APPENDIX 6: VISIT TO BERLIN AND MUNICH,
GERMANY
Members visiting Germany were: Baroness Finlay of
Llandaff (Chairman), Baroness Perry of Southwark, Lord Rea. In
attendance: Miss Sarah Jones (Clerk), Professor A. B. Kay (Specialist
Adviser), Dr Cathleen Schulte (Committee Specialist).
Wednesday 24 January
Allergie Centrum, Charité, Berlin
The Charité university hospital was split
between three different sites across former East and West Berlin.
Allergy patients were treated in the Allergie Centrum which had
two different parts: adults were largely treated in the Department
of Dermatology and Allergy, whereas children were treated in the
Department of Paediatric Pneumology and Immunology. The Committee
visited both of these sites.
Department of Dermatology and Allergy, Universitätsmedizin
Berlin
Presentation by Professor Torsten Zuberbier, Head
of the Department
The Committee was welcomed by Professor Zuberbier
who outlined the way in which allergy was treated. Allergology
training in Germany was offered as a sub-specialty. Approximately
70 per cent of the allergologists were dermatologists, but the
sub-specialty was also practiced by ENT physicians, pneumologists
and immunologists. The Department of Dermatology and Allergy treated
adults with allergic diseases and employed two doctors trained
in internal medicine who could treat patients with multi-organ
symptoms. However, the treatment of some allergies required the
expertise of other specialists, so patients with severe asthma
were referred to the pneumology department and patients with suspected
food allergies were referred to the gastroenterology department.
Professor Zuberbier did not think there was any need for allergology
to be a separate specialty, but felt that it was more important
to encourage communication between specialists.
As in the United Kingdom, it was felt that GPs in
Germany were not adequately trained to correctly diagnose or treat
allergic conditions. But unlike the English system, German patients
could usually refer themselves to specialists directly; a cost-effective
strategy which did not waste GP appointment time. However, as
a university hospital, the Charité dealt with the most
complex cases of allergy and only received patients referred by
specialists.
Professor Zuberbier noted that allergic diseases
were on the increase in Western Europe and often severely impaired
patients' quality of life. However, only a small percentage of
people who felt they suffered from an allergy truly did, and a
paradox existed whereby every medical practitioner knew the term
"allergy" but only around 10 per cent of patients were
treated correctly. Allergic conditions also had an impact on the
economy. The treatment of many allergic diseases was relatively
cheap but, if left untreated, the social and economic costs of
days lost at work or school could be far greater.
As Head of the European Centre for Allergy Research
Foundation, Professor Zuberbier explained how the Foundation aimed
to improve the knowledge, research and awareness of allergies
throughout Europe, and thereby reduce their burden. The Foundation
provided training programmes for physicians, educated patients
and established an international platform for research. It also
granted "quality seals" to products and services which
took the needs of allergy sufferers into account, and thus enabled
consumers to choose between products easily. The seal had been
granted to products such as cosmetics, cleaning agents and foodstuffs,
and also to services such as restaurants and hotels. "Allergy
friendly" hotels which had been granted the seal of approval
had pet-free levels within the building, clear food warnings on
menus, and "allergy free" rooms with wooden floors,
dust mite protective bed covers and other features aimed to reduce
allergen levels.
Professor Zuberbier also described several other
international organisations. The GA2LEN co-ordinated
research programmes and produced standardised procedures for allergy
diagnosis and treatment. It consisted of 27 clinical and experimental
research institutes and two patient organisations (the EAACI and
the European Federation of Allergy). The EAACI consisted of 39
national societies, as well as academic researchers and clinicians.
Its work included the promotion of basic and clinical research,
the provision of training and promotion of good patient care.
The European Federation of Allergy was a network of patient organisations
which focussed specifically on the needs of allergy patients and
their carers.
Tour of the Department
Approximately 100,000 outpatients were seen in the
Department each year, of which around 16,000 were allergy cases.
The clinic also had the capacity to treat 54 inpatients at any
one time, which was important because it was often necessary to
observe patients for an extended period of time after treatment.
For example, some patients suffered a reaction over four hours
after a skin provocation test, so the Department usually kept
these patients overnight. As a university hospital, the teaching,
clinical and research facilities were all in close proximity which
had many benefits. For example, biopsies could be transferred
quickly to the laboratory for analysis, and the training young
doctors received could be informed by the latest clinical developments.
Obtaining a correct diagnosis was vital, and in many
patients it was important to rule out allergy as a possible cause
of symptoms. As an example, the Committee observed a consultation
with a man who suspected he was allergic to local anaesthetic.
He had once suffered pain after receiving local anaesthetic and
a patch test several years ago had shown that he was allergic,
so therefore his dentist would not treat him using local anaesthetic.
