Examination of Witnesses (Questions 140-159)
Professor Peter Burney, Professor Aziz Sheikh, Dr
Graham Devereux and Professor John Warner
6 DECEMBER 2006
Q140 Chairman: There is no controversy
about it.
Dr Devereux: No.
Q141 Chairman: I am really glad to
have that on the record.
Professor Sheikh:
I agree with the points made, but the other area is that when
we have so many potential risk factors we need to be thinking
more about multifaceted interventions in early life. So this may
involve a combination of immune modulating treatment and allergen
avoidance, for example. There are some data which suggests that
these multifaceted interactions may be particularly promising.
Q142 Baroness Platt of Writtle: Are
grant funding bodies distributing money for research into allergic
diseases in the most promising areas? Could we be getting better
value for money from investment in research? In two lots of evidence
we have had, including Professor Warner's, there is a recommendation
for a central funding body. I am slightly nervous about that as
it might be bureaucratic, but perhaps you might like to refer
to that in answering.
Professor Warner:
At the moment, most funding for allergy research is handed out
on the basis of judgments about what is the best scientific proposal,
and therefore there is not any strategy behind that; it depends
on the individuals submitting from an area that they wish to investigate
rather than one which necessarily might be, in the end, the best
thing to do from a public health perspective. My suggestion was
maybe one should think about having some kind of co-ordination
identifying target areas for research. I do not mean being intensely
bureaucratic but just inviting people to apply in target areas
that are seen to be important from a public health perspective.
Dr Devereux: The
Food Standards Agency (?) did put out a call for studies of early
life diet and respiratory outcomes in children, and we thought
we were in a good position to get this because we are probably
leading the community in doing this sort of research, but we were
turned down on some fairly weak sort of grounds. I have been banging
my head against a brick wall for the past few years trying to
get money to fund study into nutrition and asthma, and I have
a real headache now after banging my head against a brick wall
for so long.
Q143 Lord May of Oxford: It might
be helpful, just quickly, to clarify. The Medical Research Council,
in particular, has three categories of grant: one is the responsive
mode, as you have just suggested; at the other extreme are occasional
things where they do pick out an area and, I think, very interestingly,
in between them is this third category of highlighting an area,
where they do not exactly set aside a pot but they say: "Here
is something where we think perhaps it might be useful if you
could start lobbying".
Dr Devereux: I have
been told that in the next year or so respiratory medicine will
go up the list of competing priorities, but I will wait and see
what happens.
Professor Sheikh:
One of the problems here is that we do not have a level playing
field in that we do not have a major allergy charity that the
academic community can turn to. Allergy UK and Anaphylaxis Campaign
have no money for research, unlike the Cancer Research UK or Macmillan,
for example. In the absence of dedicated charities, some kind
of central highlighting of the need for dedicated research funding
and a dedicated pot for the important translational health services
research really needs to be done. We are not in a position to
answer hardly any of these questions that you have posed, unfortunately,
because there is nowhere to go to get any substantial money to
do this kind of work. In terms of primary prevention, we need
long-term follow-up; we need 15-20 year studies. The Scottish
Executive have not, for example, prioritised this and they have
got a ceiling on project grants of £150,000[1]
There is no way you can do this kind of work on that kind of money.
Q144Lord Colwyn: This is a question that comes
from the helpful paper from Professor Burney and the outdoor environment.
I wonder whether you could make any further comments on your statement:
"there is a continuous low level of effects from allergens
in air, but the nature of these . . . is uncertain." Then
you say that some of them are likely to come from man-made sources
and need further investigation. Can you follow up on that at all?
Professor Burney:
The evidence so far is in rather general terms. The difficulty
is that an allergen is very specific to a particular person. There
are things that are commonly allergic to many different people,
but everybody has their own allergens. So it is quite a difficult
area to study in that way; it is not like studying air pollution
from, let us say, nitrogen dioxide, which is something you can
measure and it is the same for everyone. What we know now is that
allergens in air do cause exacerbations, and we can say that it
is an allergen but we do not necessarily know what the allergens
are. The other part of your question is something we can speculate
on. We know it is very likely, for instance, that moulds in the
atmosphere are part of the problem—I cannot tell you exactly
how much of the problem—but the other thing that we know,
from rather spectacular epidemics that have happened, is that
these can occur because people are storing and releasing large
quantities of allergen. So, for instance, one of the more recent
epidemics happened in the 1980s in Barcelona where they were storing
soya beans in silos in the dock. The silos were uncovered, so
when they dumped large quantities of soya bean in they released
soya bean allergen into the air. Under the wrong atmospheric conditions
in which the soya bean was spread around the town you got really
serious epidemics. So we know that there are sources of allergen.
