APPENDIX 4: SEMINAR HELD AT THE ROYAL
SOCIETY OF MEDICINE
1 November 2006
A seminar was organised at the Royal Society of Medicine
to give the Committee an opportunity to discuss issues connected
to the inquiry with a number of academic and clinical experts,
along with representatives from charities and the Department of
Health.
Members of the Sub-Committee present were: Lord Broers,
Lord Colwyn, Baroness Finlay of Llandaff (Chairman), Baroness
Perry of Southwark, Baroness Platt of Writtle, Lord Soulsby of
Swaffham Prior, Lord Taverne. In attendance were: Miss Sarah Jones
(Clerk), Professor A. B. Kay (Specialist Adviser) and Dr Cathleen
Schulte (Committee Specialist).
The participants were: Professor Stephen Holgate
(University of Southampton), Professor Peter Burney (Imperial
College London), Professor Adnan Custovic (University of Manchester),
Professor John Warner (Imperial College London), Dr Pamela Ewan
(Co-Chair, National Allergy Strategy Group), Dr Glenis Scadding
(Royal National Throat, Nose and Ear Hospital), Dr Clare Mills
(Institute of Food Research), Professor Aziz Sheikh (University
of Edinburgh), Professor William Cookson (Imperial College London),
Professor Anthony Frew (President, EAACI), Professor Tak Lee (Director,
MRC-Asthma UK Centre in Allergic Mechanisms of Asthma), Professor
Gideon Lack (Guy's and St Thomas' Hospital), Ms Lindsey McManus
(Allergy UK), Ms Mandy East (Anaphylaxis Campaign) and Mr Alan
Bell (Department of Health).
The Committee was welcomed to the Royal Society of
Medicine by Baroness Finlay of Llandaff, President of the Royal
Society of Medicine and Chairman of the Sub-Committee. The following
presentations were heard:
What is allergy and intolerance? (Professor Kay)
Professor Kay began by introducing the concept of
allergy. Since Clemens von Pirquet's original proposal of the
word "allergy", the term had been corrupted and often
used synonymously but incorrectly with hypersensitivity. The word
"allergy" needed redefining but as there was no universally
agreed definition there was still confusion.
An allergy was an exaggerated immunological response
to a foreign substance which was either inhaled, swallowed, injected,
or came into contact with the skin or eye. Therefore allergy was
a mechanism, not a disease. In contrast, other disorders such
as food intolerances and irritable bowel syndrome were not allergies
because they did not involve an alteration to the immune system.
The term "multiple chemical hypersensitivity" (MCS)
was a misnomer as patients were not sensitised to chemicals in
an immunological sense. The term MCS was used largely by lay people
and doctors practising complementary medicine to describe a condition
which conventional practitioners labelled "idiopathic environmental
intolerance."
There were different classifications of allergy.
Atopic (IgE-mediated) allergy was the domain of allergy specialists,
whereas non-atopic (IgG or T cell-mediated) allergy, which caused
conditions such as extrinsic allergic alveolitis and contact dermatitis,
was usually managed by the appropriate organ specialists.
The mechanisms of allergy and allergic disease
(Professor Holgate)
Professor Holgate discussed the mechanisms of allergic
diseases, pointing out that they were often associated with an
inflammatory response. For example, when a person suffered from
bronchial asthma, the inflamed airways resulted in constriction,
and this was often associated with remodelling or repair processes
which amplified the symptoms of asthma.
Allergic symptoms were not solely due to a persistence
of the allergen, but were also dependent on the genetic composition
of the person and a range of environmental factors. For example,
the faeces of the housedust mite contained a major allergen but
the number of mites which lived in a house was dependent on the
age of the house, ventilation, dampness and furnishing.
Professor Holgate explained the role of the IgE antibody
in the allergic response, which involved the release of inflammatory
mediators from mast cells. The T lymphocyte (T cell) was also
important in determining allergic phenotypes in genetically susceptible
people. There were still a number of questions to be answered,
such as the role that regulatory T cells played in modifying allergic
responses in early life, and why allergies were often less severe
in later life. Certain types of immunotherapy could reduce allergic
symptoms and it was important to find the role that T cells played
in this response. The way in which the allergic and inflammatory
responses in the airways interacted with structural elements to
cause an increase in airway smooth muscle, and other signs of
remodelling, was unknown.
Epidemiology and rising trends in allergy and
asthma (Professor Burney)
Professor Burney began by describing the general
increase in the prevalence of allergic disease in recent years.
There had been a general increase in male asthma admissions over
the last four decades, but there was a birth cohort effect, and
the majority of this increase had been seen in 0-14 year olds.
The trends were slightly different for women, amongst whom there
was a higher prevalence of asthma at child-bearing age.
