Eosinophils – a type of white blood cell

Eosinophils – a type of white blood cell – are a biomarker for asthma: too many of them in the lungs can cause inflammation

Severe asthma: when nature’s natural defences work against us

Around 36 million people around the world are living with severe asthma. But, hope could be on the horizon thanks to a better understanding of how certain blood cells malfunction.

What does today look like for you? Perhaps you’ll get up, head to work, meet friends for dinner – and then home to bed, so you are ready and refreshed to do it all again tomorrow.

So far, so normal. But for people with severe asthma, an ordinary day for you would be an extraordinary one for them.

In the words of one patient: “I have to schedule everything around my lungs.”

Of the 358 million people who live with asthma worldwide, it is estimated that up to 10% have severe asthma. Severe asthma is a different form of asthma in which people struggle to control their symptoms. They may continue to have asthma attacks, even when they take high doses of medicine.

For many severe asthma patients, even simple tasks can become difficult. Many live in fear of their next attack, of not being able to breathe.

Patients describe what it feels like to live with severe asthma

Not all asthma is the same

Asthma is a chronic lung disease in which inflammation in the lungs makes the airways narrow. This can lead to symptoms such as coughing, wheezing, breathlessness and a tight chest. When these symptoms become worse, it can lead to an asthma attack.

Developments in therapy mean that many patients are able to manage their disease with daily treatment. But patients who struggle to control their asthma with high doses of standard treatments are classed as having ‘severe asthma’.

Research has shown that not all asthma is the same. Asthma can have a number of underlying causes and different types of inflammation. For some people, their inflammation may be triggered by environmental allergens, such as dust mites, pollen and moulds.

For others, their own body may be turning against them.

When nature’s natural defences work against us

All of us have eosinophils in our body. They are a type of white blood cell, produced in our bone marrow, and are an important part of our immune system. Found primarily in the gut, they fight parasites and, together with other cells, they form a complex network that helps protect us and keep us healthy.

Inflammation and swelling in the airways can increase the risk of an asthma attack

But in some people, eosinophils can cause trouble. In around half of people with severe asthma, a raised level of eosinophils in their bloodstream causes inflammation and swelling in the airways that deliver vital oxygen to the lungs, making it difficult to breathe and increasing the risk of an asthma attack.

“Scientists do not fully understand why levels of eosinophils are raised in certain people,” says Steve Yancey, who is a medicines development leader in GSK’s respiratory team. After training in biology and physiology, Steve worked in academic research before joining GSK as a clinical monitor in respiratory. During his career, he has been involved in several major breakthroughs in respiratory medicine. 

“Many cases are caused by exposure to things in the environment, such as viruses (which can cause a cold) or allergens,” Steve adds. “These in turn trigger an exaggerated allergic response in susceptible people, resulting in eosinophils over-reacting.”

Eosinophils earned their name in the late nineteenth century, although they were almost certainly discovered earlier. In 1878, the German physician Paul Ehrlich introduced the term to describe cells with granules, which are highlighted by eosin – a bright red synthetic dye. He speculated correctly that these cells can cause asthma, various skin diseases and reactions to medications.[1]

“We have learned a great deal over the last few years about the role eosinophils play in causing certain types of severe asthma,” Steve notes. “This knowledge has led us to answers, allowing us to develop treatments that get to the root cause of some people’s asthma symptoms.”

Targeting biomarkers with biologics

Eosinophils are a biomarker – this is a molecule, gene or characteristic by which a particular disease can be recognised. By understanding how biomarkers work – and the part they play in the body – scientists can identify ways of developing personalised treatments for respiratory conditions.

The level of eosinophils in the blood of people with frequent asthma attacks can help direct the appropriate use of medicines

Only recently, and with the help of GSK scientists, have we understood that the level of eosinophils in the blood of people with frequent asthma attacks can help direct the appropriate use of medicines.    

Scientists at GSK have developed biologic medicines – produced by living cells, rather than a chemical process – which treat severe eosinophilic asthma by reducing levels of these troublesome white blood cells through targeting a particular protein. The eosinophil biomarker helps to identify patients who are most likely to benefit from these treatments.  

“Understanding the way that biology works differently in different people is at the heart of personalised treatment: it means that treatment can be targeted very specifically – helping us get the right treatment to the right patient,” says Steve.

Looking to the future, Steve hopes that one day, these treatments will be more preventative, not just treating the person in need.

“Ultimately, we are searching for strategies that may reset the biology of patients who are at risk of developing asthma, to prevent the onset of disease, or perhaps prevent patients from developing the most severe forms of this disease.”

[1] https://www.ncbi.nlm.nih.gov/pubmed/25544991 (accessed April 2018)