children

Review
The Role of Environmental Risk Factors on the Development of
Childhood Allergic Rhinitis
Allison C. Wu *, Amber Dahlin † and Alberta L. Wang †

Channing Division of Network Medicine, Mass General Brigham, Boston, MA 02115, USA;
amber.dahlin@channing.harvard.edu (A.D.); alberta.wang@channing.harvard.edu (A.L.W.)
* Correspondence: allisonchenwu@gmail.com
† These authors equally contributed to this work.

Abstract: Environmental factors play an important role in the development and exacerbation of
allergic rhinitis (AR) in childhood. Indoor air pollution, such as house dust mites and secondhand
smoke, can significantly increase the onset of AR, while pet dander may affect the exacerbation
of AR symptoms in children. Furthermore, traffic related air pollution and pollen are outdoor air
pollutants that can affect immune competency and airway responsiveness, increasing the risk of AR
in children. Climate change has increased AR in children, as growth patterns of allergenic species
have changed, resulting in longer pollen seasons. More extreme and frequent weather events also
contribute to the deterioration of indoor air quality due to climate change. Additionally, viruses
provoke respiratory tract infections, worsening the symptoms of AR, while viral infections alter
the immune system. Although viruses and pollution influence development and exacerbation of
AR, a variety of treatment and prevention options are available for AR patients. The protective




influence of vegetation (greenness) is heavily associated with air pollution mitigation, relieving

 AR exacerbations, while the use of air filters can reduce allergic triggers. Oral antihistamines and
Citation: Wu, A.C.; Dahlin, A.; intranasal corticosteroids are common pharmacotherapy for AR symptoms. In this review, we
Wang, A.L. The Role of discuss the environmental risk factors for AR and summarize treatment strategies for preventing and
Environmental Risk Factors on the managing AR in children.
Development of Childhood Allergic
Rhinitis. Children 2021, 8, 708. Keywords: allergic rhinitis; child; pediatrics; air pollution; allergens; traffic related air pollution;
https://doi.org/10.3390/ tobacco smoke; climate change; viruses; greenness; therapeutics; prevention
children8080708

Academic Editor: Bo Chawes

1. Introduction
Received: 10 July 2021
Accepted: 16 August 2021
A global health problem with significant economic burden, allergic rhinitis (AR) has
Published: 17 August 2021
established itself as the most common chronic allergic disease and affects approximately
40% of the population worldwide [1–3]. In the United States AR is the most common
Publisher’s Note: MDPI stays neutral
chronic illness in children [4–6]. Children with AR have decreased productivity at school
with regard to jurisdictional claims in
and lower grades [7]. AR is a chronic inflammatory disease in the upper airways that
published maps and institutional affil- is induced by an abnormal immunological response to airborne antigens [8]. It is an
iations. immunoglobulin-E (IgE) mediated type 1 hypersensitivity illness triggered by a wide array
of environmental allergens such as pollen, mold, and dust [9]. AR differs from nonallergic
rhinitis as AR includes allergic sensitization or symptoms during an exposure, whereas
nonallergic rhinitis is not associated with IgE-mediated sensitization [10]. One study
Copyright: © 2021 by the authors.
suggested that AR is associated with irreversible nasal airway obstruction and eosinophilic
Licensee MDPI, Basel, Switzerland.
inflammation, while nonallergic rhinitis is associated with no change in nasal airway
This article is an open access article
patency and less nasal mucosal eosinophilia than AR [10].
distributed under the terms and The most common symptoms of AR include nasal congestion, nasal pruritus, sneezing,
conditions of the Creative Commons and runny nose, leading to impairment in daily activities, sleep habits, cognitive function,
Attribution (CC BY) license (https:// work and school productivity, and overall quality of life [8,11,12]. Children with AR are
creativecommons.org/licenses/by/ more likely to have asthma, allergic conjunctivitis, rhinosinusitis, nasal polyposis, and otitis
4.0/). media [8]. Currently, studies evaluating the association between environmental risk factors

Children 2021, 8, 708. https://doi.org/10.3390/children8080708 https://www.mdpi.com/journal/children

Children 2021, 8, 708 2 of 12

with childhood AR have not produced definitive conclusions because of varying in study
designs and length of exposures and the complex composition of pollutants [9]. Children
may experience greater exposure to environmental allergens and pollutants and increased
morbidity from AR due to higher rates of oxygen consumption per unit body weight
and immature respiratory and immunological systems, respectively [13]. Furthermore,
children play outdoors for periods of time and thereby have increased exposure to outdoor
environmental factors [13]. While the development of AR has genetic contributions, this
article focuses on the role of environmental risk factors, including indoor and outdoor air
pollution and viruses [14].
Pollution, considered the largest single environmental risk for health, is the intro-
duction of harmful substances into the environment, contaminating air, soil, or water
with chemical substances or energy [15]. Pollution is often associated with AR, allergic
sensitization, and autoimmunity and can have detrimental health effects involving the
immune system [16]. When atopic individuals are exposed to allergens and pollutants,
they develop specific IgE antibodies that reside on the surfaces of mast cells and other
immune cells [9]. With additional exposure to allergens and pollutants, histamines, arachi-
donic acid metabolites, and other inflammatory mediators are released from mast cells,
resulting in sneezing, nasal congestion, and other common AR symptoms [17]. Pollutants
can provoke the nasal mucosa, allowing the release of mediators of allergic inflammation
and increasing nasal hyperreactivity [9]. Both outdoor air pollution, such as traffic related
air pollution (TRAP), and indoor air pollution, including pet dander, molds, and tobacco
smoke, contribute to the development of AR in children [18].

2. Indoor Exposures
Indoor air pollution including tobacco smoke, indoor allergens (e.g., dust mites, pet
dander, molds), and other pollutants (e.g., cleaning chemicals) all contribute to the develop-
ment of AR and the aggravation of symptoms [9]. Individuals in western countries spend
the vast majority of their time indoors, and more than 90% of the population live in places
where air quality does not meet World Health Organization (WHO) standards, leading to
increased rates of AR in children [19]. Furthermore, during the Health Effects of School En-
vironment (HESE) project, it was found that 78% of children attending schools in Norway,
Sweden, Denmark, France, and Italy are exposed to high levels of inhalable particulate
matter with a diameter of 10 micrograms (PM10 ), and 66% are exposed to carbon dioxide
(CO2 ) over 1000 ppm [20]. It was also demonstrated that concentrations of pollutants from
industrial emissions were higher in urban schools than rural schools, indicating that the
quality of indoor air is diminished from the diffusion of outdoor pollutants [21].
Common indoor pollutants include nitrogen dioxide (NO2 ), carbon monoxide (CO),
and volatile organic compounds (VOC) [22]. Gas fueled cooking and heating appliances
produce NO2 , while VOCs are frequently released by consumer products such as clean-
ing chemicals, cosmetics, and air fresheners [23]. Evidence suggests that exposure to
VOCs is associated with the development of AR and aggravation of AR symptoms [18].
Additionally, in a recent meta-analysis, sanitation workers exposed to high amounts of
chemicals and pollutants reported higher inflammatory and respiratory symptoms than
non-sanitation workers [24].

