Examination of Witnesses (Questions 120-139)
Professor Peter Burney, Professor Aziz Sheikh, Dr
Graham Devereux and Professor John Warner
6 DECEMBER 2006
Q120 Baroness Platt of Writtle: Does
everyone agree that the prevalence of allergic disease will continue
to increase?
Professor Burney:
As I was saying, I think it is probably true in the older age
group that that is almost inevitable, but I would hesitate in
one sense. It is very likely to be true for sensitisation, for
the reason I have given, that the younger adult generations of
people who are now going to get older have a higher burden of
sensitisation, so I think that probably is going to happen. I
would put a lot of money on that. I think the issue that follows
from that, which we are less clear about, is what will happen
to disease as a result of that increase in sensitisation. As I
say, my guess would be that disease would also increase and be
more of a problem, but there is less evidence on that.
Q121 Baroness Platt of Writtle: You
talked about the young compared with the old but would there be
a difference on a gender basis, males and females?
Professor Burney:
I think much the same for men and women. As I said though, there
are differences between men and women and I think, particularly
in the child-bearing years, women have a high burden of asthma.
The answer to your other question, what is happening in children,
is that we just do not know and that is going to be very important,
but it will be very important for the more distant future. If
there is genuinely a decrease in sensitisation amongst these generations,
this will then reverse the trend, but in another 20, 30, 50 years'
time.
Professor Sheikh:
I think with this current generation of children, where the data
in the UK show that between and 30 and 40 per cent are experiencing
allergic symptoms, it is reasonably safe to predict that this
generation will continue throughout adult life to experience allergic
symptoms of one sort or another, so I think in the short to medium
term the prevalence is going to be high and it is going to have
an impact on all sectors of healthcare provision.
Q122 Chairman: I wonder, Dr Devereux,
if I could pick up on what you were saying previously about some
of the animals and whether it is true to say that being brought
up with cats may give you tolerance, but that there is a different
cohort who are allergic and get very severe symptoms when in contact
with cats and they may be in the same house living with those
animals? Have we got two populations?
Dr Devereux: I suspect
we probably have. I suspect that the way the cat protection phenomenon
is explained is that when you get exposed to cat allergen your
immune system responds with a toleragenic response in that it
tolerates the cat allergen, whereas you have got another group
of people who, when they get exposed to cats, for whatever reason,
genetic, environmental, diet, then develop an allergic response,
so it is likely that you may have brothers and sisters living
together and one may derive protection and one may derive harm
from the cat.
Q123 Lord Colwyn: We move on now
to the burden these diseases are causing. The incidence has obviously
increased a lot since the 1950s and I think I have read in my
papers that it just about doubles every 10 years or so.
Professor Burney:
It doubles about every 14 or 15 years.
Q124 Lord Colwyn: The written evidence
we have got has highlighted the significant personal, social and
economic impact of these disorders. Are there any key measures
that you think perhaps the Government or other public bodies should
implement to try and reduce this burden at home, at school and
at work?
Professor Burney:
I will have a first go at this. I think it is very difficult,
for the reasons we have given, to give very specific answers to
that. Good healthcare would be good. Beyond that one of the things
I would say is that it would be useful, given the high prevalence
of disease, if this were something that was always considered
by departments when they develop policy. I think that people tend
to forget that there is this very large group of people who are
specifically at risk, so I think that if all government departments,
when they were developing policy, actually had a check, "Have
we thought about what the influence would be on allergic people?",
that would be good. As for giving very specific advice I would
be pretty much at a loss to give strong advice at the moment.
Dr Devereux: I think
there is something that can be done. At the moment the allergy
provision service in the NHS is not good. There is no allergist
north of Manchester. There is no allergy service for the whole
of Scotland or the north of England. What we have is a significant
proportion of the population with allergic disease who are getting
ad hoc advice from non-experts like GPs, respiratory physicians,
dermatologists. These people are desperate for help and they are
seeking help in alternative medicines, all sorts of things, so
one thing could be to try and increase allergy provision so that
a correct diagnosis of allergy is made so that the correct treatments
can be instigated and the correct avoidance measures taken.
