Memorandum by European Academy of Allergology
and Clinical Immunology
INTRODUCTION
Allergy is an increasingly common problem across
all parts of Europe. The European Academy of Allergology and Clinical
Immunology (EAACI) is a non-profit organisation whose principal
aims are to promote basic and clinical research into allergy,
to collect, assess and diffuse scientific information relating
to allergy, to encourage and provide both training and continuous
education for clinicians and scientists interested in allergy
and finally, to collaborate with patients and lay organisations
in the area of allergology and clinical immunology. Many of our
key members are involved in research projects looking at the factors
responsible for allergy in different parts of Europe and separately,
looking at treatments that may be effective in reversing the trend
and preventing the next generation from suffering from allergies.
In answer to the specific questions:
Q1. What is allergy?
Allergy is a specific immune-mediated reaction
to foreign materials such as pollens, dander, food, drugs etc.
Patients with an allergy will react more or less on every exposure
to the substance, even when it is only encountered at low levels.
Patients who are not allergic to that substance should not normally
react to it. This contrasts with toxic reactions where most people
will react to the foreign substance if they are exposed to enough
material and intolerance reactions where people have symptoms
after eating a particular food or being exposed to perfume, newsprint
etc but there is no immunological recognition of the foreign substance.
The distinction between allergy and intolerance has been blurred
in the newspapers, magazines and general popular usage. For example,
everybody understands the phrase "I'm allergic to Monday
mornings" but nobody thinks you make antibodies to them!
Q2. What is and is not known about the origins
and progression of allergic disease?
We know that there is a genetic risk for allergy
and therefore allergies tend to run in families. However, there
has been a rapid rise in the number of people affected over the
last 30 years and that rise cannot be blamed on genetic factors
alone. Rather, it seems that there is a susceptible group of the
population who can develop allergies if they are exposed to an
unfavourable environment.
From clinical observations, there is a progression
of allergic disease such that children may develop eczema in childhood
and then go on to develop rhinitis which may or may not be followed
by asthma. This is often called the "allergic march".
All three conditions involve allergic sensitisation
but the targets may change with food allergy being important in
infancy and inhalant allergies (pollen, dust, danders etc) becoming
more important for the rhinitis and asthma. Allergies developing
during childhood often regress as the child gets older. So for
example, allergies to egg and milk are common in the first two
years of life but rarely persist through into older childhood
and adulthood. An exception is peanut allergy—children with
peanut allergy aged 10 have approximately 80 per cent chance of
still having it when they reach 18. People with hayfever often
get their worst symptoms during the teenage years and the third
decade of life and it gradually gets less troublesome as they
move towards their 40s and 50s. However recent data suggests that
there may occur a second allergic march starting with hay fever
and progressing to persistent rhinitis, sinusitis and asthma in
a proportion of these patients. Childhood asthma can disappear
around puberty, particularly in boys due to their differential
lung growth at puberty. People who have had asthma in childhood
are at greater risk of developing asthma in later life, although
it is not always clear whether it is recurrence of the asthma
or a new condition occurring in someone who is predisposed to
asthma.
In the longer term, some patients with asthma
go on to develop fixed airways obstruction. This is part of the
"remodelling" process that occurs in asthma, but it
is not clear why some patients are more affected than others.
Smoking tobacco is a major risk factor but it can occur in lifelong
non-smokers. No specific preventive therapy has yet been identified.
Q3. Why is the incidence of allergy and allergic
disease rising?
The precise reasons are not known but it does
seem to be linked to some aspects of the more prosperous living
conditions that we have enjoyed since 1960. Evidence from the
United States suggests that this rise in allergies was starting
to appear during the 1930s and is therefore not just due to changes
that have happened since World War 2. However, dramatic increases
were seen between about 1964 and 1980 with continuing increases
in the presentation of allergic disease to GPs and other healthcare
providers at least into the 1990s. There is some evidence that
healthcare usage may be levelling off, perhaps due to changes
in the way the Health Service is organised but cross sectional
studies of allergic disease suggest this increase has been sustained
in the UK and is continuing to be apparent in other parts of Europe.
In particular, following the reunification of Germany and the
increased prosperity both in East Germany and in other parts of
Eastern Europe, we have seen an increase in the incidences of
allergic diseases right across the former iron curtain countries.