2.1. Tobacco Smoke

Several studies have evaluated whether tobacco smoke exposure could cause AR,
as tobacco smoke has already been demonstrated to play a major negative impact on
global public health [6,25]. The prevalence of smoke exposure is very high worldwide, and
approximately 78% of children in Europe are exposed to secondhand smoke [6]. Moreover,
14% of adolescents aged 13 to 15 years are active smokers, and 25% have had their first
cigarette by the age of 10 years [6]. Tobacco exposure induces inflammatory and immune
responses [26].
Children 2021, 8, 708 3 of 12

A meta-analysis found that children actively smoking had an increased risk of AR,
while those exposed to second-hand smoke (passive smoking) had a much larger increased
risk for AR [6]. In a French epidemiological study, children actively smoking were almost
three times more likely to experience symptoms of AR than non-smoking children [19].
Maternal smoking was also found to contribute to AR development in the child. Because
children’s respiratory, nervous, and immune systems are not yet mature, children are more
susceptible to the health effects of smoking [6,27]. Tobacco smoke can upregulate airway
mucus production and impair mucociliary clearance, inducing low-grade inflammation
within the lungs [28]. Small changes in micro-environmental conditions can also affect
local microbiota within the respiratory system and promote airway remodeling [18]. Ex-
posure to tobacco smoke may also increase aeroallergen sensitization and exacerbate AR
symptoms [19]. A birth cohort study of over 4000 children followed for 16 years found that
exposure to secondhand smoke during infancy was associated with a 1.18 increased risk of
rhinitis up to 16 years of age, but exposure to secondhand smoke throughout childhood
was not associated with the development of rhinitis, suggesting an early window of sus-
ceptibility to SHS [29]. Moreover, the Irish International Study of Asthma and Allergies
in Childhood (ISAAC) study found that children ages 13–14 years who were exposed
to secondhand smoke were significantly more likely to have symptoms of AR with an
adjusted OR 1.35 (95% CI 1.08–1.70) [30]. In a 2020 study of university students and staff,
tobacco smoke appeared to increase nasal resistance and worsen inflammation in AR
patients [19]. Additionally, another study found that tobacco causes an increase in IL-33,
a driver of Th2-oriented cytokines necessary to activate inflammatory cells and regulate
immunity [31].

2.2. Indoor Allergens

House dust mites (HDM), molds, and pet dander are common examples of indoor
allergens [18]. Indoor allergens cause more severe allergy symptoms than outdoor al-
lergens [18]. Longitudinal data collected between 2006 and 2017 suggest that exposure
to molds is tightly linked to the development and exacerbation of symptoms of AR in
children [32].
A meta-analysis suggests that the risk for AR is significantly increased with exposure to
home dampness and mold [33]. Dampness is present in around 15% of households, which
can lead to the development of mold and infestation of cockroaches [16]. Because mold
can stimulate inflammation in airways due to metabolites like glucans and mycotoxins,
mold odor and visible mold increase the risk for development of AR [18,33]. Specific molds
such as Penicillium, Alternaria, and Cladosporium are known to be associated with the
development of AR [9]. Moreover, water damaged environments can be hazardous because
they release mycotoxins, leading to respiratory tract disease, while fungal colonies can
release antigens and toxins through fungal fragments [9].
Additionally, HDM are perpetual triggers for airway allergy [16]. Data have shown
that 1 to 2 percent of the global population is sensitized to HDM [34]. HDM can be found
in household dust, mattresses, pillows, bed linens, floor carpeting, upholstered furniture,
and unwashed clothing [9]. Larger populations of HDM will be found in places of higher
humidity [34]. Although not always a linear correlation, AR development and exacerbation
are linked to HDM exposure [34]. Sensitization to HDM in newborns and school children
can promote AR later in life [9,16]. When following newborn children for the first 3 years
of life, the development of AR increased when exposed to major HDM allergens, as shown
by the German Multicentre Allergy Study [34].
Animal-derived allergens are one of the most common sources of aeroallergens and
triggers for AR with over 15% of the world’s population sensitized to furred animals
with a high rate of cross-reactivity within species [18,35]. Cats, dogs, mice, and other
animals produce allergens that are often prevalent in proximity to metropolitan areas, and
these allergens can linger after the removal of the animals or pets and continue to cause
symptoms [35]. Cat dander, specifically, can linger 6–9 months after removal of the cat [36].
Children 2021, 8, 708 4 of 12

Nevertheless, some studies have shown that children exposed to cat and dog dander have a
lower prevalence of allergic sensitization, suggesting that early exposure to allergens could
actually be protective against sensitization [37]. Adults, however, have consistently had a
significantly higher prevalence of AR symptoms when exposed to dog and cat dander [37].

3. Outdoor Exposures
The major outdoor exposures that play a role in AR include outdoor air pollution
and pollen. Outdoor air pollution caused by traffic, which produces ozone (O3 ), NO2 ,
sulfur dioxide (SO2 ), and particulate matter (PM), contributes to AR development and
symptoms in children [6,18]. Air pollution affects human health by making some plants
more allergenic while contributing to global warming [18]. Climate change has critical
influences on airborne allergens and outdoor pollution, while exposure to greenness
appears to protect against AR.

3.1. Outdoor Air Pollution

Outdoor air pollution is known to affect immune competency and airway responsive-
ness, increasing the risk of AR in children [8]. Because airways are one of the major parts of
the body that are exposed to the environment, the measure of all environmental exposures
capable of influencing human health, also known as the exposome, can greatly affect the
homeostasis of respiratory tract [18]. When changes occur in the local environment of the
respiratory tract, which houses a variety of bacteria, viruses, and fungi, long lasting bacte-
rial dysbiosis may result [18]. Low O3 concentrations and NO2 can cause inflammation of
the human nasal mucosa in cell studies, and atrophy or pre-existing inflammation increases
the sensitivity to these gases, increasing susceptibility to AR [8]. O3 can also trigger the
cellular membrane of nasal epithelia to release cytokines and arachidonic acid metabolites,
upregulating local inflammation [9]. Furthermore, exposure to PM can lead to oxidative
stress, airway hyperresponsiveness, and airway remodeling [8]. In children living close
to industrial sources, SO2 released from petroleum is associated with acute respiratory
symptoms [9].
The exposome, which accounts simultaneously for all internal and external exposures,
is associated with the development of and exacerbations from AR [38]. The external
exposome includes exposure to (1) external environmental factors, such as in utero smoking,
bio-contaminants (e.g., viruses), air pollutants, diet, allergens (e.g., pollens, molds, pets),
and consumer products and (2) nonspecific general exposures, such as climate, biodiversity
(e.g., greenspace), and social dimension, and mobility [38]. The internal exposome is
specific to each subject and includes transcriptomics, adductomics, metabolomics, and
proteomics. Together, the external and internal exposomes contribute to the risk of AR and
other allergic diseases [38].
The responses that individuals with AR have to allergens differ from healthy indi-
viduals [9]. For example, individuals with seasonal AR experience higher levels of nasal
congestion than individuals without AR when exposed to chlorine gas in a controlled cham-
ber [9]. Furthermore, allergic reactions can be aggravated when small sized PM enter the
upper respiratory tract and mucosal barrier because PM can act as allergen carriers [8,39].

