REVIEW

Risk factors of allergic rhinitis: genetic or

environmental?
De-Yun Wang
Department of Otolaryngology,
Faculty of Medicine, National
University of Singapore, Singapore

Abstract: Allergic diseases such as allergic rhinitis represent a global health problem, affecting
10%25% of the world population. There is clear evidence to support the concept that allergic
diseases are influenced by genetic predisposition and environmental exposure. Polymorphisms
of candidate genes have been associated with clinical expression of these diseases. However,
characterization of these susceptibility markers in discriminating an allergic individual from
the general population has not yet been achieved, and the value of how this genetic insight
leading to recognition of specific subtypes of these disorders still needs to be confirmed.
Environmental factors (eg, air pollution and bacterial/viral infection) also play an important
role in the development of the diseases. A number of epidemiologic studies have supported
the hygiene hypothesis, which is based on the observations that Th1 responses induced by
microbial stimulation can counterbalance allergen-induced Th2 responses. Future studies are
needed to identify the key genes or their haplotypes for atopic phenotypes and to investigate
the interactions between genetic and environmental factors that influence the complex trait of
allergic diseases. This will help us to further understand the etiology of the diseases and
develop new avenues for genetically oriented diagnosis and more effective measures of
prevention and intervention.
Keywords: allergic rhinitis, genetic predisposition, environmental factors

Introduction

Correspondence: De-Yun Wang

Department of Otolaryngology,
National University of Singapore,
5 Lower Kent Ridge Road,
Singapore 119074
Tel +65 6772 5373
Fax +65 6775 3820
Email entwdy@nus.edu.sg

Allergic rhinitis (AR) is a common manifestation of allergic diseases affecting

approximately 10%25% of the world population (Bousquet et al 2001). The
symptoms of AR include rhinorrhea, nasal obstruction, nasal itching, and sneezing.
The symptoms are reversible and are caused spontaneously by exposure to allergens
and triggering factors or whilst under treatment. Allergic rhinitis is a major airway
disease, which causes morbidity and significantly impairs a patients ability to function
and their quality of life. It is also associated with other conditions such as asthma,
sinusitis, anosmia, otitis media, nasal polyps, lower airway infection, and even dental
malocclusion (International Rhinitis Management Working Group 1994; Spector
1997; Canonica et al 1998; Apter et al 1999).
Allergic rhinitis is caused frequently by exposure to perennial or seasonal allergens
that exist in our indoor and outdoor environment. Among the most common allergens,
pollens (grass, trees, and weeds) are the predominant causes of seasonal allergic
rhinitis. House dust mites, pets, and molds are the major causes of perennial allergic
rhinitis. However, in tropical and subtropical areas pollen may become a perennial
allergen. Recently, the document Allergic rhinitis and its impact on asthma (ARIA),
which was developed in collaboration with the WHO, has recommended to replace
the old terms seasonal and perennial rhinitis by intermittent allergic rhinitis
and persistent allergic rhinitis, respectively (Bousquet et al 2001).

