This website is intended for healthcare professionals only.

Hospital Healthcare Europe
Hospital Pharmacy Europe     Newsletter    Login            

Altering the trajectory of COPD exacerbations


The King’s Centre for Lung Health aims to eliminate lung disease through a better understanding of diagnostics, prevention and treatment. Here, the Centre’s director Dr Mona Bafadhel discusses these lofty ambitions and her research and practice in COPD.

Dr Mona Bafadhel is the chair of respiratory medicine at King’s College London and director of the King’s Centre for Lung Health. Launched in June 2022, the Centre’s vision is to become a hub of world-class excellence for understanding respiratory disease, focusing on innovative and inclusive research to tackle unmet global need.

This new initiative, described by Dr Bafadhel as “very exciting” and bringing with it “lots of opportunities”, is a collaboration between multiple NHS trusts in the locality, as well as its charity partner Asthma and Lung UK.

With a large population of patients and strong “cohesion and collegiality across the associated groups from the basic scientists all the way through to clinicians, nurses, pharmacists, the palliative care team”, Dr Bafadhel hopes it will lead to lots of new insights about respiratory lung disease.

What lung diseases are being investigated at the Centre?

We’re covering the common and the uncommon lung diseases – we have very big clinical research excellence in asthma, we’re going to set up some COPD research and we have a very big presence in physiology. There’s also work being done in sleep and ventilation, cancer, of course, and infection. Pleural-based and interstitial lung disease is also a focus area. We’re covering a lot of ground.

We’re also interested in the life course, so we’re looking to share our knowledge with colleagues from early in utero and paediatrics as well, and we will be working with our imaging colleagues too. It’s a wide breadth of different disciplines coming together for the different disease states that we’re looking at.

What is your own clinical area of interest?

My main interest is in COPD, particularly COPD exacerbations. COPD probably affects one in 10 of the adult population in the UK and it’s not just a smoking disease. We’re learning a lot about these exacerbations, so these episodes or crisis moments where patients feel worse. There’s a COPD patient having one of these crisis attacks probably once every 20 seconds in this country alone, so it’s a huge health burden and a distressing time for patients. My main interest and focus for the last 15 or so years of research has been looking to try and improve how we understand these episodes and how we treat them better.

COPD is almost an umbrella term for chronic bronchitis and emphysema. The majority of COPD is caused by smoking, but we’re now recognising that the effects of air pollution – the effects of early exposure in your life – and the effects of infection may also lead to obstructive lung disease. It’s diagnosed by a classic symptom history of cough, breathlessness, sputum production and it’s confirmed by spirometry – the lung function test that we can do in community and in hospital. It’s often diagnosed later on in life, but I suspect we’re missing lots of early cases because people attribute their breathlessness to getting older or getting unfitter.

Exacerbation episodes are the greatest burden, they’re associated with worsening quality of life, worsening lung function, increased risk of needing to go to hospital and an increased risk of dying. It’s one of the greatest needs in respiratory medicine.

Can you tell us about your research on eosinophils in COPD?

I could talk about COPD and eosinophils for a very long time! The eosinophil is an immune cell that everyone has, and it was largely known to be related to allergy, asthma and parasitic infections where you’d have a higher eosinophil blood count. We never really thought about the importance of eosinophil in COPD. In my research about 15 years ago, I was able to show that eosinophil in the airway correlated to eosinophil in the blood and, importantly, the eosinophil in the blood is a very good surrogate marker for telling you that you have a particular type of airway inflammation. What’s important about that? Well, we know from asthma studies that this particular airway inflammation – T2 high inflammation – indicates that someone will have the best response to inhaled corticosteroids, oral corticosteroids or monoclonal antibodies, for example.

We saw that it had exacerbations so there was a group of people who had this eosinophilic-type exacerbation and who had a better response to prednisolone. We did some proof-of-concept studies looking at that and the blood was the easiest way to test it. We’ve subsequently shown that the blood eosinophil was related to who was going to have the best response to inhaled corticosteroids in COPD and that work has been able to influence clinical guideline practice such that now, looking at the eosinophil when you’re starting to think about inhaled steroids in patients with COPD is indicated from a global point of view.

