RTD info logoMagazine on European Research

N 41 - May 2004
  HEALTH RESEARCH  -  The allergy enigma

One in four European children under the age of 10 suffers from an allergy. Why is this a growing problem? Are the causes environmental or hereditary? Why is it that, despite relatively homogenous lifestyles in apparently comparable countries, the percentages of allergy sufferers show such marked contrasts? All in all, the scientists have certainly not finished grappling with the allergy headache. As part of their efforts, 25 leading research teams have come together within the GA2LEN European network of excellence.  

The ‘allergy sufferer’s wave’, an identifying gesture of people suffering from hay fever.
The ‘allergy sufferer’s wave’, an identifying gesture of people suffering from hay fever.
'The sound of my wheezing drowns out that of my pen, I am in a cloud of smoke which, I swear to you, you would refuse to enter, and in which you would be nothing but tears and coughing.'   The suffering and the anguish of the asthma sufferer has rarely been described with such poignancy as in this letter of 31 August, 1901, written by the French novelist Marcel Proust to his mother. Today, this suffering and anguish is becoming increasingly common, affecting almost a quarter of children in Europe.

At its present rate of growth, it is an epidemic which threatens to impair the quality of life of future generations. Of Europe's 80 million allergy sufferers, two-thirds say it presents a serious handicap in their day-to-day life. 

Hypersensitive immunity
Prevalence of allergic symptoms © Source: ISAAC study carried out among 464 000 children aged between 13 and 14 in 56 countries (1998).
Prevalence of allergic symptoms
© Source: ISAAC study carried out among 464 000 children aged between 13 and 14 in 56 countries (1998).
Over the past 20 years, a lot of progress has been made in our understanding of the biology of allergies. We now know that they are linked to the immune system producing a particular kind of antibody known as class E immunoglobulins (IgE). IgE is the human body's natural response to parasitic infections. For reasons we have yet to grasp fully, allergy sufferers produce an excess of IgE in response to exposure to a substance which usually produces no effect in non-sufferers.

Although identifying this hypersensitive immune reaction has paved the way to the development of new treatments, these have not solved the problem as a whole. The fact is a third of people who produce excess IgE do not develop any allergic symptoms. Immunologists still have questions to answer, although the principal challenge no doubt lies elsewhere: in an understanding of the reasons why the prevalence of allergies, while increasing rapidly, also varies greatly from one country to another.

Epidemiological conundrum
The epidemiology of allergies is very much an enigma. How do we explain, given the relatively homogenous lifestyles throughout Europe, allergy rates of 3.7% among 13-14-year-olds in Greece and of 32.2% for the same age group in the United Kingdom? It cannot be climate, because countries as different as Finland and Malta both show a 16% prevalence. Atmospheric pollution? Not that either. In Eastern Europe, where the air quality can be particularly poor, children suffer less from allergies than they do in Western Europe: 8% in Poland and Lithuania, but 29% in Ireland. 

Coupled with these surprising geographical differences, there is the rapid increase in the frequency of allergies over the past 20 years. Is this down to genetics or an environmental influence? As always, it is probably a bit of both. The same environmental factors are allergenic for subject X and harmless for subject Y, due to differences in their genetic make up. However, unlike for other diseases where the debate between the champions of the hereditary hypothesis and supporters of the environmental explanation leads to an impasse, the increased frequency of allergies offers a useful way forward in defining research priorities. The genetic make up of Europeans cannot have changed much over the past 20 years. This implies that it is the environmental changes which must be studied.

Asthma prevalence, children and young adults

Asthma prevalence, children and young adults  Source: Cologne University

© Source: Cologne University
Recognising the scale of the problem
'To date, there has been insufficient integration of environmental policy and health policy. It has proved difficult to study the relationships of cause and effect between these two fields,' admitted Health and Consumer Protection Commissioner David Byrne on presenting the European SCALE strategy to combat children's diseases linked to the environment. Asthma and other allergies top the list of these diseases, followed by neurological development disorders, cancers and disturbances of the endocrinal system. 