3.2. Traffic Related Air Pollution (TRAP)

TRAP is the combination of black carbon from diesel exhaust, nitrous oxides from
general traffic, carbon monoxide from petrol exhaust, zinc from automobile brakes, and
copper from tires [9,40]. In the Sydney metropolitan area, a study examined the response
of primary murine and human airway epithelial cells (AECs) to TRAP or ambient PM
and demonstrated that ambient PM10 caused stronger secretion of IL-6 and CXCL1 by
AECs [18]. In addition, a study of 2598 children suggested that TRAP exposure in utero
and the first year of life may lead to the development of AR in preschool children [3]. In
another study following children exposed to TRAP at birth until age 4 years, it was found
that those exposed to diesel exhaust particles at age 1 years were sensitized to aeroallergens
Children 2021, 8, 708 5 of 12

at ages 2 and 3 years [41]. Some studies with close proximity to traffic pollution have
demonstrated an increased risk of exacerbation of respiratory symptoms; however, other
long-term studies have failed to demonstrate any positive association [42].

3.3. Pollen
Birch pollen is the most common tree pollen in Northern and Central Europe and
is prevalent throughout the Northern hemisphere [43]. Birch pollen is a major cause of
AR, and the prevalence of sensitization to birch pollen has risen recently, contributing to
prolonged AR symptoms due to cross-reactivity with other plant allergens [43]. Alder,
hazelnut, hornbeam, oak, chestnut, and beech trees are all associated with AR, likely
because these trees are part of the Fagles and Betulaceae families, similar to birch [44].
Additionally, approximately 70% of individuals with birth pollen allergies experience
pollen food syndrome, where ingestion of raw fruits, vegetables, roots, and nuts lead to
localized IgE-mediated symptoms due to cross-reactivity between aeroallergens and food
allergens [45,46]. Multiple studies suggest that higher surrounding pollen concentration is
associated with increased AR symptoms severity [47,48].
Studies have inconsistently demonstrated that urban dwellings pose a higher risk of
AR than suburban dwellings because of the loss of biodiversity with urbanization [18,38].
With high CO2 concentrations in urban areas, plants such as ragweed can flower earlier,
resulting in longer pollen seasons and the production of more pollen [49]. Pollen grains
and fungal spores also contain bioactive elements that can exert inflammatory and allergic
effects, increasing rates of AR in children [50]. Additionally, in a study with 1360 Italian
children, the average age of onset of pollen-induced AR was 5.3 years (SD ± 2.8), and the
average disease duration was 5.2 years (SD ± 3.3) [11]. In this study, 6.2% of the children
had pollen monosensitization, while 84.9% were sensitized to at least three pollen extracts,
most commonly timothy grass or olive tree pollen [11]. The majority of the children had
AR symptoms during the spring; however, some patients reported symptoms during the
fall as well [11]. Furthermore, in a Swedish study of 764 children, IgE sensitization to Bet
v 1, the major birch tree allergen, in early childhood, was a predictor of AR by the age of
16 years [51]. A German study showed that birch trees exposed to higher concentrations
of O3 produced more birch allergen and pollen associated lipid mediators (PALMs) per
pollen grain than the ozone free trees [52]. PALMs activate Th2 cells and promote IgE
synthesis [53]. Moreover, on skin prick tests in AR patients, extract from the O3 exposed
trees demonstrated a larger wheal diameter than the less exposed trees [18].

3.4. Climate Change

Climate change, long-term shifts in weather patterns including changes in tempera-
ture, has an impact on respiratory allergies because changes in meteorological variables
affect the prevalence of airborne allergens and ambient pollution [54]. Currently, as envi-
ronmental conditions are altered due to climate change, AR in children is increasing [8].
Mathematical simulation studies suggest that climate change will increase the severity of
AR by up to 60% [55]. The majority of today’s global energy is generated by burning fossil
fuels, releasing CO2 , methane, black carbon, nitrogen oxides, and sulfate aerosols into the
environment [56–58]. Greenhouse gases keep the earth warm by absorbing the sun’s energy
and redirecting it back to the earth’s surface; however, an overabundance of the gases traps
an excessive amount of heat in the atmosphere, resulting in global warming [59]. Climate
change also influences the amount and type of pollutants in the air, which interact with
altered levels of aeroallergens [18].
The seasonality and severity of AR are affected by the growth patterns of different
allergenic species, and global warming and air pollution are known to affect these pat-
terns [18]. Global warming changes local vegetation patterns and increases the growth
rate of plants, increasing airborne pollen concentrations [60]. Different North American
and European studies have interlinked climate change with the increased duration of the
ragweed pollen season [49]. Birch pollen levels have risen over the past few decades due
Children 2021, 8, 708 6 of 12

to climate change [43]. Additionally, climate change has contributed to alterations in the
geographical spread of plants [61]. For example, ragweed is a native North American plant
but is now invading several European areas [61]. The colonization of these new areas by
novel species is suspected to induce respiratory symptoms by de novo sensitization and
cross-reactivity with pre-existing species [62]. Moreover, climate change causes more fre-
quent extreme climate events, including intensive rain and flooding, which can lead to the
deterioration of indoor air quality by promoting dampness and mold [63]. Heavy rainfall
and thunderstorms can also increase the atmospheric concentration of allergenic particles,
increasing airway inflammation [63]. Climate change is implicated in the worsening of
symptoms and increased frequency of use of medication to control AR symptoms [64].

3.5. Greenness
Greenness, areas with increased presence of trees and green spaces, helps mitigate air
pollution [65]. Greenness can protect individuals by removing PM, CO, CO2 , NO2 , O3 , and
SO2 , from air pollution [66]. During a plant’s life cycle, 0.5 to 6 tons of excess atmospheric
CO2 can be consumed [67]. In 2008, a Spanish ecological study found that trees and shrubs
removed 305.6 tons of pollutants (166 tons of PM10 , 73 tons of O3 , 55 tons of NO2 , 7 tons of
SO2 and 6 tons of CO) [68]. Species with excellent removal of outdoor air pollution include
elm trees, common ash, wild lime trees, verrucous birch, curly maple, and hackberry [69].
The Normalized Difference Vegetation Index (NDVI) uses different intensities of reflected
and near-infrared light to estimate the density of chlorophyll containing vegetation [70].
NDVI ranges from −1 to +1, with positive values indicating high greenness [70]. Healthy
vegetation reflects more near-infrared and green light, while it absorbs more red and blue
light [70]. Overall, children residing in places with less greenness have higher prevalence
of AR [70].
Although findings from studies of greenness are inconsistent, greater greenness may
prevent AR and its symptoms [66,71]. A possible contributing factor is mountain soil, due
to the diverse microbial communities it contains that confer a protective effect against AR in
children in settings with soil exposure [72]. Additionally, having a garden at home may be
associated with a decreased likelihood of AR because gardens provide a nearby bio-diverse
neighborhood and rich density of outdoor microbiota [73]. A larger distance to nature was
associated with more AR symptoms likely related to higher levels of NO2 based on an
Austrian study [74]. Furthermore, greater NDVI and tree cover (surfaces covered by woody
vegetation taller than 5 m) were marginally associated with fewer AR symptoms, as NO2
levels are lower [74]. A study that followed adults sensitized to Betulaceae pollen during
tree pollen season assessed exposure to green space and allergenic trees while tracking
daily symptom severity scores [75]. The study concluded that exposure to green space may
decrease tree pollen allergy symptom severity but only when the density of allergenic trees
is low [75].