Although it was thought very unlikely that this man was allergic
to local anaesthetic, patch tests and lung function tests were
prescribed in order to rule out the possibility. If these proved
to be negative it would then reassure the dentist and allow the
patient to live a more normal life.
Presentation by Mr Federico Grego, Director of
Laboratorios Leti
Mr Grego explained that allergy training was offered
as a monospecialty in Spain; doctors had to undergo four years
of specialised training to qualify as allergists, of which there
were approximately 1,300 within the state medical system and private
clinics. GPs referred serious or "difficult to treat"
allergy patients to these specialists. Although allergists in
Spain prescribed immunotherapy widely, only around 10 per cent
of the allergic population received the treatment because other
physicians did not offer it. Mr Grego estimated that around 25
per cent of the immunotherapy treatments offered were sublingual,
and expected this figure to increase in the future, although subcutaneous
immunotherapy remained the preferred treatment option for the
majority of allergists. He conceded that immunotherapy was expensive:
a course in Germany could cost €450-1300 per year, and some
patients required treatment for three years. However, the effects
of immunotherapy lasted for many years, reducing the need for
further medication, so it was felt to be a cost-effective strategy
in the long term.
Presentation by Professor Margitta Worm, Deputy
Head, Allergie Centrum, Charité
Professor Worm described an Anaphylaxis Register
which had been established in 2006 to monitor the frequency of
anaphylactic cases, increase awareness, and provide educational
programmes in how to deal with anaphylaxis. An internet-based
surveillance questionnaire for doctors had been validated, and
30 centres across Germany, Austria and Switzerland were involved
in reporting cases. By December 2006, the register had received
reports of 174 cases of anaphylaxis in patients ranging from two
months to 84 years old. 54.2 per cent of these patients were women
and the mean age was 39 years. From the initial data collected,
the most common causes of anaphylaxis appeared to be insect stings,
various foods (including vegetables, fruits, tree nuts and peanuts),
and medicines such as painkillers. A large proportion of anaphylaxis
incidents appeared to happen in the home.
The Anaphylaxis Register was still in its infancy,
but in the future it planned to involve all allergists across
Germany, and aimed to develop a national task force for anaphylaxis.
The project also aimed to develop educational programmes and wanted
to expand its reporting network across the whole of the EU.
Department of Paediatric Pneumology and Immunology,
Charité-Virchow-Klinikum, Humboldt University Berlin
Presentation by Professor Ulrich Wahn, Head of
the Department
Professor Wahn welcomed the Committee and led a tour
of the outpatients unit. Children with allergic conditions were
treated by paediatricians with a sub-specialty in allergology.
The clinic saw many patients with lung deficiency problems for
which a variety of tests were offered, including cold-air challenges,
treadmill trials and lung function tests. The clinic also carried
out a large range of allergy diagnostic procedures such as allergen
challenges, skin prick and patch tests, and various treatments
including immunotherapy.
It was estimated that one in four children suffered
from an allergic condition of some kind, and the "allergic
march" meant that many of those might progress to develop
more serious allergic conditions such as chronic asthma. Sensitisation
to food was often the first indicator that a child would develop
other allergies in later life, so early diagnosis was vital. An
atopic allergy at a young age indicated that the allergy was likely
to persist, whereas a non-atopic allergy suggested that the allergy
symptoms might reduce at around eight to nine years of age.
Compared to the United Kingdom, specific immunotherapy
was used to a much greater extent in Europe. Germany prescribed
around 700,000 courses a year and France prescribed around 500,000,
whereas the United Kingdom only prescribed around 5,000 per year.
Professor Wahn commented that in European countries such as France,
a high proportion of these treatments were administered sublingually,
but sublingual immunotherapy was almost unavailable within the
United Kingdom.
Presentation by Professor Kirsten Beyer, Co-ordinator
of the European Anaphylaxis Initiative
Professor Beyer introduced two different European
initiatives which had been developed to monitor allergy and anaphylaxis:
EuroPrevall and the GA2LEN Anaphylaxis Initiative (GAIN).
EuroPrevall was an EU-funded project which had been
established to monitor the prevalence, basis and burden of food
allergy across Europe, in order to improve the quality of life
for food allergic patients. Over the next four years the project
aimed to develop methods to improve the diagnosis of food allergies,
to investigate the role of diet, environment and infection on
the development of food allergy, and to train a new generation
of allergists in food allergies.
Professor Beyer noted that food allergies tended
to peak in prevalence at around one to two years of age and a
trans-European birth cohort had therefore been established in
2005 to examine the patterns and causes of food allergies in infants.
The aim was that the cohort would include 9,000 babies born between
September 2005 and February 2007 at nine centres in Germany, Greece,
Iceland, Italy, Lithuania, the Netherlands, Poland, Spain and
the United Kingdom. It was hoped that the results of the cohort
study would help to elucidate the mechanisms involved in the development
of food allergies, and would allow an analysis of the impact that
food allergies have on quality of life and the economy.
