Examination of Witnesses (Questions 460-479)
MR JOHN
BRYSON, PROFESSOR
ADNAN CUSTOVIC,
DR PAUL
HARRISON AND
MR GRANT
AGER
7 FEBRUARY 2007
Q460 Lord May of Oxford: We have
heard that the hygiene hypothesis suggests that better living
standards these days and increased hygiene is the cause of the
rise of allergenic disease. I wondered if you could tell us a
bit more about the extent to which this idea is borne out by evidence
and understanding and is not just correlation without causation.
Professor Custovic: Hygiene hypothesis within
the context of allergic disease was proposed in 1989. It is still
a hypothesis so I think that says it all. It is still a working
hypothesis. It is in a great umbrella under which we are looking
to understand the cause for the incredible increase in allergic
diseases that we have witnessed over the last 30 to 40 years.
Let us not forget the increase has been three to four fold thus
allergy epidemics are environmental. Hygiene hypothesis is one
of the working hypotheses, probably the most likely one. Hygiene
hypothesis originates from epidemiological data but there is also
quite solid basic immunology data that would support that at least
part of the hygiene hypothesis—this concept that the increase
in allergy is partly due to us becoming cleaner—may well
be correct. Let us not forget that it is still a working hypothesis
and not a fact.
Q461 Lord Taverne: What I find difficult
about that hypothesis is that the instance of allergies generally
is much higher in the United Kingdom and we are not notably more
hygienic than countries in continental Europe which have a much
lower rate. I can see the stories that are told about the apparent
correlation between the two but does the continental experience
really cast considerable doubt on that hypotheses?
Professor Custovic: Let us not forget that we
are talking about the differences in the prevalence of allergic
disease in the developed world. We are talking about shades of
grey; we are talking about a difference between 23 and 27 per
cent. Real differences lie between countries that are currently
on-going transition; real differences you can see in areas of
the world like Africa, and Africa give you a great example of
the potential role of hygiene. For example, numerous studies have
demonstrated unequivocally that the prevalence of allergic diseases
is markedly higher amongst affluent populations which have adopted
westernised lifestyle compared to populations living in the same
areas but not adopting westernised lifestyle. That is where you
see the differences of two to three fold rather than percentage
differences. Without any doubt there is not a single thing that
would explain the overall incredible increase in the prevalence
of allergies. We are looking at different facets, at different
parts of a puzzle that we are trying to put together and hygiene
may well be one of them.
Q462 Lord May of Oxford: What, if
any, are the other competing hypotheses?
Professor Custovic: I think we are all fairly
certain about the fact that the increase in the prevalence of
allergic diseases is environmental which raises the really beautiful
question as to what is environment. I personally subscribe to
Einstein's definition of environment which is that environment
is everything that is not me. Within this very broad description
of environment you have hygiene or, broadly speaking, exposure
to microbes but also another very important aspect, diet. Diet
has changed tremendously. There is indoor environment and I am
sure that some of my colleagues are going to talk about indoor
environment much more. There are changes in the pattern of exercise
that kids have undergone. There are quite a number of aspects
of modern life so we should not be saying that the increase in
the prevalence is due to a single factor; almost certainly not.
Q463 Lord May of Oxford: I did ask
because what many of the subsequent questions are going to do
is explore the fact that we do, as you have just said, tend to
lead more sedentary lives in houses that are by and large less
draughty and we spend less time outdoors.
Professor Custovic: Absolutely.
Dr Harrison: I would like to say that there
is evidence that supports the hygiene hypothesis but not every
study confirms it, so it clearly has some kind of role in the
etiology. But if you think about what it means, it is suggesting
that excessive hygiene—that is the prevention of early life
exposure to allergens/antigens—could have negative consequences
because the body is not able to build up its natural resources
to combat later exposure. That might be true for some substances
in the environment but it might not be true for others. In other
words, early life exposure to some antigens could be a good thing;
early life exposure to some others could have a negative consequence
later on. There are very many confounders, as with many scientific
studies, which make it very difficult to quantify any one factor.
There is clearly some usefulness to the hypothesis but it does
not explain everything.