4. Viruses
Viruses, such as adenoviruses, coronaviruses, influenza viruses, parainfluenza viruses,
rhinoviruses, and respiratory syncytial viruses, trigger upper respiratory infections (URI),
which are the most common infections in humans [76]. Viral infections can lead to both
the development and exacerbation of AR [76]. Viral infections activate the immune system
and contribute to both an enhancing effect, exacerbating symptoms of AR, and protective
effect, decreasing the chance of allergic development [77]. Furthermore, symptoms of a
viral respiratory illness can be more pronounced in individuals with a history of AR [76].
Rhinovirus infection has been shown to increase early and late phase reactions to
allergens and, thus, may promote the development of allergic airway disease [76]. In a
study of 38 individuals with and without seasonal AR, subjects with AR had an earlier
onset of sneezing, nasal congestion, delayed mucociliary clearance, and eustachian tube
obstruction after being infected with Rhinovirus 39 (RV39), but there was no statistical
difference in the magnitude, frequency, or duration of symptoms between the allergic
Children 2021, 8, 708 7 of 12

and nonallergic subjects [78]. Furthermore, total serum IgE levels acutely increased from
baseline in RV39 infected AR patients compared to RV39 infected non-AR patients [79].
When observing the effect of RV39 infection on nasal responsiveness to histamine and
cold air, allergic subjects experienced twice as much sneezing, rhinorrhea, and secretions
prior to RV39 infection, and both subjects with AR and non-AR experienced an increase in
sneezing and secretions to intranasal histamine challenge after RV39 infection [80].

5. Prevention and Treatment of Allergic Rhinitis

5.1. Indoor strategies
For prevention of AR, general allergen and pollution avoidance are recommended
when possible [9]. Nasal filters and blockers act as nasal mucosal barriers and can be a
useful alternative for some individuals [9]. Additionally, circulating air when indoors
is important, as indoor air pollutants can be reduced by improving outdoor and indoor
air exchange [9]. In addition to central heating, ventilation, and air conditioning (HVAC)
systems, high efficiency particulate air (HEPA) filters can be used to extract 0.3 µm size
particles to help reduce allergic triggers [9]. Surgical and N95 masks filter particles with
sizes of 3 µm or 0.04 µm, respectively [35]. Extracting inhaled airborne allergens such as
pollen, fungal spores, and HDM can significantly decrease IgE-mediated immunologic
responses [35]. Hardwood floors, new mattresses and carpets, and bedrooms on higher
floors can help reduce HDM concentration and reduce AR [34]. Spending time outdoors in
clean air has also been associated with a lower prevalence of AR symptoms [74].

5.2. Outdoor Strategies

Multiple studies have shown that exposure to clean air helps decrease the prevalence
of AR in children. For example, a retrospective study conducted between 1997 and 2006
found that a decrease in NO2 , PM, and CO correlated with a yearly decrease in rates
of AR [9]. Smoke-free legislation has been adopted in many countries and has been
demonstrated to be associated with an improvement in overall child health, although
allergic rhinitis was not specifically studied [81].
Air pollution monitoring is essential to help prevent the development and exacerbation
of AR in individuals as well. Many countries are now enforcing new policies to help with
the prevention of climate change, which in turn will help decrease the onset of AR and
aggravation of symptoms. The European Union’s framework for environmental policy
has already significantly contributed to diminishing the emissions of air pollutants and
improving air quality across Europe [18]. Moreover, environmental performance standards
in Europe have been put in place for large combustion plants, limiting emission ranges
for NO, NO2 , SO2 , PM, and mercury [18]. In the United States, the Clean Air Act has
been established to help improve air quality by regulating hazardous air pollutants [9].
Another prevention method that has become more popular recently is shifting from private
motorized transport to public transport, cycling, or walking to help reduce greenhouse
gases [18].

5.3. Phamacotherapeutic Strategies

A variety of treatment options for AR symptoms exist. The most commonly used
pharmacotherapy for AR is oral antihistamines with a preference for second-generation
antihistamines (e.g., cetirizine, levocetirizine, fexofenadine, loratadine, desloratadine) over
first-generation antihistamines (e.g., diphenhydramine, hydroxyzine, chlorpheniramine)
because of fewer side effects related to sedation, disrupted sleep, and anticholinergic
symptoms [12,82]. Intranasal corticosteroids, which decrease the inflammatory cells and
inhibit the release of cytokines, decreasing inflammation of the nasal mucosa, are recom-
mended as the initial treatment for AR, as they have been found to be equally or more
effective than oral antihistamines [12,82,83]. Other pharmacologic treatment options for
AR include intranasal corticosteroids, intranasal or ocular antihistamines, decongestants,
intranasal cromolyn, intranasal anticholinergics, oral leukotriene receptor antagonists, and
Children 2021, 8, 708 8 of 12

oral corticosteroids; however, intranasal cromolyn and decongestants are not always suit-
able for young children [82,83]. AR symptoms may be controlled with monotherapy, but
combination therapy is necessary in patients with persistent or severe symptoms [82,83].
Some epidemiological data suggest that the intake of dietary antioxidants may de-
crease the prevalence of AR [9]. Some studies have suggested that vitamin D supplementa-
tion in conjunction with antihistamines may improve treatment response; however, the role
of vitamin D in allergic rhinitis has not been definitively established [84,85]. An anti-IgE
antibody, omalizumab (Xolair), is effective in reducing nasal symptoms in AR patients as
well, although it is not currently approved by the Food and Drug Administration for this
indication [83]. The only intervention that can modify AR is specific immunotherapy with
aeroallergen extracts (e.g., cat, dog, molds, cockroach, mice, dust mites, pollens, etc.) [11].
Immunotherapy can be considered for patients with moderate or severe AR that is not
responsive to typical AR treatments or for patients who wish to avoid or reduce long-term
medication use [82]. Targeted immunotherapy consists of patients visiting a physician’s
office at regular intervals (typically initially weekly for build-up, then monthly for 3–5 years
for maintenance therapy) to receive a small amount of allergen extract subcutaneously
or sublingually [83]. Subcutaneous immunotherapy may be more efficacious than sub-
lingual immunotherapy but is less convenient as subcutaneous immunotherapy should
be administered in the medical office for monitoring of anaphylaxis, whereas sublingual
immunotherapy can be administered at home after the initial dose [83]. A further benefit
of allergen immunotherapy in children is that it may prevent asthma onset in children with
allergic rhinitis [82].

