Examination of Witnesses (Questions 100-119)
Professor Peter Burney, Professor Aziz Sheikh, Dr
Graham Devereux and Professor John Warner
6 DECEMBER 2006
Q100 Lord Rea: I wonder if you can
bring us up to date about recent trends in the UK in the incidence
and prevalence of allergic diseases.
Professor Burney:
Amongst children the main evidence comes from a study called the
ISAAC study, which is an international study that has studied
children about 10 years apart and looked at the difference between
not individual children but schools of children, so they are looking
at the same age groups, 6 to 7 year olds and 13 to 14 year olds
on each occasion. In the UK among younger age groups there were
insignificant increases in asthma and rhinitis during that period,
and there was a significant increase in eczema, but in the older
children there were significant reductions in the prevalence of
asthma and rhinitis and a non-significant reduction in eczema.
That is important in a way and it has got a lot of attention because
up until those studies and studies published over the last few
years almost all the studies that had looked at trends in disease
had shown upward for asthma, eczema and rhinitis, so it looks
as if there is a flattening off of this trend, though this is
not seen in all countries. In some places the prevalence is still
going up, in some places it seems to be going down, so for the
first time there is a rather mixed set of evidence. That is for
children. The other issue is the issue that I referred to a little
bit earlier, and that is what is happening in adults. In adults,
as I say, the picture is dominated by what happens from cohort
to cohort, in other words, from one birth generation to the next,
and what we know about is people born up to about 1970. We know
in this group that the prevalence of people who are sensitised
to allergens has increased in each successive generation and that
these are therefore likely to be increasingly affected by the
kinds of diseases that follow from sensitisation. We do not have
that information for children yet, so what is happening there
is a bit of a blank and we cannot answer the question of when
this increase stopped. The ISAAC study, the study that I talked
about earlier, did not measure sensitisation. They looked just
at the change in the resulting diseases.
Q101 Lord Rea: What further work
do we need to do in order to explain further these trends in children,
adolescents and adults?
Professor Burney:
Explaining why those changes have happened is an even more difficult
question. However, just to know how the epidemic is going to evolve
there are two big issues that need to be reviewed. I have said
that sensitisation is increasing from generation to generation
from people born in about the 1930s to the 1970s. I think we do
need to know what is happening to sensitisation in birth cohorts
since then; that is important. We also need to know more about
what happens to people who are sensitised in terms of disease
later on in life. There would be a reasonable guess that things
will get worse because by and large as you get older you get frailer,
you pick up more complications, you pick up more problems, so
we suspect that they would have more disease as well as this added
burden of sensitisation, but we do not really know that and I
think that will be important to know at the end of life. At the
beginning of life, as I say, I think it will be interesting and
important to know what is really happening to sensitisation rates.
Q102 Lord Taverne: In your paper
you mention that there is this unsolved puzzle of why only a proportion
of individuals who test positive for specific IgE develop atopic
forms of allergy. Is this becoming more common or is this something
which is a complete mystery? Does this have an effect on the development
of allergies?
Professor Burney:
As I say, it is a mystery. I do not think that we know. Someone
else on the panel may know more. There are some hypotheses about
why some people seem to be able to carry an allergy and not have
a disease as a result, but most of them are really quite speculative
at the moment and people have been looking at why these things
may happen. I suppose the interesting results, which are not really
relevant to the UK, are from places from where there are a lot
of parasites and in some of those studies there is a suggestion
that the parasites will provide some chemical signal for the body
to dampen down inflammation and that might be an explanation in
some places. Another reason might be, for instance, the diet,
so that again we do not have a very specific answer to that question
but it may be that diet is important in your response to allergen
if you have an allergy. The short answer is that we do not know
but I think it is a very important area to investigate.
Q103 Lord Taverne: Is it a high proportion
or a very low proportion of those who do not develop as you would
expect?
