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REVIEW ARTICLE

Prevalence and associated factors of allergic rhinitis

and atopic dermatitis in children
J. Torres-Borrego, A.B. Molina-Tern and C. Montes-Mendoza
Pediatric Allergy and Pulmonology Unit. Department of Pediatrics. Reina Sofa Childrens Hospital. School of
Medecine. Crdoba. Spain.

ABSTRACT
Allergic disorders are the chronic diseases of
greatest pediatric morbidity, affecting over 25 %
of the pediatric population. Indeed, this situation has
been referred to as an allergic epidemic. In comparison with asthma, atopic dermatitis and allergic
rhinitis have been less extensively investigated, although this does not mean that they should be regarded as minor disorders but rather as alterations
that affect the quality of life of the patients and their
families, which generate considerable direct and indirect costs.
Despite an important research effort, the reason
for this allergic epidemic is not well known. These
are multifactor disorders without a single causal
agent, in which the most important component is the
genetic predisposition of the patient (atopy), modulated by environmental factors, exposure to allergens, infections and irritants, among others. A confounding element is the fact that the concept of
allergic diseases encompasses phenotypes of rhinitis, atopic dermatitis or asthma in which no IgE-mediated atopic mechanism is demonstrated, and

which can manifest in a way similar to true allergic

phenotypes. Differentiation between the two is difficult to establish on the basis of self-administered
questionnaires alone, in the absence of a precise etiological diagnosis.
The present article reviews the numerous factors
suggested to be responsible for the increase in allergic diseases recorded in the last few decades, and
for the differences in prevalence observed among
centres. For most of these factors the results published in the literature are contradictory, in some cases due to a lack of control of the associated interacting or confounding factors. Consensus exists for only
some of these causal factors, such as the established parallelism between the increase in allergic
diseases and the reduction in infectious processes
on one hand, and the increase in particles generated
by diesel fuel combustion on the other.
In addition, the implicated factors could act differently (and in some cases even antagonically) upon
atopy and on the different disease phenotypes,
thereby complicating the study of these interactions
even further.
Key words: Rhinitis. Rhinoconjunctivitis. Atopic
eczema. Atopy. Allergic diseases. Prevalence. Children. ISAAC.

Correspondence:
Javier Torres-Borrego
Unidad de Alergologa y Neumologa Peditricas
Servicio de Pediatra
Hospital Universitario Materno-Infantil Reina Sofa
Avda. Menndez Pidal, s/n
14004 Crdoba. Spain
E-mail: [email protected]

Allergol Immunopathol 2008;36(2):90-100

INTRODUCTION
The prevalence of allergic diseases has increased
considerably in the last 30-40 years, and in the industrialized world it is estimated that over 25 % of
all children have some form of allergic problem.

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Specifically, atopic dermatitis and allergic rhinitis are

diseases that typically develop in childhood and
should not be regarded as minor disorders but rather
as chronic diseases that cause very unpleasant
symptoms and affect the quality of life of the patients and their families. In addition, these illnesses
generate important costs both directly (consumption
of health care resources and drugs) and indirectly (reduction in parent work yield).
Epidemiological studies have revealed important
differences in the prevalence of allergic disorders
among different countries, and even within single
countries, as well as contradictory results in relation
to the possible associated risk or protective factors.
However, variability in the methodology used may influence the observed differences, thereby complicating comparisons among studies and the drawing of
conclusions.
The ISAAC (International Study of Asthma and Allergies in Childhood) was created in 1991 with the
aim of establishing and comparing the prevalence of
allergic disorders in childhood and adolescence in different countries, and to explore their trend over time,
thanks to the adoption of standardized methodology.
For this purpose, the study used a questionnaire comprising simple questions in an attempt to homogenize
the diagnostic criteria in the different parts of the
world, thereby preventing the reported differences in
prevalence from being attributable to methodological
differences. Up until that time there were few multinational epidemiological studies on pediatric allergic
diseases, and most were referred to asthma. The
studies focusing on atopic dermatitis and rhinitis
were practically anecdotal, though the idea that asthma and rhinitis are closely related is now gaining
strength.