5.4. Knowledge Gaps

Future studies could help advance prevention and treatment of AR in children. First,
definitive studies of whether vitamin D supplementation could treat AR are needed as
vitamin D is an inexpensive, simple intervention. The development of new treatments to
mitigate or counteract the effects of environmental pollutants on the immunologic regula-
tion of AR can also be considered. More importantly, strategies to reduce environmental
factors associated with AR need to be more aggressively studied and implemented. Finally,
additional studies demonstrating the positive impact that environmental policies have on
health, including prevention of AR, may help policy makers make decisions.

6. Conclusions
Lifestyle and environmental factors play an important role in the development of
allergic rhinitis, one of the most common chronic conditions in the world. Specifically,
indoor air pollution, such as HDM, tobacco smoke, and pet dander can significantly in-
crease the onset of AR. Moreover, outdoor air pollution, including TRAP and pollen can
increase the risk of AR in children. Preventive measures for AR control through environ-
mental protection policies also have great promise to improve public health. Additionally,
viruses may increase the risk and exacerbate the symptoms of AR. The avoidance of these
environmental triggers may reduce the development of AR and AR symptoms.

Author Contributions: Conceptualization, A.C.W., A.D., and A.L.W.; writing—original draft prepa-
ration, A.C.W.; writing—review and editing, A.D. and A.L.W.; visualization, A.C.W.; supervision,
A.D. and A.L.W. All authors have read and agreed to the published version of the manuscript.
Funding: Dr. Dahlin is funded by NHLBI R01 HL-152244. Dr. Wang is funded by NIH NHLBI
K23HL151819.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest. The funding agencies had no role in
the design of this review.
Children 2021, 8, 708 9 of 12

References
1. Bousquet, J.; Anto, J.M.; Bachert, C.; Baiardini, I.; Bosnic-Anticevich, S.; Canonica, G.W.; Melén, E.; Palomares, O.; Scadding, G.K.;
Togias, A.; et al. Allergic rhinitis. Nat. Rev. Dis. Primers 2020, 6, 95. [CrossRef]
2. Colás, C.; Brosa, M.; Antón, E.; Montoro, J.; Navarro, A.; Dordal, T.; Dávila, I.; Fernández-Parra, B.; Ibáñez, M.D.P.; Lluch-Bernal,
M.; et al. Estimate of the total costs of allergic rhinitis in specialized care based on real-world data: The FERIN study. Allergy 2017,
72, 959–966. [CrossRef]
3. Deng, Q.; Lu, C.; Yu, Y.; Li, Y.; Sundell, J.; Norbäck, D. Early life exposure to traffic-related air pollution and allergic rhinitis in
preschool children. Respir. Med. 2016, 121, 67–73. [CrossRef]
4. Meltzer, E.O.; Blaiss, M.S.; Derebery, M.J.; Mahr, T.A.; Gordon, B.R.; Sheth, K.K.; Simmons, A.L.; Wingertzahn, M.A.; Boyle, J.M.
Burden of allergic rhinitis: Results from the pediatric allergies in America survey. J. Allergy Clin. Immunol. 2009, 124, S43–S70.
[CrossRef] [PubMed]
5. Newacheck, P.W.; Stoddard, J.J. Prevalence and impact of multiple childhood chronic illnesses. J. Pediatr. 1994, 124, 40–48.
[CrossRef]
6. Saulyte, J.; Regueira, C.; Montes-Martínez, A.; Khudyakov, P.; Takkouche, B. Active or passive exposure to tobacco smoking and
allergic rhinitis, allergic dermatitis, and food allergy in adults and children: A systematic review and meta-analysis. PLoS Med.
2014, 11, e1001611. [CrossRef] [PubMed]
7. Drazdauskaitė, G.; Layhadi, J.A.; Shamji, M.H. Mechanisms of allergen immunotherapy in allergic rhinitis. Curr. Allergy Asthma
Rep. 2021, 21, 1–17. [CrossRef]
8. Zou, Q.-Y.; Shen, Y.; Ke, X.; Hong, S.-L.; Kang, H.-Y. Exposure to air pollution and risk of prevalence of childhood allergic rhinitis:
A meta-analysis. Int. J. Pediatr. Otorhinolaryngol. 2018, 112, 82–90. [CrossRef]
9. Naclerio, R.; Ansotegui, I.J.; Bousquet, J.; Canonica, G.W.; d’Amato, G.; Rosario, N.; Pawankar, R.; Peden, D.; Bergmann, K.C.;
Bielory, L.; et al. International expert consensus on the management of allergic rhinitis (AR) aggravated by air pollutants: Impact
of air pollution on patients with AR: Current knowledge and future strategies. World Allergy Organ. J. 2020, 13, 100106. [CrossRef]
10. Chawes, B.; Kreiner-Moller, E.; Bisgaard, H. Objective Assessments of allergic and non-allergic rhinitis in young children. In
Proceedings of the American Thoracic Society 2009 International Conference, San Diego, CA, USA, 15–20 May 2009; pp. 1547–1553.
[CrossRef]
11. Dondi, A.; Tripodi, S.; Panetta, V.; Asero, R.; Businco, A.D.R.; Bianchi, A.; Carlucci, A.; Ricci, G.; Bellini, F.; Maiello, N.; et al.
Pollen-induced allergic rhinitis in 1360 Italian children: Comorbidities and determinants of severity. Pediatr. Allergy Immunol.
2013, 24, 742–751. [CrossRef]
12. Dykewicz, M.S.; Wallace, D.V.; Amrol, D.J.; Baroody, F.M.; Bernstein, J.A.; Craig, T.J.; Dinakar, C.; Ellis, A.K.; Finegold, I.; Golden,
D.B.; et al. Rhinitis 2020: A practice parameter update. J. Allergy Clin. Immunol. 2020, 146, 721–767. [CrossRef]
13. Moya, J.; Bearer, C.F.; Etzel, R.A. Children’s behavior and physiology and how it affects exposure to environmental contaminants.
Pediatrics 2004, 113, 996–1006. [PubMed]
14. Jiang, F.; Yan, A. IL-4 rs2243250 polymorphism associated with susceptibility to allergic rhinitis: A meta-analysis. Biosci. Rep.
2021, 41. [CrossRef] [PubMed]
15. World Health Organization. Update of WHO Global Air Quality Guidelines; World Health Organization: Geneva, Switzerland, 2016.
16. Schraufnagel, D.E.; Balmes, J.R.; Cowl, C.T.; De Matteis, S.; Jung, S.H.; Mortimer, K.; Perez-Padilla, R.; Rice, M.B.; Riojas-Rodriguez,
H.; Sood, A.; et al. Air pollution and noncommunicable diseases: A review by the forum of international respiratory societies’
environmental committee, part 2: Air pollution and organ systems. Chest 2019, 155, 417–426. [CrossRef] [PubMed]
17. Canonica, G.W.; Tarantini, F.; Compalati, E.; Penagos, M. Efficacy of desloratadine in the treatment of allergic rhinitis: A
meta-analysis of randomized, double-blind, controlled trials. Allergy 2007, 62, 359–366. [CrossRef] [PubMed]
18. Eguiluz-Gracia, I.; Mathioudakis, A.G.; Bartel, S.; Vijverberg, S.J.H.; Fuertes, E.; Comberiati, P.; Cai, Y.S.; Tomazic, P.V.; Diamant,
Z.; Vestbo, J.; et al. The need for clean air: The way air pollution and climate change affect allergic rhinitis and asthma. Allergy
2020, 75, 2170–2184. [CrossRef]
19. Songnuy, T.; Scholand, S.J.; Panprayoon, S. Effects of tobacco smoke on aeroallergen sensitization and clinical severity among
university students and staff with allergic rhinitis. J. Environ. Public Health 2020, 2020, 1–7. [CrossRef]
20. Simoni, M.; Annesi-Maesano, I.; Sigsgaard, T.; Norbäck, D.; Wieslander, G.; Nystad, W.; Canciani, M.; Sestini, P.; Viegi, G. School
air quality related to dry cough, rhinitis and nasal patency in children. Eur. Respir. J. 2010, 35, 742–749. [CrossRef]
21. Ruggieri, S.; Longo, V.; Perrino, C.; Canepari, S.; Drago, G.; L’Abbate, L.; Balzan, M.; Cuttitta, G.; Scaccianoce, G.; Minardi, R.;
et al. Indoor air quality in schools of a highly polluted south Mediterranean area. Indoor Air 2018, 29, 276–290. [CrossRef]
22. Azizi, B.H.I.; Zulkifli, H.; Kasim, S. Indoor air pollution and asthma in hospitalized children in a tropical environment. J. Asthma
1995, 32, 413–418. [CrossRef]
23. Logue, J.M.; Klepeis, N.; Lobscheid, A.B.; Singer, B.C. Pollutant exposures from natural gas cooking burners: A simulation-based
assessment for Southern California. Environ. Health Perspect. 2014, 122, 43–50. [CrossRef] [PubMed]
24. Zolnikov, T.R.; Furio, F.; Cruvinel, V.; Richards, J. A systematic review on informal waste picking: Occupational hazards and
health outcomes. Waste Manag. 2021, 126, 291–308. [CrossRef]
25. Gómez, R.M.; Croce, V.H.; Zernotti, M.E.; Muiño, J.C. Active smoking effect in allergic rhinitis. World Allergy Organ. J. 2021, 14,
100504. [CrossRef] [PubMed]
Children 2021, 8, 708 10 of 12