Professor Burney:
Quite a high proportion. I guess 50 per cent of the population
probably in some age groups will have sensitisation to a common
allergen, but the proportion that will have recognisable asthma
will be less than 10 per cent probably, so it is quite a high
proportion.
Q104 Lord Rea: Are we making the
best use, in looking into the epidemiology and course of allergic
conditions, of the very considerable database that we hold in
the NHS, particularly general practice records? Could we do more
to make use of this information?
Professor Burney:
People certainly are using the data. The data are becoming more
available now and they are more easily accessible. Perhaps Professor
Sheikh could say more.
Professor Sheikh:
I will take this with your previous question about disease trends.
Building on Professor Burney's response, we know relatively little
about disease trends in the more severe systemic allergic problems
such as anaphylaxis, food allergy, urticaria, because a lot of
the primary work has not been done. When we do begin to exploit
these national data sets what we find is that hospital admissions
for the systemic allergic disorders have increased very rapidly
over the last decade and a half, and these increases seem to be
continuing. We are involved in work using primary care databases
to look at these trends to see whether similar patterns hold true
and these data also show that the systemic allergic disorders
are increasing. What we also know is that multiple allergic disorders
also seem to be increasing so, whilst currently in the older age
spectrum approximately five per cent of people will have multiple
allergic problems, if we look in the younger groups it is something
like 10 per cent. These are some of the people who are getting
into most problems and are running into most difficulties with
NHS care provision. In terms of unlocking the potential of the
data sets, we still have quite a long way to go and one of the
key things is allowing data linkage to take place, because not
only do we have healthcare data sets; we also have educational
data sets, we have got census records, so we can begin to look
at the impact of allergic diseases if we can make progress on
data linkage, but that needs some thinking through because of
the factor around confidentiality and privacy issues.
Q105 Chairman: Do you think the UK
Biobank will have a role here?
Professor Sheikh:
In terms of data linkage it could possibly because it is going
to be a vast resource and the idea of linking with other national
data sets would be very interesting.
Q106 Lord Haskel: When we were discussing
the first question we spoke about the importance of defining terms.
In oral evidence the Department of Health said that the introduction
of the Systemised Nomenclature of Medicine, or SNOMED, as they
call it, would help to classify allergic diseases in a much more
specific way. Do you think that this will improve the way in which
clinicians and researchers exchange clinical knowledge and aid
research into national trends?
Professor Sheikh:
Certainly SNOMED has the potential to do that and the advantage
of SNOMED is that it has been developed in the US, together with
the SNOMED CT version, the clinical terminology version, which
has been developed in association with the NHS. It is being used
in about 40 countries in the world at the moment and so in terms
of international comparisons through routine data sets the potential
is phenomenal. It also allows more specific coding because there
is far more flexibility within this new coding structure in the
way that the system is configured, so in terms of potential, yes.
However, what I am slightly concerned about is that at the moment
we need to get the allergy community involved in the range of
terminology that exists to see whether it is fit for purpose and
I do not think that has been done as yet. What also concerns me
is that for use in real time settings there needs to be simulation
work that as far as I know has not been done yet. Retrospective
coding is one thing but, in terms of real term consultation coding,
again, that work needs to be done to see whether this system is
fit for purpose. We also need to ensure that there is training
in place because a particular advantage of this is that SNOMED
CT through Connecting for Health would be implemented across the
NHS, so in primary care and in hospitals and NHS Direct, for example,
and so we have a potential for linked data which is very powerful.
What we need to ensure is that there is consistent training across
all of those different NHS sectors to ensure that the data we
collect are ultimately meaningful because in order for Professor
Burney and I to correctly interpret data it is essential that
these are collected accurately.
Q107 Lord Haskel: The problem with
classifying data in this way, of course, is that if something
new comes along you tend to miss it because it does not fall into
any classification. Do you think there is any danger of that?