91

INCREASE IN PREVALENCE
OF ALLERGIC DISEASES
In the last few decades the increase in such diseases, particularly in the developed parts of the
world, has been so notorious that the phenomenon
has been referred to as an allergic epidemic. Studies have shown this increase to be genuine, and not
attributable to the fact of diagnosing a larger number
of cases as a result of improved knowledge of allergic disorders among both physicians and the general
population.3,4 The high prevalence of reported allergic
diseases in children of parents without a family history of atopy suggests that much of the prevalence
increase in allergic disorders is occurring in children
without a significant genetic predisposition.
The starting point and causes of this increase are
not fully clear, and different hypotheses have been
proposed to explain the situation. Most of these hypotheses are related to changes in lifestyle and to environmental and domestic factors that interact with
the immune system in the early stages of life. The increase in the cases diagnosed in industrialized countries appears to occur at the expense of allergic phenotypes, since a parallel increase has been recorded
in positive skin tests.5 This is not extrapolatable to
the developing world, where a high prevalence of
respiratory symptoms is observed, although these
situations correspond to non-allergic phenotypes
characterized by earlier and more severe alterations,
associated with crowded living conditions and early
exposure to environmental pollutants.6
In the last few years a number of studies have reported a certain slowing in the increase in prevalence
of allergic diseases.7,8 However, rather than a case
of true deceleration, this situation may reflect a lesser reporting of symptoms due to the availability of
more effective treatments.9

PREVALENCE OF ALLERGIC DISEASES

Although the prevalence of allergic diseases is
growing throughout the world, there are marked inter-regional differences, thus pointing to the influence of environmental factors upon the development
of allergic disease. Phase 1 of the ISAAC study1
reported worldwide rates of rhinoconjunctivitis in
the range of 1.4-39.7 % in adolescents of 13-14 years
or age, and between 0.8-14.9 % in children aged
6-7 years. With regard to atopic dermatitis, these
figures range from 2-16 % in children between
6-7 years of age, and from 1-17 % in those between
13-14 years of age. In Spain, the prevalence of allergic rhinitis and atopic dermatitis in schoolchildren
aged 13-14 years in Cartagena was found to be
17.5 % and 6.3 %, respectively.2

THE HYGIENE THEORY

In 1989, Strachan10 observed that atopy predominates among first offspring and single children, and
for the first time suggested that this may be due to
a lack of immune system maturation stimulus on the
part of certain infections.
Physiologically, intrauterine life is characterized by
important Th2 cell polarization, with intense expression of cytokines (IL-4, IL-10, leukaemia inhibiting factor), the function of which is to counter Th1 responses that are toxic for the placenta.11 It has been seen
that atopic mothers suffer fewer miscarriages and
have a larger number of pregnancies,12 with a greater
frequency of deliveries to term, and without compliAllergol Immunopathol 2008;36(2):90-100

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cations. In contrast, the placentas of women who suffer spontaneous miscarriages show lesser Th2 cytokine expression.14 After birth, and as a result of microbial stimulation (pathogenic or saprophytic), a shift
occurs from Th2 responses towards Th1 responses,
which in turn consolidate through successive exposures to the microbial antigens thereby protecting
the host against the germs and avoiding the Th2 reactivity that leads to allergic processes.
The hygiene theory postulates that the increase in
the prevalence of allergic diseases is linked to a decrease in exposure to germs. In this sense, a more
adequate term could be microbial reduction hypothesis. Allergy thus would be the price to pay for reducing morbidity-mortality, particularly in children, by
curbing or eliminating infections such as measles,
hepatitis A or tuberculosis, which have dropped in
both industrialized15 and developing countries.16 In
this sense, the hygiene theory appears to be related
to the increase in atopy (understood as sensitization)
and allergic phenotypes in the developed world, but
would not explain the increase in the prevalence of
respiratory diseases in developing countries where
certain purported protective factors in the industrialized world (e.g., respiratory or gastrointestinal infections in early life) are not applicable.

