Select Committee on Science and Technology Minutes of Evidence


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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