Select Committee on Science and Technology Minutes of Evidence



Memorandum by Professor Peter Burney, Professor and Hon Director Social Medicine and Health Services Research Unit; Deborah Jarvis, Senior Lecturer; Seif Shaheen, Asthma UK Senior Research Fellow Respiratory Epidemiology and Public Health, National Heart and Lung Institute, Imperial College

1.  DEFINITIONS

  1.1  Allergies are conditions that arise from immunological responses that are not of obvious benefit to the person experiencing them. The majority are mediated by immunoglobulin IgE. This is a normal part of the immune response which is of particular importance in protection against parasites. In a proportion of people this is too easily raised against other foreign proteins that are not normally harmful. These are mostly associated with airborne proteins from pollens and animals, including the microscopic house dust mites. These proteins are referred to as allergens. In children the response is often first seen against foods, though these often fade out as the children grow, though if they persist they can lead to severe reactions.

  1.2  There are several clinical conditions that are more common in those who raise this type of response to common airborne allergens. These include rhinitis (hay fever), asthma and eczema. These are often known as "atopic" conditions. All these conditions are also found in people who do not appear to have an increased production of IgE, and not all people who have raised IgE levels have clinical consequences. The form of the disease that is not associated with IgE is often referred to as "non-atopic" or "intrinsic". "Intolerance" is often used to indicate a non-immunological response particularly to a food, or is used when it is not known if there is an immunological basis to the condition or not.

  1.3.  In what follows we shall refer to raising IgE against specific allergens as "sensitisation".

2.  INCREASING PREVALENCE

  2.1  An increasing prevalence of asthma was first noted in studies of Birmingham school children, starting in the mid 1950s. Between these studies and the mid 1990s almost all studies that measured the prevalence of asthma or wheezing in children in the same population on two or more occasions found an increase. The findings were very consistent and amounted to an estimated doubling of the prevalence approximately every 14 years. There was less evidence on other atopic conditions but where there was evidence these also seemed to be increasing at the same rate.

  2.2  There was debate as to the extent to which this was due to changes in diagnosis or reporting. From the early 1980s doctors have been encouraged to make the diagnosis of asthma and prescribe treatment, though this would not explain the increase in wheeze. Subsequent evidence has shown that the prevalence of sensitisation has also increased. This would in part explain the increase and confirms from a more objective measure that the increase is likely to be real.

  2.3  Since the 1990s the recorded increases have been less consistent and for the first time there are some studies that have shown a decrease in prevalence in children. The evidence is not, however, entirely consistent. In the UK there was a significant fall in the prevalence of self-reported asthma and rhinitis, but not eczema, among 13-14 year olds. There was, however, no fall among 6-7 year olds. There are no measures of sensitisation.

  2.4  The UK has a high prevalence of disease when compared with other countries. This is true for reported disease, symptoms and diagnoses and for markers of disease such as specific IgE to common allergens and airway responsiveness (a marker of asthma). Other places with a high prevalence include other English speaking countries such as the USA, Canada, Australia and New Zealand, possibly indicating a common cultural origin.

  2.5  In developing countries there is a much lower prevalence of allergic disease in the poorer rural areas. Such evidence as there is suggests that this is not due to a lower prevalence of sensitisation (IgE to specific allergens) though it is accompanied by fewer positive skin tests. Although the ISAAC study shows little association between per capita gross national income and the prevalence of rhinitis or eczema in children, very high levels of asthma are only found in the moderately rich or rich economies and the allergic forms of the disease (with positive skin tests against allergens) are also found more commonly in the richer countries.

3.  FUTURE TRENDS

  Although the more recent findings in children are encouraging, the prediction is that the problem will become worse still over the next decades. It is commonly believed that atopy is less common in older people than younger people because as they age people are less able to mount allergic responses. This interpretation is, however, based on cross-sectional studies that have examined younger and older people at one time. Longitudinal studies show little evidence that atopy disappears as adults age. This means that the prevalence of atopy and probably allergic diseases in older people is likely to increase over the coming years, reflecting the longer term effects of the increases in atopy and allergic diseases that were reported for children during the late 20th century.

4.  THE CAUSES OF THE EPIDEMIC

  4.1  We have yet to discover what changes in western lifestyle and environment have been responsible for the rise in allergy and asthma over the last four decades. Clarification of the factors responsible should provide opportunities for primary and secondary prevention. The reason why the UK, along with other English speaking countries, has one of the highest rates of asthma and allergies in the world is also unknown. One unsolved puzzle is why only a proportion of individuals with atopy (as measured by skin test positivity or specific IgE in the blood) develop atopic disease (asthma, hayfever, or eczema). Some patients with asthma are not atopic, and the causes of this condition may be different to those for allergic asthma.