It was important to take age and gender into consideration
when studying the prevalence of allergies. In general the prevalence
of allergy was on the increase, but there was some ambiguity as
to whether it was increasing in all age groups. The conclusion
was that the incidence of atopic disease in childhood had probably
stopped increasing, but older age groups were more likely to suffer
from an epidemic of sensitisation in the decades to come. Entirely
new food allergies were also appearing, such as allergy to kiwi
fruit, but increases in allergy prevalence did not seem to correlate
with increases in obesity. Professor Burney noted that policies
in all areas should take account of these recent trends.
Environment and lifestyle (Professor Custovic)
Professor Custovic noted that asthma was a heritable
condition, but the results of genetic studies relating to allergy
prevalence were inconsistent. The fact that asthma had increased
in prevalence over the last five decades was not due to a change
in the genetic gene pool, but to environmental factors.
However, there was still uncertainty regarding the
role that the environment played. Conflicting studies examining
environmental factors such as cat ownership or breastfeeding,
had shown to protect against, increase the risk, or even make
no difference to the likelihood of developing allergic diseases.
It was not urban life per se that increased
the risk of allergy, but affluent life. Some studies had demonstrated
that an increased exposure to endotoxins reduced the risk of developing
allergies, but exposure levels produced different results in different
parts of the world. Professor Custovic believed that this was
due to the genotype of the populations studied. Polymorphisms
in "risk alleles" meant that endotoxin exposure was
protective in some populations but not in others. However, a single
genetic polymorphism could increase, decrease or have no effect
on the risk of developing an allergic disease, as the environment
played a vital role in establishing allergy. This implied that
no single drug would be effective at treating allergy in everybody,
so tailor-made treatments and prevention measures needed to be
developed for each patient or population.
Early life origins of allergy (Professor Warner)
Professor Warner highlighted the need for a new approach
to tackle allergies considering their increase in prevalence,
impact on quality of life and the lack of any cure. Even in the
second trimester of pregnancy, there were factors which could
start to influence the risk of a child developing an allergy,
such as the nutritional state of the mother. In the past it was
thought that avoiding specific allergens during pregnancy reduced
the chance of a child developing those particular allergies. But
recent evidence had disagreed with this, and had shown that exposure
to some allergens in appropriate contexts actually helped to protect
children. In addition, it was thought that the genotype of a mother
affected the chance of her child developing an allergy, as did
environmental considerations such as whether the mother smoked
or what medication she took during pregnancy.
Prevention of allergic diseases (Professor Sheikh)
Professor Sheikh noted that there were four different
levels of allergy prevention: primary, secondary, tertiary and
primordial. Primary prevention described interventions which aimed
to reduce the incidence of disease, whilst secondary preventative
interventions aimed to reduce the prevalence of disease by shortening
its duration. Tertiary preventative measures aimed to reduce the
impact of long-term conditions, and primordial prevention described
actions that inhibited the emergence and establishment of environmental
or behavioural conditions which increased the risk of disease.
Immunotherapy was a valuable tertiary preventative measure, but
due to the risk of hypersensitivity reactions, was no longer used
regularly in the United Kingdom.
Primary preventative strategies focussed on well
individuals who were yet to develop the condition, and needed
to be developed using a robust evidence base. However, high quality
clinical data regarding allergy prevention was limited. Professor
Sheikh noted that to establish a good evidence base, future clinical
studies were needed with robust methodological approaches and
long-term follow-ups. Future research would need to consider genetic
and environmental interactions, test multi-faceted interventions
and also consider the health services involved. Data collection
was hampered by the fact that investigators had difficulty accessing
the range of data needed to assess the overall impact of any interventions.
Innovative data linkage techniques and a change in the regulatory
framework were needed to overcome these barriers.
Genetics of asthma and atopy (Professor Cookson)
Professor Cookson explained that allergic diseases
were caused by both genetic and environmental factors, but it
was the genetic research that had contributed to the majority
of our understanding about allergic mechanisms. The study of allergic
disorders was complicated by the fact that various genetic polymorphisms
could predispose individuals to allergies, and allergic disorders
could exhibit many different phenotypes.
A number of genome screens had been carried out to
identify possible genes that may be important in the development
of conditions such as asthma and atopic dermatitis. It had been
found that the development of allergic conditions might be secondary
to epithelial damage. It was possible that a normal bacterial
flora helped the epithelial barriers to develop, and that when
this barrier was deficient it predisposed the person to conditions
such as asthma and atopic dermatitis.
The results of the ISAAC studies suggested that different
genes were involved in allergy development in different parts
of the world, and that the genetic risk was substantial. They
also indicated that the genetic risk was multiplicative as combinations
of certain genes could greatly increase the risk of a person developing
an allergy. Since the human genome had been sequenced, there were
very powerful genomic tools that could be used to measure expression
levels across the whole genome, which provided a valuable insight
into the function of cells and tissues. However, this technology
was very expensive and it would take a long to evaluate the data
produced.
