Examination of Witnesses (Questions 91-99)
Professor Peter Burney, Professor Aziz Sheikh, Dr
Graham Devereux and Professor John Warner
6 DECEMBER 2006
Q91Chairman: Can
I start by welcoming you here today? Thank you for coming to give
evidence to us as a committee. We have a members' note of our
declared interests so we will not be going round declaring our
individual interests as a committee today. We will ask you questions
and there may be supplementary questions to the main questions
as we go through. I wonder if you would like to start by introducing
yourselves.
Professor Burney:
I am Peter Burney. I am Professor of Respiratory Epidemiology
and Public Health at Imperial College.
Professor Sheikh:
I am Aziz Sheikh, Professor of Primary Care Research & Development
at the University of Edinburgh.
Dr Devereux: I am
Graham Devereux. I am Clinical Senior Lecturer at the University
of Aberdeen, and I am a respiratory physician at Aberdeen Royal
Infirmary.
Professor Warner:
I am John Warner. I am Professor of Paediatrics at Imperial College,
having moved from Southampton only four months ago where I was
Professor of Child Health. My special area of interest and expertise
is in early life origins of allergy.
Q92 Chairman: I wonder if I might
start with a question to all of you. In written evidence we have
had described the progression from eczema and food allergy in
infancy to asthma in the pre-teen years as the "allergic
march". I wonder if you could explain to us what are the
mechanisms of the allergic march and how we can halt it.
Professor Warner:
It is a clinical observation that many infants who develop food
allergy and eczema go on subsequently to have asthma and allergic
rhinitis and there appears to be a progression from one disease
to another which has been termed the "allergic march".
Whether having eczema per se makes you more likely to go on to
have asthma I think is not clear because it is more probable that
there are common underlying factors that predispose you to both
conditions, but for some people they only inherit and are exposed
to environmental factors that predispose to one and not the other.
At the moment we are still unclear about all the mechanisms that
are involved in the generation of the individual diseases within
that allergic march, but one thing we can say for certain is that
if an infant starts with evidence of allergy there is a very high
probability that they are going to show one or more problem associated
with that.
Q93 Chairman: You suggested in your
answer that there are certain unknowns about the origin and progression
of allergic disease. I wonder if you could highlight where you
feel the main unknowns are and how we could find out about them.
Professor Warner:
I think we have got a long way in identifying the genetic components.
What we do not know is how genetic factors interact with environmental
factors in individuals, to lead to disease, so it is focusing
on how the geno-type is influenced by the environment to create
the clinical manifestations.
Q94 Chairman: Do people suffering
from allergic disease ever lose their sensitisation?
Professor Burney:
Not once people have become adult. People tend to accumulate their
sensitisation during childhood and early life. One of the things
that is noted in cross-sectional surveys is that older people
have less allergy, but the important thing is that if you follow
the same people as they get older they do not generally lose their
allergies. The explanation for the lower prevalence of allergies
in older people is that people who were born towards the beginning
of the 20th century tended to get less allergy during their early
years, so they are people who never became very allergic rather
than people who have lost their allergies. The importance of this
is that it helps us to predict what will happen to the allergic
epidemic that we have at the moment and how soon it will start
to subside.
Q95 Lord Taverne: Just following
that up, you mention in your paper that 80 per cent of asthmatics
tend to lose their allergy during puberty and then start recovering
some of it again. Have you any idea why that might be?
Professor Burney:
I do not think that I said that. That might be from someone else's
paper. Maybe.
Professor Warner:
Perhaps I can add a bit to that. There are infants who show various
food allergies who lose their allergies once they get to four,
five, six years of age. However, once they have reached about
seven to eight years of age, if they retained the allergies then
in general they persist for evermore and they might actually increase
the range of allergies. However, even amongst those who lose sensitivity,
say, to egg or to milk, which is very common in infancy and less
common in older children, they are still at higher risk of developing
new allergies to inhalants like house mites and pollens. As far
as adolescence is concerned, yes, there is no doubt that particularly
boys tend to improve their asthma and many of them lose their
symptoms, although the majority, if you do sophisticated lung
function tests, still show an abnormality and many of those come
back in their late twenties with a recurrence of problems. We
think part of that is physiological in that the lungs are at their
best in early adulthood and, as they begin to lose some of their
elastic recoil with age the problem shows itself again.
Q96 Lord Taverne: The suggestion
seems to be that there is still a net decrease after puberty.
Only some then develop the allergies again. Is that right?
Professor Warner:
It is always very difficult. The problem is that paediatricians
lose sight of their patients. I think it has been said that they
are more likely to outgrow their paediatricians than their asthma.
From the longitudinal studies a pretty high per centage, even
of milder asthmatics who lose their symptoms in adolescence, by
30 have had a recurrence of symptoms, not necessarily as severe
as they were in childhood but certainly they are wheezing again
and they are requiring some treatment for their asthma.