Q464 Lord May of Oxford: Do you think
enough is being spent in basic research to try to answer this
question and essentially on the basic interplay between the semantic
construction of the immune system in the first few years of life
and the environment in which it is being constructed, which is
not really a mainstream fashionable thing as I understand it in
the molecular biological kinds of studies of the immune system?
Dr Harrison: I am not an immunologist but maybe
my colleagues can comment.
Professor Custovic: The answer in terms of investment
is that clearly not enough money has been spent. We are suffering
from the fact that we are not in one of these big identified programmes
like cardiovascular disease or diabetes. If you look at the proportion
of the population that is suffering from allergic diseases and
respiratory diseases and the proportion of funding that goes towards
allergic diseases and respiratory diseases you will see an incredible
discrepancy.
Q465 Baroness Perry of Southwark:
I wondered if any of the studies or research there has been an
investigation to look at the total overload of the change in the
environment. It is not only the things you referred to earlier
but different materials—we wear man-made fibres; we have
man-made fibres in our carpets and our sheets and our furniture
and so on—and we have had huge changes in diet as has been
said. Is there any evidence that if you reduce even part of that
overload it decreases the incidence or helps the sufferer?
Mr Ager: Strathclyde University certainly carried
out research that very simple things like steam cleaning furniture,
changing bedding, boiling bedding and the introduction of floors
like linoleum and laminate flooring could make a 70 per reduction
in asthma attacks. This was a study done on existing families
and that certainly worked, just reducing dust and factors in the
atmosphere.
Dr Harrison: In addition to allergens themselves,
constant exposure to irritant substances can provoke a response
to sensitisers. To answer your question, over the last few decades
there has been a vast increase in the use of chipboard furniture,
for example, which is constituted with formaldehyde resin and
the formaldehyde is a well-known irritant substance. It is possible
that that could be a factor in modern housing which exacerbates
a reaction to existing allergens in the environment.
Q466 Chairman: Do you think the term
"hygiene hypothesis" is a misnomer? It has also been
called the "jungle hypothesis".
Professor Custovic: It really is a broad umbrella
under which we try to carry out research to understand the increase
not only in the prevalence of allergic diseases but also some
other immunologically based diseases. It is only one of the hypotheses
as everybody stressed and certainly not the only one.
Q467 Lord Taverne: Coming to indoor
factors, what evidence is there about the role that dust mites
play in the development or exacerbation of allergic diseases?
Dr Harrison: Very many people are sensitive
to house dust mite allergen and most homes in the UK have house
dust mites; they are essentially ubiquitous. The amount and concentration
of antigen obviously varies but it is ubiquitous. The fact that
somebody is sensitised to house dust mite does not mean, however,
that they will show any clinical symptoms. It is a kind of three
stage process: becoming sensitised to the substance as revealed
by a skin prick test, for example, development of a bronchial
response to that substance and then manifestation of clinical
symptoms. The dose response curves for each of those different
stages is probably different, so it is a very complicated scenario
where you cannot easily predict whether a particular exposure
is going to have a particular effect in a particular individual.
Professor Custovic: I would absolutely agree
with that. Generally speaking, to simplify it, if you are allergic
to house dust mite, if you have asthma, then exposure to house
dust mite is not a good idea. If you have asthma and you are not
allergic to dust mite it probably does not matter. The really
interesting question that Dr Harrison raised was what is the role
of the house dust mite in the development of asthma and that is
where evidence is not as strong as the one linking disease severity
in patients with already established disease. Generally speaking,
allergens are very important in individuals who are allergic to
them.
Q468 Lord Taverne: What success is
there to point to in attempts to eliminate house dust mites in
either secondary or primary prevention of asthma, rhinitis or
eczema?
Dr Harrison: I would say that there has been
a lot of debate about this as to what practically you can do to
help alleviate symptoms in people that might be suffering from
reactions to house dust mite. It is very difficult to totally
eradicate house dust mites from a home, but what they enjoy is
warmth and moisture. They like living in certain places and some
of those places are very important for personal exposure. For
example, they like living in pillows and mattresses so there are
very practical things that can be done to reduce exposure by eliminating
or at least removing either the source or exposure to the source
of allergens in those materials where close contact occurs; but
it is probably not very productive or cost effective to believe
that you can totally remove house dust mites from a whole house,
or even that you would want to try to do that. I think it is better
to be very focussed on the activities that are undertaken and
the efforts that are made to reduce levels and to reduce exposure.