The acronym SCALE is an entire programme in itself. The ‘S’ for ‘Science’ evokes the need for scientific research on pollutants and allergens. How do they interact and travel? How do we come into contact with them – through the air, water or diet? The ‘C’ for ‘Children’ indicates the priority given to studies on childhood, the period when the body is most sensitive to the action of pollutants and when exposure can have effects that last a lifetime. The ‘A’ for ‘Awareness’ highlights the importance of ensuring that the general public, economic players politicians and other stakeholders are all well informed. The ‘L’ for ‘Legislation’ and the ‘E’ for ‘Evaluation’ stress the need to adapt European legislation to take full account of this public health priority and to assess regularly the effectiveness of all action taken. 

In the food
The SCALE strategy's action programme will be presented at the Interministerial Conference on the Environment and Health, to be held in Budapest in June. Research directly relating to this strategy has already been carried out in the field of food allergies. This is partly in response to strong public concern over the matter.

Fears of allergies relating to the consumption of products containing genetically modified (GM) maize or soya has a lot to do with the suspicions harboured by many Europeans on the subject of genetic modification in general. Moreover, the debate extends beyond this issue. Globalisation brings more opportunities to consume new products. Peanuts, virtually unknown in Europe 50 years ago, are now served with drinks everywhere, not to mention kiwis and Brazil nuts which appeared on European tables even more recently. Finally, the modern processing practices of the agrifoodstuffs sector, in particular the use of preservatives, are also elements to be watched.   

There is now a general consensus that European consumers are entitled to close monitoring of the potential allergic risks posed by new foods and to information on them. In addition, the technical tools are needed to permit the implementation of regulations in an area which has given rise to a number of projects supported by the Union (see boxes). 

'We are often unaware of what quantity of an allergen in food triggers an allergic reaction. Experience shows that it can vary from 1 to 100 000 from one patient to another,' explains Lars Poulen of the Laboratory for Medical Allergy at the Copenhagen University National Hospital (DK). Poulen is coordinator of the FAREDAT (Food Allergy Risk Evaluation Based on Improved Diagnosis, Allergens and Test Methods) project.

Many people believe, rightly or wrongly, that they suffer from an allergy and change their lifestyles accordingly. This self-medication can be harmful if an unbalanced diet is adopted. Above all, it closes the door on any treatment targeting the root of the problem, the antigens responsible. 

A breath of fresh air
Research on food allergens relates to just one aspect of the questions raised by multiple allergies. A real understanding of these pathologies and the development of strategies to treat them entails drawing on several disciplines: nutrition, genetics, immunology and epidemiology, pneumology, dermatology, paediatrics and ear, nose and throat specialisations.

This is precisely the aim of the new Global Asthma and Allergy European Network (GA2LEN) Network of Excellence, launched last February. Its acronym is a reference to the famous Greek physician from the second century AD who was the first to understand that the lungs fill with air inhaled through the nasal passages.   GA2LEN is distinctive not only for bringing together researchers from 14 Union countries, plus Switzerland and Norway, but also the principal groups affected by the problem, that is the patients and health professionals who treat them. The project partners are the European Academy of Allergology and Clinical Immunology  (3 000 physicians from learned societies from all over Europe) and the European Federation of Allergy and Airways Diseases Associations (250 000 members in 19 countries). The project received immediate initial funding from the Commission of €14.4 million out of a total €29 million budget.

A question of hygiene
Dust mite © Source: American Academy
Dust mite
© Source: American Academy of Allergy, Asthma and Immunology
This support will result in a wide-ranging programme covering nine main avenues of research investigating most of the enigmas posed by the increase in allergies. Why, for example, are allergies less frequent among children who grow up in a rural environment? Some researchers believe that urban life, by reducing exposure to pollen, insects and other natural immunogens during childhood, makes the immune system lazy to the point where it fails to recognise these antigens. This hygiene hypothesis implies that the increase in allergies is the unexpected consequence of more sanitary living conditions. This possibility is being tested by GA2LEN, in particular by researchers at the Ludwig Maximilians Universität in Munich (DE).

Another typical question is: why are office workers more subject to allergies than others? In this case, the cause may be linked to modern wall coverings or paper solvents. This is the aspect being studied by the team from Barcelona's Instituto Municipal Investigacio Medica (ES).   Meanwhile, GA2LEN teams and the University of Utrecht are looking into indoor pollution (poor air circulation, dust mites, passive smoking, etc.).  

Gender divisions
Another mystery is being studied at the Institut de la Science des Etudes et de la Recherche Médicale (INSERM) in France: small boys are more prone to allergies than girls, but the gender gap balances out during adolescence. What is at work here? Is this difference due to biological, sociological or simply statistical factors?