THE GENETICS OF ALLERGIC DISEASES

Despite important research efforts, the etiology
of allergic diseases is not well known. These are multifactorial disorders without a single causal agent, in
which the most important component is the genetic
predisposition of the patient (atopy), modulated by
environmental factors, exposure to allergens, infections and irritants, among others.
Atopy is the most important risk factor for the development of allergic disorders. In effect, the risk of
allergy in atopic individuals is between 10 and
20 times greater than in non-atopic subjects. It is
moreover estimated that the risk of developing allergy is 25-35 % in the presence of an atopic sibling, between 30-50 % if one or both parents are atopic, and
70 % if both parents have the same allergic disease.17 The difficulty posed by genetic studies is represented by the numerous atopy markers involved,
and the fact that atopy and allergic diseases are not
always jointly inherited. Some genetic markers have
been shown to be linked to bronchial hyperreactivity
(chromosome 4), total IgE and eosinophilia (chromosome 6), and bronchial hyperreactivity, total IgE and
eosinophilia (chromosome 7), among other phenotypes. In a recent review, Cookson describes the
genes and genetic loci that are associated with inAllergol Immunopathol 2008;36(2):90-100

creased susceptibility to asthma and atopic dermatitis.18 It is of great interest that genetic loci linked to
eczema and asthma are not shared, suggesting that
the risk of suffering these two diseases is mediated
by different genes, rather than related through a
common atopic susceptibility.

FRACTION ATTRIBUTABLE TO ATOPY

In the same way that some subjects suffer asthma,
rhinitis or atopic dermatitis in the absence of atopy
(i.e., without allergic sensitization), other individuals
present sensitization (positive testing for allergens)
but suffer no disease as such. These situations correspond to subclinical or asymptomatic sensitization.
In order to calculate the degree to which allergic
disease is attributable to atopy, Pearce et al.19 conducted a meta-analysis of articles describing the relationship between asthma and atopy. The authors
concluded that the percentage of asthma cases (children and adults) attributable to atopy is between
30-40 %. Posteriorly, Arshad et al.20 confirmed these
results not only for asthma, but also for rhinitis and
eczema proposing a model of allergic diseases for
children at the age of four in which 30-40 % of all
cases are attributable to atopy and the remaining
60-70 % to other factors. In this model, atopic dermatitis could be regarded as the least atopic of the
allergic diseases (with intervention of a dual type I
and type IV hypersensitivity mechanism), while
asthma and rhinitis disorders that are intimately
related would have a greater atopic component.
The fraction of allergic diseases attributable to
atopy is calculated by means of the formula P(R-1)/R,
where R is the relative risk of suffering a given allergic disease in sensitized individuals, and P is the proportion of atopy in the patients with such allergic disease. However, it must be pointed out that this
fraction depends on percentage sensitization among
patients with a given allergic disease, and this in turn
depends on factors such as the number and quality
of allergenic extracts used, and the age of the patient
when establishing the allergic diagnosis. Another
point to be taken into consideration is that other pathogenic elements derived from the Th2/Th1 imbalance (distinct from IgE) cannot be measured by prick
tests or the determination of specific IgE, and are
therefore not represented in this formula.

ATOPY AS AN EVOLUTIVE BENEFIT

The immune system of the atopic individual
shows an exaggerated response, producing IgE

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against substances that are harmless for the rest of

the population, and causing deleterious consequences. For this reason, in theory there are no biological or evolutive reasons for the existence of allergic diseases, since the latter afford no advantage for
those who suffer them. However, some authors
have suggested that such disorders could constitute
an evolutive advantage by favouring survival among
those who suffer them,21 and protecting them
against most types of cancer,22 although another recent study has reported no association between allergy and cancer.23

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Table I
Microbial factors associated to atopy and allergy

Factors related to pregnancy and delivery

Number of siblings and attending nursery school
Systematic vaccination
Infections and the use of antibiotics
Intestinal flora, prebiotics and probiotics
Exposure to animals

Table II
Non-microbial factors associated to atopy and allergy

FACTORS ASSOCIATED TO RHINITIS

AND ATOPIC DERMATITIS
Many investigations, mostly referred to asthma,
have attempted to associate the increase in allergic
processes to environmental pollution and to changes
in population habits of hygiene, diet and life-style
(sedentarism, the generalization of antibiotic use,
poorly ventilated living spaces), among other factors,
which in practical terms could be summarized in the
form of two large groups: 1) factors related to the decrease in microbial burden; and 2) other factors unrelated to the latter (Tables I and II).