There are certain housing features which predispose a house to
have high house dust mite levels and those, as I said, are extended
periods of warmth and dampness.
Mr Bryson: Could I just to add to that on the
housing conditions, clearly one of the factors in this is the
way that older housing has been improved. In older housing quite
often what you find is that there is double-glazing put in which
seals out all the drafts and lack of ventilation and the increase
in heat in older houses but not eradicating dampness all contribute
to the right growth conditions as well.
Q469 Lord Taverne: What can we learn
from the Fairfield project?
Mr Ager: As Paul mentioned, you cannot completely
get rid of dust mite and I do not think that was our intention;
it would be impossible to create a sanitised environment where
there would be no dust mites present. The features we majored
on where trying to control the environment within the houses to
keep the heat and moisture at a level where dust mites would not
produce as much. That was done mainly by looking various strategies,
mainly ventilation for cleaning the air in the house, creating,
if you like, a sponge effect wall which took water out. In older
housing it is easier to describe. Damp would sit on walls or windows
and water is taken away which reduces the environment so that
the dust mites cannot breed. It certainly worked and it is becoming
more and more common in housing where breathing walls, as they
are called, are used.
Q470 Lord Taverne: Is there any conflict
between the low energy approach and the elimination of dust mites
in the sense that you need more ventilation?
Mr Ager: I think the building sector has become
very focussed on energy and creating airtight boxes that are easy
to heat and reduce energy costs but the other cost has been indoor
air quality which is not focussed on as much. We have become obsessed
with as cheap heat as possible and creating, if you like, vacuums
where people spend 90 per cent of their lives and the air quality
in the modern homes is not high.
Q471 Chairman: What is the evidence
for the specific link between house dust mite and eczema?
Professor Custovic: Probably the best house
dust mite allergen avoidance trial comes from eczema rather than
from asthma carried out by Peter Friedman in Liverpool about a
decade ago, probably one of the very, very few clear, simple mite
allergen avoidance studies showing unequivocal beneficial effect.
I really would like to draw a parallel here between what we are
talking about—asthma, allergic rhinitis or eczema in a community—with
occupational allergic disease. Occupational allergic disease gives
us a beautiful example as to what actually may be going on, an
individual getting into a situation of a novel exposure (be it
in a laboratory with rats or whichever) developing sensitisation
and then soon after symptoms of allergic disease. The treatment
of choice is removal of that individual from the exposure situation.
Providing we remove the patient quickly, providing the diagnosis
is established early in the natural history of the disease, we
have a potential for cure. If the patient is left in this occupational
environment exposed to sensitising allergens for a long period
of time, even complete cessation of exposure will not result in
the improvement of the disease because the disease becomes a self-perpetuating
process. This really teaches us several very important lessons.
If we are going to try to address the disease by environmental
control then we have to develop methods to reduce exposure very,
very substantially. We can send patients to Switzerland and they
improve but we need to do something about creating that sort of
environment in our homes. That is one challenge. The other challenge
is identifying patients who may benefit early enough in the natural
history of the disease because a lot of studies are confounded
by the simple fact that we have drawn patients who have had the
disease for 20 or 30 years. They could have started with allergy
but by the end of this long process the allergy is not the only—and
certainly not the main—reason for the perpetuation of the
disease. The message is, identify individuals early and reduce
exposure substantially if there is going to be a benefit.
Q472 Lord Colwyn: Moving on to other
allergens, we are aware that there is a wide range of fungal and
bacterial species which can be isolated from indoor air. Is there
evidence that specific moulds, fungi and bacteria can trigger
sensitivity and allergic diseases such as asthma, rhinitis or
eczema?