Q97 Chairman: Are there any specific
measures you feel should be recommended routinely for children
to prevent the development of asthma and eczema?
Professor Warner:
I would love to be able to say that there were measures right
now that one could recommend but there is none other than saying,
"Do not smoke in pregnancy", and, well, "Do not
ever smoke", not only because of the adverse effect it has
on the child's health but also because of the bad example it sets
for the children who then take up smoking themselves, which in
turn increases the risk of relapse of asthma if it has improved.
Other reasonable recommendations are "Sustain a good diet",
and, "Breast feed if at all possible". I think beyond
that at the moment we do not have enough evidence to make any
other statements.
Q98 Lord May of Oxford: Can I ask
a question in this context for which one of the data points is
myself? When I was 12 I missed half the school year with asthma
and since the age of 18 I have essentially never had it, and I
know other people like that, so may it not be that the word "asthma"
embraces quite a wide range of things? It is not something like
measles. There will be some that are allergy based and some that
have other bases, so it is difficult to make generalisations.
Is that true?
Professor Burney:
I would agree with that. One of the confusing issues, particularly
in childhood, is that there are a lot of other conditions that
are probably not allergic which make people wheeze. The view generally
is that these are very common in infancy and in very young children,
but I suspect that they actually continue for a bit longer than
that so that throughout childhood you have probably got a mixture
of people with other conditions, just as in older life you get
people who get rather different wheezy conditions which can be
confused with asthma, so I think your distinction between those
that have an allergic basis and those that do not may well be
a good distinction. One other thing which I think is sometimes
missed, at least in relation to more severe disease, is that asthma
gets worse among women during the child-bearing years so that
from puberty up to the menopause women probably have a worse deal
during that time of their life than at other times of their life.
Professor Sheikh:
As the Committee may be aware, The Lancet recently published
a very provocative editorial saying that the term "asthma"
has outlived its usefulness; it is far too crude a term, so I
think in due course we will have a more refined understanding
and a more refined range of terminology because it is very much
a catch-all at the moment. In relation to primary prevention strategies,
which you were asking about, to try and stop the initiation or
halt the progression of the allergic march, as Professor Warner
has said, the key recommendations that we would suggest are suitable
at a population level,—that is, taking all-comers,—are
minimising exposure to tobacco smoke and breast feeding wherever
possible. However, we do have some clearly high risk families
and in these families there are some interventions which appear
to be promising. One in mothers who are unable to breast feed,
for whatever reason, is the use of hydrolysed formula milk preparation.
What is happening there is that the cows' milk protein is being
broken down. There is evidence now from a few randomised control
trials to show that this can halt the progression of allergic
problems and the other area that seems quite interesting and promising
is looking at the role of pro-biotics. This involves giving particular
forms of lactobacillus and bacteria in early life, perhaps in
combination with other approaches, and again there is early evidence
that these may be promising interventions, but overall as we are
advocating intervening in healthy individuals at the moment before
they have developed any disease in early life the burden of evidence
for intervening is very high if we are advocating primary prevention
strategies. What underlies this is that we are at the early stages
in terms of our understanding of which interventions work and
there needs to be far more work done in building on those early
trials.
Professor Warner:
This is a very difficult area. Recently there has been a meta-analysis
of all studies of using hydrolysed milk formulae in allergy prevention
and, whilst there are clearly some trials which have shown an
impact, at the moment the conclusion is that more work is required.
It is a promising area, but before making recommendations in particular
groups there is a lot more research to do; likewise with pro-biotics
but now the more exciting area looks to be pre-biotics, that is,
just creating the right environment in the gut for organisms to
grow normally, and there are one or two trials in process at the
moment and one has just been published with what looks like very
good results.
Q99 Lord Colwyn: You covered the
point about smoking and breast feeding. I pulled something out
of The Telegraph a month ago saying that there is
evidence that maternal diet and maternal exercise are important
in the development of the child's in uterus lungs. Is that
correct? Are you aware of that?
Professor Warner:
Yes. Dr Devereux has done a lot of work in that area as well,
but that is nutrition rather than trying to avoid food allergens.
There are lots of nutrients that may be important. Dissecting
out which are important is what is difficult, but Dr Devereux
can answer that question better.
Dr Devereux: The
work we have been doing in collaboration with people in America
is that it looks quite promising that maternal diet during pregnancy
is influencing the development of asthma in children. I am not
talking about maternal ingestion of allergens; I am talking about
maternal ingestion of nutrients, particularly vitamin E, possibly
vitamin D and even zinc. There are now two studies showing associations
that low maternal intake of vitamin E during pregnancy is associated
with the increased risk of children having wheeze, asthma, reduced
lung function and increased markers of lung inflammation. The
$64,000 question is what happens if you intervene to change women's
diet in pregnancy, and that is a study that needs to be done.
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