From these studies, we can tell that it is the conditions during
the first few years of life that seem to matter most. For example,
people born in West or East Germany before 1960 have similar rates
of allergic disease, even the West Germans had much better living
conditions during the 60s, 70s and 80s. However, those born in
the 60s in West Germany have higher rates of allergic disease
which appears to link in with the better living conditions that
were present in West Germany during the 1960s. Other data from
farming communities in Bavaria and Switzerland suggest that there
is a critical window of exposure in the first year of life during
which the child's immune system can be influenced and their risk
of allergic disease substantially reduced. Once the child passes
their first birthday, the same factors that would have prevented
them from becoming allergic no longer operate. This implies that
any intervention to change the prevalence of allergy would have
to target the very early phase of life and not be brought in at
five years +.
Q4. Why does the UK have such a high prevalence
of allergy?
If one allows for international differences
in general levels of prosperity, then it is not so clear that
the UK has substantially higher levels of allergy compared to
other European or developed countries. Because the UK is relatively
prosperous, there is certainly a higher cross-sectional rate of
allergy but the highest rates worldwide appear to be in Australia
and New Zealand. To the best of our knowledge, nobody has identified
a UK-specific factor which would explain why we have a higher
rate of allergy than would be expected simply from our general
levels of prosperity.
In terms of the precise aspect of prosperity
that may be important, many different suggestions have been made.
These include changes in housing stock, changes in food technology,
air pollution, vaccinations, exercise etc. It is true that modern
housing and furnishing tends to increase the level of house dust
mite allergens in houses. House dust mites prefer warm, damp environments
which are favoured by the increased insulation of modern housing,
carpeting, taking more baths etc. Reducing the level of house
dust mite exposure has not been convincingly shown to reverse
the trend. However, the data has often related to single interventions,
such as provision of mite-proof bedding in adults and further
controlled trials involving multiple interventions are needed,
particularly in children who are more likely to respond to avoidance
strategies. The biggest single influence on childhood immune development
is food and intestinal bacteria. It is clear that there have been
changes in intestinal microbial flora since the 1950s and the
lack of certain gut bacteria may predispose children towards developing
allergies. This is part of the "hygiene hypothesis"
and is currently being tested in Scandinavia as a possible means
of reducing the onset of allergy. This suggests that the change
in the incidence of allergy flow from the large scale change that
has taken place in food technology and our diets over the past
50 years. Other changes have been the increase in both parents
working with a consequent decrease in daily shopping and rise
in consumption of ready meals. Fresh foods, especially fruits
and vegetables contain anti-inflammatory antioxidants which decrease
on storage, those obtained from supermarkets are low in this respect.
Q5. What gaps exist in establishing the overall
disease burden of allergies?
There are difficulties in obtaining precise
diagnoses for these conditions, especially where they merge into
normal health. Many people are sensitised to grass pollen, cat,
house dust mite etc but have no definable symptoms or little difference
in symptoms compared to normal healthy individuals. There is a
fundamental need to understand why some "atopic" (skin
test positive individuals) develop allergies (symptoms of rhinitis,
asthma and eczema) whereas others do not. Many allergic conditions
are handled by self-medication and do not therefore come into
conventional Health Service statistics. Cross-sectional surveys
are always difficult to interpret because those with the condition
are more likely to respond than those without.
Q5A. What are the social and economic consequences
of allergic disease? We believe that there is substantial
absence from work and school as a result of allergic disease.
Importantly, allergic diseases tend to affect young people who
are either in education or economically active. Both hay fever
and its treatment have clear adverse effects on exam grades and
school attainment.
Q6. What are the effects of current treatments
on the natural history of allergic disease?
Standard drug therapy including antihistamines,
inhaled steroids and beta-agonist anti-asthma medication has no
real effect on the natural history of allergic disease. These
are effective drugs for containing the symptoms but they do not
"cure" the disease in the sense of getting rid of it.
They are also more useful in preventing exacerbations rather than
eliminating symptoms. We do tell patients that inhaled steroids
may prevent the progression of their disease but there is little
hard evidence for this.
Q8. What is the evidence base for pharmacological
and non-pharmacological management strategies?
We have good evidence for symptom control with
ordinary pharmacological strategies. For example, about 35 per
cent of patients with hay fever report good symptom control with
the combination of antihistamines and topical steroids, 45 per
cent have partial control and about 20 per cent have poor control.