Aspects related to pregnancy

and delivery
It has been reported that sex hormone levels during pregnancy can influence maturation of the foetal
immune system, favouring the development of allergic diseases. The maternal estrogens produce increases in Th2 cytokine production,24 and an
increased prevalence of allergic disorders has been
reported in the offspring of women who have taken
oral contraceptives prior to pregnancy.25,26 However,
Maitra et al.27 in 2005, published a study in
5765 mother-offspring couples in which no association was found between the earliness of maternal
menarche (associated with increased oestrogen levels) and the presence of asthma, eczema, pollinosis
or atopy in the offspring at 7 years of age.
The role of prenatal exposure to allergens and
drugs in the development of atopic diseases has
been studied. The evidence points to production in
the newborn infant of a prenatal T-cell response
against environmental antigens before actual exposure to them has taken place.28,29 In this sense, a reduction in the exposure to dust mites during pregnancy and early infancy has been associated with
lesser rates of sensitization to acarids.30 Likewise, a

Family history (genetics)

Hormone factors
Type of nursing and timing of the introduction of supplementary
feeding
Population genetic diversity (immigration)
Diet, obesity, sedentarism
Autoimmune diseases
Socioeconomic level and Western life-style
Residential setting (rural versus urban)
Environmental pollution
Home living conditions (indoor pollution)
Exposure to tobacco smoke
Climatologic factors
Stress

dose-dependent association has been found between the use of paracetamol at the end of pregnancy and the presence of asthma, sensitization and
high IgE titers in the preschool period of life.31,32 Likewise, an increased risk of asthma and eczema has
been reported in the children of mothers who used
antibiotics during pregnancy,33 though a review of
5 studies on this subject failed to confirm the latter
observation.34
In addition, it has been suggested that the influx of
immigrants in industrialized countries could contribute to the increase in the prevalence of allergic
diseases in such countries, since the greater genetic
heterogeneity of mixed-race couples causes women
to over-express Th2 cytokines (IL-4, leukaemia inhibiting factor) during pregnancy, in order to avoid rejection of the foetal haplotype.35
On the other hand, attempts have been made to
relate caesarean section to an increased predisposition towards sensitization to pneumoallergens
and foods, due to the lack of colonization of the
newborn infant with the birth canal flora, 36,37 although this hypothesis is also controversial, and
has not been supported by the findings of other
studies.38,39
Allergol Immunopathol 2008;36(2):90-100

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Gender

Systematic vaccination

It has been described that in the pre-puberal

stage, males show a greater prevalence of allergic
sensitization,40,41 rhinitis, and asthma.40 This situation
inverts in adolescence, with a greater frequency of
these diseases in females42-44 (with the exception of
atopic dermatitis, which is more common in females
than in males at all ages). This observation can be explained in endocrine terms. In effect, estrogens are
proinflammatory hormones, while the male steroids
are immune suppressors.45 This hormonal and immunological dimorphism also appears to influence
the greater prevalence of autoimmune diseases in
women of child-bearing age46 who have been treated
with tamoxifen (an anti-estrogen drug)47 and dehydroepiandrosterone.48 In the specific case of asthma,
further consideration is required of functional and
structural differences in the airways between sexes.
In effect, boys are characterized by disynaptic lung
growth (lung volume grows relatively more than the
airways), while girls show a proportional growth up
until adolescence, after which the caliber of the airways and lung function increases in males.49

There is considerable controversy regarding the

possible influence of vaccination in infancy upon allergic disease. Some studies have related systematic vaccination, particularly against whooping cough
and measles, to the development of allergic diseases,53,54 as a result of the decrease in protective
native infections and the development of IgE responses mediated by the vaccine itself. Bremner et
al.55 found no association between DTP and MMR
vaccination and an increased risk of allergic rhinitis,
and conducted an analysis of possible confounding
factors such as the fact that allergic children visit the
physician more often and are more likely to receive
their vaccines on time, while children with many siblings and recurrent viral infections (protective factors)
can suffer delays in vaccination.
Koppen et al.56 in turn conducted a systematic literature review, selecting epidemiological studies that
linked vaccination in infancy (DTP, MMR and BCG)
to the development of allergic diseases. Quality and
validity varied considerably among the reviewed
studies, some of which did not take into account
possible confounding variables such as life-style. The
studies with the greatest scientific evidence reported
that the analysed infant vaccinations did not increase
the risk of developing allergic diseases, and that BCG
vaccination appears to exert no protective effect
upon the development of allergy in contrast to the
reports of other studies.57,58 In two recent studies
carried out in The Netherlands, systematic infant vaccination was not associated with an increased risk of
atopic disorders.59,60 According to Anderson et al.61, it
is unlikely that the international discrepancies in the
prevalence of allergic diseases can be ascribed to differences in immunization practices among countries.