Professor Warner:
I agree with what Graham Devereux has said. I think that is the
most important thing. There are some other issues though. It is
about raising awareness across the whole of Government. For instance,
recently the Department for Education has been recommending that
the junk food which is sold in vending machines at schools should
be replaced by nuts and peanuts as healthy foods. That is failing
to consider the impact on the peanut and tree nut allergic child
in that school. It is a question of joined-up thinking between
different departments that might take account of this very common
problem.
Q125 Baroness Platt of Writtle: What
about the problem of children with rhinitis and exams, because
in two lots of evidence it said that they are achieving one grade
less due to their allergy?
Professor Warner:
Yes, very much so. There is now good evidence for that. Exams
are virtually always in the middle of the pollen season and that
brings down grades appreciably. People have now done studies looking
at results of mock exams, which are out of the pollen season,
and comparing them with the results that have occurred in the
real GCSEs and showing that pollen allergic children do drop a
grade.
Q126 Lord Colwyn: I am surprised
to have read in our evidence that there is not any evidence that
the increase is attributed to allergen exposure or even the famous
house dust mite at all. The gaps in our knowledge could perhaps
be dealt with by having better training at undergraduate level,
courses for doctors and more specialist allergists. Would that
solve it?
Professor Sheikh:
Undergraduate training is a key issue. We have been looking in
detail in Edinburgh at our undergraduate training provision. For
example, allergy diagnosis is not covered at all. Food allergy
is not covered at all in the curriculum. Multiple allergies are
not covered at all. This is a reflection almost certainly of what
is going on in most other medical schools. At postgraduate level
there is very little training provision at the moment. In response
to your previous question, what else can be done, one of the pieces
of work that we are currently doing is looking at anaphylaxis
management in schools. Schools are, on the whole, at a loss to
know how to deal with this problem. They are saying, "This
is a healthcare issue; we are educationalists". GPs and,
where they are involved, consultant paediatricians are saying
that it is not their remit to go into schools. Children are therefore
falling through the gap. For those with life-threatening allergies
and with severe allergies one important step would be to think
about case management. Case management now exists for a number
of other long term disorders. Everything needs to be done within
an evaluative context because there can be unintended consequences,
but it would be one step forward to begin thinking of these as
long term disorders, which the NHS historically has not done.
Q127 Countess of Mar: Before I ask
my question I should declare my interest because I am not a member
of the Committee but I am allowed to come in on it. I am a farmer.
I produce raw goats' milk, which we have quite a lot of custom
for, and I also have an interest in toxic chemicals arising from
organophosphate poisonings from sheep dip. Do you think that the
Government's and the European Union's efforts now to control the
proliferation of chemicals and chemical exposures, and particularly
chemicals that are used in domestic situations, are worthwhile?
I know that there is a lot of research now which is showing that
the placenta is not as protective of the unborn child as it was
thought to be. Do you think there might be some connection between
the effects on the immune system that might have happened in
utero and the subsequent allergies that are showing up? That
is rather a lot of questions all together.
Dr Devereux: The
goats' milk—
Q128 Countess of Mar: You need not
answer that.
Dr Devereux: No,
no. The work from Switzerland, Austria and Germany showed that
one of the protective effects of living on a farm was from consuming
unpasteurised milk before the age of one. Whether you want to
advocate that as a widespread measure I doubt because of the problem
with tuberculosis.
Q129 Countess of Mar: No, in fact
I never recommend goats' milk to a child under the age of one
and we know that our goats do not have TB.
Dr Devereux: If you
put it in context that is quite an interesting point. There is
increasing interest in the possibility of environmental pesticides
and things like that. There is this interesting work from various
groups around the world showing that you can detect these chemicals
in the blood of newborn babes and the exposure seems to influence
the neonatal immune system responses. Whether these translate
into current disease we are not really sure. I did look at one
paper. The problem was that the levels of some of the chemicals
have gone down, so it would be difficult to link. The other aspect
of this is your cleaning agents thing. There is a study from ALSPAC
associated with internal exposure to various chemicals and whether
that needs to be all firmed up. Moving on to a different phase
of investigation, we have looked at the allergen phase and most
people would accept that probably the increase in asthma and allergy
is not due to increasing allergens. Dealing with the hygiene and
the dietary hypotheses at the moment, I think the things in the
future are going to be the environmental pesticides, environmental
chemicals and cleaning agents. That is where the research is going
to be going to.