Professor Sheikh:
I think there is less danger of that with SNOWMED-CT because it
does allow you to construct codes using a number of fields. Also,
there is a commitment to this being an iterative process, so,
as with the current coding system, if there is a need there is
the potential to include new codes, although at the moment this
is quite a laborious process. With SNOMED-CT it has been thought
through a bit better as far as I can see.
Professor Warner:
In a way one of the problems in relation to feeding data into
this system goes back to the previous question that was asked
about being allergically sensitised and having a raised IgE as
distinct from having IgE mediated disease. It is very easy for
somebody to misinterpret information based on a history and allergy
tests in relation to the patient's individual problem and then
the data go in incorrectly and that rather destroys the whole
object of the exercise. That is a feature of allergy practice
at the moment, not being something that is uniformly included
in undergraduate training or in postgraduate education programmes,
means that there is not sufficient allergy expertise around to
ensure that the data feed-in in the first place is accurate.
Dr Devereux: As a
chest physician I often see people who are sent to my clinic with
a diagnosis of asthma and a huge per centage of them do not actually
have asthma. This is where the database is going to collapse.
It is so easy for a GP to make a diagnosis of asthma because it
is the commonest thing that is around, whereas when they come
to my clinic I will do the tests and find that some of them do
not have asthma; some of them have bronchitis and emphysema, some
of them are just overweight, so maybe out of 10 people I see with
a GP diagnosis of asthma probably only about three or four of
them turn out to have asthma in the end, so you are right.
Q108 Lord May of Oxford: What do
we know about the incidence and prevalence of allergic afflictions
compared with other countries, and particularly, in so far as
it looks like we are high among the OECD countries, how much of
this is real prevalence as distinct from differences in the definition
of things we are talking about or, more importantly, the statistics?
Professor Burney:
Again, most of that information does not come from routine statistics;
it comes from surveys, so they are relatively well controlled.
There is a problem, obviously, in using questionnaires in being
very precise about what people have and whether the questionnaires
are working exactly the same way in one language as against another,
but for the most part we can be fairly confident. If I go back
to the ISAAC studies, which are worldwide studies of children,
they are based on questionnaires essentially. Some of them are
rather elaborate video questionnaires where the children are shown
videos of something and asked, "Are you like that?".
They took quite a lot of trouble to try and take out the effect
of language problems that you might have. For the ISAAC studies
it is quite true, certainly in Europe that the UK comes high in
the lists. In the six to seven year olds I think there was nowhere
that was higher, if we include the Channel Islands and the Isle
of Man within the UK. I do not think there was anywhere that was
higher in Europe for asthma and rhinitis in the reports that were
made from these questionnaires. For eczema I think it was only
Sweden that had a higher prevalence. For the 13 to 14 year olds,
again, in asthma only Ireland was higher and in rhinitis there
were a number of places that were higher, but by and large the
answer is that for those questionnaire-based data we can be pretty
sure that that is true. For the adults we have less information
across the world, but certainly in western Europe, and here we
have evidence from serology, from looking at specific IgE to allergens
in the sera from people from different parts of Europe, again
the UK has, or rather in the centres in the UKI should
be a little bit more precise because these are not universal studies;
they do not try and capture the whole population of Englandthey
had amongst the highest prevalence of sensitisation, and that
was pretty well true for all of the centres that we looked at,
and they had correspondingly higher levels of disease, so I think
we can be pretty sure that that is true. The only places in the
ECRHS, the European study that looked at adults, which had as
high or higher rates of sensitisation were other English speaking
places like Australia and New Zealand, which had very high rates
as well, so we can be pretty sure about that. In the ISAAC study,
which looked at more places worldwide, the other hotspot was Latin
America where they seemed to report very high levels, but for
those we do not have the equivalent data yet on sensitisation
rates, so we do not have an objective measure to measure that
against, but that will come.
Q109 Lord May of Oxford: What are
the ideas that are floating round about the underlying reason
for our being higher than others?