Breastfeeding
The relationship between breastfeeding and its
possible protective effect against the future development of allergic diseases is very controversial.
Some publications report a preventive effect, while
others document a partial effect (protection only in
the first years of life, or only of certain subgroups),
or even unfavourable effects. Ethical considerations
make it very difficult to conduct randomized,
double-blind placebo-controlled trials capable of clarifying this important point.
A meta-analysis of prospective studies showed
that exclusive breastfeeding during at least the first
four months of life is associated with a lesser rate
of atopic dermatitis, and that the effect is more pronounced in children with a family history of atopy.50
Other studies suggest that breastfeeding prevents
the appearance of allergic disorders in children
without parental antecedents of allergy, although
not in the subgroup with family atopy.51,52 However,
this could be explained as a consequence rather
than as a cause, i.e., these are children with family
history of atopy whose allergic disease tends to develop earlier and is more severe and/or persistent,
thus causing the mothers to prolong breastfeeding.
This in turn is erroneously interpreted as representing an association between breastfeeding and allergic risk.
Allergol Immunopathol 2008;36(2):90-100

Infections and antibiotic use

Repeat infections of any location favour the production of cytokines that inhibit Th2 responses, such
as IL-12, IL-18 and IFN-. Lowered levels of the latter
are found in patients with asthma,62 rhinitis,63 and
atopic dermatitis;64,65 as a result, it could serve as an
in vitro marker of atopic disease.
A study involving 24,341 mother-offspring couples
concluded that early infections do not protect against
allergic disorders, although other indirect markers of
microbial exposure (such as number of siblings, nursery attendance, living on farms or having pets in the
home) were indeed found to be protective factors66
thus suggesting that the concept of microbial burden is more important than the existence of specif-

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ic infections as a protective factor in early childhood.67

In relation to the hygiene theory commented
above, if contact with microorganisms protects
against allergic diseases, then antibiotic use in infancy would have the opposite effect, i.e., it would constitute a risk factor for such diseases.68-70 This is a
tempting interpretation, since the widespread and
sometimes abusive use of antibiotics would partially
explain the increase in the prevalence of allergic disorders seen in the last 3-4 decades. However, on
analysing the studies on this subject, the association
between allergic disorders and antibiotic use disappears when children that have received antibiotics
for infections involving wheezing are included.34
Therefore, this association can be explained in inverse terms: asthmatic children (which may have associated rhinitis and/or eczema) show a greater risk
of infections and these moreover generate more
symptoms, as a result of which they are more likely
to be treated with antibiotics.

Intestinal flora, probiotics and prebiotics

Establishment of the intestinal microflora is essential for correct modulation of immune system
maturation in newborn infants.71 In this context there
are differences between the composition of the intestinal microflora in allergic and non-allergic children,
with a greater presence of Clostridium difficile,72 coliform species and S. aureus73 in allergic infants, and a
predominance of Lactobacillus in non-allergic children.73 Differences have also been observed in the
intestinal flora of children with an anthroposophic
life-style that avoid the use of antibiotics, vaccines
and antithermal drugs, and consume vegetables fermented with Lactobacillus. Such differences could
contribute to the lesser rate of allergic diseases
found in these children.74
In recent years, a number of groups of investigators have evaluated the benefits of probiotics administered in the last weeks of pregnancy and the first
months of life as protection against allergic diseases.75-77 The problem here is posed by the choice
of the most adequate probiotic germ, since the exact
composition of the intestinal microbiota in healthy
children is not known, though it must include properties such as resistance to the digestive enzymes,
adhesion to the intestinal epithelium, competition
with pathogens and the absence of antibiotic resistance transmission to the saprophytic flora. An alternative is to supplement infant foods with prebiotics
(oligosaccharides that favour the development of
beneficial saprophytic bacteria present in the intes-

95

tine). There are promising results with the use of

both types of products in atopic dermatitis, though
the work carried out to date involves only small samples and with a short duration of follow-up.78,79