Therapeutics and Clinical Risk Management 2005:1(2) 115 123

2005 Dove Medical Press Limited. All rights reserved

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Wang

IgE-mediated immunologic mechanisms are known to

play a key role by triggering the release of mediators that
are responsible for allergic symptoms. Transendothelial
migration of inflammatory cells and their activation within
the reactive tissue are characteristic features, which represent
the result of a complex network of interactions between
various mediators, cytokines, chemokines, and adhesion
molecules. It has been suggested that an imbalance of Th1
and Th2 cells, especially Th2 cells, plays an important role
in regulating IgE synthesis and cell recruitment at the sites
of inflammation. In allergic rhinitis, many studies have
demonstrated that mucosal inflammation is characterized
by the tissue infiltration of T-lymphocytes (CD4+ T cells
and CD25+ T cells) in the submucosa and epithelium
(Durham et al 1992; Varney et al 1992).
During past decades, the prevalence of allergic rhinitis
has increased, especially in developed and industrialized
countries. The complete etiology for the development and
expression of atopic disease is not yet understood. Several
putative factors have been proposed such as changes in
lifestyle; increase in exposure to allergens, pollution, and
irritants (smoke, gas, etc); changes in diet responsible for
the diminution of protective nutrient intake; decrease in
infections; and stress (Bousquet 2001). Thus, interaction
between environmental factors and individual susceptibility
is essential.
This paper reviews recent understanding of the
pathogenic mechanisms, which are influenced by a complex
immune procedure, including interaction of multiple genes,
interaction of environmental and genetic factors, and
population heterogeneity. Understanding the etiology of
allergic rhinitics will lead to the development of genetically
oriented diagnosis and more effective environmental control
measures.

The genetic characters of allergic

rhinitis
A genetic background in terms of a family history of atopic
disease has been the strongest risk factor for the development
of allergic symptoms, irrespective of the varying prevalence
and environmental risk factors in different societies. The
most convincing evidence for genetic effect in the
development of atopy is derived from twin studies. The
earliest study by Edfors-Lubs, dating back to 1971, showed
the hereditary character of allergic rhinitis in twins
(Edfors-Lubs 1971). Later, Hopp and colleagues (1984)
found a greater concordance of allergic manifestations in
monozygotic than dizygotic twins in terms of correlation

116

coefficient of serum total IgE (0.82 vs 0.52), skin test

response (0.82 vs 0.46), and bronchial reactivity to inhaled
methacholine (0.67 vs 0.34).
Atopy is a key condition in the development of allergic
diseases, particularly with the IgE-mediated mechanism. It
is a disorder with strong familial tendency, usually starting
in childhood or adolescence, when patients become
sensitized and produce IgE antibodies in response to
ordinary allergens (Johannson et al 2004). The complex
mechanisms of inheritance, from genetic predisposition of
atopy to atopic (allergic) diseases, are still incompletely
understood (Figure 1). Some studies suggest that the
pathogenesis of allergic diseases is complex and may be
caused by a contribution of genetic and environmental
factors, especially at the stage of allergen sensitization.
In the area of human genetic study, many candidate genes
have been identified using position cloning and linkage
analysis techniques (Moffatt and Cookson 1999; Peden
2002; Toda and Ono 2002). The genome-wide search
approach has shown an association between certain
phenotypes of allergic diseases (rhinitis and/or asthma) with
markers on more than 14 pairs of chromosomes (ie,
chromosome 1, 2, 3, 5, 6, 7, 9, 11, 12, 13, 14, 16, 17, 19,
and more). Some of these genes are involved in the specific
immune response (ie, HLA-D, TCR, CD14, toll-like
receptor, STAT6) and Th1/Th2 cell differentiation; others
are genes coding the (total) IgE response or functions of
the IgE receptors (ie, IL-4, IL-4R, FcRI, FcepsilonRI)
and genes involved in the inflammatory process (TNF-,
IFN-, IL-3) (Cookson et al 1989; Marsh et al 1994; Barnes
et al 1996; Noguchi et al 1997, 1998b; Baldini et al 1999;
Deichmann et al 1999; Shek et al 2001; Nisiyama et al 2004;
Park et al 2004; Weidinger et al 2004; Pykalainen et al 2005).
However, studies on association of allergic manifestations
with candidate gene polymorphisms have yielded conflicting
results. Limited sample size with insufficient statistical
power is always a critical methodological issue, which is
often neglected in some of the case-control or populationbased studies.
Various ethnic background influences the outcome of
genetic epidemiological studies. There is the presence of a
large difference in allele distribution of several allergyrelated gene (eg, IL-4 and IL-4-R gene) polymorphisms
among various ethnic populations. For the IL-4 gene, a C to
T polymorphism at IL-4/-590 was reported to be associated
with serum total IgE level (Rosenwasser et al 1995),
development of asthma (Noguchi et al 1998a), and atopic
dermatitis (Kawashima et al 1998). It seems that T allele

