The National Heart and Lung Institute (NHLI) was delighted to have Asthma UK fellowships awarded to Dr Adam Byrne and Dr Louise Fleming.

WHO estimates 235 million people suffer from asthma around the world. It is the most common chronic disease among children. Although many people are familiar with the disease, you may be unaware of the possible severity of the disease - according to the latest WHO estimates, released in December 2016, there were 383 000 deaths due to asthma in 2015. For many, as with any chronic condition, even ‘milder’ forms of the disease can have a massive impact on daily life due to the demands of everyday management of the disease.

As part of Asthma UK’s mission to stop asthma attacks and cure asthma they fund world leading research into asthma. The charity has spent over £50 million on basic and clinical research to understand more about asthma, its causes and treatments. NHLI researchers Dr Louise Fleming and Dr Adam Byrne were both awarded Asthma UK fellowships to further their work on asthma. I sat down with them both to find out what the award meant for them and their research.

Dr Louise Fleming has been awarded a 3 year Asthma UK Senior Clinical Fellowship Award for her project entitled “Identifying and improving adherence in children with asthma using novel technologies”. 

What is your research about?

My main interests include distinguishing children with true severe asthma from those whose asthma is worsened by poor asthma control, due to reasons that we can work on. My research includes identifying different types of asthma and tailoring management strategies, including non-pharmacological interventions, to the individual. At present we use a “one size fits all” approach to treatment. If someone’s asthma isn’t well controlled their asthma medication (usually inhaled steroids) is increased.

“Having an Asthma UK fellowship means a great deal to me. I have worked closely with Asthma UK for a number of years and know first-hand the great work they do in patient support and advocacy." Dr Louise Fleming

I have recently completed studies measuring how much inhaled steroids children are actually taking using electronic monitoring devices. These devices are attached to the inhaler and record when it is used so we can look at how often a child uses their inhaler (adherence) and how adherence varies over the trial period. We can use this information to inform what we do next for the management of their asthma. For example, if adherence is poor we need to find out why the child isn’t taking their inhaler and find ways to improve adherence. If, on the other hand, adherence is good during the trial, but asthma control remains poor, then we need to step up treatment, which could include starting expensive novel therapies. However, the problem with the current electronic devices is that they record only whether the inhaler has been activated, but not whether it was actually inhaled, or inhaled properly. If a patient is not getting the proper dosage due to incorrect use of their inhaler and hence we see no improvement in their symptoms as a consequence, you can understand why they would stop using their inhaler.

We know that there are many reasons why children have poor adherence. For this new study I will be using the “practicalities and perceptions” framework.  There may be  practical reasons for a child not taking their inhaler, for example they don’t know how to take it properly or forget to do so. Or there may be perceptual issues, for example a patient may not think the inhaled steroid works or is concerned about side effects. We will use this framework to improve adherence by addressing both the practical and the perceptual barriers to adherence. 

How will you go about achieving this?

The Fellowship involves a two-stage study. The first part of the study will road test novel devices which monitor both activation (actuation) and inhalation – is the inhaler being used and if it is, is it being used properly? Currently there are no commercially available devices but there are a number in development. One has a flow sensor that can measure if the right breath is taken, another has an acoustic sensor that can ‘hear’ if the intake of breath is correct. The other options are App based; for example a parent films the child taking the inhaler and then uploads it for a specialist nurse to review; or using the inhaler correctly generates a noise that unlocks a game on an App for the child to play (as an incentive).

The device which performs best in the feasibility study will be taken forward to the second part of the study: a clinical trial to compare the new device with existing electronic monitoring devices and usual care (no monitoring). However, this only addresses the practical aspects of inhaler use. We will combine this with an intervention to address perceptual issues. This will be in the form of a short animation to help educate children and their parents.

There has been an increase in new drugs (mostly monoclonal antibodies) for severe asthma over the past few years. These drugs are expensive. Currently only one monoclonal is licensed for children. In time we hope that more will be licensed. It is therefore of vital importance that we identify appropriate children for these add-on therapies and determine which add-on is most appropriate for which patient. I collaborate with Professors Sejal Saglani and Clare Lloyd who have done a great deal to advance our understanding of the mechanisms of true severe asthma in children and identify novel therapeutic targets. The foundation of this work is to ensure that children with problematic severe asthma (poor control despite high intensity treatment) are carefully characterised and we know that they are truly steroid resistant, rather than that they are simply not taking their treatment. That is why studies such as this one are of vital importance. 

Where could this lead in next 5-10 years?

I would hope that we have digital technologies available that are cheap enough that they can be widely rolled out so that they can be a core component of asthma care for all patients with asthma. When making decisions about a patient’s management knowledge about how much they are taking, and whether they are taking it properly will inform decisions as part of mainstream care. Ideally such devices will be inbuilt in all inhalers, not added on, so all this data can be recorded and a simple read out is available to ensure the  large amounts of data produced are easy to analyse.

Dr Adam Byrne has been awarded a 3 year senior non-clinical fellowship with Asthma UK for his project entitled ‘Investigating the role of innate glycolytic reprogramming in asthma’. 

What is your research about?

Cells need energy to carry out their jobs and there has been a lot of work to date looking at how the metabolic processes of immune cells affect their role in disease, this relatively new field is called ‘immuno-metabolism’. It has been recently discovered that manipulating the metabolism of cells can enhance or reduce inflammation. These studies gave us key insights into how the body fuels inflammation, but so far these studies have been mainly carried out in vitro. We will be taking lung samples from patients or healthy volunteers, to get close to a real life study and further our understanding of what happens in an asthma sufferer’s lungs. Ultimately we want to understand how asthma and metabolism are linked. 

"The fellowship is a great honour and as someone who is a newly appointed lecturer, this is a fantastic chance to create a programme of research to build my career." Dr Adam Byrne

Asthma does not always happen in the same way, but is basically an umbrella term for various ‘strains’ of the condition. So we want to look at how cellular metabolism works for each permutation. 

Similar work in this area for cancer has already been used to design drugs that act on metabolic processes to treat the disease. Part of our work will be investigating how these drugs that act on the metabolic pathway influence the inflammation of the airways associated with asthma. We want to find out whether we can improve asthma by correcting defective metabolic pathways. If we can understand how metabolic processes are altered during disease, we could potentially use a wide range of currently available drugs, to directly target immune cell metabolism in patients. Like a car bellowing smoke, to get to the route of the problem, rather than look to fix the smoke itself, you would look under the hood at the engine – to find what is causing the problem. We are similarly looking at the metabolic pathway to better understand how this is influencing the restriction of a person’s airways during an asthma attack, as a result of the inflammatory response. Rather than treating the symptoms of the attack itself we want to prevent it happening. 

Other work in my lab is focusing on metabolic changes in people with Idiopathic Pulmonary Fibrosis (IPF) and has found they work until ‘metabolic breaking point’. My work in IPF, funded by the Wellcome Trust, also showed that different macrophages are linked with different severities of the condition and we would expect the same in asthma. 

We hope to answer questions such as, will different types of asthma have different metabolic profiles? Could this profile be a clue to type of asthma a patient has?

Where could this lead in next 5-10 years?

Mild asthma is more treatable as it stands but finding something that can be used by severe sufferers would be a great next step. My hope is that research in this area could lead to improved treatment for these patients, which may seem a way off, but I am hopeful. Perhaps this work could be used to identify severe sufferers from their metabolic profile.