Five big questions at NACFC

Feature -

A round up of research funded by the Cystic Fibrosis Trust and presented at the North American Cystic Fibrosis Conference (NACFC) in November 2019, including CF registry research on lung function and bone marrow density, and three updates on projects tackling Pseudomonas aeruginosa infection in cystic fibrosis.

1. Is lung function the same in people with CF around the world?

Nearly ten years ago, a research study showed that the lung function of children with CF in USA was higher than in children in the UK, but this difference wasn’t present in adults. Does this mean that lung function declines quicker in people with CF in the USA and were the differences in children real, or were they due to the small differences between people included in the study on either side of the Atlantic? Dr Daniela Schlüter at the University of Liverpool, who works within the CF-EpiNet Strategic Research Centre (SRC), has been working with US colleagues to apply the same statistical analysis to data from both the UK and US CF registries to find out.

The researchers found that the rate of lung function decline was the same in both countries, but US children at the age of six started off with a better lung function. The next step in the analysis is to investigate why six-year-old children have better lung function. One reason may be that the non-CF US population has better lung function overall than the non-CF population in the UK.

2. What can analysis from the UK CF Registry tell us about the causes of CF-related bone disease?

Our bodies keep our bones healthy by adding new bone tissue, and clearing out old tissue. If the balance of new and old tissue isn’t correct, then it can lead to bone thinning or a loss of bone mineral density (BMD). BMD is measured using DEXA scans (dual energy X-ray absorbtiometry), which measure how much low-dose X-ray is absorbed by the bones as a way of measuring how dense they are. In people with cystic fibrosis, BMD levels can drop and in adults this can lead to the development of osteoporosis, something that according to the 2018 UK CF Registry data report, approximately 8% of adults with CF have.

CF centres around the world monitor their own rates of CF complications, including BMD, but a more complete picture of how many people have low BMD, how it’s measured and who might be most likely to have it, can be found by analysis of data from a national registry. Working within our CF-EpiNet SRC programme, Dr Danielle Edwards presented her analysis of BMD and the frequency of DEXA scans using UK CF Registry data. Her work shows that the majority of people with CF in the Registry who were eligible had been monitored with DEXA scans, and that in addition to the known risk factors for low BMD – low FEV1, being older and taking oral steroids – being male, and having CF-related diabetes was also a risk factor.  

3. How do methods of looking for Pseudomonas in children compare to adults?

If someone with CF develops Pseudomonas aeruginosa it is important that it is treated effectively and completely. After a course of treatment, any remaining Pseudomonas can become significantly harder to treat the longer it stays in the lungs. Detecting Pseudomonas more effectively is one of the aims of our SRC investigating a Personalised Approach to Pseudomonas Aeruginosa (PAPA). The team are investigating accurate and sensitive ways of detecting the bug, specifically checking the success of a course of antibiotics, and diagnosing a new infection.

Detecting Pseudomonas at all can be really difficult in children with CF, particularly as they are often unable to cough up sputum. Clinicians at the Royal Brompton Hospital in London use cough swabs or a ‘sputum induction’ procedure to check for it. At NACFC physiotherapist Nicola Collins, working with Professor Jane Davies, the Pseudomonas SRC lead, presented her analysis which showed that sputum induction is more sensitive than cough swabs for detecting Pseudomonas. This adds further evidence to ongoing discussions about the best way to monitor Pseudomonas infection in children.

4. How might having more than one infection affect what’s happening in the lungs?

Some people with CF develop both the fungal infection Aspergillus fumigatus and the bacterial infection Pseudomonas. People who have both bugs appear to be more unwell than those that are infected with only one of them.

To understand these co-infections better, research fellow Dr Dominic Hughes has been studying what happens when these two bugs are grown together in the lab. Rather than supporting each other to grow, the two bugs battle each other for space and food. The weapons used in this fight may trigger more inflammation than is caused by one infection alone. If we can understand which ‘weapons’ are used by the bugs and when, (like knowing the cause of the fire so the correct fire extinguisher can be used), clinicians can prescribe treatments to reduce their effects. Dominic shared his latest results with peers at NACFC.

5. Recap on ‘ribbeting’ research on novel antibiotic

The skin of frogs contains proteins with antibiotic properties and a similar version of these proteins known as Glatiramer Acetate (GA) is approved as a drug for multiple sclerosis (MS). Professor Davies’ Pseudomonas SRC is studying this drug’s effectiveness against Pseudomonas, and the potential for ‘repurposing’ the drug to treat infections in people with cystic fibrosis. Since we last told you about this research, PhD student Ronan Murphy has been looking at the effect of GA in combination with currently-used antibiotics.

Ronan’s results suggest that GA can reduce the amount of antibiotic needed to kill Pseudomonas in the lab. As there are so many different strains of Pseudomonas that people with CF have, researchers need to be sure of the effects of GA in as many of them as possible under lab conditions, before GA might be able to be tested as an effective treatment strategy for Pseudomonas in people with cystic fibrosis.

Talk of the conference

Professor Davies gave a plenary talk at the conference, which was livestreamed and is available to watch online (take a look at Plenary 2 on Friday 1 November – please not that a free registration step is required to watch it). She gave a comprehensive overview of how precision medicines can benefit most people with cystic fibrosis. We’ve given her the final word in this article:

“The focus of the NACFC was on the recent success of triple CFTR modulator drugs, which dramatically improve lung function and exacerbation rates. They are suitable for up to 90% of people with CF based on their gene mutations.

“However, the long-term evidence from the first highly-effective modulator, ivacaftor (Kalydeco) would suggest that most people chronically infected with Pseudomonas do not clear the infection when they take the drug. We will continue to need research into this very common bug for many years to come. The team would like to thank the Cystic Fibrosis Trust for their funding and support in increasing awareness of our research”.

Please consider making a donation today to fund ground-breaking research like this.

Donate today

Your donation will make a difference:

Select amount