Therapeutics and Clinical Risk Management 2005:1(2)

Allergic rhinitis

Environmental risk factors

Genetic disposition

Allergen exposure
Exposure to indoor and outdoor
air pollution
Bacterial/viral infection
Others

genetic polymorphisms
or haplotypes

Allergic diseases
Induce/enhance symptoms
and allergic sensitization

Allergic rhinitis
Asthma
Eczema

Specific immunologic mechanism

IgE- / non IgE-mediated

Differences in lifestyle

Early life features

Nutrient intake
Family and sibship size
Hygiene standard
Food
Vaccination
Stress
Ownership of pets
Others

Chromosomes
1, 2, 3, 5, 6, 7, 9, 11, 12, 13, 14, 16, 17, 19, etc

Specific immune response

Imbalance of Th1 and Th2 cells and
cytokine production
IgE production
Response or functions of the IgE
receptors
Recruitment and activation of
inflammatory cells and airway
inflammation
Others mechanisms

Figure 1 Risk factors of allergic diseases.

frequency is less frequent in Caucasians than Asian

populations with a difference of up to 6-fold. The T allele is
common (70%73%) in Japanese (Noguchi et al 1998b),
but less common (12.5%) in Germans (Kabesch et al 2003).
Our recent study showed a significant difference of T allele
frequency at IL-4/-590 among Chinese (non-atopic 90.2%
and atopic 87.3%), Malays (non-atopic 83.3% and atopic
77.1%), and Asian Indians (non-atopic 38.1% and atopic
44.1%) (Unpublished data). For the IL-4R, the association
of atopy with a gain-of-function mutation in the subunit
of the IL-4 receptor (Q576R) was found to be a critical
condition of atopy (Hershey et al 1997). On the contrary, a
study performed in Singapore has reported a significant
ethnic variation of this polymorphism among Chinese,
Malays, and Indians, and no association was found between
this polymorphism and atopy in all three ethnic groups (Tan
et al 1999).
To date, neither fine mapping nor particular genetic
polymorphisms have been confirmed to be a critical
condition in the development or clinical manifestations of
allergic diseases. It is not surprising since predisposition to
atopy is influenced by a complex immune procedure,
including interactions of multiple genes, interaction of

Therapeutics and Clinical Risk Management 2005:1(2)

environmental and genetic factors, and population

heterogeneity. Future studies are needed to identify the key
genes or the joint effect of several susceptibility genes
(haplotypes) that leads to allergic phenotypes. Furthermore,
statistical methods for discovering sets of susceptible genes
and environmental factors, as well as systematic verifications
of the gene-environment-disease network would have a great
impact on future genetic epidemiological studies (Hoh and
Ott 2004).

Environmental factors
Environmental factors such as increased air pollution,
changed lifestyle, and decrease in bacterial/viral infection
are frequently quoted as adjuvant factors for allergic
sensitization and possible causes of the increased prevalence.

Protective effect of infections on atopy

hygiene hypothesis
During the past decade, the simulative question of why
atopic diseases are increasing in prevalence, which is
inversely proportional to the prevalence of communicable
diseases, is due to the improvement of healthcare policy