Dr Harrison: There is a difference between biological
allergic responses and responses that individuals can show which
do not have, at least at the present time, biological explanations—these
are the sensitivities or intolerances that individuals specifically
show. To answer your question, the evidence that I reviewed—a
few years ago now, admittedly—showed very clearly that children
in damp and mouldy homes have self-reported symptoms of respiratory
disease. When measurement is made of specific mould species it
is not possible to relate any one particular mould, for example,
or certainly bacteria, to the outcome. That is because it is,
in any case, a mixed exposure that people are having. Moulds and
bacteria consist not only of the antigenic properties but also
they might produce toxic metabolites and components of their cell
walls can induce a response. There is a kind of mixed medium,
if you like, of potential insults to an individual's health. Apart
from possibly Alternaria species, where there have been studies
that show a specific risk factor from exposure to those moulds,
generally speaking the evidence shows the connection between damp
and mould generally rather than with specific species.
Q473 Chairman: Am I correct that
Alternaria is associated with asthma but not rhinitis?
Dr Harrison: I do not know that.
Professor Custovic: That is correct, moreover
it is associated with very severe asthma and with asthma deaths.
In the UK what we have is a fairly clear association between sensitisation
to moulds and asthma severity. Sensitisation to moulds is overwhelmingly
present amongst individuals with very severe asthma.
Q474 Lord Colwyn: I gather that penicillin
is often found in this air; might that be associated with penicillin
sensitive reactions? How do you relate the exposure to small amounts
against something like peanut allergy where we are beginning to
find out that exposure to small amounts of peanut might ameliorate
a more severe reaction as the child gets older?
Professor Custovic: That is a very different
context of the route of exposure, one being inhaled and another
one being ingested. Really for development of oral tolerance you
need a higher dose of exposure, but that is a slightly different
context and I would not really like to embark down that road.
I think the problem that we have with moulds is our inability
to measure exposure appropriately. The whole of the research into
dust mite has been empowered by the fact that we can accurately
quantify exposure and like any science the ability to measure
created a whole range of studies looking into association between
exposure and response. With mould and fungi our ability to measure
is still very, very poor.
Dr Harrison: I think there is a better correlation
between an observation of damp and mould in a house and symptoms
than there is between measured levels, and that might reflect
just the fact that we do not have the technology to properly measure
these things, or it might reflect the fact that it is not the
mould per se but the whole environment. If a house is damp and
mouldy it implies that it is poorly heated and poorly ventilated
which means that exposure to other pollutants is likely to be
higher as well, so there are many confounders in that sense.
Q475 Lord Colwyn: Does that answer
my question as to how these effects can be controlled?
Dr Harrison: I would also urge more public education
about ventilation. The question was raised about energy use; it
will not diminish of course and will probably increase the push
to reduce energy consumption. There are ways of balancing it,
although it is a conflict between fresh air—possibly cold
fresh air—and keeping a house warm. I think even in more
modern housing where ventilation is appropriately supplied people
do not tend to like draughts and they will often stop up any ventilation
bricks that they have in the home because they do not know that
there is any dis-benefit of doing so. I think there is an element
of education about informing people that maintaining natural ventilation
in their home as well as working to reduce exposure from particular
sources is important.
Q476 Lord Rea: Is the answer not
to make greater use of heat exchanger mechanisms such as we have
in Portcullis House here and is used in the Beddington Zero Energy
Development (BedZED) where the air that comes in is heated by
the air that goes out by contraptions on the roof. I imagine they
are probably rather expensive but if it were widely used maybe
the cost would come down.
Mr Ager: They are not prohibitive in cost. A
heat exchanger would be about £350; installation is slightly
more.
Mr Bryson: Could I just add that the types of
householders that environmental health practitioners meet very
often have no money at all. If you try to explain to them that
trying to control condensation, dampness and mould is partly within
their own hands, that is a very difficult concept to put across
them. What they want to find is a simple cause for it. It is not
about the way they use the heating and ventilation. As was mentioned,
the educational side of it is a very big thing, to try to educate
people on this. For a lot of the people who suffer those conditions,
the prospects of even spending £300 would be impossible;
we are talking about people at the very bottom of the housing
market.
Q477 Chairman: Can I go back for
a moment to mould exposure because we live in a climate with high
environmental humidity, but as far as I understand it some of
these studies have been done in parts of the US where the atmosphere
is very dry. I wonder if there are problems transposing across
and also, if you are looking at mould exposure, whether detection
of IgG and possibly IgE would give you an idea of exposure to
different moulds.