Professor Warner:
Certainly that is something where we need more information, but
also we need to think about the other pollutants or other factors
to which people are exposed where maybe there is a bit more evidence.
We know that allergic sensitisation can be increased and the allergic
reactions themselves can be increasing if you have simultaneous
exposure with an allergen and, say, diesel particulates or ozone
or nitrogen oxides, and so there are air pollutants that might
be adding to the burden and certainly increasing the severity
of disease. Pollutants may be also contributing to the increasing
prevalence as well, although the data are a bit more tenuous,
I think.
Professor Sheikh:
Can I come back on the raw milk point because there are data now
from a number of studies which show that raw milk consumption
may be protective, including data from the UK which have recently
been published. The point here is that now we need prospective
work and interventional work to understand this phenomenon better.
One of the issues of relevance is that if we do introduce legislation
around milk or other issues it is important, bearing in mind how
little we know about early life influences, that that work is
in an evaluative context. For example, raw milk sale, as you are
no doubt aware, is banned in Scotland, so the scope for any interventional
work is therefore very limited, but was there any evaluation put
into place to look for unintended consequences which may have
resulted from that ban? We need to be thinking much more broadly.
Dr Devereux: The
other thing is that people who purchase farm milk, unpasteurised
milk, have different lifestyles from the rest of us and so it
may not be the milk; it may be some other factor that they are
exposed to or not exposed to. It may be a mark of lifestyle.
Countess of Mar: It is quite interesting.
Our customers come from a very wide range and generally they have
children who are allergic to "dairy", as they call it.
With my reading, apparently there are two different sorts of casein.
There is alpha casein and beta casein, and I cannot remember which
way round it is, but there is one that is found in goats' milk
and Guernsey and Jersey cows, and the other is found in the black
and white cows that nearly everybody's milk comes from. It may
be that since the fifties farmers have tended towards having Holstein
herds, the black and white cows, rather than the Channel Island
cows, and there is a possibility there that it may have changed
the metabolism somehow. The other one is the altered protein on
pasteurisation, where the protein itself is altered on pasteurisation.
Cheese-makers know that pasteurised milk does not make the same
sort of cheese as unpasteurised milk.
Q130 Lord Soulsby of Swaffham Prior:
Can we talk about housing conditions and poor housing, and whether
that contributes to the burden of allergic disease by way of,
for example, increased dust mites, moulds and other environmental
bacteria organisms? If there is anything there, should that danger
in housing accommodation and other buildings be reflected in the
Building Regulations?
Professor Burney:
Yes, I am sure that is true. I think there is quite good evidence
that damp housing with mould causes problems, particularly for
patients with asthma. Clearly, that is an avoidable risk that
they run. That certainly could be important. We know that also,
for instance, in some places, where you get very high build-up
of, for instance, oxides of nitrogen from gas cooking—particularly
with gas stoves—that can have an adverse effect on patients
with asthma. That is quite easily remedied by having proper ventilation.
I think it goes back to what I was saying about regulatory bodies
always taking account of the fact that a very high proportion
of the population is allergic, and I think Building Regulations
should reflect that.
Professor Warner:
I think it is important, however, to distinguish between housing
conditions that may contribute to the development of allergy in
the first place. After all, everybody lived in damp, cold housing
one hundred years ago and there was much less allergy, so it is
not necessarily increasing the risks of being allergically sensitised.
However, once you are allergic and have a problem there is no
doubt that living in damp, cold housing makes your problems worse.
For instance, in the United States, the inner city deprived population
have infinitely more severe and even life-threatening asthma at
higher prevalence than those living in better housing. So there
is certainly a need to address that, but we need to think about
whether in changing the indoor environment, this which might increase
the risk of allergic sensitisation. I know that sounds a paradox
but there are very different influences between creating the problem
in the first place and aggravating it once it has occurred. There
is, again, more work to be done to understand the indoor environment
and how it contributes. By having energy saving we are creating
tight homes which are increasing the levels of nitrogen oxides
and volatile organic compounds which might be contributing to
enhancing sensitisation in the first place. If we are going to
have tighter housing for energy saving then we need proper ventilation
systems with heat exchangers in order to achieve benefit for everybody.
