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11th May 2023
Professor Adel Mansur specialises in asthma, leading one of the largest severe asthma clinics in the UK. Here, he discusses the centre’s involvement in primary care diagnostic hubs and his most recent practice-altering research.
Adel Mansur is a consultant physician at University Hospitals Birmingham NHS Foundation Trust and honorary professor in respiratory medicine at the University of Birmingham. Originally from Libya, where he attended medical school, Professor Mansur completed a research PhD in asthma genetics at the University of Leeds and joined Heartlands Hospital as a consultant in 2002.
Asthma is where Professor Mansur’s specialist interest lies, and he leads the trust’s severe asthma service – one of the largest and busiest centres of its kind in the UK, serving a local population of over 1.5 million and a regional population of 7.3 million.
We are a regional hub centre for severe asthma, so we receive referrals from across the region, from the West Midlands and beyond. Because of that, it’s a busy centre. There are currently just over 1,000 patients with severe asthma seen at the hub, and on a weekly basis we see 50 to 60 patients. We have a multidisciplinary team looking after our patients, comprised of doctors, specialist asthma nurses, physiotherapists, psychologists and speech therapists.
Our service is geared to deal with the complex and multifactorial disease of difficult to treat asthma, which forms a minority group of all asthma. However, most patients with asthma in primary care have mild or moderate disease but still many remain uncontrolled due to inadequate access to good quality diagnostics and treatment optimisation rather than because of disease severity. On this basis, we piloted with our primary care colleagues in Birmingham a respiratory community diagnostic hub. This provided a service of high-quality diagnostic and specialist input to optimise treatment and triage patients when necessary to our severe asthma network. We were pleased with the pilot outcomes, which led to its adoption by NHS locally and was also quoted by NHS England as an exemplar model.
We believe that we have now a good integrated pathway model in our locality to build on. The University Hospitals Birmingham NHS Foundation Trust still, however, receives 2,000 admissions every year due to asthma – the majority of which would be preventable with proper management in the community, thus arguing for increased capacity of this service model.
In many respects what we’re trying to do is to filter out those who are sub-optimally managed before they come to us. However, poorly controlled asthma can become severe, and that’s the danger that people will end up with sub-optimally managed disease that deteriorates to become more severe. It’s about being able to find those patients first, and that’s what the diagnostic hubs are doing.
Uncontrolled asthma is serious on its own because patients are exposed to potentially fatal attacks. A study looking at fatality in asthma found almost 60% of patients who sadly died from asthma attacks did not have severe asthma, but instead had uncontrolled asthma and weren’t on appropriate medication. This is a major current issue for which there are guidelines aimed at improving asthma management and outcomes. However, the implementation of such guidelines has been a challenge across the board, although I believe that progress has been made in terms of recognition of this issue and provision of clearer asthma management pathways for patients.
When you’ve optimised patients with uncontrolled asthma, you are left with around 10-20% who have severe asthma and will need, for example, a biologic treatment. For the majority of the others, regular preventer inhalers are usually adequate to control their asthma.
I would say up to 90% of asthma is a primary care issue that, with the right treatment and support, should be controlled. Those patients’ management would be best served in the community and wouldn’t require referral to come to severe asthma centres.
Yes, for example we have a research fellowship where junior doctors could do research with us as well as getting clinical experience. That could be for year, or two or three. We have visitors from different disciplines who come to sit in our clinics and shadow our multidisciplinary team members for experience. They’re not just doctors, we have visitors from various disciplines including pharmacists, physiotherapists, speech therapists and nurses who come from primary or secondary care, or even tertiary severe asthma centres, looking for exchange of expertise. We currently have a pharmacist from Saudi Arabia spending three years with us doing his PhD on treatment adherence in severe asthma.
At Heartlands, we have a respiratory research clinical trials unit, where we take part in various clinical trials that include cystic fibrosis, COPD, interstitial lung disease, occupational lung disease, asthma and some other acute presentation conditions such as pneumonia. It’s an active and large R&D department, so there are many other disciplines. Sometimes there is some overlap with other departments, for example, research into infectious diseases, Covid and viruses.
Primarily, I do clinical work, but I take part in research as an academic as well. With clinical work you have more direct interaction with patients, and more insight into patients’ needs. We can use that to explore the main research questions, and that will lead to conducting trials or taking part in studies locally. That could be through collaborations with other centres, either in the UK or internationally.
We then apply that in the clinic because clinical trials allow us to adopt cutting-edge treatments for our patients. They allow us to take the lead in providing our patients with access to cutting-edge and novel treatments, which, in many ways, transform the lives of many of our patients.
We developed in-house an assay for measuring prednisolone and cortisol simultaneously in the blood using high-performance liquid chromatography and spectrometry methodology. There are currently about four centres in the UK who provide this test clinically.
One of the issues in severe asthma is that 40% of patients are on oral maintenance steroids, and we assume that if a patient is prescribed 30mg prednisolone daily, for example, that is what they take. But with the assay we developed, we could actually look for adherence to prednisolone. We’ve done a case-controlled study using this assay among patients who are on steroids and patients who aren’t. We found that 40% of patients who are meant to be on maintenance steroids are not taking it. The assay results from non-adherent patients were similar to those who were not on maintenance prednisolone.