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Wang

and hygiene standard, especially in developed countries. The

so-called hygiene hypothesis of allergy was first suggested
by Strachan (1989), who noted that the risk of developing
allergies and asthma is inversely related to the number of
children in the family. This effect has since been confirmed
using various markers of infectious burden such as number
of older siblings (von Mutius et al 1994a; Jarvis et al 1997;
Bodner et al 1998), attendance at day care facilities (Krmer
et al 1998), positive serology to orofecal infections
(Matricardi et al 1997, 2000), and regular contact with farm
animals before the age of 7 years (Radon et al 2004).
To explain the hygiene hypothesis requires an
appreciation of the developing immune system. T helper
cell (Th2)-like cytokines (eg, IL-4, IL-5, and IL-13)
produced in the uterine environment induce similar Th2like responses in the immature immune system of the
newborn, which increases the likelihood that postnatal (and
possibly even prenatal) exposure to allergens leading to
production of allergen-specific IgE and eosinophilic
inflammation (Warner et al 1998). According to the hygiene
hypothesis, infections with viruses and perhaps other
intracellular organisms also influence the developing
immune system: the T-cell responses to these infections
generate Th1-like cytokines such as IL-12 and IFN- that
down-regulate Th2 responses. Thus, the core of the hygiene
hypothesis is based on the observations that Th1 responses
induced by microbial stimulation can counterbalance
allergen-induced Th2 responses. According to the hypothesis
of endotoxin switch, a dose-dependent relationship exists
between environmental exposure to bacterial products and
the outcome of the immune response. The quantity of
environmental endotoxin may also affect the balance of the
Th1/Th2 cytokine level. It has been suggested that repeated
viral infections other than lower respiratory tract infections
early in life may stimulate the immature immune system
towards the Th1 phenotype, thereby reducing the risk for
the development of asthma up to school age (Illi et al 2001).
The underlying mechanisms of these protective immunologic effects are still unclear.
Which environmental or microbial factors are the culprits
for atopic manifestation? It should not be assumed that all
infectious diseases have the same effects on the development
or clinical manifestation of allergic diseases. It is known
that lower respiratory tract infections including respiratory
syncytial virus bronchiolitis, pneumonia, perhaps pertussis,
and measles in childhood may increase the subsequent risk
of childhood asthma without modifying the likelihood of

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sensitization to allergens (Gern and Weiss 2000). A larger

Finish population study (n = 517 910) showed a strong
positive association between measles and atopic manifestations, which does not support the hypothesis that
experiencing natural measles infection offers protection
against atopic diseases (Paunio et al 2000).
More work is needed in the area of longitudinal
epidemiologic studies to evaluate the effects of childhood
infections (eg, viral and bacterial infections) on the
development of the immune system and pathophysiology
of allergic diseases. The challenges for future studies include
identification of those factors that confer the protection
proposed by the hygiene hypothesis, and, if possible, to find
strategies to modify the environment without causing harm
to susceptible individuals (Eder and von Mutius 2004).

Air pollution
In addition to previously described allergens, exposure to
high levels of pollutants including oxides of nitrogen, ozone,
sulfur dioxide, black smoke large particulate matter, small
particulates, carbon monoxide, and volatile organic
compounds have been considered as important contributing
factors in both exacerbation and etiology of allergic airway
diseases (Utell and Samet 1993; Devalia et al 1994; Krishna
et al 1995).
It is still not clear whether the increasing prevalence of
allergic diseases is distinctly different between the areas with
higher or lower degrees of air pollution. The quantity and
types of pollutants also influence the development of allergic
disease. This has already been explained by an epidemiological study performed in two cities of Germany. Von
Mutius et al (1994b) have studied a total of 7653 children
in Munich (n = 5030) and Leipzig (n = 2623). In Leipzig,
there was a considerably higher degree of air pollution, with
sulfur dioxide produced by coal, while an automobile type
of pollution was found in Munich. The prevalence rates of
allergic rhinitis, asthma, and positive skin tests to
aeroallergens were significantly lower in Leipzig (2.7%,
3.9%, and 18.2%) than in Munich (8.6%, 5.9%, and 36.7%).
Therefore, it was suggested that an effective pollution control
policy will require an understanding of how measures to
alter emissions from different sources influence personal
exposure, and hence health outcomes (Ashmore 1995).
Air pollution certainly plays an important part, if not a
pivotal role, in the pathogenesis of allergic and respiratory
diseases. Some pollutants can either impair defense
mechanisms in the airways rendering them more susceptible

Therapeutics and Clinical Risk Management 2005:1(2)