Q131 Lord Soulsby of Swaffham Prior:
It is interesting what you are saying. The question naturally
arises, are the people who are making proposed regulations aware
of the dangers of energy saving and things like that? If they
are not, how do you get that information to them?
Professor Warner:
Many years ago, I was involved in research with the Building Research
Establishment, and at that stage they were very aware and doing
quite a lot of work, but the BRE is not now predominantly government-run
or sponsored; it is an independent organisation and I am not aware
of what they are doing. There are other countries, notably Denmark,
that have put quite a lot of work into housing design and its
effect for allergy sufferers.
Q132 Chairman: Can you clarify for
me from your answer whether you are saying that low-allergen housing
is actually unlikely to prevent allergy?
Professor Warner:
Based on studies so far done, the low-allergen housing is almost
certainly not going to prevent allergy because you are not just
reducing exposure to the allergen. There are other knock-on effects
of reducing allergen exposure such as reducing exposure to bacterial
products, which might increase allergy risk, with ventilation
systems, and reduced exposure to irritants might reduce allergic
sensitisation. So there is a bit of a balance: some things are
perhaps not making any difference and others may actually be having
some benefits. Studies that have looked at, say, reducing house
mite avoidance in early life to prevent disease have shown that
there is a reduced rate of early wheezing illnesses not associated
with allergy, but later with no difference or, maybe, marginal
increases in allergic-associated wheezing.
Q133 Viscount Simon: For the last
15 years or so, I think it is acknowledged, there has been a year-on-year
increase in hospital admissions for anaphylaxis, which suggests
an underlying change in the epidemiology of this sort of allergic
emergency. What can be done to reduce the number of people admitted
suffering from anaphylactic shock?
Professor Sheikh:
You are absolutely right the data show very dramatic increases
over the last 15 years or so, and these are year-on-year increases,
and they continue. There are three issues that need to be considered
primarily. One is that in those presenting with acute anaphylaxis
in hospital accident and emergency departments we know that very
many of these patients are still getting sub-optimal care, so
many of them will still not receive adrenaline, which is a potentially
life-saving treatment; they will often get other forms of treatment,
in the form of antihistamines or steroids, and here there is emerging
evidence to suggest that we may actually be doing more harm than
good in those cases. One of the things we need to be doing is
developing a far more secure base around how we manage this in
an emergency context and seeing if that will improve outcomes.
That is challenging to do because this is a life-threatening emergency,
so it needs an appropriate regulatory framework and it needs ethics
committees to think more flexibly than they have done hitherto.
That is one issue. I think the second issue is about long-term
provision for those who have a history of anaphylaxis. We have
tended to think about this as an acute problem only, but this
condition has life-long implications and multifaceted implications.
One of the things we could be thinking about is developing anaphylaxis
long-term management plans, as is now common in some other allergic
problems, such as asthma or other chronic disorders, and that
needs to be done, but again within an evaluative context. There
needs to appropriate incentives in place in general practice,
but I think with a will we could probably devise these. That would
commit us to identifying the allergens that are responsible for
provoking anaphylaxis so patients know how to avoid these products,
and also training them in appropriate emergency provision if they
do get exposed. Taking that twin-strand approach would probably
help us in reducing some of this burden.
Q134 Chairman: In your response to
Viscount Simon you were saying that the current management where
they are not going to use adrenalin early may be doing more harm
than good. I wonder if you could expand on that.
Professor Sheikh:
Certainly. Adrenaline is internationally recognised as the treatment
of choice in anaphylaxis. Unfortunately, very many patients who
present with anaphylaxis still do not receive adrenaline. Having
said that, there have been very few empirical studies on which
to base the decision to treat with adrenaline, so we do not know
the correct dose to be using, we do not know what the correct
route of administration is, and we do not know when is the appropriate
time to give the next dose of adrenaline. So there are massive
gaps. What people do get when they walk into an A&E department
is antihistamines, and they will be given antihistamines intravenously,
typically. There are some data which suggests that, particularly
in hemodynamically compromised individuals, they may be increasing
the risk of arrhythmias in these patients. They are also often
getting steroids, which, if given intravenously, again, are going
to have virtually no impact on the acute illness. Again, there
are no real scientific data on which to base those treatments,
so in such a case we need to be rethinking some of these guidelines.
