Select Committee on Science and Technology Minutes of Evidence

Examination of Witnesses (Questions 140-159)

Professor Peter Burney, Professor Aziz Sheikh, Dr Graham Devereux and Professor John Warner


  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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