Allergic rhinitis

to viral and/or bacterial infection, or cause an immunological

toxicity in the airways (Krishna et al 1995). Pollutants may
also play a direct or indirect role in the pathophysiology
and the development of allergic diseases (Cookson et al
1989; von Mutius et al 1994a; Hershey et al 1997; Matricardi
et al 1997; Jarvis et al 1997; Bodner et al 1998; Krmer et
al 1998; Shek et al 2001; Riedl and Diaz-Sanchez 2005)
(Figure 2). More work is needed to identify which pollutants
have an impact on human health and in which subgroups,
and the mechanism for disease development. This will need
to include the pathways of chemical, molecular, and cellular
interactions. A more powerful epidemiological study must
be performed on the basis of prospective settings in several
regions, and with unique investigational criteria to assess
the prevalence and severity of allergic disease.

Control measures for indoor allergens

Exposure of indoor allergens in our house environment is a
common cause of perennial allergic rhinitis. Young children
especially, spend most of their time inside the house. It is
true that when a high concentration of one or more allergens
is present in the house, the risk of allergenic sensitization in
the early stages of life will increase consequently. In highrisk newborns, prenatal exposure to mite allergens from dust
of the living room and the maternal mattress was found to
be associated with total serum IgE at birth (Schonberger et
al 2005).

House dust
House dust is a heterogenous mixture, which varies
according to region and household. It consists of various
allergenic substances, consisting primarily of somatic and
metabolic allergens of mites and secondarily of allergens
derived from domestic animals, human skin scales, domestic
insects such as cockroaches, and endotoxin of gram-negative
bacteria. In addition, fungal spores or mycelia and other
products of animal or vegetable origin such as feathers, wool,
and natural fibers may be sources of dust allergens.
Endotoxin, a component of the cell wall of gram-negative
bacteria, is a potent proinflammatory agent commonly found
in house dust. Exposure to endotoxin will induce an
inflammation of the airways, characterized by a neutrophil
invasion, irritation on the mucus membranes, and restricted
airway diameter (Michel et al 1991, 2001). These effects
are undoubtedly an enhancing factor for the severity of
established allergic inflammation in rhinitis and asthma. It
has been postulated that exposure to endotoxin at a critical
time might shift the developing immune system to a
predominantly Th1-type (increasing IFN- and IL-12
productions) responsiveness, thus protecting against asthma
and allergies (Martinez and Holt 1999). Further studies are
still needed to determine the duration and dose-related
effectiveness of endotoxin on Th1 cell polarization in terms
of allergen sensitization and the existence of allergic
inflammation in allergic rhinitis or asthma patients.

Enhance allergic
sensitization
IgE production
Decrease allergen clearance
IL-4 production
organic compounds/substances
Reduce ciliary beat

Pollutants
Production of mediators
ie, histamine, LTC4, PGs

Induce symptoms and

hyperresponsiveness

Production of cytokines and

chemokines

Proliferation and activation

of inflammatory cells

Figure 2 Possible effects of air pollution in allergic diseases.

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Wang

Muramic acid, a constituent of peptidoglycant in gramnegative and gram-positive bacteria in the environment, was
suggested to be an additional marker of microbial exposure
(van Strien et al 2004). A recent study was conducted on
553 farm and non-farm school children from Austria,
Switzerland, and Germany. Their mattress dust muramic acid
concentrations were determined and their health condition
was assessed by using IgE measurements and questionnaire
information. The muramic acid concentration was found to
be significantly higher in dust from farm childrens
mattresses than in dust from non-farm childrens mattresses
(157 ng/mg vs 131 ng/mg). Interestingly, children with
higher mattress dust muramic acid concentrations had a
significantly lower prevalence of wheezing regardless of
farming status and endotoxin exposure (van Strien et al
2004).