26. Lee, A.; Lee, S.Y.; Lee, K.-S. The use of heated tobacco products is associated with asthma, allergic rhinitis, and atopic dermatitis
in Korean adolescents. Sci. Rep. 2019, 9, 1–8. [CrossRef]
27. Singh, S.; Sharma, B.B.; Salvi, S.; Chhatwal, J.; Jain, K.C.; Kumar, L.; Joshi, M.K.; Pandramajal, S.B.; Awasthi, S.; Bhave, S.; et al.
Allergic rhinitis, rhinoconjunctivitis, and eczema: Prevalence and associated factors in children. Clin. Respir. J. 2018, 12, 547–556.
[CrossRef]
28. Nikasinovic, L.; Momas, I.; Seta, N. Nasal epithelial and inflammatory response to ozone exposure: A review of laboratory-based
studies published since 1985. J. Toxicol. Environ. Health Part B 2003, 6, 521–568. [CrossRef] [PubMed]
29. Thacher, J.D.; Gruzieva, O.; Pershagen, G.; Neuman, Å.; Wickman, M.; Kull, I.; Melén, E.; Bergström, A. Pre and postnatal
exposure to parental smoking and allergic disease through adolescence. Pediatrics 2014, 134, 428–434. [CrossRef]
30. Kabir, Z.; Manning, P.J.; Holohan, J.; Keogan, S.; Goodman, P.G.; Clancy, L. Second-hand smoke exposure in cars and respiratory
health effects in children. Eur. Respir. J. 2009, 34, 629–633. [CrossRef]
31. Grillo, C.; La Mantia Ignazio, M.; Giorgio, C.; Martina, R.; Claudio, A. Influence of cigarette smoking on allergic rhinitis: A
comparative study on smokers and non-smokers. Acta Biomed. 2019, 90, 45–51.
32. Caillaud, D.; Leynaert, B.; Keirsbulck, M.; Nadif, R. Indoor mould exposure, asthma and rhinitis: Findings from systematic
reviews and recent longitudinal studies. Eur. Respir. Rev. 2018, 27, 170137. [CrossRef]
33. Jaakkola, M.S.; Quansah, R.; Hugg, T.; Heikkinen, S.A.; Jaakkola, J. Association of indoor dampness and molds with rhinitis risk:
A systematic review and meta-analysis. J. Allergy Clin. Immunol. 2013, 132, 1099–1110.e18. [CrossRef] [PubMed]
34. Calderón, M.A.; Linneberg, A.; Kleine-Tebbe, J.; De Blay, F.; de Rojas, D.H.F.; Virchow, J.C.; Demoly, P. Respiratory allergy caused
by house dust mites: What do we really know? J. Allergy Clin. Immunol. 2015, 136, 38–48. [CrossRef]
35. Dror, A.A.; Eisenbach, N.; Marshak, T.; Layous, E.; Zigron, A.; Shivatzki, S.; Morozov, N.G.; Taiber, S.; Alon, E.E.; Ronen, O.; et al.
Reduction of allergic rhinitis symptoms with face mask usage during the COVID-19 pandemic. J. Allergy Clin. Immunol. Pract.
2020, 8, 3590–3593. [CrossRef]
36. Shah, R.; Grammer, L.C. Chapter 1: An overview of allergens. Allergy Asthma Proc. 2012, 33, 2–5. [CrossRef]
37. Shargorodsky, J.; Umanskiy, R.; Lin, S.Y.; Navas-Acien, A.; Garcia-Esquinas, E. Household pet exposure, allergic sensitization,
and rhinitis in the U.S. population. Int. Forum Allergy Rhinol. 2017, 7, 645–651. [CrossRef] [PubMed]
38. Cecchi, L.; D’Amato, G.; Annesi-Maesano, I. External exposome and allergic respiratory and skin diseases. J. Allergy Clin. Immunol.
2018, 141, 846–857. [CrossRef] [PubMed]
39. Ormstad, H. Suspended particulate matter in indoor air: Adjuvants and allergen carriers. Toxicology 2000, 152, 53–68. [CrossRef]
40. Atkinson, R.W.; Analitis, A.; Samoli, E.; Fuller, G.W.; Green, D.; Mudway, I.S.; Anderson, H.R.; Kelly, F.J. Short-term exposure to
traffic-related air pollution and daily mortality in London, UK. J. Expo. Sci. Environ. Epidemiol. 2015, 26, 125–132. [CrossRef]
41. Codispoti, C.D.; Lemasters, G.K.; Levin, L.; Reponen, T.; Ryan, P.H.; Myers, J.B.; Villareal, M.; Burkle, J.; Evans, S.; Lockey, J.E.;
et al. Traffic pollution is associated with early childhood aeroallergen sensitization. Ann. Allergy Asthma Immunol. 2015, 114,
126–133.e3. [CrossRef]
42. Porebski, G.; Woźniak, M.; Czarnobilska, E. Residential proximity to major roadways is associated with increased prevalence of
allergic respiratory symptoms in children. Ann. Agric. Environ. Med. 2014, 21, 760–766. [CrossRef]
43. Biedermann, T.; Winther, L.; Till, S.J.; Panzner, P.; Knulst, A.; Valovirta, E. Birch pollen allergy in Europe. Allergy 2019, 74,
1237–1248. [CrossRef] [PubMed]
44. Niederberger, V.; Pauli, G.; Grönlund, H.; Fröschla, R.; Rumpold, H.; Kraft, D.; Valenta, R.; Spitzauer, S. Recombinant birch pollen
allergens (rBet v 1 and rBet v 2) contain most of the IgE epitopes present in birch, alder, hornbeam, hazel, and oak pollen: A
quantitative IgE inhibition study with sera from different populations. J. Allergy Clin. Immunol. 1998, 102, 579–591. [CrossRef]
45. Geroldinger-Simic, M.; Zelniker, T.; Aberer, W.; Ebner, C.; Egger, C.; Greiderer, A.; Prem, N.; Lidholm, J.; Ballmer-Weber, B.K.;
Vieths, S.; et al. Birch pollen-related food allergy: Clinical aspects and the role of allergen-specific IgE and IgG4 antibodies. J.
Allergy Clin. Immunol. 2011, 127, 616–622. [CrossRef]
46. Siekierzynska, A.; Piasecka-Kwiatkowska, D.; Myszka, A.; Burzynska, M.; Sozanska, B.; Sozanski, T. Apple allergy: Causes and
factors influencing fruits allergenic properties–review. Clin. Transl. Allergy 2021, 11, e12032. [CrossRef] [PubMed]
47. De Weger, L.A.; Hiemstra, P.S.; Buysch, E.O.D.; van Vliet, A. Spatiotemporal monitoring of allergic rhinitis symptoms in the
Netherlands using citizen science. Allergy 2014, 69, 1085–1091. [CrossRef] [PubMed]
48. Pfaar, O.; Karatzas, K.; Bastl, K.; Berger, U.; Buters, J.; Darsow, U.; Demoly, P.; Durham, S.R.; Galán, C.; Gehrig, R.; et al. Pollen
season is reflected on symptom load for grass and birch pollen-induced allergic rhinitis in different geographic areas—an EAACI
task force report. Allergy 2019, 75, 1099–1106. [CrossRef]
49. Ziska, L.H.; Gebhard, D.E.; Frenz, D.A.; Faulkner, S.; Singer, B.; Straka, J.G. Cities as harbingers of climate change: Common
ragweed, urbanization, and public health. J. Allergy Clin. Immunol. 2003, 111, 290–295. [CrossRef] [PubMed]
50. García-Mozo, H. Poaceae pollen as the leading aeroallergen worldwide: A review. Allergy 2017, 72, 1849–1858. [CrossRef]
51. Westman, M.; Lupinek, C.; Bousquet, J.; Andersson, N.; Pahr, S.; Baar, A.; Bergström, A.; Holmström, M.; Stjärne, P.; Carlsen,
K.C.L.; et al. Early childhood IgE reactivity to pathogenesis-related class 10 proteins predicts allergic rhinitis in adolescence. J.
Allergy Clin. Immunol. 2015, 135, 1199–1206.e11. [CrossRef] [PubMed]
52. Schmitz, R.; Ellert, U.; Kalcklösch, M.; Dahm, S.; Thamm, M. Patterns of sensitization to inhalant and food allergens—findings
from the german health interview and examination survey for children and adolescents. Int. Arch. Allergy Immunol. 2013, 162,
263–270. [CrossRef]
Children 2021, 8, 708 11 of 12