Professor Custovic: You are asking all the right
questions and we do not have answers to most of them. Certainly
the work on alternaria has been done predominantly in Tucson because
it is big, it is seasonable, et cetera, beautifully reproduced
by Jon Ayres in Birmingham. Asthma is in part due to exposure
to pollen, in part due to exposure to fungal particles. There
is very little doubt about the fact that potentially fungal exposure
may be important, but until we can assess not only the biological
effect of exposure but also measure exposure it will be very,
very difficult to make a dose response curve trying to estimate
the effect of exposure on any of the outcomes. Let us not forget
that it may as well be pretty non-specific; they may act as adjuvants,
they may act as irritants; we simply do not know. What we do know
is that in all the epidemiology the association between them and
mouldy houses is much more than the association between dust mite
and asthma. The fact of mouldy homes overwhelms the effect of
dust mites alone. The strongest evidence of that probably comes
from Holland and I would put to you that their climate is pretty
close to ours and that is where the real strong body of evidence
comes from.
Q478 Viscount Simon: What impact
do pollutants, such as airborne particles, carbon monoxide, formaldehyde,
pesticides and cleaning agents have on allergic diseases?
Dr Harrison: I alluded before to the fact that
exposure to substances in the home can exacerbate the responses
to allergen exposures. I mentioned formaldehyde because it is
a well known respiratory irritant and sensitiser in its own right.
I think people tend to be worried, for example, about low levels
of pesticides but they do not seem to be so concerned about the
liberal use of bleach and ammonia. A personal thought that I have
is that individuals who are exposing themselves to levels of ammonia
and bleach, for example, that could actually irritate the respiratory
system, could well be making themselves more susceptible to allergic
insults. I think there is a role for chemicals in that sense and
a role possibly in the sense that some might be responsible for
so-called multiple chemical sensitivity or idiopathic chemical
sensitivity. In terms of biological allergenicity it is really
those irritant substances that are going to be most important.
Professor Custovic: I think the evidence is
pretty unequivocal that if you are asthmatic or if you are a patient
with established allergic disease exposure to a high level of
indoor air pollution may make your disease worse. Whether it will
cause it per se is much more difficult and much less clear. The
evidence up until now is probably against. There is also quite
an interesting body of evidence mounting on the potential role
of outdoor air pollution if we can differentiate between the two,
for example the way potentially diesel exhaust particles actually
affect pollen grains and pollen allergens making them more allergenic.
I think probably what we have done for ease of our understanding
for years is to be obsessed with single issues; we went from house
dust mite to fungi to pets. In reality our patients are exposed
in their own homes and in their outdoor environments to a soup
of different allergens and different irritants and different viruses
on top of them. All of these exposures interact with each other
giving you the final effect. There are beautiful studies now showing
unequivocally that there is interaction between indoor air pollutants
and viruses; interaction between viruses and allergens; interactions
between allergens and indoor air pollutants. It is part of a complex
picture in which various allergens and irritants probably synergistically
act upon individuals with different susceptibilities to various
environmental triggers. What is sufficient to put somebody in
hospital will hardly be noticed by another patient. That does
not mean it is not important.
Dr Harrison: I think historically something
like 60 per cent of British homes have a gas cooker, an unflued
appliance which is liberating nitrogen dioxide and formaldehyde,
for example, into the air. I think that is something which could
also be important. There have been studies showing the interaction
between NO2 and allergen exposure (house dust mite and other allergens),
which has been tested experimentally. Unflued appliances in the
home are generally a bad thing I think.
Q479 Viscount Simon: Are you aware
of any research being done into the effects of chemicals in, let
us say, woodworm and dry rot treatments, fly papers (the things
that hang up), plug in air fresheners and fabric conditioners?
If research is taking place, do you know who it is being done
by?
Dr Harrison: The question of research into consumer
products has been left behind a little bit. There have been scares
recently about the use of air fresheners and children's health
in the home and causing migraines in mothers. It is rather speculative
work; it is a rather Cinderella subject and requires a little
bit more focus.
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