4.2  Hygiene

  Epidemiological research over the last 10 years has been dominated by two main hypotheses. The hygiene hypothesis, proposes that the rise in atopy has occurred because exposure to protective infections in early childhood has declined, through reductions in family size and other changes in lifestyle. To date, there is no definitive evidence to support this and in parts of rural Africa, which are presumably "unhygienic" in this sense, there is no problem in raising IgE to environmental allergens such as grass. Nor are there convincing data to suggest that vaccinations, antibiotics, or changes in bowel flora have been responsible. Whilst the apparently protective effects of growing up on a farm might be explained by infections resulting from animal contact, there are other possible explanations. Despite the lack of convincing epidemiological evidence, research is underway to see if giving Mycobacterial vaccines might reduce the severity of allergic disease, though the long-term safety of manipulating the immune system in this way is uncertain. The jury is still out on whether parasite infestation reduces symptoms of allergy and asthma; one recent trial has failed to support this idea.

4.3  Diet

  Evidence that the rise in asthma has occurred because of an increase in intake of n-6 relative to n-3 fatty acids has been unconvincing, and trials of fish oil supplementation (rich in n-3) have been disappointing. Alternatively, it has been proposed that the rise is attributable to a declining intake in dietary antioxidants. However, epidemiological evidence in support of this hypothesis is conflicting, and recent trials of vitamin and selenium supplementation in adults have been negative. Given the complexity of nutrition, and the many ways in which diet has changed in recent decades, further research is required to investigate the possible role of other nutrients and to see whether food-based interventions might hold more promise for secondary prevention. We know less about the role of diet in childhood. Birth cohort studies in the UK are underway to study the possible role of nutrition in pregnancy and early childhood to see whether this might lead to strategies for primary prevention.

4.4  Other risk factors

  4.4.1  In recent years many epidemiological studies have identified obesity as a risk factor for asthma in children and adults. At present we do not understand what underlies this link, but it seems unlikely that the relation is causal. Obesity is, however, associated with poorer lung function and this is a concern for those with asthma. It is clear that the obesity epidemic is a major public health problem in the UK which needs to be tackled for many health reasons other than asthma.

  4.4.2  There is no evidence that the rise in allergy can be attributed to increases in allergen exposure in the home, nor that house dust mite exposure causes asthma. Trials of dust mite avoidance in the home have been unsuccessful in reducing asthma symptoms and, paradoxically, may even lead to an increase in allergic sensitisation in children.

  4.4.3  Smoking is associated with wheezing in adults, and passive smoking and maternal smoking in pregnancy have been linked to asthma in children. However, smoking is unlikely to increase sensitisation and may even reduce sensitisation to some allergens. Air pollution in general has been declining sharply over the time of the increase in allergies, though some have speculated that the increase in pollution from traffic sources may have been responsible. There is little direct evidence for this.

  4.4.4  Evolving areas of research include understanding links between paracetamol, a commonly taken pro-oxidant, and the pattern of disease in women and how this is influenced by sex hormones. There are reports of increased asthma in women who use hormone replacement therapy and in those with evidence of gynaecological morbidity.

5.  THE CONSEQUENCES OF THE EPIDEMIC

  5.1  The likely increase in allergy in an aging population raises several issues relating to public policy apart from the obvious need to provide adequate services. Those who are allergic are more vulnerable in many ways and with almost half of the population now being at least to some extent sensitised to common allergens, this needs to be taken into account when setting standards in several areas.

5.2  Treatment

  Although treatment is not the subject of the current review it is important to point to the evidence that good treatment may also be preventive of later problems. One of the primary goals of the treatment of asthma is the maintenance of good lung function. One of the most important treatments for asthma is inhaled steroids which have been shown in randomised controlled trials to reduce symptoms and improve quality of life. Long term randomised controlled trials to look at their effect on lung function over a long period of time are unlikely to be performed as their efficacy in the short term renders the use of "placebo" over a prolonged period unethical. An observational study of young adults has however shown that over a period of eight years regular use of inhaled steroids is associated with a lower rate of lung function decline especially in those who have evidence of an allergic aetiology (raised total IgE) for their asthma.

5.3  Indoor environment and home ventilation

  5.3.1  Most adults spend substantial amounts of their normal day indoors. Good quality indoor air is imperative for good respiratory health although randomised trials to demonstrate this clearly are lacking. Adults living in homes with mould report more asthma symptoms, particularly if blood tests show they are allergic to mould species. In the UK we have shown that the use of gas for cooking is associated with more symptoms particularly in women, particularly in those who are allergic to allergens and particularly in those who do not ventilate their homes by using doors and windows. People who regularly open their windows at night also have lower levels of dust mite allergen. Good ventilation is required for good respiratory health and this may be a particular issue for those who are allergic. The current emphasis on household energy efficiency may lead to lower standards of ventilation and the implications of this need to be reviewed.