53. Reinmuth-Selzle, K.; Kampf, C.J.; Lucas, K.; Lang-Yona, N.; Fröhlich-Nowoisky, J.; Shiraiwa, M.; Lakey, P.; Lai, S.; Liu, F.; Kunert,
A.T.; et al. Air pollution and climate change effects on allergies in the anthropocene: Abundance, interaction, and modification of
allergens and adjuvants. Environ. Sci. Technol. 2017, 51, 4119–4141. [CrossRef] [PubMed]
54. D’Amato, G.; Vitale, C.; Rosário, N.; Neto, H.J.C.; Chong-Silva, D.C.; Mendonça, F.; Perini, J.; Landgraf, L.; Sole, D.; Sánchez-
Borges, M.; et al. Climate change, allergy and asthma, and the role of tropical forests. World Allergy Organ. J. 2017, 10, 11.
[CrossRef] [PubMed]
55. Kurganskiy, A.; Creer, S.; de Vere, N.; Griffith, G.W.; Osborne, N.J.; Wheeler, B.W.; McInnes, R.N.; Clewlow, Y.; Barber, A.; Brennan,
G.L.; et al. Predicting the severity of the grass pollen season and the effect of climate change in Northwest Europe. Sci. Adv. 2021,
7, eabd7658. [CrossRef] [PubMed]
56. Saxena, M.; Sharma, A.; Sen, A.; Saxena, P.; Mandal, T.K.; Sharma, S.K.; Sharma, C. Water soluble inorganic species of PM 10
and PM 2.5 at an urban site of Delhi, India: Seasonal variability and sources. In Atmospheric Research; Elsevier: Amsterdam, The
Netherlands, 2017.
57. Tiwari, S.; Srivastava, A.K.; Bisht, D.S.; Parmita, P.; Srivastava, M.K.; Attri, S.D. Diurnal and seasonal variations of black carbon
and PM2.5 over New Delhi, India: Influence of meteorology. In Atmospheric Research; Elsevier: Amsterdam, The Netherlands,
2013.
58. Wang, Y.; Zhang, Q.Q.; He, K.; Zhang, Q.; Chai, L. Sulfate-nitrateammonium aerosols over China: Response to 2000–2015 emission
changes of sulfur dioxide, nitrogen oxides, and ammonia. Atmos. Chem. Phys. 2013, 13, 2635–2652. [CrossRef]
59. Stocker, C. Climate change 2013: The physical science basis. In Working Group I Contribution to the IPCC Fifth Assessment Report;
Stocker, C., Ed.; Cambridge University Press: Cambridge, UK, 2013.
60. Ziello, C.; Sparks, T.; Estrella, N.; Belmonte, J.; Bergmann, K.C.; Bucher, E.; Brighetti, M.A.; Damialis, A.; Detandt, M.; Galán, C.;
et al. Changes to airborne pollen counts across Europe. PLoS ONE 2012, 7, e34076. [CrossRef]
61. Storkey, J.; Stratonovitch, P.; Chapman, D.S.; Vidotto, F.; Semenov, M.A. A Process-based approach to predicting the effect of
climate change on the distribution of an invasive allergenic plant in Europe. PLoS ONE 2014, 9, e88156. [CrossRef] [PubMed]
62. Pinkerton, K.E.; Rom, W.; Akpinar-Elci, M.; Balmes, J.R.; Bayram, H.; Brandli, O.; Hollingsworth, J.W.; Kinney, P.L.; Margolis,
H.G.; Martin, W.J.; et al. An official american thoracic society workshop report: Climate change and human health. Proc. Am.
Thorac. Soc. 2012, 9, 3–8. [CrossRef]
63. D’Amato, G.; Annesi-Maesano, I.; Cecchi, L.; D’Amato, M. Latest news on relationship between thunderstorms and respiratory
allergy, severe asthma, and deaths for asthma. Allergy 2019, 74, 9–11. [CrossRef]
64. D’Amato, M.; Molino, A.; Calabrese, G.; Cecchi, L.; Annesi-Maesano, I.; D’Amato, G. The impact of cold on the respiratory tract
and its consequences to respiratory health. Clin. Transl. Allergy 2018, 8, 20. [CrossRef]
65. March, D.; Williams, J.; Wells, S.; Eimicke, J.P.; Teresi, J.A.; Almonte, C.; Link, B.G.; Findley, S.E.; Palmas, W.; Carrasquillo, O.; et al.
Discrimination and depression among urban hispanics with poorly controlled diabetes. Ethn. Dis. 2015, 25, 130–137.
66. Franchini, M.; Mannucci, P.M. Mitigation of air pollution by greenness: A narrative review. Eur. J. Intern. Med. 2018, 55, 1–5.
[CrossRef]
67. Bowler, D.E.; Buyung-Ali, L.M.; Knight, T.M.; Pullin, A.S. A systematic review of evidence for the added benefits to health of
exposure to natural environments. BMC Public Health 2010, 10, 456. [CrossRef] [PubMed]
68. Chaparro, L.; Terradas, J. Ecological Services of Urban Forest in Barcelona; Institut Municipal de Parcs i Jardins Ajuntament de
Barcelona, Àrea de Medi Ambient: Barcelona, Spain, 2009.
69. ISO Emissions. Available online: http://www.es.lancs.ac.uk/cnhgroup/iso-emissions.pdf (accessed on 1 July 2021).
70. Gernes, R.; Brokamp, C.; Rice, G.E.; Wright, J.M.; Kondo, M.C.; Michael, Y.L.; Donovan, G.H.; Gatziolis, D.; Bernstein, D.;
LeMasters, G.K.; et al. Using high-resolution residential greenspace measures in an urban environment to assess risks of allergy
outcomes in children. Sci. Total Environ. 2019, 668, 760–767. [CrossRef] [PubMed]
71. Nieuwenhuijsen, M.J. Green infrastructure and health. Annu. Rev. Public Health 2021, 42, 317–328. [CrossRef] [PubMed]
72. Adamczyk, M.; Hagedorn, F.; Wipf, S.; Donhauser, J.; Vittoz, P.; Rixen, C.; Frossard, A.; Theurillat, J.-P.; Frey, B. The soil
microbiome of GLORIA mountain summits in the Swiss Alps. Front. Microbiol. 2019, 10, 1080. [CrossRef] [PubMed]
73. Parajuli, A.; Hui, N.; Puhakka, R.; Oikarinen, S.; Grönroos, M.; Selonen, V.A.; Siter, N.; Kramna, L.; Roslund, M.I.; Vari, H.K.; et al.
Yard vegetation is associated with gut microbiota composition. Sci. Total Environ. 2020, 713, 136707. [CrossRef] [PubMed]
74. Dzhambov, A.M.; Lercher, P.; Rüdisser, J.; Browning, M.H.; Markevych, I. Allergic symptoms in association with naturalness,
greenness, and greyness: A cross-sectional study in schoolchildren in the Alps. Environ. Res. 2021, 198, 110456. [CrossRef]
75. Stas, M.; Aerts, R.; Hendrickx, M.; Delcloo, A.; Dendoncker, N.; Dujardin, S.; Linard, C.; Nawrot, T.; Van Nieuwenhuyse, A.; Aerts,
J.-M.; et al. Exposure to green space and pollen allergy symptom severity: A case-crossover study in Belgium. Sci. Total Environ.
2021, 781, 146682. [CrossRef]
76. Fireman, P. Virus-provoked rhinitis in patients who have allergies. Allergy Asthma Proc. 2002, 23, 99–102.
77. Tantilipikorn, P. The relationship between allergic rhinitis and viral infections. Curr. Opin. Otolaryngol. Head Neck Surg. 2014, 22,
249–252. [CrossRef] [PubMed]
78. Doyle, W.J.; Skoner, D.P.; Fireman, P.; Seroky, J.T.; Green, I.; Ruben, F.; Kardatzke, D.R.; Gwaltney, J.M. Rhinovirus 39 infection in
allergic and nonallergic subjects. J. Allergy Clin. Immunol. 1992, 89, 968–978. [CrossRef]
79. Skoner, D.P.; Doyle, W.J.; Tanner, E.P.; Kiss, J.; Fireman, P. Effect of rhinovirus 39 (RV-39) infection on immune and inflammatory
parameters in allergic and non-allergic subjects. Clin. Exp. Allergy 1995, 25, 561–567. [CrossRef] [PubMed]
Children 2021, 8, 708 12 of 12