House dust mites

House-dust mites (HDM) are the most common indoor
allergens for allergic diseases such as allergic rhinitis and
asthma. International studies have demonstrated that
Dermatophagoides pteronyssinus (Der p), Dermatophagoides
farinae (Der f) are the most common mite species worldwide
(Bousquet et al 2001). In the tropics, Blomia tropicalis (B.
tropicalis), another dust mite species, was found to be the
most prevalent domestic mite (Zhang et al 1997; Wang et al
2003; Fernandez-Caldas and Lockey 2004). HDM are
commonly found in association with bedding products,
carpets, curtains, and fabric products. HDM hypersensitivity
is strongly associated with persistent allergic rhinitis (PAR).
Allergen avoidance, including house dust mites, is
recommended to be an integral part of a management
strategy for allergic rhinitis and asthma (Bousquet et al
2001).
The real challenge is to create a low allergen environment
in patients homes, and unfortunately, the majority of single
interventions have failed to achieve a sufficient reduction
in allergen load leading to a clinical improvement (Bousquet
et al 2001). It is possible to reduce the concentration of house
dust mites either by chemicals (tannic acid or solidified
benzyl benzoate) or bedding encasings. House dust mite
encasement products such as pillow and mattress covers are
widely available for sale. Reimbursement from insurance
companies for the purchase of such products in the United
States is estimated at $42 million in 2001 (Terrehorst et al
2003). Although laboratory studies have demonstrated the
high filtering capabilities of these barrier products,
surprisingly, few clinical trials studies have been done to

120

date reporting the clinical efficacy of such prevention

methods (Sheikh and Huwitz 2001). A multicentered,
randomized, placebo-controlled study has been done so far
to evaluate the efficacy of HDM impermeable bedding
covers in the bedrooms of patients with allergic rhinitis,
showing no significant improvement on clinical symptoms
between treatment and control groups (Terrehorst et al
2003). This may be due to the high HDM load from other
non-bedding products common in the home environment
that may confound the results of the study.
It is commonly understood that exposure to HDM
allergen in infancy increases the risk of developing asthma.
However, a recent study was unable to find any relationship
between the level of HDM allergen exposure in childrens
bedrooms in early childhood and development of bronchial
hyperresponsiveness or physician-diagnosed asthma by age
67 years (Carter et al 2003). Another study was performed
to compare the association between dust mite allergen level
and asthma symptom prevalence across multiple countries
in the Asia-Pacific region. Among children aged 67 years,
neither allergen (Der p 1 and Der f 1) was related to asthmatic
symptoms or severity prevalence (Wickens et al 2004). To
address this conflicting issue, one needs sensitive measures
to assess quantitatively and qualitatively the HDM exposure,
as well as the exposure to other adjuvant factors in the home.
The relationships between house and household
characteristics and allergen concentrations in both air and
dust were complex (Peterson et al 2003). The concentrations
of Der f 1 in dust increased with increasing number of
residents and relative humidity and declined when forced
air heating was used. Dust concentrations of Der p 1 were
lower in new homes and during forced air heating use but
higher with higher relative humidity and in the presence of
dogs. A study was performed to compare indoor allergens
(Der p 1 and Der f 1) and endotoxin levels between urban
and rural settings as important determinants for asthma and
atopy in children. The results showed that indoor
environmental factors such as dampness seemed to be
important determinants for allergen and endotoxin, but living
habits such as lack of mattress cover appeared unimportant
(Wickens et al 2004).
In the tropics, the majority of allergic rhinitis is persistent
in nature (Wang et al 2002). The year-round warm and humid
climate is conducive to the proliferation of dust mites and
molds, two of the most common aeroallergens implicated
in persistent allergic rhinitis (Wang et al 2003). As patients
with persistent allergic rhinitis are often symptomatic
throughout the year and need long-term control of HDM

Therapeutics and Clinical Risk Management 2005:1(2)

Allergic rhinitis

exposure, ensuring compliance is essential. It is recommended that educational programs be implemented for
physicians and patients as to the most effective therapeutic
strategies leading to optimal outcomes (Wang et al 2004).

