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 trialsthe 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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