80. Doyle, W.J.; Skoner, D.P.; Seroky, J.T.; Fireman, P.; Gwaltney, J.M. Effect of experimental rhinovirus 39 infection on the nasal
response to histamine and cold air challenges in allergic and nonallergic subjects. J. Allergy Clin. Immunol. 1994, 93, 534–542.
[CrossRef]
81. Faber, T.; Kumar, A.; Mackenbach, J.P.; Millett, C.; Basu, S.; Sheikh, A.; Been, J.V. Effect of tobacco control policies on perinatal and
child health: A systematic review and meta-analysis. Lancet Public Health 2017, 2, e420–e437. [CrossRef]
82. Bousquet, J.; Pfaar, O.; Togias, A.; Schünemann, H.J.; Ansotegui, I.; Papadopoulos, N.G.; Tsiligianni, I.; Agache, I.; Anto, J.M.;
Bachert, C.; et al. 2019 ARIA care pathways for allergen immunotherapy. Allergy 2019, 74, 2087–2102. [CrossRef]
83. Sur, D.K.; Plesa, M.L. Treatment of allergic rhinitis. Am. Fam. Physician 2015, 92, 985–992.
84. Bhardwaj, B.; Singh, J. Efficacy of vitamin D supplementation in allergic rhinitis. Indian J. Otolaryngol. Head Neck Surg. 2021, 73,
152–159. [CrossRef]
85. Feng, Q.; Bønnelykke, K.; Ek, W.E.; Chawes, B.L.; Yuan, S.; Cheung, C.L.; Li, G.H.; Leung, R.Y.; Cheung, B.M. Null association
between serum 25-hydroxy vitamin D levels with allergic rhinitis, allergic sensitization and non-allergic rhinitis: A Mendelian
randomization study. Clin. Exp. Allergy 2021, 51, 78–86. [CrossRef]