Management of allergic diseases (Professor Frew)
Professor Frew emphasised that allergy prevention
should be attempted where possible, but when this failed to halt
an allergic disorder there were four areas of allergy management:
Diagnosis: it was vital that doctors correctly identified
whether a patient actually had an allergic disorder and what triggered
the attacks or episodes.
Allergen avoidance: once an allergic disorder had
developed, the chances of further attacks could be minimised by
avoiding the allergen or other environmental conditions which
aggravated the condition. However, the question of whether the
avoidance of factors such as housedust mite resulted in substantial
clinical improvement, whether these approaches were cost-effective,
and who should pay for such measures, was controversial.
Appropriate use of drugs: a number of drugs, such
as antihistamines and corticosteroids, were used to relieve the
symptoms of allergic diseases and prevent their progression. However,
many allergy sufferers were not prescribed appropriate treatments
because they chose to self-care rather than visit their GP. Of
those who did visit their GP, a substantial proportion did not
achieve full control of their disease and were not referred to
specialists. It was important to empower patients who suffered
from conditions such as asthma. This could be achieved by providing
sufficient education and medication to allow patients to treat
themselves, and by carrying out regular reviews of their management
plan.
Specific immunotherapy: this involved the administration
of increasing doses of allergen extract to desensitise allergy
sufferers. Specific immunotherapy was particularly useful in patients
at risk of anaphylactic shock following wasp or bee stings, for
whom the effects of desensitisation treatment could last around
10 years. Specific immunotherapy was also useful for patients
who suffered from allergic rhinitis whose symptoms could not be
controlled using standard drug therapy, and for cases where allergen
avoidance was difficult to achieve, such as patients who suffered
from cat allergy. However, immunotherapy was still relatively
expensive and there had been concerns regarding its safety.
Research funding: present and future (Professor
Lee)
Professor Lee drew attention to the recent analysis
of health research funding, produced by the UK Clinical Research
Collaboration, which had shown that the amount of funding for
research into different health categories was not proportionate
to their disability adjusted life years. Research into allergic
diseases crossed several health categories, and research into
areas such as immunology and asthma was only partly allergy-related,
so it was difficult to identify allergy funding per se.
Funding for allergy came from a variety of sources
including the BBSRC, MRC, Wellcome Trust, Asthma UK and the Department
of Health, but was insufficient for the level of research required.
Compared to other countries, the United Kingdom was not distributing
funding for allergy research in a sufficiently co-ordinated manner.
Funding bodies needed to recognise that immunology, microbiology,
genetics and epidemiology were all complementary when researching
allergic diseases. Longitudinal interventional studies were needed
to pursue long term research goals, but these required funding
which could be guaranteed for a number of years. Multidisciplinary
projects were important for fostering translational research.
Food allergies and intolerance (Professor Lack)
Professor Lack explained that there was a wide range
of adverse reactions to food, and only some of these were allergic.
An allergic reaction had to involve an alteration within the immune
system directed against the specific food protein. Food allergies
could have a significant impact upon patients' quality of life,
and caused symptoms ranging from skin rashes and swelling of the
mouth, to anaphylaxis and death. Food allergies were particularly
difficult to control in children, whose diets had to be constantly
monitored by their parents.
The prevalence of food allergy in children was on
the increase, but there were only eight paediatric allergists
within the United Kingdom, a relatively small number compared
to other European countries. This meant that parents often turned
to complementary procedures such as Vega testing. However, Professor
Lack felt that many complementary approaches were not clinically
proven and could be dangerous. In addition, unnecessary food exclusion
could lead to malnutrition and the development of conditions such
as rickets or iron deficiency anaemia.
Professor Lack felt that current Government advice
regarding food allergies was not sufficiently evidence-based.
For example, studies had previously suggested that food allergen
avoidance in infancy might prevent the development of food allergies,
but more recent observations had suggested the opposite. Therefore
the recommendation that pregnant women and infants should not
be exposed to peanuts needed re-appraising. To investigate this
further, Professor Lack had been granted funding from the Immune
Tolerance Network for the LEAP study. The LEAP study would investigate
whether the consumption or avoidance of peanuts in infancy could
affect the development of peanut allergy.
Professor Lack thought that an evaluation was also
needed of DH breastfeeding guidance, which recommended exclusive
breastfeeding for the first six months to protect against atopic
disease. In summary, public health policies to prevent food allergies
had not only been failing, but might have contributed to the problem.
More funding was therefore needed to research these issues and
formulate reliable public advice.
