“This is something that's intrusive to everyday life - and that was a strong motivation for me to do more in this area”: Professor Alan Smyth, Principal Investigator of our new SRC on CF gut symptoms

News -

We’re delighted to announce the launch of a new Strategic Research Centre opening at the University of Nottingham, which aims to establish the causes of gut symptoms in people with CF. As the research gets underway, Katie Gathercole, who lives with CF and chairs the Patient Advisory Group within this SRC, quizzed principal investigator Professor Alan Smyth about why this area of research is so important, how people with CF can get involved, and the difference it could make to the CF community.

Photo of Professor Alan Smyth

Katie: Hi Alan, could you start by explaining what exactly led you to apply for funding to set up this SRC that focuses on CF gut symptoms?

Alan: I think it all began with work we did on engaging the CF community through the James Lind Alliance priority setting partnership. It just so happened that the second question on a list of 10 that came out of this project was, ‘How can we relieve gastrointestinal symptoms in CF?’ What follows from that is a bit of good luck. I met up with some fabulous colleagues in the University of Nottingham who've been doing MRI scanning on the intestines for many years, looking at patients who have inflammatory bowel disease and some who have irritable bowel syndrome. They had developed techniques which were just waiting to be applied to the gut problems that people with CF experience, and that is the kind of journey we went on to start this research.

Katie: As a person with CF, it’s been wonderful to see this interest in the gut, because it has sometimes felt like research has focused a lot on the CF lungs. Why do you think this research is important?

Alan: One of the most influential things for me was that when we did a survey with people with CF and children with CF and their parents, the standout message was that two thirds of adults and children miss school or work because of gut symptoms. So clearly this is something that's intrusive and disruptive to everyday life, and things that people who don't have a chronic disorder might take for granted. So that was a strong motivation for me to do more in this area.

Katie: What approach will you use in this SRC?

Alan: We’re using some new and novel approaches.

We’re working on the basis that not everybody's the same and not every person with CF experiences the same symptoms. If that's the case, the mechanisms behind those symptoms are different in different people and we want to explore that.

Our first stage will be to use a symptom questionnaire to try and identify clusters of symptoms. We think that by using statistical analysis we can identify clusters of symptoms. For example, there might be people for whom the biggest problem is pain, bloating or distension of the tummy. There might be another group who are troubled with urgency, loose stools or poor digestion. We think that the mechanism behind each of those will be different, and what that means is the treatment you might give for each of those symptoms will also be different.

To understand the mechanisms, we are going to look at that with detailed measures of inflammation, studies of the bacteria that live in the bowel called the microbiome, and finally through MRI scans that show the physiology and action of the way the gut functions in CF.

Katie: Could you tell us how people with CF are going to be involved in this research?

Alan: We have a patient panel which will help shape this research. I think it’s really important for us to work with people with CF in a much more holistic way to mould and determine the direction of travel of this SRC.

We will also be recruiting people with CF to complete questionnaires through centres in Leeds and Nottingham. There will be 300 adults and 50 children. What we will then do is go back and look at the work of a previous SRC in Leeds which had the same questionnaire, and we apply what we call latent class analysis to that group and see if it also holds true in a separate population.

We’re working on the basis that not everybody's the same and not every person with CF experiences the same symptoms. If that's the case, the mechanisms behind those symptoms are different in different people and we want to explore that.

Professor Alan Smyth
Photo of Katie Gathercole

Katie: It seems to me then that the research that will be done through the SRC is going to be really important for all people with CF, regardless of modulator therapy access or not. Is that fair to say?

Alan: Absolutely. My hunch is that CFTR modulator therapies such as Kaftrio will contribute in large part to symptom reduction. That's the anecdotal information we're getting from patients, but we need to know a lot more about that. Does it solve the problem? Does it only solve the problem for some symptom clusters? And what, if any, additional treatment might be necessary for people with CF who are on modulators and want to get much better control of their bowel symptoms? And what about people who can't have modulators, either because their genotype is unsuitable or because they experience side effects?

Katie: And finally, what do you hope to see happen as a result of the findings of this SRC?

Alan: In simple terms, what I want at the end of this is to know whether all gut symptoms experienced by people with CF are the same or whether we have these different clusters of symptoms. I suspect it's going to be the latter and therefore we should tailor our treatments accordingly. I would like to get to a point where we can design something like a phase two trial. So we can take a treatment and randomly assign patients to that treatment and then measure outcome measures: physiological outcome measures such as MRI but also an improvement in symptoms. And then ultimately, through a phase two and a phase three trial, I think we can look at how we can repurpose drugs existing drugs to treat these symptoms.

Katie: Thank you Alan! It’s really exciting and I think a lot of people with CF will be delighted to know that we are going to get more focused understanding and to see how that translates to real treatments and real solutions for people experiencing these symptoms.

Cystic fibrosis (CF) is a genetic condition which causes sticky mucus to build up in the lungs and digestive system. It affects more than 10,800 people in the UK. One in 25 of us carries the faulty gene that causes it, usually without knowing.

Since 1964, we've supported people with cystic fibrosis to live longer, healthier lives -and we won’t stop until everyone can live without limits imposed by CF.

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