The GAIN was established in January 2007 with three
main aims: to develop an educational program for patients, relatives
and healthcare workers; to raise awareness of anaphylaxis amongst
the public; and to co-ordinate a European registry for anaphylactic
reactions. It was noted that anaphylaxis could be fatal and often
involved more than one organ system including the skin, respiratory,
neurological, cardiovascular or gastrointestinal systems. The
majority of patients were not correctly treated. Although adrenaline
could be life-saving the majority of children were not prescribed
this treatment, and the poor quality of patient education meant
that this treatment was used incorrectly in the majority of cases.
Presentation by Dr Susanne Lau, Co-ordinator for
aspects of paediatric allergology in the GA2LEN
network
Dr Lau outlined the work of the European GA2LEN
birth cohort co-operation which aimed to examine different birth
cohorts within Europe. Birth cohort studies were particularly
useful because they were longitudinal and therefore detected cause-effect
relationships. They were also the best study design for diseases
that began in infancy. The objectives of the co-operation were
to describe the different designs and methods used within birth
cohorts across Europe and to identify the strengths and weaknesses
of each of them.
The project examined 19 birth cohort studies carried
out in various centres across Europe. Most of the studies had
examined similar factors and tended to suggest that family history,
tobacco smoke exposure, pet ownership and nutrition all had an
effect on allergy development. However, the practices used to
assess these were not standardised so the various methodologies
made international comparisons difficult. Therefore the project
was trying to standardise methodologies for future studies, and
was attempting to harmonize the procedures used for follow-up
work to existing birth cohorts.
Friday 26 January
Department of Dermatology and Allergology, Technical
University Munich
Presentation by Professor Johannes Ring, Head
of the Department
The Committee was welcomed by Professor Ring, who
explained that the Department was part of the Technical University
Munich and its situation near other university Departments, such
as pharmacology, allowed close collaboration between specialists.
The clinical problems surrounding allergies arose
because allergic conditions involved multiple organs and often
exhibited manifold, subjective symptoms. Allergic conditions could
be chronic, of variable intensity, and could alter as the patient
matured. Professor Ring thought that over the last 20 years, the
number of more complex cases had increased, and many allergic
conditions also had a psychosomatic influence.
The prevalence of allergic disease in both children
and young adults was on the increase. Possible hypotheses for
this included the hygiene hypothesis, altered genetic susceptibilities,
changes in allergen exposures and environmental pollution. An
increased awareness of allergic conditions, and improved diagnostic
tests, may also have been partly responsible for the increase
in reported allergy cases over the last 50 years. Although there
was an abundance of hypotheses it was not known which, if any,
were correct and the true reason for the increase in allergy had
still not been determined.
Professor Ring commented that allergic conditions
were often incorrectly thought to be minor inconveniences, but
there were several types of allergic emergency that could be life
threatening. These included angioedema, uterine contractions (a
condition suffered by pregnant women which could be fatal for
the baby), and anaphylactic shock.
Some of the molecular mechanisms of allergic diseases
had been elucidated. For example, the progression of eczema appeared
to be linked to the development of the epidermal skin layer, and
some of the genetic complexes involved in this had been discovered.
Specific IgE antibodies present in the serum of allergic individuals
had also been characterised. However, now that the mechanisms
were relatively well understood, future research needed to focus
on broader issues such as why allergy was on the increase, whether
the brain played a role in allergy and what made a substance an
allergen. Further preventative work was also needed, and possible
strategies for the future included true "vaccination"
for children with a family history of allergy, and environmental
planning with hypoallergenic plants or animals. Professor Ring
emphasised the fact that every patient was different, so individually
tailored management plans would need to be used in the future.
Presentation by Professor Markus Ollert, Head
of Laboratory
Professor Ollert outlined the procedures used for
allergy diagnosis. These ranged from bedside techniques, such
as taking a family history, physical examination and skin tests,
to laboratory tests such as IgE measurements and provocation tests.
The "component-resolved approach" to diagnosis
and treatment was being developed, which tested the reactivity
of patients to various components of an allergen. This technique
was mostly used to assess allergy to bee and wasp venom. The genetic
sequences from the venom were cloned and the appropriate nucleotide
sequences characterised. These were then expressed in insect cells
to produce recombinant allergens, against which patient serum
was tested. It was felt that the component-resolved approach could
not only be useful for diagnostic purposes, but recombinant allergens
could also be used in specific immunotherapy. In the future, immunotherapy
treatment using hypoallergenic "fusion molecules" containing
several allergens at once, could prove more cost-effective than
the prescription of different treatments for each allergen. However,
work was still needed to determine which molecules could be used,
how their performance could be improved and how the treatment
could be refined.
