Where have we got to in the fight against Cystic Fibrosis?

The recent European Cystic Fibrosis conference was a great showcase of the latest research and insights surrounding cystic fibrosis (CF).

Cystic fibrosis is a genetic condition affecting more than 10,400 people in the UK. The National Heart and Lung Institute (NHLI) was delighted to have such a high involvement at the European Cystic Fibrosis conference, held in Liverpool earlier this month, including Professor Jane Davies giving an opening address on ’30 years since the discovery of the CF gene’ as conference president. The primary gene responsible for causing CF was ‘discovered’ in 1989 offering fresh hope to combat this fatal disease. Over the past 30 years research has led to developments in diagnosing, treating and understanding the progression of the disease. However there are still unanswered questions remaining but networks and collaborations have been highly effective in making strides forward.

We are currently in CF week during which the Cystic Fibrosis Trust aims to increase awareness about the condition and celebrate what we can achieve together. Much of the work at the NHLI is funded directly by grants from the Cystic Fibrosis Trust, for which the teams are extremely grateful. The strength of CF research at the NHLI is thanks to the strong collaborations with the Royal Brompton Hospital, one of the largest CF centres in the UK, which ensures we are working together towards the best outcomes possible for current and future generations.

The research presented by NHLI researchers during the poster and spoken sessions at the conference fall into three main themes; infection, big data and monitoring, and finally, new treatments and how to measure their effect. 

Infection 

Four years ago, the Strategic Research Centre for Pseudomonas infection was established by Professor Davies and colleagues with funding from the CF Trust . Within the SRC, early career researchers study various aspects of Pseudomonas aeruginosa (Pa), the most prevalent bacterial infection in CF.

People with CF are rarely infected with only one organism. Dominic Hughes is looking at how the most common bacterial and fungal infections of the airways in CF patients interact with each other. The detrimental effects of Pa are well documented however less is known about the fungus, Aspergillus fumigatus. He has confirmed an inhibitory relationship between the two pathogens, with Pa reducing the growth of the fungus, the mechanisms of which Dominic is looking into in more detail. 

Dr Leah Cuthbertson presented her work comparing the bacterial and fungal microbiome in CF and bronchiectasis. Although next generation sequencing technologies have been used to better understand the bacterial microbiome in patients, the fungal microbiome is less well understood. With fungal infections increasing globally it is important we understand the true burden of fungal disease, which is most likely underestimated at present due to a lack of reliable diagnostics.

Antimicrobial resistance is a global problem. Isaac Martin is investigating multi-drug resistance in CF patients with chronic Pa infections and the possibility of using naturally-occuring antibacterial viruses, or bacteriophage instead of conventional antibiotics. He has previously shown that even antibiotic-resistant and biofilm strains of the bacteria can be killed by bacteriophage, but his current work highlighted the variability in this not only between patients, but in the same patient over time, something that needs to be considered if this approach is to be advanced towards the clinic. 

On a similar theme, Ronan Murphy’s work looks at whether the drug Glatiramer acetate, currently used to treat multiple sclerosis, could be used to combat Pa infection. Ronan demonstrated that this drug could be used as an ‘antibiotic resistance breaker’, decreasing the dose of antibiotics required to kill bacterial infections in CF patients. This could reduce the chance of resistance developing and potentially also limit side effects of current antibiotics.

The power of big data and remote monitoring

As part of the CF Trust’s SmartCare initiative and in collaboration with CF Canada, Dr Claire Edmondson has been investigating the feasibility of home monitoring for young CF patients through designing an app. This aims to give doctors a more up to date record of how CF is affecting their patients, and give the young patients more control over their condition. However, it is important first to establish what people with CF are prepared to do at home and whether there is a downside to too much focus on their health. In collaboration with the University of Cambridge, we will also apply machine learning tools to this data in an attempt to identify ‘flare-ups’ or periods of deterioration more quickly. 

Dr Siobhan Carr, Dr Diana Bilton and Professor Paul Cullinan lead another of the CF Trust-funded Strategic Research Centres, CF-EpiNet, using data from national registries. The team presented several pieces of research at the conference: Olga Archangelidi explored the increased risk of cancers in people with CF, reporting a link with pancreatic disease (both digestive and endocrine with CF-related diabetes) and having received a transplant previously; Danielle Edwards described the association between CF-related diabetes and poor lung function in the UK population; Amy McDougall reported that CF infants who were already symptomatic at the time of diagnosis had poorer health outcomes at the age of 6 years, underscoring the importance of early diagnosis and treatment for CF.   

New drugs and measuring trial outcomes

Dr Rebecca Dobra and Katherine Huband shared their research on communication between the multidisciplinary teams supporting CF patients, with regards unplanned admissions of patients on clinical trials. Trial participants are asked to inform the research team of unplanned hospital admissions, however, despite interventions put in place to ensure this happens, there is still an inadequate proportion of staff asking about trial participation proactively. Their study is seeking new ways to improve communication between teams.

Gemma Stanford, a physiotherapist awarded an NIHR PhD fellowship, is investigating how the benefits of chest physiotherapy and airway clearance can be effectively measured in adults with CF. Gemma suggests that impedance tomography, lung clearance index and impulse oscillometry may provide more sensitive measurements of a patient’s progress and is mid-way through a randomised, controlled trial to assess these. The identification of a more robust measurement of the effectiveness of airway clearance is essential to future research and the application of personalised therapy for patients. Clare Saunders and Chris Short, respiratory physiologists, provided training courses for trials teams across the European CF Society’s Clinical Trials Network in their role as Core Facility for Lung Clearance Index. Katie Bayfield presented her work on reference values for LCI using multibreath nitrogen washout.

Newborn screening for CF now provides the opportunity for early interventions to improve growth and lung function. Professor Jane Davies is the global lead investigator on the  ARRIVAL study which is looking at the effect of ivacaftor, a CFTR potentiator, on infants under 24 months. She presented data from the youngest cohort (6-12 months) ever to have received this drug. The study has provided very exciting results to date, showing that the exocrine pancreas is not irreparably damaged at time of birth, as had been previously thought. In addition to the benefits to lung health demonstrated in older patients, these results offer hope for the improvement in other organs for these young patients. 

As part of a session focused on new therapies, Professor Eric Alton presented the UK Cystic Fibrosis Gene Therapy Consortium’s latest data and progress. The Consortium has developed a novel viral vector to deliver the CF gene and following encouraging preclinical data, has completed a major tripartite agreement with Boehringer Ingelheim and Oxford BioMedica. This partnership will enable the product to move more rapidly and efficiently towards clinical trials and this work is now well underway. A key feature of gene therapy is its likely suitability for all patients irrespective of mutations class and this product aims to provide long-lasting, high efficiency correction of the basic defect at affordable cost.

The conference was followed by the patients’ and families’ day which the CF Trust live-streamed - watch the videos. Professor Jane Davies presented highlights of the research to this valued audience whom researchers are keen to involve and inform with regards their work. 

Despite all the exciting research presented, for many attendees, the highlight of the meeting was the opening ceremony. The conference organisers wanted to use this opportunity to illustrate two important aspects of life with CF: the incredible resilience, determination and achievements of people living with the disease and the isolation they can feel (they can’t mix with each other due to the risks of cross-infection). These themes were poignantly illustrated by Thomas Oakley, a 15-year old with CF who performed a beautiful solo dance piece against the backdrop of a ‘virtual choir’ comprising people with CF, each individually recorded singing Hozier’s ‘Take me to Church’. View the video on the ECFS webpages.