Number of siblings and nursery attendance

A lesser prevalence of rhinitis and asthma has
been observed in children with many siblings80,81 or
who attend the nursery from an early age.80,82,83 Karmaus et al. found that with each pregnancy, maternal
tolerance of allergens increases, and the umbilical
cord blood levels of IgE decrease, suggesting that
this may be due to an in utero effect of the number
of siblings.84,85

Exposure to animals

Domestic pets
There is considerable controversy over whether to
have furry pets during infancy protects or favours the
ulterior development of allergic diseases. It is believed that the effect of the pet depends on the age
and degree of allergen exposure, as well as on the
type of animal.86 In this context, while some studies
have reported a protective effect,87-91 others consider
exposure to pets to be a risk factor for sensitization92,93 and allergic diseases.94
These studies must be interpreted, however, with
caution, however, since is it possible an inverse
causal relation whereby families with a history of allergies would spontaneously apply preventive measures (e.g., avoiding pets or smoking in the home, or
the prolongation of breastfeeding) that are not systematically adopted by families without such antecedents. In such situations it would be erroneous
to attribute protective properties to the fact of having
a pet in the home.

Farm animals. The importance

of endotoxins
A number of studies have reported that early exposure to bacterial endotoxins from farm animals
protects against allergic diseases,95-99 since such endotoxins are potent inducers of type Th1 cytokines.
Paradoxically, however, exposure to endotoxins may
induce IgE-mediated responses to allergens in subjects that have already developed allergic disease,
thus constituting a risk factor for more serious symptoms in these cases.100
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Exposure to tobacco smoke

Annesi-Maesano et al.,101 in french adolescents, reported the presence of asthma, rhinoconjunctivitis
and eczema to be significantly associated with active
smoking. The authors concluded that asthma or allergy status does not constitute a dissuading factor
against starting to smoke or continuing to smoke in
adolescence. On the other hand, the study of the effects of passive smoking in children is controversial,
due to the difficulty of assessing the degree of exposure and of comparing studies with different methodological designs. In Trinidad-Tobago, a country where
the benign climate causes children to stay little indoors (and thus with less exposure to tobacco
smoke), Monteil et al. found passive exposure to tobacco smoke to be closely correlated to an increased
prevalence of asthma and rhinitis in schoolchildren.102
Surprisingly, a Swedish study demonstrates an association between current exposure to tobacco smoke
and a lower risk for atopic disorders, in smokers
themselves and a similar trend in their children.103

Autoimmune diseases
Both allergy and autoimmunity are the result of immune system dysregulation, with the predominance
of Th2 action in the former and Th1 activity in the latter. A genome search has been made to establish a
genetic link between both groups of diseases, with
the identification of certain shared regions such as in
the case of asthma with respect to ankylosing
spondylitis, type 1 diabetes, multiple sclerosis and
rheumatoid arthritis.104
A number of investigators have suggested that allergic diseases could protect against type 1 diabetes
on the one hand,105,106 and that there are lower rates
of atopic diseases among type 1 diabetics on the other.107,108 A meta-analysis published in 2003 confirmed
a small but significantly lesser prevalence of asthma
in these patients although the same could not be
concluded for the rest of atopic diseases.109

Socioeconomic level. Western life-style

Stewart et al.110 found that countries with a gross
domestic product in the lower quartile range present
a significantly lesser positive response rate in the
questionnaires on asthma, rhinitis and eczema in the
ISAAC among adolescents in the 13-14 years age
range. This casts doubts as to the true role of the
economic development of countries in relation to the
presence of allergic diseases.
Allergol Immunopathol 2008;36(2):90-100

Conversely, it has been proposed that socioeconomic progress does not influence the development
of allergic diseases, although such progress does improve the diagnosis and treatment of these disorders.111 Therefore, rather than socioeconomic status,
associated factors such as smoking, the adoption of
preventive measures,112 educational level,113 health
care accessibility, language and cultural factors114
would be the true elements influencing the prevalence of these illnesses.