What does the eosinophil do?

We’re not really sure yet. It’s a tough old cell, it does lots of different things and I think what we’re slowly trying to find out is how it links to what’s going on in the airway, what’s going on in the blood and how it’s affecting other organs. There are two schools of thought, one who think it actually does something and one who think it’s just a bystander. I’m in the former group, I think they do something important. We’ll try to tease it out in the next few years, I hope.

For an acute exacerbation event, I think there’s potential to look at the eosinophil count at the acute time in a point-of-care analysis. We’ve just done a study about that – it’s currently in preparation for manuscript and peer review – and really it does look like you can use a point of care analysis to tell you that someone may not need steroids. And, of course, oral steroids themselves have side effects so we’re trying to be much more personalised and precise in treatments. We’re not fully there yet, but I don’t think it’ll be too long before things change in clinical practice – the next five or 10 years, I suspect.

Is there a role for monoclonal antibodies in COPD?

The studies didn’t reach their primary endpoints, so they weren’t positive in the first go for using monoclonal antibodies. The two monoclonal antibodies that have been tested with COPD so far have been mepolizumab or benralizumab and they’re not licensed yet. When people have delved down into the characteristics a bit more, there probably is a subgroup that do best, and that’ll be the group that have higher eosinophils and more exacerbations.

The trials are being redone; I know the benralizumab study is being repeated for monoclonal antibodies in COPD – that’s the RESOLUTE study. And we also have the dupilumab studies being done in COPD, so we’ve got a few more trials that will hopefully come out in the next 12-18 months that will give us more insight into whether there is a role for monoclonal antibodies in COPD. I would hope that there might be, but it’s going to be in a subgroup, it’s not going to be for everyone.

The King’s Centre for Lung Health is involved in shaping how the studies are reported and how they get started so it’s very exciting for us.

What other areas of research are you exploring?

We’re currently doing an early phase study looking at the use of a monoclonal antibodies at the acute exacerbation stage. If these are positive then we’ll go on to work on the bigger trials. We’re also looking at research trying to understand the cardiovascular risk for patients with COPD, there’s work looking at readmissions in people with COPD and we’re interested in the immunology and the response people have with infections such as viruses.

We’re also interested in looking at the effect or hormones in COPD, particularly the menopause in women. There are oestrogen receptors are present in the lining of the lungs and, if there are receptors there, it must mean that oestrogen is probably playing a role and doing something. The interest has been sparked because we’ve learnt that women have a quicker loss of lung function when exposed to cigarette smoke and they’re often more severe in their disease categories when they’re diagnosed with asthma and COPD. The menopausal effect is something that we need to consider a little bit more when we’re doing our clinical trials, our basic science experiments and when we’re recruiting our patients.

What are your hopes for lung disease research in the future?

I’d like us to be able to diagnose lung disease earlier. Ultimately, I’d like us to prevent it from happening. I think that requires us to understand how it happens, what the exposures are and what the interactions are at the immune level. Earlier diagnosis will be key to influence starting treatment earlier to be able to alter disease trajectory. That’s one really key aspect. Of course, what I’d really like us to do is prevent these exacerbations from happening completely, so almost have the ability for the human response to be able to manage when you have a lung disease. There are colleagues at Imperial, for example, who are looking at early COPD cohorts, so I think we’ll get lots more information on this as that data comes out.

The Covid-19 pandemic showed us that we’re now understanding how important our lungs are. We all recognise that symptoms of cough or breathlessness aren’t normal and so many of us are empowered now to go and say, ‘I’m not feeling right, we need to do some tests.’ That’s a step forward and, of course, we’re recognising the impact of viruses on lungs whether you’ve got healthy lungs or unhealthy lungs. With time, I’d like to see the next five or 10 years really transform lung health and the health of our patients.

This article is part of our Clinical Excellence series, which offers valuable first-hand insights into how experts from renowned Centres of Excellence are pursuing innovative approaches to optimise patient care across the UK and Europe.

Clinical Excellence Click here to read more Clinical Excellence content