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Contents lists available at ScienceDirect

International Journal of Hygiene and

Environmental Health
journal homepage: www.elsevier.com/locate/ijheh

Allergens, air pollutants, and childhood allergic diseases

I.-Jen Wang a,b,c,∗ , Tao-Hsin Tung d,e , Chin-Sheng Tang d , Zi-Hao Zhao d
a
Department of Pediatrics, Taipei Hospital, Ministry of Health and Welfare, Taipei, Taiwan
b
Institute of Environmental and Occupational Health Sciences, College of Medicine, National Yang-Ming University, Taipei, Taiwan
c
Department of Health Risk Management, China Medical University, Taichung, Taiwan
d
College of Public Health, Fu Jen Catholic University, Taipei, Taiwan
e
Department of Medical Research and Education, Cheng-Hsin General Hospital, Taiwan

a r t i c l e i n f o a b s t r a c t

Article history: Background: The synergistic effect of allergens and air pollutants on the risk of allergic diseases is unclear.
Received 27 May 2015 Objective: To evaluate the joint effect of outdoor pollutants and indoor allergens on the risk of allergic
Received in revised form 3 August 2015 diseases.
Accepted 9 September 2015
Methods: We enrolled 2661 kindergarten children from the CEAS cohort. Data on allergic diseases and
environmental exposure were collected. Skin prick tests were performed. Individual exposure to air
Keywords:
pollution was estimated using a geographic information system with the mean concentration of air
Air pollutant
pollutants. Multiple logistic regression analysis was performed to estimate the association between air
Allergen
Asthma
pollutants, allergen exposure and the risk of allergic diseases with adjustments for potential confounders.
Results: Overall, 12.6% of the children had asthma, 30.0% had allergic rhinitis (AR), and 14.4% had atopic
dermatitis (AD). Mite sensitization significantly increased the risk of AD, AR, and asthma (OR (95%CI) 2.15
(1.53–3.03), 1.94 (1.46–2.58), and 2.31 (1.63–3.29), respectively). Exposure to PM10 , PM2.5 , CO, and O3
was associated with asthma (OR (95% CI) 1.39 (1.03–1.87), 1.45 (1.07–1.97), 1.36 (1.01–1.83), and 0.68
(0.51–0.92), respectively). PM2.5 may have increased the risk of AR (OR (95% CI) 1.54 (1.03–2.32). Mite
sensitization showed a synergistic effect with PM2.5 on the development of asthma (p < 0.001). Moreover,
mite allergens may modify the effect of air pollutants on allergic diseases.
Conclusion: Dust mites and PM2.5 play an important role on the risk of asthma and AR. Exposure to
PM2.5 and mite allergens had a synergistic effect on the development of asthma. Avoiding co-exposure
to allergens and air pollutants is important.
© 2015 Elsevier GmbH. All rights reserved.

1. Introduction respiratory infections and may program respiratory morbidity in

Levels of traffic-related pollutants (TRAP) are increasing rapidly
across many Asian countries in parallel with the level of urbaniza-
tion and economic development (Leung et al., 2012). Air pollution
increases asthma symptoms, the use of medication, bronchocon-
striction, emergency room admissions and hospitalizations due
to pollutants such as ozone (O3 ), nitrogen dioxide (NO2 ) and
particulate matter (PM) (Sandström and Kelly, 2009). Prenatal
exposure to PM2.5 was reported to increase susceptibility to
Abbreviations: SO2 , sulfur dioxide; NO2 , nitrogen dioxide; O3 , ozone; CO, carbon
monoxide; PM10 , particulate matter ≤ 10 ␮m; PM2.5 , particulate matter ≤ 2.5 ␮m;
8hO3 , 8-h average ozone concentration; AD, atopic dermatitis; AR, allergic rhinitis.
∗ Corresponding author at: Department of Pediatrics, Taipei Hospital, Ministry of
Health and Welfare, No. 127, Su-Yuan Road, Hsin-Chuang Dist., New Taipei City 242,
Taiwan. Tel.: +886 2 2276 5566x2532; fax: +886 2 2998 8028.
E-mail address: wij636@gmail.com (I.-J. Wang).
early childhood (Jedrychowski et al., 2013). Children appear to be
most vulnerable to the harmful effects of ambient air pollutants. As
their lungs have not completely developed, they may experience
greater exposure to environmental pollutants than adults, and
a higher amount of these pollutants may remain in their lungs
for a greater duration (Tzivian, 2011). Particulate and gaseous
pollutants can act on both the upper and lower airways to initiate
and exacerbate cellular inflammation through interactions with
the innate immune system (Bonay and Aubier, 2007).
In addition to air pollution, early and persistent allergic sensi-
tization is known to be a risk factor for the development of asthma
(Sly, 2011). Indoor allergens from dust mites, cockroaches and
cats have been associated with asthma exacerbation in children
(Sly, 2011). It has also been reported that allergen sensitization
is associated with allergic diseases and also with air pollutants
(Pénard-Morand et al., 2005). While many studies have focused on
the association between TRAP and exacerbations of existing respi-
ratory conditions, few studies have reported the impact of TRAP