Environmental pollution
Pollution is an important cause of respiratory
symptoms in both atopic and non-atopic individuals.
The degree of pollution, particularly that caused by
combustion engines and produced in buildings, has
been associated with the greater prevalence of allergic diseases in industrialized countries. The increase
in these illnesses in recent decades has paralleled the
replacement of coal with diesel fuel as an energy
source resulting in an important decrease in smog,
but also in a change in the composition of the polluting particles, which presently originate mainly from
the combustion of diesel fuel (70 %). The main mechanisms by which diesel exhaust fumes enhances allergic responses are the adsorption of aeroallergens
which ensures a greater concentration and permanence of such particles in the atmosphere and a decrease in mucociliary activity with an increase in respiratory epithelial permeability to allergens, which
thus gain easier access to the immune system.
A definitive study in this context compared the
prevalence of pollinosis in children living in Munich
and Leipzig before the reunification of Germany.115
Munich was a non-polluted city whose only sources
of pollution were motor vehicles and buildings, while
Leipzig was an intensely industrialized city with high
levels of SO2 from factories that operated mainly with
coal. Curiously, it was observed that both the presence of allergic rhinitis and the rate of positive prick
tests were greater in Munich (18.2 % and 36.7 %, respectively) than in Leipzig (2.4 % and 8.6 %). Following the reunification of Germany, the obsolete coal
burning facilities in Leipzig were eliminated, resulting
in an apparently less contaminated city, although from
that point onwards the incidence of pollinosis increased spectacularly. It can be concluded that diesel
engines, which generates up to 150 times more particles than gasoline, constitute a main cause of the increase in allergic processes associated with the Western life-style.
Ozone is a colourless, scantly soluble and intensely irritating gas produced by photochemical reactions

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AND ATOPIC DERMATITIS IN CHILDREN

in the upper atmosphere. It is a direct oxidant that

leads to the formation of free radicals and macromolecular damage, thus giving rise to nasal symptoms,
bronchial hyper-responsiveness and airway inflammation. This in turn has been related to the rates of
hospitalization due to respiratory problems in infants
under two years of age.116

Rural versus urban setting

Although pollen exposure is more intense in the
rural setting, the prevalence of pollinosis is lower117
than in the urban setting118 probably because of the
lesser traffic pollution on one hand, and contact with
farm animal endotoxins on the other.95,96
Differences are also seen in the rural setting. In effect, the prevalence of allergy to cedar tree pollen
among Japanese living near highways practically
triples the prevalence found in areas near cedar
forests.119 Likewise, the prevalence of wheezing and
atopic dermatitis is greater in adolescents that live
less than 100 metres from main roadways.120

97

Stress
Stress is a risk factor for the development of allergy, by inducing alterations in the neuroimmune regulation mechanisms that modulate hypersensitivity response. These alterations occur at a number of levels
such as the hypothalamus-hypophysis-adrenal system (with decreases in cortisol and increase in cytokines and inflammatory and immune-stimulating
hormones), autonomous airway control (increasing of
substance P), corticoid resistance, oxidative stress,
and alterations in the intestinal flora, among others.126
In conclusion, it can be stated that there is great
diversity in the results of the many studies of the risk
factors associated with allergic diseases. After discarding the discrepancies attributable to methodological differences and/or deficiencies, it seems that
the factors that exert a more relevant effect upon the
atopic genotype causing the manifestation of allergic disease are: 1) the decrease in general microbial
burden; and 2) the increase in environmental pollution to which the paediatric population has been exposed in the last few decades in different parts of
the world.

Diet, obesity and sedentarism

Although the results have been controversial, the
ingestion of antioxidants has been related to a lesser prevalence of asthma and other allergic disorders, while diets rich in monounsaturated fats have
been associated with an increased risk of such diseases.121 The explanation for this is that these fats
undergo peroxidation, with the consequent production of free radicals - as a result of which it is possible that the antioxidant needs are currently greater
in industrialized countries than they were in the
past. It must also be taken into account that individuals with more healthy eating habits may have other
associated protective factors such as a higher socioeconomic level, a longer duration of breastfeeding, or less exposure to tobacco smoke, among other factors.
Some studies showed a consistent pattern of decreased symptoms of asthma, rhinoconjunctivitis
and atopic eczema, associated with increased consumption of cereals, nuts, starch, and vegetables,122
and with Mediterranean diet (rich in monounsaturated fats, vegetables and fruits and moderate in
milk).123
On the other hand, although a modest association
has been found between obesity and asthma,123,124
due fundamentally to the effects of proinflammatory
molecules such as leptin,125 no such relationship has
been reported between obesity and atopy.124

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