  5.3.2  Unpublished work suggests that people with atopy who are exposed to cats have more reactive airways (bronchial hyper-responsiveness), most likely because of worse "airway inflammation" than those who are not atopic, even if they are not specifically sensitised to cats. As cat allergen is very pervasive (it is found in homes that do not own cats) this raises a difficult problem of how to deal with exposure of an increasingly allergic population to general allergens.

5.4  The outdoor environment

  Currently air quality standards are set in relation to their effects on cardiovascular morbidity and mortality, where the effects are very clear. Despite common beliefs the effects of air pollution on asthmatic patients are not clear. There is some evidence that allergen in air may be important for patients with asthma. Mortality from asthma in the summer months, when allergen levels may be high, is high among young asthmatics who have the highest prevalence of allergy. Rarely major outbreaks of asthma have been observed when levels of allergen in the outdoor air are very high. There is further evidence that there is a continuous low level of effects from allergens in air, but the nature of these allergens is uncertain. Many of these would probably be very difficult to control, but some are likely to be from man-made sources and need further investigation.

5.5  The work environment

  5.5.1  It is estimated that around 10 per cent of patients with asthma have asthma that is of occupational origin. With an increasingly allergic population this is likely to be an increasing problem. It may be compounded by the fact that many processes are now carried on in small firms where problems may be more difficult to identify and where there is less likely to be a professional occupational health service. Almost 3 per cent of young adults in one study said that they had had to change a job because of breathing problems at work.

  5.5.2  There are occupations that cause respiratory problems that are due to exposure to irritants. These are not specifically associated with allergies but may be important as some of the exposures are common and found in dispersed workforces such as cleaners.

  5.5.3  The recent banning of smoking in the workplace will certainly have made the workplace more tolerable for allergic members of the workforce and is extremely welcome.

5.6  Diet

  5.6.1  The role that diet has in possibly contributing to the asthma epidemic has been outlined above. This effect is still controversial but may be important not just in the causes of allergy but also in maintaining the health of those who are allergic.

  5.6.2  Less controversial is the problem that food allergens pose to those who are sensitised to them. Food allergy has important consequences for those who suffer from the condition, for their families and for food manufacturers, and caterers including, for instance, those providing school meals. This is in part because the consequences of ingesting hidden allergen can, on rare occasions, be catastrophic. The steady increase in the rates at which people are admitted to hospital for food allergy and anaphylaxis probably reflects the general increase in allergy in the population.

6.  PRIORITIES FOR FURTHER RESEARCH

6.1  Monitoring of trends

  It is important to know what the trend is in sensitisation, particularly in children and among the elderly. It is also important to know more of the effects of allergy among the elderly.

6.2  Early life environment

  Evidence is accumulating to implicate the environment in utero and infancy in the aetiology of asthma and allergy. A number of birth cohort studies are under way which will hopefully shed further light on causes of asthma and allergy which operate during pregnancy and postnatally. The ultimate goal is to devise strategies to modify the early life environment in order to prevent asthma and allergy developing in the first place.

6.3  Gene-environment interaction

  One promising way forward in epidemiology is to identify interactions between genes and environmental/lifestyle risk factors. If relevant gene variants can be shown to modify the effect of such risk factors this provides more compelling evidence that the risk factors are causing allergy or asthma.

6.4  Occupational asthma

  A priority area of research should be occupational asthma. This is under-recognised and makes a substantial contribution to the total burden of adult asthma. Furthermore, it is amenable to prevention and "cure"—removal of relevant allergens from the environment will lead to improvement in asthma symptoms.

6.5  The effects of outdoor allergen

  More needs to be known about the effects of outdoor allergen, its sources and the effects that it has on sensitised individuals.

6.6  Adolescence

  For many children, asthma seems to "go away" during adolescence, for reasons which are unclear. We need a better understanding of the natural history and prognosis of asthma through adolescence, a time when physiology and lifestyle change markedly. Improved understanding of "remission" may lead to opportunities for prevention.

6.7  Gender

  The relation between sensitisation, disease and gender is still poorly understood as are the consequences of increased exposure to endogenous, therapeutic (oral contraceptives and hormone replacement therapy) and environmental oestrogens.

6.8  Trials

  Definitive evidence on whether risk factors are causes of asthma and allergy can only come from randomised clinical trials—the setting up of a respiratory/allergy trials network in the UK, or more widely, would facilitate recruitment and faster completion of trials.

7.  FURTHER READING [NOT PRINTED]

3 October 2006



 
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