http://dx.doi.org/10.1016/j.ijheh.2015.09.001
1438-4639/© 2015 Elsevier GmbH. All rights reserved.

Please cite this article in press as: Wang, I.-J., et al., Allergens, air pollutants, and childhood allergic diseases. Int. J. Hyg. Environ. Health
(2015), http://dx.doi.org/10.1016/j.ijheh.2015.09.001
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Table 1 consecutive half-month periods over elbows, knees, face, wrists,

Comparison of basic demographics of the study population.
neck, peri-auricular and eyebrow areas?” Cases of allergic rhinitis
Characteristics Study population All participants (AR) were identified through the questions, “Has your child ever
(n = 2661) (n = 3246) been diagnosed as having AR by a physician?” and “Has your child
Age (years)a 5.5 ± 1.1 7.7 ± 1.6 ever had a problem with sneezing, or a runny or blocked nose, when
Gender (male) (%) 54.1 54.1 they did not have a cold or the flu?” Asthma was defined as positive
Weight (kg)a 18.8 ± 3.9 19.6 ± 6.4 responses to “physician-diagnosed asthma” and the presence of
Height (cm)a 107.6 ± 8.5 108.9 ± 11.5
nocturnal cough or exercise wheeze in the past 12 months.
BMI (kg/m2 )a 16.2 ± 2.0 16.3 ± 2.3
Sleep duration (h)a 9.0 ± 1.2 8.9 ± 1.2
ETS exposure (%) 64.1 57.8 2.3. Exposure measurements
Family history of atopy (%) 55.9 55.0
Breast feeding (%) 75.8 74.7
The long-term exposure to background air pollution was esti-
Family income per year (%)
<1,000,000 NT$ 69.7 69.4 mated by linking the home addresses to six air quality monitoring
>1,010,000 NT$ 30.3 30.6 stations in six districts in Taipei Figure S1. The home addresses
Maternal age (years)a 34.2 ± 4.3 29.3 ± 4.5 and the monitoring stations were geo-coded using a geographic
Maternal education (%) information system. An expert identified the nearest and most
<High school 27.6 27.4
representative background monitoring station for each child. The
≥High school 31.5 35.0
>College 40.8 37.7 distance between the home and the nearest monitoring station
was determined using Google’s online maps Figure S1. The tem-
Abbreviations: BMI, body mass index; ETS, environmental tobacco smoke; NT$,
Taiwan dollar. perature and relative humidity in each monitoring site were also
a
Mean ± SD. recorded. The mean concentrations of sulfur dioxide (SO2 ), nitrogen
dioxide (NO2 ), ozone (O3 ), carbon monoxide (CO), and particulate
matter ≤ 10 ␮m and ≤2.5 ␮m in aerodynamic diameter (PM10 and
on the development of asthma and allergies over time. In addition,
PM2.5 ) from when the children were born to the end of the study
most of the studies on the relationship between exposure to air pol-
were measured at the relevant monitoring station, and averaged to
lutants and the risk of asthma in children have been cross-sectional
represent long-term cumulative exposure to air pollutants for each
(Evans et al., 2014; Bowatte et al., 2015; Zhang et al., 2002).
child.
Both air pollutants and allergens play important roles in the
development of allergic diseases, however whether they synergis-
2.4. Laboratory methods
tically increase the risk of developing allergic diseases is unclear.
Therefore, the aim of this study was to evaluate the joint effect of
Skin prick tests to six common allergens (house dust mites
long-term exposure to allergens and air pollutants on the risk of
including Der p, Der f, Der m, and Blot allergens, cockroaches, ani-
developing allergic diseases, and to investigate whether exposure
mal dander, milk, eggs, and crab allergens, all from ALK-Abell &
to allergens modifies the effect of air pollutants on allergic diseases.
Oacute, USA) were performed. The tests were read at 15 min. In the
presence of a positive control (>3 mm), a mean wheal diameter of