Professor Burney:
There are a number of reasons. It has been very difficult to demonstrate
a reason in a lot of different kinds of studies. When you actually
get to the data you say, "Let us adjust for the following
things", and then look to see whether that explains the difference,
and almost always the answer is that it does not explain it, so
explaining the differences has been extremely difficult. There
are general thoughts around.
Q110 Lord May of Oxford: We have,
of course, heard some of them. I wondered what your view of their
comparative merits was.
Professor Burney:
I would probably at the moment put quite a lot of emphasis on
diet. I think diet is probably important, but the detail of what
in the diet is much more difficult to disentangle at the moment.
There could be genetic differences. We know that there are, but
whether they are relevant in this case I am not sure. It has been
noted, for instance, that by and large genes follow language and
quite a lot of the places with high prevalence are English speaking.
Against that the Australian centre in the ECRHS is Melbourne,
where the population is very largely of south European origin,
so maybe this is not a good explanation.
Q111 Lord May of Oxford: It is not
really part of Australia.
Professor Burney:
The other hypothesis that is causing a lot of interest at the
moment is the so-called hygiene hypothesis. Again, we are not
entirely sure what it is in the hygiene hypothesis that is explaining
the differences. It is still really a hypothesis and, to be truthful,
it is probably lots of hypotheses which are adapted to fit different
stories and I think that has to mature a bit. We need to know
a little bit more about exactly what it is about "hygiene"
that is important. I suppose those would be the two main hypotheses,
diet and hygiene, that people are most interested in at the moment.
Q112 Lord May of Oxford: What about
the playing in dirt hypothesis?
Professor Burney:
That is the hygiene hypothesis. There are a lot of separate bits
of information about that. Some of the early theories on mechanisms
really do not seem to stack up so well but the basic original
data were that if you have older brothers and sisters you are
less likely to be allergic, and that seems to be very consistent
in all the data sets. That was the original part of the hypothesis.
It has since been expanded in various ways so, for instance, one
of the interesting groups that have been looked at, mostly in
central Europe, is farmers and it is noted that people who are
brought up on farms, particularly farms with animals, are less
likely to become allergic, which was a bit of a surprise to some
allergists who thought that being in amongst all those allergens
might have had the opposite effect, but it does not seem to. That
is a strong part of that hypothesis. In other parts of the world
the hypothesis does not stack up so well. If you go to Africa
where the environment is completely different hygiene does not
seem to explain the distribution of disease. People have tried
to explain it, for instance, by looking at parasites as part of
this general hygiene hypothesis. In fact, parasites do not protect
against sensitisation, as predicted by the original hygiene hypothesis,
but have a different effect and on a different part of the mechanism,
so that is probably a different story.
Q113 Lord Soulsby of Swaffham Prior:
Having started off on the hygiene hypothesis, I have two questions.
The first one is what practical advice should the Government be
giving to parents regarding hygiene to minimise the risk of their
children developing allergies?
Professor Burney:
My view would be none. Again, we have been into this a little
bit before. You have to have a very high level of understanding
of something before you start giving advice to people. One of
the things that people should be a little bit aware of is that
there is a hint in some of the studies that the same risk factors,
that protect you from allergy are also associated with lower lung
function, so it may well be that nanny is right, that playing
in the dirt is not such a good thing. It may be good for your
allergies but you really need to know across the board what the
effects are going to be before you start giving advice.
Professor Warner:
I think the word "hygiene" is now probably the wrong
one to use to explain this hypothesis. There was a very nice paper
published in the journal that Professor Kay edits very recently
where it has been suggested by the authors, and indeed other people,
that we should talk about microbial exposure or microbial deprivation
hypothesis. Hygiene hypothesis gives out the wrong message to
people, and the problem is that it is interpreted as suggesting
that you should roll your babies in dirt. The consequence is all
kinds of nightmares of infections that we have effectively eliminated
by good hygiene, and that is not what we want. It also gives out
a very bad message, for instance, in relation to immunisation.