Such events are quite rare but in order to find them you have
to have these big epidemics, and then they are obvious; you do
not need an epidemiologist to tell you there is a problem, you
just go into the casualty departments and they are filling up
with asthmatic patients. We know that this has happened, also,
with castor bean from processing places. We don't know whether
this happens on a smaller scale. So it is really speculation.
We know that there are conditions under which this can happen,
and I think it is an area we need to know a lot more about. We
need to know what allergens can cause such problems and we want
to know, really, whether they are controllable. If they come from
an industrial source they are probably controllable; if they are
natural allergens there is probably not a lot you can do about
them.
Q145 Lord Colwyn: It is advantageous
to live in areas of non-pollution.
Professor Burney:
Yes, in a way, but it is a different kind of pollution.
Q146 Lord Colwyn: One other thing
is a subject I have spoken about in the House of Lords, probably
for 25 years now. Have you anything you can comment on in relation
to electromagnetic pollution?
Professor Burney:
No, not in this context.
Q147 Lord May of Oxford: I think
probably the most useful thing I did while I was the Chief Scientific
Officer was promulgate rules for handling science advice in policy
making and giving advice to the public, but these things are much
more easily said than done. This is a very good example, it seems
to me, where, as we have heard, there are so many of the issues
where there are various ideas and conflicting evidence. How do
you see, against that background, in this particular instance,
formulating the advice we give to the public—guidance?
Professor Sheikh:
One of the issues we can do is we can advise which interventions
are not working, and that can be useful advice. For example, taking
measures to avoid aero-allergen exposure domestically is very
unlikely to prevent allergic disease. A number of people are doing
this with no clear evidence base. In terms of the positive recommendations
that we can make, I think we need to appreciate that we are at
a very early stage in this story. Overall, advice has to be evidence
based and this evidence will accrue. If you can help in allowing
us to do the research in any way then certainly we can feed into
that process.
Professor Warner:
I have had my fingers burnt over this. I was on the Committee
in the Department of Health that made the suggestion that in families
that have allergies it would be sensible for mothers to avoid
eating peanuts and tree-nuts and not giving them to their babies
for the first three years of life. That advice still stands, but
evidence is now accruing which suggests that that might not just
be having no effect but it might actually be having the opposite
effect. So although it was made in good faith at the time, based
on evidence available, it was indirect evidence rather than direct
evidence. Perhaps we have to be very cautious about any recommendations
we make until we have got good evidence from controlled intervention
rather than just observational studies.
Q148 Lord May of Oxford: Can I ask
a follow-up, mounting another of my hobby horses? I am very down
on the wasteful and energy-consuming over-packaging of food in
supermarkets, and so may I ask you if there is any reliable evidence
to show that preservatives used in plastic food packaging increases
the risk of allergic diseases? If so, should the public be advised
of this?
Dr Devereux: There
are some preservatives that will exacerbate your asthma. There
are some, like tartrazine and metabisulphite, which will exacerbate
your asthma and make it worse, but whether they actually cause
asthma is a different matter.
Q149 Chairman: Did you want to make
a comment, Professor Warner?
Professor Warner:
No, we just do not know, really.
Lord May of Oxford: If
you were to offer such advice you have to say you cannot be sure.
Q150 Lord Haskel: Would you advise
that we should inform the public that we do not know an awful
lot about this, or do you think that is very dangerous?
Professor Warner:
I do not think it is dangerous. There is a great tendency for
people to think that there should be an absolute answer, and yet
actually I think the public are perfectly capable of understanding
when we do not know and therefore cannot make a recommendation.
Professor Burney:
I think the real danger is in coming out with these pronouncements
based on indirect evidence. A lot of these hypotheses are very
intriguing, they catch the imagination, and we want them to be
true because they are rather beautiful ideas, and we are in danger
of going beyond the evidence. Then we give advice and people are
disappointed; they say: "You told us one thing last year,
it is a different thing this year", and I think we lose credibility.