The list of GA2LEN research projects is long. They include: the modelling of the effects of asthma on lung tissue by Palermo University (IT); the role of traditional food allergens – such as seafood and peanuts – a research project headed by Southampton University (UK); the compiling of a DNA databank of allergic diseases, coordinated by the INSERM; and exchanges between European physicians on medical treatment, organised by the Institut Karolinska in Stockholm (SE).

The importance of diagnosis
This blossoming of projects also shows how important it is to place improvements in diagnostic methods at the heart of research. Existing tests are based on detecting IgE synthesis in response to exposure to antigens. These are of imperfect predictive value as some people produce IgE without developing allergic symptoms.

Researchers with the GA2LEN network aim to overcome these obstacles. 'I have every confidence that we will succeed, within the next five years, in obtaining a simple test, perhaps requiring no more than a teardrop or saliva sample. This would tell us to what substances and to what degree a child is allergic,' believes   network coordinator Paul van Cauwenberge of Ghent University(Belgium).

  Data on plant proteins  
  One of the difficulties posed by the study of food allergens is the lack of a centralised source of useful information. When a patient shows significant symptoms of an allergy, it is rare to know the precise ingredient of the food which is responsible. Even the clinical diagnosis can sometimes be imprecise.   Is it a genuine allergy? If so, is it an anaphylaxy – an extreme and sometimes lethal form which begins a few minutes after eating even very small quantities of a particular food? Or is it a food intolerance – a phenomenon which is very different to an allergy – manifested in the form of cramp in the stomach and headaches, as in the case of coeliac disease (cereal gluten intolerance) or diarrhoea, which can indicate an intolerance to the lactose contained in milk?

Dwarf ragweedSweetgum
Dwarf ragweedSweetgum
Mulberry Orchard grass
MulberryOrchard grass
Source : American Academy of Allergy Asthma & Immunology

The Protall database – accessible online free of charge  – helps shed light on these questions. It was developed by a network of 30 researchers from 12 Union countries, specialists in plant biology, food science and clinical allergology. It presents virtually all the available information on a total of 77 allergens found in 48 plant species (clinical description of allergies, chemical nature of the allergen, biochemical properties).  A comparison of these molecules has made it possible to define a number of common properties. This improved knowledge of the biochemistry of allergenic molecules has important applications. It may, one day, enable us to predict the possible allergenic properties of new plant proteins and develop simple precautions for avoiding food allergies, such as peeling peaches, as it is the skin which contains the principal allergens. 

Protall : Food allergens of plant origin the relationship between allergenic potential and biological activity


  Apples, false friends  
  'An apple a day keeps the doctor away'. This popular and scientifically sound saying overlooks the fact that apples, Europe's most widely grown fruit, can also provoke allergies. The Safe project recently identified chemically five allergens: four in the fruit, known as Mal D1 to 4, and a fifth in the pollen. 'Approximately 10% of the population is allergic to pollen. More than half of these people will also develop an allergy to plant foods,' explains Safe’s Karin Hoffman of the Department of Pathophysiology at Vienna University (AT). ‘Our study made it possible to better understand the relationship between these two types of pathology triggers.' 

The epidemiological aspect of the Safe research – to which Austrian, Spanish, Italian, Finnish, Dutch and Swiss laboratories contributed – showed two dominant forms of geographically distinct allergies: reactions to the pollen are typical in Northern and Central Europe while, in Southern Europe, the main problem is posed by allergies to the fruit itself. Present research is trying to identify the levels of expression of the various Mal D variants among the principal varieties of apple trees and to develop tests with which to identify these antigens in the fruit as well as in the juices and purees made from it.

Safe: Plant Food allergies. Field to table strategies for reducing their incidence in Europe

Four allergens are found in the apple, a fifth (above) in the pollen. © Source: American Academy of Allergy, Asthma and Immunology

Four allergens are found in the apple, a fifth (above) in the pollen.

© Source: American Academy of Allergy, Asthma and Immunology


  Pollen alert  
  The Internet site [ http://www.polleninfo.org/ ]  of the European network of aerobiological monitoring presents data collected at monitoring centres for allergic risks located throughout Europe. In addition to the newsletter on pollen content, visitors can also check seasonal maps per pollen type and country. Explanations are also provided on each variety of allergenic plant. Check it out this spring…