Non-pharmacological management includes allergen
avoidance and immunological approaches such as desensitisation.
The evidence for using allergen avoidance is rather mixed. There
are significant criticisms of many studies in this area, particularly
in terms of failure to target advice to those patients who are
likely to benefit and failure to choose correct end points. Specific
immunotherapy (also known as desensitisation) is effective on
symptom control and has some effect on the natural history of
the disease. In particular, desensitisation of children with rhinitis
can prevent them from developing into asthma, and may reduce the
likelihood of acquiring new sensitivities. However, desensitisation
is not widely practised in the UK. This reflects concerns about
safety, but elsewhere in Europe and North America, desensitisation
is commonly used in patients presenting with rhinitis and asthma.
Sublingual desensitization is becoming available in the UK—it
is amenable to home use after the first dose. A major question
is whether this can, like injection immunotherapy, prevent disease
progression.
Q9. Is the level of UK research into allergy
and allergic disease adequate?
Allergy represents a modern epidemic in UK and
Europe and there is an urgent need for more investment in research
if this trend is to be reversed. Such research requires the existence
of high quality allergy services at secondary and primary care
level, which can serve to expand research capacity and build research
networks in which the necessary clinical research and clinical
trials can be conducted.
EAACI would particularly welcome research across
Europe looking at how different risk factors operate in different
countries. There is quite good evidence that there are gradients
of risk across Europe and these may reflect both genetic variation
and environmental variations such as diet, air pollution etc.
different risk factors are likely to have a variable instance
in different parts of Europe. In this sense, the European countries
represent a very useful laboratory in which to study the causes
and management of allergy and asthma. Two UK Universities (London
and Southampton) are already engaged in a EU-funded network of
excellence (GA2LEN—Global Allergy & Asthma European
Network), and others are involved in a food allergy research network
(EUROPREVALL).
A corollary is that it is quite likely that
individual risk factors may operate differently in the UK than
other European countries, so interventions need testing in the
UK, even if they appear to work elsewhere. This type of applied
research needs more support and this may be forthcoming through
the new DH R&D programme (research for patient benefit—RfBP).
Current basic and mechanistic research in the UK is of a very
high standard but funds are limited.
Q10. What are the most promising areas of
research into preventing or treating allergy?
Interesting data is developing in preventing
allergy through the use of probiotics and nutritional strategies
in childhood. These are reviewed in detail in Tricon et al
2006 (funded as part of an EU network of excellence under
the sixth framework programme). Whereas drug therapies are well
established, they have no impact on the long-term course or progression
of allergic diseases. In contrast, the use of allergen specific
immunotherapy is promising in this regard. A study of immunotherapy
in children with seasonal allergic rhinitis (hay fever) has found
that about 45 per cent of children will develop asthma if they
are untreated, while only 20-25 per cent develop asthma if they
receive immunotherapy (Niggemann et al 2006). This benefit has
been sustained for 7 years after completing treatment, so it is
not simply delaying the onset of asthma. Roughly speaking you
need to treat four children to prevent one from becoming asthmatic.
One of the four will become asthmatic anyway, and in the other
two you will have improved their hay fever but they would not
have gone on to get asthma. There is also an urgent need for research
into controlling the long-term downstream consequences of allergic
disease, particularly in relation to asthma. Further details of
research priorities in allergy are contained within the submission
from the British Society for Allergy & Clinical Immunology
and will not be repeated here.
Q11. How effective has Government policy
and advice been in addressing the rise in allergies?
Current rising trends in allergic diseases argue
that policies have been less than effective, although a good example
of successful intervention is the reversal of asthma mortality
trends following the implementation of asthma guidelines, whereas
the trend for ever increasing hospital admissions for life-threatening
anaphylaxis is particularly worrying, as is the less serious but
none the less bothersome allergic rhinitis that now affects a
quarter of the UK population and is associated with considerable
impairment in work/school performance. From the existing data,
the most important single thing we could do to reduce allergy
in childhood is to reduce smoking by mothers and mothers-to-be.
Maternal nutrition is probably important, but we are not yet in
a position to give hard evidence-based advice to pregnant mothers.