2. Methods at least 3 mm greater than the negative control was taken to be
positive.
2.1. Study population
2.5. Statistical analysis
We conducted a school-based survey on allergic diseases in
kindergarten children at 11 communities in Taipei in 2010 (Child- The daily average concentrations of each air pollutant (PM10 ,
hood Environment and Allergic Diseases Study cohort). A total of PM2.5 , SO2 , NO2 , CO and O3 ) were calculated. More than 75% of the
3246 children were recruited with written informed consent. After data (for at least 18 h in a 24-h period) had to be available to be
excluding those who were multiple births, premature, had con- included in the analysis. We then calculated the average concen-
genital and chronic diseases, were unable to answer questions in tration from birth until the end of the study to estimate long-term
Chinese, had moved in or out of their current home, lived more than cumulative exposure. Adjustments were made for temperature and
10 km from air monitoring stations, 2661 children were entered relative humidity at each monitoring site. The air pollutant data
into the analysis (Table 1). Those who lived more than 10 km from obtained from the geographic information system were taken as
air monitoring stations were excluded because of the relative lower independent variables in the regression model.
correlation between monitoring station data and children’s real Multiple logistic regression analyses were performed to esti-
exposure for those living more than 10 km from air monitoring mate the association between air pollutants, allergen sensitization,
stations (Clark et al., 2010; Romieu et al., 1996; Rich et al., 2009). and the development of allergic diseases. Odds ratios (ORs) and a
The average distance from monitoring stations to the children’s 95% confidence intervals (CIs) were adjusted for important poten-
addresses was 2.14 ± 0.72 km. The International Study of Asthma tial confounders. Potential confounders which were selected based
and Allergies in Childhood (ISAAC) questionnaires with extra ques- on the previous literatures, including age, gender, body mass
tions on basic demographics, residential environmental factors, and index, environmental tobacco smoke, maternal history of atopy,
family history of allergic diseases were answered by parents. The maternal education and nationality, family income, duration of
study protocol was approved by the Institutional Review Board at breast feeding, duration of sleep, number of siblings, dampness
our hospital, and this study complied with the principles outlined of the house, fungus on the house wall, residence, temperature,
in the Helsinki Declaration. relative humidity, and distance from the home to the air mon-
itoring station were all taken into consideration. Variables were
2.2. Case definition included in the model if they changed the univariate point esti-
mate by at least 10% (Beggs and Bambrick, 2005; Jenerowicz et al.,
Cases of atopic dermatitis (AD) were identified through the 2012; Weiland et al., 2004).
questions, “Has your child ever had AD diagnosed by a physician?” To further assess the joint effect and interactions between air
and “Has your child ever had recurrent itchy rash for at least 6 pollutants and allergen sensitization, we stratified our subjects into

Please cite this article in press as: Wang, I.-J., et al., Allergens, air pollutants, and childhood allergic diseases. Int. J. Hyg. Environ. Health
(2015), http://dx.doi.org/10.1016/j.ijheh.2015.09.001
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Table 2 Table 4
The prevalence of allergic diseases and sensitization. The association of allergen sensitization with allergic diseases.