The public can tolerate ignorance. That is not to say that we
cannot find an answer, but it will take time.
Professor Sheikh:
Ideally we would like to see newborns in very large numbers entering
into the trials that are so urgently needed. So any advice that
you can give to say that we do not know would be very helpful.
Q151 Lord May of Oxford: I would
gratuitously add that the guidelines on science advice say: "If
you are not sure you say you are not sure". My personal belief
is, as you said, it is confidence enhancing.
Dr Devereux: It works
with patients when you do not know what is wrong with them and
you tell them you do not know.
Q152 Lord Rea: We move on to another
wide area which is the association between diet and allergic diseases.
I found Dr Devereux's review article that we were circulated with
extremely useful in this area, particularly with regard to the
diet of the pregnant woman and the effect on the foetus and the
subsequent child. Could you develop this theme?
Dr Devereux: We have
been conducting a study for the last four or five years where
we recruited a large number of women up in Aberdeen, looked at
what they ate during pregnancy and then have been following their
children up. We have done it for five years so far and have been
able to show that in mothers who had a low vitamin E intake it
affects the core blood immune responses, it affects their children's
wheezing outcomes at the age of 2 and it affects outcomes at the
age of 5. You have got objective associations with things like
lung function measurements and we have got associations with measures
of airway inflammation. These have been repeated by an American
study very much along similar lines, called Project Viva in Massachusetts,
which is showing very similar associations with vitamin E and
core blood responses and wheezing at the age of 2. We have also
more recently looked at the data showing associations between
zinc and vitamin D. Vitamin D is particularly interesting because
there is this latitudinal association with asthma. If you look
at the map of where asthma prevalence is high it tends to be the
extreme northern and southern hemispheres. Vitamin D intake has
gone down, and vitamin D has some very interesting properties
on the immune system. So what we are coming up with is early evidence
to suggest there is an association. There is not enough to make
a recommendation yet but it is probably enough for us to want
to go ahead and do an intervention study to see whether intervening
has an effect and whether it is practical to intervene during
pregnancy, and whether pregnant women would be willing to change
their diet in order to prevent their children developing asthma.
We have looked at the magnitude of the effect and we have worked
out that if we could get pregnant mothers to increase their vitamin
E intake during pregnancy from what it is now to what it was in
1950 you would halve the prevalence of childhood asthma at the
age of 5. Those are big claims and it needs to be backed up with
some intervention.
Q153 Lord Rea: You said earlier that
you were searching for funding to do an intervention study like
this.
Dr Devereux: I would
like to, yes.
Q154 Lord Rea: Would this have to
involve big numbers? Is that why it is going to be difficult to
get the funding?
Dr Devereux: The
numbers are going to be about 1,000, I think. The problem is (a)
getting somebody interested in a nutritional theme—there
have been lots of studies looking at giving antioxidants, like
big, big doses of vitamin C, to prevent cancer and heart disease
and they have all turned out to be ineffective if not detrimental,
whereas we are thinking along a different line here; we are thinking
of small doses of vitamin E, maybe changing diet rather than giving
a supplement—and (b) the duration. You are going to have
to recruit pregnant women during pregnancy, intervene and follow
the children up for at least five years, and that is a big study;
it takes a lot of money to do that sort of study. So it is a question
of funding bodies' interest and funding—the actual cost.
Q155 Lord Rea: We have discussed
on a number of occasions the role of pre-biotics and pro-biotics.
Do you think if pregnant women take these it is worth looking
to see what the result is, and is there any evidence that there
is any benefit?
Professor Warner:
There is for pro-biotics at the moment. The pre-biotic work is
only in progress at the moment. The studies have tended to give
the pro-biotics to the mothers in the last month of pregnancy
and then also to the babies for the first few months of life if
they are being bottle-fed rather than breast-fed. So we do not
know whether it is an ante-natal effect or a post-natal effect,
or both. The difficulty is if you have the kind of studies that
Dr Devereux is proposing funding, say, for two or three years—which
is what tends to happen—and then he goes back in two or
three years to say: "Now can we sustain the follow-up, and
give me the extension funding to get it through to five and six
years of age when we can be more certain about the diagnosis of
asthma?" the grant-giving bodies turn round and say: "What
is your hypothesis?" You say: "It is to carry on what
we were previously doing", but they may well come back and
say: "The situation has changed now; we are working on a
whole new area; we are no longer interested in this any more."