Government advice on diet during pregnancy has been of questionable
value, especially in relation to peanuts. It was tempting to offer
advice that sounds sensible, but the evidence suggests this has
not affected rates of peanut allergy and may even have increased
it.
There is a separate issue regarding the way
that the public view government information. We live in an age
when official information is distrusted, even when its credentials
are impeccable. Advice from doctors is also mistrusted and routinely
rubbished in the press and other media. Patients are left wondering
who to believe and often end up going to unofficial sources for
information. Separately, there is an impression that Government
is not particularly interested in allergy and has yet to be convinced
that this is a significant Public Health problem.
Q12. How is current knowledge about causes
and management of allergic disease shared within Government?
Recently, a UK indoor environment group has
been formed which is looking at the interaction between health
and the environment in terms of housing and housing design. People
from social services, local government, schools, architecture
and the Building Research Establishment have all come together
around this, although they are interested in several other issues
as well as allergy. Further evidence is really required from scientific
studies before one could make definitive advice on how housing
policy should be altered.
Food policy and labelling regulations are really
two separate issues. There are questions about food policy that
relate to the development of allergies and asthma. In particular,
if the nutritional evidence is to be believed, then we should
be looking at advice on dietary content and supplementation.
Food labelling regulations are more to do with
risk containment in people who are sensitised. There is a major
issue at the moment regarding foods that are labelled as "may
contain traces of nut". This term has caused considerable
disquiet and confusion among patients and their advisors, since
there is an enormous difference between foods that may occasionally
contain large quantities of nut as opposed to foods that do regularly
contain small amounts. Indeed, recent anecdotal reports suggest
that there is probably less nut in a food that "may contain
traces of nut" than in a food that has no mention of nuts
on the label. A widespread perception that food manufacturers
are putting this label onto their foods in order to avoid blame
for allergic reactions does not help to increase confidence amongst
the general public.
PATIENT AND
CONSUMER ISSUES
Q13. What impact do allergies have on the
quality of life of those experiencing allergic disease and their
families?
Asthma can seriously affect patients and their
families. It limits people's life ambitions, their ability to
participate in sport and in a number of occupations including
the armed forces, police force, baking, car repair workshops etc.
Hayfever and rhinitis have been shown to have even more impact
on quality of life than allergic asthma. These are not trivial
conditions, even though they do not kill very many people.
Food allergies can lead to considerable psychological
trauma and difficulties for children and their families. Most
schools now have sensible policies in place for managing nut allergy
but in the absence of any specific treatment, the whole management
strategy has to depend on containing the risk exposure. This can
lead to considerable friction both between parents and child and
between the family and others concerned in the child's social
activities.
Q14. What can be done to better educate the
public?
There is a plethora of information available
to the patient and public but much of it is unfiltered and can
be confusing. The problem is not giving more information but making
sure there is some way of encouraging people to go for high quality
information. Whether this should be by offering lists of preferred
internet sites or quality stamping sources of information is a
difficult judgement. It is not helped by the fact that there are
a wide range of views out there, held by both patients and practitioners.
While these may be applicable to individual cases, they are not
always applicable to all patients. Better access to NHS allergy
services would be a big step forward.
Q15. Are current regulatory arrangements
for private clinics etc satisfactory?
Many alternative and complementary therapists
claim to offer allergy diagnostic tests. In some cases these are
unconventional tests for diseases that are accepted by everyone
to be allergic. So for example, they may offer an alternative
way of testing for sensitivity to explain your asthma or your
hayfever. Others are offering to look for allergy as an explanation
for symptoms that we do not think are allergic. So for example,
someone might offer to test for an allergic basis for fatigue,
headache, weight gain etc.
We have to assume that the people offering these
tests genuinely believe allergies may be responsible for this,
despite the fact that there is no evidence to support this belief.
Obviously if anybody offered such tests while knowing that they
were false then this would be fraudulent behaviour and come under
the trades descriptions act.
We believe that much of the current provision
of alternative and complementary services for allergy is driven
by failure of provision within the state-funded healthcare sector.
Even reputable tests such as specific IgE cannot be interpreted
without a detailed clinical history taken by an allergy-trained
individual, thus over the counter and postal testing is open to
misinterpretation unless expert opinion is available. If adequate
NHS advice and information were available, then it is likely that
many of these private sector clinics and over the counter allergy
tests would no longer be necessary.
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