Dairy, yeast, pollen, nuts, dander

A blonde man wearing glasses and a red shirt sits in a cafe with a coffee and sandwich, looking to camera

Pollen, dust, nuts, milk, fur… allergens are everywhere.

We use various treatments to keep them under control, but for me that’s not enough. I’m much more interested in achieving health, rather than just treating the disease. So, understanding what causes the allergy in the first place is fundamental, not just in treating it, but also in helping us to get to grips with the bigger picture. I firmly believe that by understanding what is causing the increase in allergic diseases, we may ultimately come to understand the causes of the increase in a number of other complex non-communicable diseases, such as diabetes, arthritis or even leukaemia.

A good place to start is to gather a realistic and accurate picture of the change in prevalence of different allergic diseases and the consequences of living with them. For example, hay fever was extremely rare in the 19th century, but by the mid-1950s it was declared a public health emergency in New York. The allergy clinic at St Mary’s Hospital in London had thousands of patients on pollen immunotherapy as early as the 1960s, and today, around 25 per cent of our UK population suffers from it.

An increase in hay fever was followed by a rapid increase in cases of asthma from the 1960s to the end of the 20th century. Now its prevalence stands at nearly 15 per cent. Finally, in the past couple of decades, we’ve experienced an extraordinary rise in the number of children developing food allergies. When I was running allergy services in the north-west of England in the 1990s, I could see all my young patients with nut allergies in just three or four clinics. It’s vastly different today. And for me, that poses a remarkable challenge.

A spectrum of diagnoses

My efforts to grasp what triggered this huge increase took me outside the UK. I believed we would learn more by observing a part of the world where those changes might be in the process of happening. So, for more than a decade, from the early 1990s to 2005, we conducted a series of studies in Ghana.

It was important not to take the approach of simply asking people whether they had allergies or asthma, because at that time awareness of these conditions was growing. Instead, we used a spectrum of objective diagnostics – such as skin testing and exercise challenge testing – across more than a thousand children. The results were staggering. In the course of just a decade, the prevalence of airway hyperreactivity, asthma and allergic sensitisation among the children doubled.

Interestingly, in the UK, asthma is strongly associated with allergic sensitisation and increased body mass index. But what we saw in Ghana in the early 1990s was different, and children with asthma were not allergic. And yet, the “new asthma disease” that emerged there over the subsequent decade looked precisely like the one we have in the UK. It was a ‘wow!’ moment – there was a brand new phenotype emerging, not a simple increase in the disease that was already there.

A bunch of pink lilies in a vase, with a label stating 'Allergy to pollen affects up to one in five people at some point in their lives'

Eye-watering stats: the NHS estimates that there are more than 10 million people with hay fever in England.

Eye-watering stats: the NHS estimates that there are more than 10 million people with hay fever in England.

A peanut butter sandwich with a label 'Peanuts are the food most likely to cause anaphylaxis and death'

Danger zone: peanut allergy is the most common cause of food induced anaphylaxis.

Danger zone: peanut allergy is the most common cause of food induced anaphylaxis.

Finding answers

And it has got me thinking about another question. We observe the symptoms of asthma – but could ‘asthma’ actually be an umbrella term for a number of very different sets of disease mechanisms? You quickly see in clinical practice that patients with asthma may be very different from each other, and that their disease is caused by fundamentally different mechanisms.

By extension, they will respond differently to different treatments, and the only way to deliver personalised management is to understand which mechanism gives rise to symptoms in an individual patient, and administer treatment that targets that specific mechanism.

Say you have a child with a fever. The fever is what you can see – a phenotype. But what is the cause of that fever? It could be bacterial, in which case, give them antibiotics. But it’s more probably viral, in which case antibiotics are really counterproductive. In certain regions of the world, it’s quite likely to be malaria. Three different causes, all manifesting in fever. What that tells us is that unless you understand what process is contributing to the expression of an individual’s symptoms, you won’t be able to treat them appropriately.

Sometimes gaining a realistic and accurate picture of the consequences of living with an allergy can be helpful itself. A diagnosis of food allergy can be frightening for both child and parent, and lead to all sorts of unfortunate results: a child feeling excluded by their peers, an anxiety that can hugely impact the quality of life for all involved. One problem we are facing is that we can’t yet accurately identify those who are at greatest risk from severe allergic reaction. The tools simply aren’t there yet, although colleagues in my group, such as Dr Paul Turner, are working hard on them.

The core of my own work in the past 20 years has been the use of machine learning to help interrogate all these questions. In the paediatric allergy field in the 1980s and 90s we had relatively small datasets – you could look at the data and see patterns. Then technology kicked in and we were suddenly able to collect vast amounts of data. But in that situation, you risk no longer quite knowing what question you’re asking, because what’s available to you for interrogation is so huge. So, I knew we needed to invest in ways of understanding patterns within these very large datasets. Machine learning and AI are extremely powerful tools to achieve this, and we’re harnessing them to understand the complexity underpinning common complex diseases such as allergic diseases, and to help tease out the mechanisms. This is challenging, but I am convinced it’s solvable.

People still want answers to those fundamental questions of causation, of course. The hygiene hypothesis broadly proposes that as a species we have evolved over millions of years, and our immune system has been fine-tuned to expect a certain kind of environment. Environmental exposures play a crucial role in educating the immune system as to how to develop properly. If you suddenly remove all these exposures, or most of them, the biodiversity disappears, and so it’s no surprise that your immune system does not mature as it should. That’s a given, and it’s one with consequences – allergic diseases.

There’s no reason why our goal shouldn’t be a return to a world without allergies and asthma

Asthma and allergic diseases are probably the least of the problems arising from this ecosystem change. For the first time ever, we’re getting into a situation where life expectancy may be going down. We’re seeing a vast increase in inflammatory diseases, such as arthritis and diabetes. There could be catastrophic consequences unless we do something because it’s entirely due to lifestyle and environmental factors. A fivefold increase in a disease incidence in 50 years? Genes are not responsible for that.

But amid the pessimism, there is hope. Because it is the sheer commonness of these diseases that now gives us the best chance of understanding them. We’re seeing a welcome move toward viewing patients as individuals, requiring individual treatment approaches. But our goal as physicians should not be to have our patients’ symptoms well controlled by taking drugs for the next 50 years of their lives. If 100 years ago there were almost no allergic diseases and precious little asthma, then there’s no reason why our goal shouldn’t be to return to a world without allergies and asthma. By understanding the changes that have contributed to this, we can reverse the trend. You could say that my career goal is to put myself out of business.

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This story was published originally in Imperial 53/Winter 2022-23.