This is an area where there is enormous worry that families are
not immunising their children because they have got the message
that immunisation means less infection, means more allergy. That
is an incredibly bad public health message and we have got to
counteract that. In fact, all the studies that are being done,
and I have been involved with one that we are just putting together
a paper on at the moment, show quite the converse, that if you
immunise babies effectively there is, if anything, marginally
less allergy. This is a complex area and we have to disentangle
all the different components. I still think it is an interesting
area in relation to potential for intervention but we are going
to have to understand what microbial factors are involved and
how they can be administered to reduce allergies.
Q114 Lord Taverne: Is it the new
Liu & Leung paper, the paper you mentioned?
Professor Warner:
The paper I mentioned is by Bloomfield et al. I am sure Professor
Kay would be able to give you the details. It is Clinical and
Experimental Allergy 2006, volume 36, pages 402-425.
Q115 Lord Soulsby of Swaffham Prior:
I just want to come back on the hygiene hypothesis. There has
been a suggestion that domestic pets, dogs and cats and maybe
other pets, play a role in this. Would you subscribe to that?
Professor Burney:
There is certainly some evidence that children brought up with
dogs have less sensitisation. I think we probably need a little
bit more evidence to support it, but that seems to be true.
Q116 Lord Soulsby of Swaffham Prior:
Because this country, the United Kingdom, has a high companion
animal population but it is not the only country in the European
Union that does, of course. France and Germany have high populations
too, and then there is the reverse of that: countries that do
not keep domestic animals because of religious reasons. What is
the issue there? For example, in a Muslim country is there as
much sensitisation and rhinitis as in a non-Muslim country?
Professor Burney:
I do not think we know much about that. I should also add another
issue over the pets, and that is that, again, there is misunderstanding
about this. Pets can be a problem for people who have already
been sensitised, so they are not an undiluted joy in this way.
I think the answer would be that in Muslim countries by and large
they are often exposed to allergens but cats are kept outside
the house and therefore they have a much lower exposure. That
may not be such a good thing as some people believe that very
high doses of cat allergen may be protective and lower levels
are more likely to sensitise but that is talking about the allergen,
so there is a paradox about this. Cats carry allergen but they
also probably carry some of this microbial exposure that might
be protective as well, so it is a paradoxical issue. I cannot
really answer your question about the countries in the Muslim
world. I do not have any data on that.
Q117 Lord Taverne: Is there anything
in the suggestion "dogs good, cats bad"?
Dr Devereux: The
first data were with cats and most of the studies have shown that
cats are beneficial; you are less allergic to cats than you should
be, but also there is some dog work. On the stuff about Muslim
countries, there is a study from Saudi Arabia showing that Saudi
Arabians, if they live in the cities, have a very high prevalence
equivalent to what we have in the westernised countries, whereas
the ones living out in the deserts with a nomadic lifestyle have
a very low prevalence of asthma and allergic disease. It is not
Muslim; it is where you live. It depends where you developed or
whether it was in the traditional lifestyle.
Q118 Viscount Simon: Is that the
same in, let us say, central Africa?
Dr Devereux: In Africa
there are studies showing very similar things, that populations
living in the towns and cities have more asthma and allergic disease.
People living in the townships out in the bush are less likely
to have asthma and allergic disease. However, the first studies
in the 1970s showed that there was quite a big gap but now the
gap is narrowing and it is thought that people in the townships
and the bush are taking on westernised lifestyles and that is
maybe why the gap is disappearing now.
Q119 Viscount Simon: Or maybe second
homes.
Dr Devereux: I suspect
that if you are poor in Africa you cannot afford a second home.
Professor Burney:
No, but movement between urban and rural areas does happen, particularly
with children. Children will be sent from the towns in some places
to the country to be educated because it is a less dangerous environment,
so that is a complication.
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