I am, together with colleagues in Canada and the US, involved
in those discussions, so I think we will get progress internationally
in the next few years.
Q135 Lord May of Oxford: Under the
heading of hospital admissions I want to ask a follow-up that
goes a little wider, although it does relate to this. One of the
background papers we were given is a report from the Office of
National Statistics, by the authors Gupta and Strachan, and it
shows that there has been a decline in hospital admission rates
in relation to asthma among children in the last decade, and it
goes on to say: "after three decades when prevalence studies,
primary care contacts and hospital admission rates all suggested
a rise in the burden of asthma in children". They became
disassociated in decade 1990 to 2000 (possibly, it has been suggested,
it is just more widespread use of preventers reducing the incidence)
but then they go on to say: "At a regional level in England
[and they quote studies] there was a very poor correlation between
admission rates for asthma [which have gone down] and the prevalence
of wheeze (even of severe wheeze) [which had gone up] among children,
[and here comes the question] suggesting that referral and admissions
policies, rather than the incidence of acute attacks, are potentially
the important determinants of asthma admission rates". So
I have two questions: the first is—and I imagine you are
quite sure but it would do well to affirm it—that the rise
in admission rates for anaphylactic shock is real and not a change
in policy. But then I would like to cheat and ask a second question:
do you have a comment on the thing I have just read, which really
is quite an important statement if true.
Dr Devereux: Fundamentally,
the person who decides whether a patient should go to the hospital
is the GP, so referral patterns are very important. That is what
decides whether a patient gets referred. I personally feel that
the reason why admission rates have gone down is because GPs are
managing asthma much better than they used to: the increased use
of preventative medication, as you have just said, asthma plans
at home, patients are basically able to take their own steroids
when they get symptoms, they have peak flow-meters at home, it
is far more controlled and you get fewer patients coming in who
have just acutely deteriorated. Most people are able to manage
it at home and GPs are increasingly confident about their ability
to manage asthma at home. As you said, they are more confident,
the medication and management plan is in place and fewer people
are getting referred.
Q136 Lord May of Oxford: So the severe
wheezing attacks that previously would have had them admitted
are now managed at home.
Dr Devereux: Yes.
Q137 Viscount Simon: Following what
Professor Sheikh was saying, I have two questions: one is personal,
I am afraid to say, and the other one is more to do with this
inquiry. You were talking about cetirizine and allied medicines
and, also, adrenalin. I take a huge doze of cetirizine every day
of the year and I carry adrenalin with me. From what you are saying,
should I use the adrenalin in an emergency? The second question,
which is the general one, is do you think it would be worthwhile
starting or instituting a national anaphylaxis surveillance programme?
Professor Sheikh:
Maybe I can try and take both of these questions together. In
terms of your personal question, if you are experiencing symptoms
of anaphylaxis then certainly use your adrenalin and get some
help. I think everybody would be in agreement about that. In relation
to hospital admissions, hospital admissions are the tip of a clinical
iceberg, so studying those is subject to all sorts of potential
variables. However, we are on reasonably firm ground, when we
have got data pointing in the same direction irrespective of the
data source, as in asthma for example—we know that hospital
admissions are declining and we have got a pretty good idea of
what is happening in general practice as well—really what
we are seeing is a decreasing burden, or at least a stabilising
in the disease burden. In relation to anaphylaxis, what we are
seeing is that hospital admissions are going in a certain direction,
very clearly. When we have investigated the possibility of diagnostic
transfer taking place, and it seems that is unlikely to be taking
place, we have looked for regional differences and it seems, again,
that there are similar patterns all across England. We have looked
across different age groups and, again, it seems that there are
similar patterns in most age groups. In terms of primary care
data, which are as yet unpublished but hopefully will be within
the next few months (once I have finished with this I can get
back to writing the paper), what we see there is that there is
improved diagnosis taking place in general practice but, over
and above that, there is an increased number of people with anaphylaxis.