Presentation by Professor Ulf Darsow, Clinician
Professor Darsow outlined the various ways in which
allergic diseases could be managed in Germany. It was vital to
correctly diagnose the allergic disease, as the type and severity
of the condition determined the type of treatment that was required.
Where possible, allergen avoidance was the most basic approach
to manage allergies. Basic medication such as nasal sprays, corticosteroids
and antihistamines were also needed to manage symptoms in many
cases.
For some patients, allergen avoidance and medication
did not adequately control their disease, so specific immunotherapy
was prescribed. This treatment was widely used in Germany for
the treatment of allergic rhinoconjunctivitis, insect venom anaphylaxis
and bronchial asthma. Professor Darsow noted that the WHO placed
great value by specific immunotherapy as it was the only treatment
which could influence the natural course of allergic disease.
Of all the patients that presented to the clinic with allergy
to insect venom, approximately 90 per cent would receive immunotherapy,
and around 90 per cent of those people would be successfully desensitised.
However, there was a small proportion of patients that were refractive
to immunotherapy treatment.
Presentation by Professor Heidrun Behrendt, Head,
Centre for Allergy and Environment
Professor Behrendt introduced the Centre for Allergy
and Environment (the ZAUM), which was a research unit within the
Technical University Munich, founded by the Bavarian government
in 1999. The purpose of the centre was to investigate the impact
of biogenic and anthropogenic environmental factors on the development,
maintenance and aggravation of allergic diseases, in order to
provide evidence for preventative or regulatory interventional
strategies. The centre had access to patients and clinical expertise
through its affiliation with the Department of Dermatology and
Allergology. Access to environmental measurements was provided
by its association with the National Research Centre for Environment
and Health. The centre ran an environmental medicine outpatient
clinic and also had four laboratory research groups.
Professor Behrendt outlined current research into
two types of environmental substances—biogenic compounds,
such as pollen associated lipid mediators (PALMs), and anthropogenic
adjuvants:
Under natural conditions, pollen grains functioned
as allergen carriers that released allergens when they came into
contact with aqueous mucosal membranes such as the airway. Recent
research had shown that pollen grains also contained lipid mediators
which were released upon contact with the membranes. It was thought
that these mediators recruited and activated complexes within
the body which contributed to allergic inflammation, so the PALMs
might therefore contribute to the elicitation phase of allergic
reactions. Further research was therefore being carried out into
the role of these PALMs in allergy development.
The centre was also carrying out research into the
role of anthropogenic adjuvants such as PAHs and VOCs. These adjuvants
had a carbonaceous core to which other compounds could be absorbed.
It was thought that substances such as diesel exhaust particles,
which were allergic sensitizers, could be absorbed into these
particles and in this way they could act as mediators in allergy
development. The role of pollution in the development of allergy
could therefore be extremely important.
Tour of the ZAUM and the Department of Dermatology
and Allergology
Professor Behrendt led a tour of the clinical and
experimental research facilities of the ZAUM. The Committee viewed
the pollen trap and cascade impactor used to measure pollen and
allergen levels, and Members were given the opportunity to talk
with researchers about their work.
The Committee viewed the facilities at the allergy
clinic and observed patients receiving skin tests and provocation
tests. Patients who received immunotherapy at the clinic often
received a concentrated course of treatment over several days.
The risk of adverse reaction following immunotherapy treatment
meant that it was important to keep patients overnight so that
their response could be monitored.
Presentation by Professor Erika von Mutius, Head
of Asthma and Allergy Outpatient Clinic, University Children's
Hospital, Ludwig Maximilians University Munich
Professor von Mutius described the results of various
studies which had examined the environmental causes of allergy.
Some studies had suggested that early exposure to low levels of
microbial compounds could protect against the development of allergic
conditions, an idea which had been developed in the "hygiene
hypothesis." For example, children brought up on farms in
rural Germany, Austria and Switzerland had been shown to have
a lower prevalence of atopy, hayfever and asthma compared to other
children. This was thought to be due to the close proximity of
animals and consumption of dairy milk during pregnancy and infancy
on these farms.
To analyse these ideas further, Professor von Mutius
was co-leading the Gabriel study with Professor Cookson (Imperial
College London). This was an EU-funded project involving 150 scientists
from 14 European countries, which aimed to examine how genetic
and environmental interactions contributed to the development
of allergic diseases in over 40,000 individuals. It was noted
that the analysis of large and complicated datasets had previously
been extremely difficult, but recent developments in genomics
and bioinformatics had made analysis of such interactions much
simpler. It was hoped that by elucidating the genetic and environmental
interactions, preventative advice regarding the environment could
be developed in the future.
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