Now, we use the assay in practice and around our network, and it has been advocated by NHS England as well. We don’t really want our patients to be on maintenance steroids because there are newer treatments available now, and steroids are a legacy treatment that should be a last resort.
But we still have a substantial number of patients who are prescribed maintenance steroids, and knowing if they are taking the treatment or not is crucial – if they’re not we’ll stop the prescription of prednisolone and look for other treatments. The assay has also proved useful in managing adherent patients by allowing us to taper the prednisolone dose in a more controlled way. So, this is an example of something we developed here that has been quite crucial for the way we manage our severe asthma patients.
We have a registry for all of our severe asthma patients. There’s a local one and a national one, and the registry nationally produced more than 20 papers in good-impact journals in the last 10 years or so. One of the recent publications, of which I was the primary author, was on the UK practice of biologics in asthma. It looked at variation in practice between different centres, using registry data. We also looked at the outcomes of various biologics and observed that seven to eight in 10 patients do get a worthwhile benefit from biologic treatments.
The aim of having the registry for severe asthma is to promote standardisation of care across the country as well as cross-learning between different centres and adding to debate. We complemented the severe asthma registry analysis with a survey of specialists across the UK. We asked specialists why they choose a certain biologic over others, and which one they would start with and why, and we found variation in practice. It largely stems from the fact that there wasn’t a head-to-head trial to say one biologic is better than another one.
There is always going to be unmet need. We are not going to run out of jobs here, that’s for sure! One thing is the adherence issue, either to a biologic or to other preventer treatments. As humans we don’t like to adhere to things consistently. Some people can master it, but a lot of us can’t. So how can we really help people to have a treatment regime that works for them, and which they can maintain?
There are things like the interconnected digital inhaler, with sensors connected to the inhaler itself, which we are working on. I feel future practice in severe asthma will mean that the majority of patients will have smartphone apps with sensors connected to their inhalers. They’ll have their management plan and their treatment records on their app, which the physician can see on a separate platform, so we know when there are gaps in treatment.
The cost of severe asthma management to health services is high. Ensuring basic treatment in the form of regular use of preventer inhaler therapy may prove effective in controlling asthma without the need to escalate to expensive biologic treatment, as well as reducing burden to the NHS through a reduction in emergency room visits and hospital admissions. The adoption of digital inhalers as routine in severe asthma services is likely to be a much cheaper way of making sure patients’ disease remains under control. I think most severe asthma patients should be, at least in part, on this type of electronically monitored treatment.
Another unmet need is biologics – we still don’t have long-term data on those. I have seen patients whom, after two or three years, will have a viral illness or other trigger and then they feel the treatment is not working as it used to be. Or they suddenly start to flare up, so we look at switching biologics. Sometimes that works, but why does it happen in asthma? Why do some people have a super response, like remission, while others have had some response but still get exacerbations, and they still have residual disease of significance?
We have patients who have not been lucky enough to get a biologic treatment because of their disease type. They are not what we call T2-high, which is a type-2 inflammation that responds well to currently available biologic agents. About 20-30% of patients within the service are in this T2-low class, and these are the ones for whom there is unmet treatment need. Unfortunately, the asthma-related clinical outcomes of this group of patients remain significantly worse than those who could have, and respond well to, biologic treatments.
Things have moved on hugely in terms of the availability of good treatment for patients with severe asthma since I started practising 20 years ago. Our main treatment was lots of steroids, which, as lifesaving as they are, have short- and long-term serious side effects. We then had other things of questionable efficacy such as continuous terbutaline infusion. Nowadays, treatment for severe asthma has been transformed by a precision medicine era with the development of effective yet safe treatment options in the form of biologic treatments. There are currently six NICE-approved biologics and these cover around 60-70% of patients with severe asthma.
Tremendous progress has been made in dissecting the immunological cascades and mechanistics of inflammation in asthma. This provided plethora of therapeutic targets with many currently being trialled for asthma in general and severe asthma in particular. For example, there is a drug called masitinib, which is a tyrosine-kinase inhibitor that is being trialled as a possible treatment for asthma. Another example is the ongoing trialling of JAK-family inhibitors as a treatment option in asthma.
In addition to us being the hub here at Heartlands, we created a severe asthma network that included various centres – or spokes – within the West Midlands, Derbyshire and Gloucestershire, which covers a total population of 7.3 million people. Currently, the network is comprised of about 10 spokes. The spokes can initiate biologics in their respective hospital following approval from a monthly conducted regional multidisciplinary meeting with the hub. This model increased our region service capacity so patients can get the treatment in a quicker time and could have it initiated closer to home than if all patients have to travel to the hub in Birmingham.
This model provided resilience to service delivery due to the high number of asthma specialists included in the running of the service. We have 10 physicians, for example, and more than 10 nurses, who serve the network, contrasted to a small group in any single centre. So, that has been one of the strong points for our service – having a good, strong network. We are maintaining the quality through the performance and standardisation of patients being presented. That’s led to a successful network. It’s still a work in progress, as always, but we think we have good infrastructure.