Failing that, the only next step that remains in unpicking this
jigsaw is going back and doing some validational work, so looking
at people who are admitted with anaphylaxis and then extracting
some of their individual case records, subjecting them to a panel
of experts and seeing to what extent the data are valid. That
work, again, is on my agenda—we need to do that. In relation
to surveillance, with these numbers and this rate of increase
then surveillance is entirely appropriate. Our estimates, at the
moment, are that in England there are some 38,000 people (these
are unpublished data) who have had a history of anaphylaxis at
some point in their lives. These are still relatively small numbers,
so a surveillance programme for anaphylaxis could prove feasible.
Some kind of longitudinal tracking of a sample of these individuals
would help us to far better understand the epidemiology of this
condition. I am part of an international group looking at the
epidemiology of anaphylaxis, and you are right to point out there
are massive gaps, but in the UK we are probably the most developed
in terms of our understanding.
Professor Warner:
May I make some comments? Firstly you are not doing yourself any
harm taking regular cetirizine and you might actually be helping
some of your allergic manifestations, which is rather different.
In relation to the increasing rates of severe, acute allergic
reactions, particularly in relation to food allergy—clearly
there has been a dramatic change in people's eating habits and
what kind of foods they are accessing. It would be relatively
easy to avoid peanuts if everything you ate was cooked yourself
having bought fresh food in the market and from the butcher. Of
course, that is not what happens now and people are buying products
that have gone through a whole series of processes and been manufactured
and packaged. Under those circumstances the potential for there
to be unexpected peanut within those products, unfortunately,
is significant and creating a problem, and it is a nightmare for
sufferers. They now have a poorer quality of life than someone
with diabetes requiring insulin every day. That is now well established.
It is a question of, maybe, changing our eating habits and raising
awareness that ought to, in the end, have an impact. Yes, we have
to understand why the whole problem has increased but, at the
same time, to help people that are suffering now I think there
are things we can do.
Professor Sheikh:
The degree of distress that some young people experience by being
confronted with labels saying "may contain traces of nut"
is something I think we underestimate. Let us turn that on its
head. I think there is a market now for products which are guaranteed
to be nut-free and similar other products which are guaranteed
dairy-free, for example. Some work needs to be done to look at
that and that would, again, be something that would be very useful
to a lot of people.
Chairman: We have quite a lot of questions
still and I am aware of the time, so I think we are all going
to try to be concise with our questions and appreciate if you
could with your answers. It would be really important to get through
questions on primary prevention and research.
Q138 Lord Taverne: Turning to research,
in an area where there is so much uncertainty, what are the most
promising areas of research into primary prevention? What would
be likely to produce best value for money? For example, would
it be diets of pregnant mothers, pre-biotics, pro-biotics? What
is your view?
Dr Devereux: I am
very biased. I think there is increasing evidence that we should
look at maternal diet during pregnancy. I am being encouraged
by various people to actually go ahead and try and do an intervention
study. Whether I get funding for it or not—it is clearly
going to be a hell of a job to get funding. Pre-biotics certainly.
If you speak to the people who make pro-biotics, they think the
case is made, with a couple of well-designed intervention studies
in pregnant women showing a reduction in eczema with pro-biotics.
So I am biased, and that is my biased view. I would go for maternal
diet, but I am sure other people will go for other things.
Professor Warner:
I would agree. I would put diet as number one, although I prefer
to call it nutrition rather than diet because it is nutritional
enhancement rather than avoidance. After that I would still focus
on pre-biotics, not pro-biotics—I do not think the case
has been made for pro-biotics. I think the interactions of all
the different organisms in the gut are very complex but pre-biotics
look more promising. After that it is some form of immune modulation
using other microbial agents to induce an appropriate immune response.
Those are the three areas I would focus on.
Q139 Chairman: I wonder, too, what
you feel about maternal smoking and the effect of maternal smoking
on the risks of a child developing allergy.
Dr Devereux: It is
well known and accepted; it is well documented and I think everybody
accepts that.
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