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In this month’s blog, Dr John Blakey from Respiratory Medicine considers why research is important to healthcare, highlighting some of the current research activities in asthma. Amongst other responsibilities, Dr Blakey is the regional Respiratory Lead for the NIHR Clinical Research Network.

When Darth Vader wants to terrify someone, he restricts their breathing. A usually healthy person is suddenly struggling to get air in and out of their lungs. You can imagine that is frightening at the time, and must have an effect on how the victim feels afterwards. Unfortunately, one in ten people in the UK don’t have to stretch their imagination.

They have asthma, a condition that can make people abruptly and seriously unwell. It causes long-term lung damage, and impacts on mood and anxiety. Over the last forty years, many new medicines have become available for asthma, but admissions to hospital are not falling. Sadly, the number of people dying of asthma is at a ten-year high. 

  • Fig.1: Representation of yearly asthma deaths. One blue figure represents 100 deaths.

 

Asthma outcomes have been particularly bad in the Cheshire and Mersey area over the past 20 years. Children in Liverpool were more than ten times more likely to be admitted for their asthma than children in London when the charity Asthma UK published its “Wish you were here?” report in 2008. There is clearly a serious unmet need in asthma, but progress is being made.

How Can Research Help?

Clinical research isn’t just about comparing a new drug with a standard one (though we do that too). Here are some examples of other ways research can positively influence clinical practice from the asthma clinic.

  1. 1. Describing what is happening now, so we can identify how to improve

If we want to make something better, we must first describe in detail what is currently happening. It isn’t enough to look at broad measures such as admissions. That would be like trying to manage a football team but only looking at the final scores. Ongoing studies such as UNTWIST and NOVELTY describe the experience of large numbers of people with asthma, so we can better see what treatments and systems work well for whom, and which areas should be a particular focus for improvement. Similar studies are open for other respiratory diseases, such as the European Bronchiectasis Registry (EMBARC).

  • The UNTWIST study describes the time taken between having uncontrolled asthma and starting specialist treatment, and the events along the way. 
  1. 2. Making better use of existing treatments

Over the past 40 years, there have been an increasing number of treatments and other interventions (such as educational sessions or weight loss programmes) that have been shown to be effective for asthma in clinical trials. However, these benefits haven’t been translated into a widespread improvement in asthma outcomes. We are therefore undertaking research to understand how best to increase awareness of these interventions, and to target them toward the people that should gain most benefit: a more personalised approach to asthma care. We work with collaborators across Europe and North America to develop and improve tools for assessing asthma that give a personalised risk score and suggestions for tailored care. This not only involves clinical studies, but also NIHR funded work into new statistical methods to analyse large and complex datasets.

  • Screenshot of the Future Asthma Risk Calculator for healthcare providers, currently in beta version [link]. It gives a percentage chance of a patient having an asthma attack in the next two years. We’ve worked with Asthma UK on a similar tool for people with asthma. Try one out!

 

Sometimes these research questions are more simple. The current CAPTAIN study asks whether putting three medicines in one once-daily inhaler will be better for patients than having them separated, as is currently the norm. Although this might only lead to a modest improvement, several of this type of small gain do add up. 

  1. 3. Unpicking the molecular mechanisms

For many conditions, we aren’t able to answer basic questions. For example, we don’t fully understand why some people have asthma and others don’t. It’s therefore extremely important that we continue to undertake research that looks to improve our knowledge of basic molecular mechanisms, such as unpicking the genetic predisposition to asthma.

  • Manhattan plot from the AUGOSA study of genetic predisposition to asthma. This shows the association between genetic markers across genes and a lung function measure, to illustrate the kind of complex results that discovery research produces.

 

For many of these studies there is a long lag time before they influence clinical practice. However, this is not always the case: for example, the Royal hosts a unique and award winning set of studies where volunteers are exposed to small amount of the commonest cause of pneumonia, and their responses are measured. This allows us to understand why people with asthma are more susceptible to pneumonia, but also to make recommendations regarding vaccination strategies in the short term.

  • Members of the large pneumonia research team on a participant recruitment drive

 

We also investigate why medicines are successful, to learn broader issues. The current MRC supported SOMOSA study uses newer kinds of measurements such as breathomics to better characterise people with asthma and describe what alters with specialist treatment.

  • An example of how people with asthma can be divided into subgroups using newer biomarkers such as sputum lipidomics (data from U-BIOPRED).
  1. 4. By the process of research itself

One key aspect of undertaking clinical studies that is usually overlooked is the overall benefit from having research activity. Studies provide more treatment options beyond standard NHS care and increase the contact time between clinical staff and patients. Most importantly for complex syndromes like asthma, the specific inclusion and exclusion criteria of most studies force clinicians to be extremely careful in their management and documentation: the diagnosis must be robust and management optimised before people can enter studies. As might be expected, the NHS Trusts with the highest recruitment into studies usually have excellent clinical outcomes. Last year, the Royal recruited almost 9000 people into studies overall. If the planned merger with Aintree had been completed, the combined total of almost 11000 would have been more than the number recruited in Cambridge or University College London.