Discussion and closing remarks (under Chatham
House rules)
Discussion was prompted by short presentations from
Dr Ewan, Dr Scadding, Dr Mills, Ms McManus and Ms East. Discussion
focussed on the following areas:
Service provision
Allergy patients often felt let down by NHS services,
and parents did not know where to go for advice. Many doctors,
nurses and dieticians did not recognise or understand allergy
symptoms so could not appropriately treat them or refer patients
to specialists. This was not only a waste of time and resources,
but could prolong patients' discomfort or frustration, and could
be dangerous if potentially fatal allergies were left undiagnosed.
A general improvement in allergy training for GPs was therefore
required.
To correctly diagnose and treat an allergic condition,
diagnostic allergy tests had to be interpreted in the context
of a patient's history, which required the skills of a specialist
allergist. Allergy specialists were often needed to determine
the cause of a patient's allergic reaction, to discover whether
they suffered from multiple allergies, and to prescribe the appropriate
treatment. However, many people who suffered from severe allergic
reactions were not referred to allergy specialists because there
was only a very small specialist workforce in comparison to the
large clinical need.
Although the Department of Health had conceded the
problem, its solution that PCTs should develop allergy services
was not practical. In 2003, the Royal College of Physicians had
recommended that one allergy centre should be established in each
of the eight former NHS regions, which had been estimated to cost
around £5.6 million per annum. Due to a lack of economists
in clinics it was hard to estimate the financial impact of misdiagnosing
and mistreating allergy. But in the long-term, it was felt that
the indirect costs of undiagnosed allergies (such as the treatment
of serious anaphylactic shocks and allergic complications following
earlier misdiagnoses), would outweigh the initial costs of establishing
allergy centres. The NHS therefore needed to develop better ways
to analyse the cost-effectiveness of specialist allergy centres.
The provision of allergy services within the United
Kingdom was very different to other European countries. In the
United Kingdom, allergy treatment was split between many organ-based
specialities, such as ENT, gastroenterology and dermatology; whereas
Germany, for example, had a more cross-cutting multidisciplinary
approach to allergy treatment. However, it was difficult to draw
comparisons between countries because their medical systems had
evolved in different ways.
Allergy research
Prevention was preferable to treatment so it was
vital to prevent the "allergic march" and halt the increase
in the prevalence of allergic conditions. Funding was needed for
long-term research projects to investigate interventions that
could reduce the risk of children developing allergies. As a large
proportion of the population already suffered from some form of
allergic disease, it was also important to find general principles
that could be implemented to prevent their conditions worsening.
Without a clinical infrastructure to inform a national
database of allergy cases, it was hard to co-ordinate clinical
research appropriately. Allergy research was complicated as the
development of allergic conditions depended on a number of factors
including a person's genotype, exposure to environmental substances,
diet and immune reactions experienced in early life. Allergy
research therefore had to be co-ordinated to cover all these aspects
in an integrated manner, and needed to incorporate quantitative
research, social science and clinical studies. However, funding
for each of these fields came from different bodies, so a co-ordinated
national strategy was needed. Asthma was the only allergic condition
with a research council, so there was a need for a national research
strategy for anaphylaxis, food allergies, allergic dermatitis
and other allergic conditions.
Further research was needed into the role that early
infections played in the development of food allergies. This
would require the use of well defined animal models and model
systems in vitro, complemented by focussed studies in humans.
Burden of allergic diseases
It was felt that the DfES did not adequately recognise
the effect of conditions such as hayfever on children's academic
performance. Conditions such as atopic dermatitis could cause
major problems for many people at work, leading to temporary or
permanent unemployment and financial difficulties. It was therefore
important to consider the socio-economic burden of allergic diseases
in addition to their health impact.
Immunotherapy
There was a spectrum of allergic diseases that ranged
from the mild, such as hayfever, to the severe, such as anaphylaxis.
Even at the mild end of the allergic spectrum, diseases such as
hayfever could have a significant social impact on sufferers.
Furthermore, a large proportion of asthmatic people also had rhinitis,
and research had shown that the early treatment of rhinitis could
prevent the development of asthma in later life. The use of immunotherapy
to treat rhinitis was therefore crucial in halting the increase
of asthma and other allergic diseases. A long-term cohort study
was needed to compare the effectiveness of sublingual immunotherapy
and pharmacotherapy in the treatment of allergic conditions.
Complementary medicine and self-testing kits
Some private practitioners offered non-conventional
procedures to diagnose and treat allergic conditions, such as
kinesiology, Vega testing and the "freedom technique."
There was concern that practitioners who offered these treatments
exploited vulnerable patients and did not provide a reliable diagnosis
or treatment. This was not only expensive for patients, but could
also be dangerous if they were incorrectly informed about their
risk of reaction.
It was also felt that many self-testing allergy kits,
and accompanying diagnostic services, did not provide a reliable
diagnosis as they did not take into account the patient's symptoms
or history. Stronger regulation of these services was therefore
required.
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