinical trials. 

The CF AMR Syndicate’s patient focussed Therapeutic Target Product Profiles provide a guide to innovators developing new medicines to treat lung infections for people with CF. It provides insight into the needs of people with CF in developing new medicines, and support in how to test their effectiveness in the lab and in clinical trials. 

Repurposing existing medicines as treatments for CF lung infections

Many different approaches are being studied to treat CF infections. Designing new antimicrobial medicines is one way to do this. Another is to use additional medicines that reduce resistance and improve the effectiveness of existing antibiotics. 

Previous Trust-funded research led by Professor Jane Daves at Imperial College London in collaboration with researchers at Aarhus University in Denmark has shown that an existing drug called Glatiramer Acetate (GA), approved for use to treat multiple sclerosis (MS), improves the effectiveness of medicines used to treat Pseudomonas aeruginosa lung infections in the lab. This work is being further funded by a grant from LifeArc .

Prof Davies has expanded these studies to investigate if GA is effective at improving treatments for lung infections caused by other bugs. These additional studies are funded through a Venture and Innovation Award from the Trust.

Developing better treatments for M. abscessus infections

M. abscessus is one of the ‘non-tuberculous mycobacteria’ (NTM) group of bacteria that causes serious lung infections in people with CF. It is a very difficult infection to treat and the antibiotics used have very severe side effects. New ways to treat it are urgently needed. In a Trust-funded SRC programme, researchers are exploring better ways to use existing antibiotics and innovative new ways to treat these infections. This research programme is led by Professor Andres Floto at the University of Cambridge.

Find out more about these studies

Answering questions about lung inflammation in CF to design future treatments

Lung inflammation remains a major concern for everyone with CF, and anti-inflammatory treatments are an important part of managing lung health, alongside treatments for infections. However, we need better and more specific anti-inflammatory treatments. Led by Professor Robert Gray at the University of Glasgow, researchers within the DEFINE-CF SRC programme will apply cutting-edge new techniques, alongside existing methods of analysis to find and test possible new ways to treat inflammation. 

Read a more detailed summary of the research programme

Learning more about having different lung infections at the same time

The lungs of people with CF usually contain a mixture of many different bugs. These are known as polymicrobial infections. Researchers are beginning to understand that a bug’s ‘neighbours’ can change how it causes infection and how it responds to treatment. It’s important to find out more about this, to be able to treat CF lung infections as effectively as possible and ensure people with CF have as healthy lungs as possible.

We’re co-funding a VIA award in partnership with Cambridge University to fund a PhD student in Professor Martin Welch’s research group who is using innovative new methods to study polymicrobial infections in the lab. In particular, they are studying the effects of hard-to-treat strains of Pseudomonas aeruginosa and the effects of this infection on other bugs growing in the lungs.

Research within the Precision-CF Innovation Hub is also focusing on understanding the effects of polymicrobial infections on lung health.

Understanding more about repeated Pseudomonas aeruginosa infections

Bacterial infections usually develop in the liquid that lines the lungs. Sometimes people with CF will develop repeated infections caused by the bacteria Pseudomonas aeruginosa. One reason why this happens is that some of the bacteria are able to move from the liquid lining the lungs, into the lung cells themselves. This means that the bacteria are able to ‘hide’ from antibiotic treatments and live to cause new infections. Dr Camilla Godlee at the University of Cambridge is an expert at understanding why some bacteria are able to enter cells, and how they get there. The Trust has awarded Dr Godlee VIA funding to work in CF research for the first time. Working alongside Prof Martin Welch, together they are investigating how some Pseudomonas bacteria are able to enter cells.

Find out more about this new collaboration

Phage therapy could become another option to treat CF lung infections. Also known as ‘phages’, bacteriophages are naturally occurring, bacteria-killing viruses. They kill bacteria by infecting them. They are very specific about which bacteria they infect, sometimes only infecting a specific variant of an infection-causing bacteria.

Researchers hope phage therapy can be used as a treatment for long term CF lung infections, particularly where antibiotic options have become very limited. In the future phage therapy may also be considered as a treatment to clear early infections from the lungs.

More research into phage therapy is needed. The Trust is funding and supporting a number of programmes to accelerate the development of phage therapy as a treatment for CF lung infections.

• Research within the Trailfinder-CF Innovation Hub is underway to develop new combinations of phages, test the best way of giving them, and ensure the UK can produce phages to medical standards.
• Researchers within the Trailfinder-CF Innovation Hub have joined forces with colleagues in the CF AMR Syndicate to deliver a set of guidelines for the development of phage therapies to treat lung infections in CF. These guidelines known as Target Product Profiles (or TPPs for short) have been informed by the experiences and insights of people living with CF.
• Two studies are underway to investigate phages as a treatment for Burkholderia cepacia complex (BCC) group of infections. We’re supporting Dan Shelley’s PhD research Cardiff University through VIA funding to isolate and test new phages against BCC. University of Leicester-based Dr Jessica Lewis has been awarded an Early Career Researcher Development Award to advance research in this area and provide a strong foundation for treatments in the future.

Improving how the lung health of people with CF is monitored is an important area of research for the early detection of lung infections and assessing the effectiveness of new CF treatments. 

More accurate and sensitive measures of lung health are needed, particularly for young children and those on CFTR modulator medicines, who may be experiencing subtle changes in lung health that current methods cannot detect. 

Using new MRI techniques to understand lung health in people with CF

Led by Professor Jim Wild and Dr Laurie Smith at the University of Sheffield, researchers in our ‘Pulmonary Magnetic Resonance Imaging for Cystic Fibrosis or MAGNIFY SRC’, are investigating an exciting new type of magnetic resonance imaging (MRI), known as hyperpolarised Xenon-MRI, that could be used to track subtle changes in lung health over time. 

Their studies include how their MRI approaches can improve knowledge of lung health in people with CF and the practicalities of introducing the techniques into more hospitals, to exploring software to interpret the results and the best way to support people with CF and their families to understand this new information.

Read more about MAGNIFY SRC

Could existing lung scanning methods be helpful in CF care? 

With funding from the Medical Research Council (MRC) and with additional funding from a Trust VIA award, clinical fellow Dr Mina King is investigating whether a type of lung scan known as oxygen-MRI can be used to provide more detailed information on the lung health of people with CF. Oxygen MRI scans are routinely available in hospitals across the country, but they are not used in CF care. Dr King hopes that these scans could help detect earlier signs of lung damage than other ways to monitor lung health in people with CF.