Ownership of pets
Pet ownership was found to markedly increase the risk of
sensitization to pets (Al-Mousawi et al 2004). The
prevalence of asthma, rhinitis, and skin allergy was
significantly more common in families with animals than
in those without (Bener et al 2004). The secretary proteins
from a large number of animals carry or contain powerful
allergens capable of causing severe hypersensitivity
reactions. Cats and dogs are the main culprits particularly
if they are allowed to enter and remain in the bedroom.
Allergic rhinitis and asthma are common clinical manifestations of allergies to animals. Therefore, removal of the
pet (cat or dog) from the home is still recommended for
sensitized patients with ongoing allergic diseases.
The major cat allergen (Fel d 1) is a glycoprotein that is
transported in the air by particles smaller than 2.5 m
(Luczynska et al 1990), and these particles can remain
airborne for long periods. They are also adherent,
contaminating an entire environment for weeks or months
after cessation of allergen exposure (Wood et al). A typical
example is that allergens adherent to the clothing of people
who have cats at home can trigger allergic reactions in
sensitized individuals. It makes avoidance and prevention
by sensitized individuals much more difficult, requiring
public cooperation and awareness. It has been suggested in
almost all clinical guidelines for sensitized patients with
allergic rhinitis and/or asthma that pets (ie, cats and dogs)
should be removed and to also carefully vacuum clean all
carpets, mattresses, and upholstered furniture.
During the last few years, data of several epidemiologic
studies have challenged the conventional understanding for
pet avoidance in sensitized patients. Thus, the role of pet
keeping during infancy for the development of allergy and
asthma remains controversial. It was found that early
exposure to a furry animal at home would lead to tolerance
and reduced asthma at school age (Hesselmar et al 1999). A
recent cohort study in Sweden with 1228 infants who were
born over a 1-year period was investigated by questionnaires,
and 817 of the children were skin prick tested both at age 1
and 4 years (Sandin et al 2004). The results showed that pet
keeping during the first year of life was not associated with
an increased risk of atopy at 4 years of age, although a
positive skin prick test to cat was more common at 1 year.

Therapeutics and Clinical Risk Management 2005:1(2)

These findings may even suggest that dog keeping during

the first year of life might provide some protection from
pollen allergy and late-onset wheezing and increase the risk
of early-onset transient wheezing in children with heredity
for asthma.
A wide range of allergens have been associated with
allergic diseases. Total allergen avoidance appears to be
effective (eg, symptom-free patients outside the pollen
season or occupational exposure). However, patients are
often sensitized to many allergens and the degree of exposure
varies within indoor and outdoor environments. Moreover,
the magnitude of reduction of allergen load needed to reduce
symptoms is still unclear. However, it is clear that allergen
exposure leads to symptoms. Thus, avoidance measures are
still recommended but more research is strongly needed
(Bousquet et al 2001).

Others
The clinical expression of allergic disease has been reported
in relation to other factors, such as changes in lifestyle,
modification in diet, geographic variations, climate,
socioeconomic conditions, family structure or history, infant
feeding, excessive allergen exposure especially during early
life, and cigarette smoking.

Conclusion
An increasing worldwide prevalence of allergic diseases
such as allergic rhinitis and asthma has been observed over
the last decades. The reasons for the increase of prevalence
of these diseases are still incompletely understood. Many
epidemiological studies have shown that environmental
exposure to bacterial products (ie, endotoxin) may have a
crucial role in the development of tolerance to ubiquitous
allergens found in natural environments. Thus, the hygiene
hypothesis becomes particularly attractive, since it is closely
linked to modernization of lifestyles and improvement in
living conditions. The future challenge is to understand the
complex interplay between epidemiology and molecular
genetics that have eventually caused sensitization and
clinical manifestation of allergic diseases. It will have
important implications for the development of new
therapeutic strategies and prevention of allergic diseases.

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