That study loses any opportunity to derive meaningful information
because of that. I think that is something that many people suffer
from—not being able to sustain cohorts for long enough to
get the proper results at the end. There is a large number of
studies that have faltered because of that in recent years.
Lord Rea: Thank you very much for making that point.
Q156 Chairman: Can I ask you, Dr
Devereux, in relation to food, is there any evidence of a difference
in, particular vitamin E which you have been talking about, in
its content between locally produced and locally ripened fruit
and vegetables versus those which are imported, picked relatively
unripe and artificially ripened and transported large distances?
Dr Devereux: I am
not aware of any data for vitamin E but there are one or two very
obscure papers that purport to show that with food that is transported
a lot and is old, the vitamin C content goes down in pineapples,
and also in food grown out of season in poly-tunnels the flavonoid
content is meant to be altered as well. These are pretty obscure,
German-type, papers which you have to get translated, but it is
not very strong data. However, common sense would tell you that
the diet we are eating nowadays is different to what we were eating
during the war, and just after the war.
Q157 Viscount Simon: Can vaccines
and drugs be used to prevent as well as treat allergic diseases?
If they can, what sort of advantages or disadvantages does this
approach have compared to dietary manipulation?
Dr Devereux: I would
point out that 100 years ago we were not vaccinating children
against allergic disease. Also, as a father, if I had a choice
between getting my wife to eat a diet which was healthy and having
my child vaccinated, I would go for getting my wife to eat healthily.
There are also the concerns that you are doing something to a
newborn child, and there have been scenarios explained here today
where allergen avoidance has given you exactly the opposite to
what you expect. We have to be certain that any proposed vaccination
schedule doesn't have the opposite effect to what we want. So
you have to be very careful about using vaccination as a primary
prevention.
Q158 Lord Rea: There is, surely,
a case for de-sensitisation in cases where anaphylaxis is the
problem. I know personally, because I had an anaphylactic reaction
to a wasp sting and the Brompton Hospital very nicely de-sensitised
me. Of course, I do have an EpiPen but I have not ever had to
use it. Other than wasp stings, are there not several allergens
that it is worth de-sensitising from?
Professor Warner:
Yes, indeed. There is good evidence that house mite vaccines,
pollen vaccines and vaccines against cat and dog will have benefits
in people who are already allergic. So as a treatment, yes. The
issue for this country and a number of others is generating vaccines
that are safe and are not going to cause adverse reactions whilst
they are being administered; there is the potential for them to
cause an anaphylactic reaction as they are being administered.
The new developments are to find safe vaccines to generate components
of the proteins that will immunise without causing an allergic
reaction. I am sure that is going to come. There are some very
exciting developments in that area. The other thing is whether
these vaccines might have a role somewhere earlier in the process.
There is evidence from a trial conducted around Europe of giving
pollen vaccines to children who had just allergic rhinitis but
not yet asthma, which showed that less asthma developed in the
children that received the vaccines compared with those that did
not but had similar allergies. There is potential for looking
at it in an earlier stage in the evolution of disease but I think
we would have to be very cautious about starting in the newborn
baby. This is in children who have already showed the first signs
of allergy, where it looks as if this might change the longer-term
outcomes in a way that no other pharmacotherapy has been shown
to be able to do.
Q159 Viscount Simon: Would a strong
family history, perhaps, be sufficient?
Professor Warner:
One of the things that a colleague of ours in Swansea has wanted
to do is look at early BCG vaccine in a trial in babies born into
allergic families, to see whether that would reduce outcomes in
relation to allergy. He has applied repeatedly for money to support
that study and it has never been supported. I think the state
of knowledge has moved on now and there is, perhaps, less evidence
to support him doing that than there was five years ago, but people
have tried to suggest these sorts of studies and, hitherto, have
not been supported. There is one study just about to start which
is being funded from the United States—Professor Gideon
Lack to do a study of administering peanuts in very young children
who are just showing the first signs of allergy. These are in
very small babies who are beginning to show eczema but are not
peanut-allergic, and giving them large doses of peanuts in a controlled
trial. So these sorts of studies are being thought about and are
just beginning.
1 This has since been increased to £225,000 Back
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