Total Boys Girlsb Allergen Allergic diseases

(N = 2661) (N = 1439) (N = 1221) sensitization

Asthma (%)a 12.6 15.1 9.7 Asthma Allergic rhinitis Atopic dermatitis
Allergic rhinitis (%)a 30.0 33.8 25.4
a
Atopic dermatitis (%) 14.4 14.9 13.8 OR (95% CI) OR (95% CI) OR (95% CI)
Allergen sensitization rate (%) Dust mite 2.17 (1.71–2.74)*** 1.94 (1.64–2.29)*** 1.70 (1.37–2.12)***
Dust mitea 43.1 45.1 40.8 Cockroach 1.43 (1.06–1.94)* 1.35 (1.07–1.71)** 1.12 (0.83–1.52)
Cockroach 14.0 13.0 15.1 Animal dander 1.38 (0.94–2.03) 1.23 (0.91–1.65) 1.19 (0.82–1.75)
Animal dander 8.0 7.7 8.3 Milk 1.37 (1.02–1.84)* 1.03 (0.83–1.30) 1.35 (1.02–1.78)*
Milk 15.9 15.1 16.9 Egg 1.32 (0.96–1.81) 1.10 (0.87–1.40) 1.23 (0.91–1.66)
Egg 13.6 13.2 13.9 Crab 1.18 (0.85–1.64) 0.94 (0.73–1.21) 1.06 (0.77–1.46)
Crab 12.8 12.0 13.8
Abbreviations: OR, odds ratio; CI, confidence interval.
a
p < 0.05, represents a significant difference by gender using the chi-square test. *
p < 0.05.
b
Boys vs. girls. **
p < 0.01.
***
p < 0.001.
a
Models are adjusted for age, gender, BMI, environmental tobacco smoke, mater-
nal history of atopy, maternal education and nationality, duration of breast feeding,
four groups: low air pollutant exposure without allergen sensitiza- duration of sleep, number of siblings, temperature, relative humidity.
tion, high air pollutant exposure without allergen sensitization, low
air pollutant exposure with allergen sensitization, and high air pol-
lutant exposure with allergen sensitization. Bonferroni correction
was used to address the problem of multiple comparisons. In addi- 2.17 (1.71–2.74) (Table 4). Cockroach sensitization also increased
tion, gene–environmental interaction was tested by adding a prod- the risk of asthma 1.43 (1.06–1.94) and AR 1.35 (1.07–1.71),
uct term in the regression model. Within the allergen sensitization whereas milk sensitization significantly increased the risk of AD
category, a one degree of freedom trend test was used to evaluate 1.35 (1.02–1.78). There were no significant differences in the asso-
the possible exposure–response relationship across categories of ciation of other allergen sensitizations with allergic diseases.
the air pollutant variables. All tests assumed a two-sided alternative Since the correlation of each air pollutant was high, they were
hypothesis and a 0.05 significance level. All analyses were con- put into different independent models to avoid collinearity in
ducted using SAS software version 9.1 (SAS Institute, Cary, NC, USA). subsequent analysis (Supplement Table S2). After controlling for
potential confounders, PM10 , PM2.5 , and CO were significantly asso-
3. Results ciated with asthma with ORs (95%CI) of 1.39 (1.03–1.87), 1.45
(1.07–1.97), and 1.36 (1.01–1.83), respectively (Table 5). O3 showed
A total of 3264 children were recruited with written informed a protective effect on asthma 0.68 (0.51–0.92), however SO2 and
consent. After excluding those who were multiple births (n = 27), NO2 were not significantly associated with allergic diseases. The
premature (n = 152), had congenital and chronic diseases (n = 105), air pollutants had a positive relationship with AD, but this did not
were unable to answer questions in Chinese (n = 126), had moved reach statistical significance.
in or out of their current home (n = 114), and those living more Since only mite sensitization was associated with asthma, the
than 10 km from air monitoring stations (n = 79), 2661 children association between air pollutants and mite sensitization on aller-
were entered into the analysis. Among 2661 children participated gic diseases was further examined. Mite sensitization showed a
in the study, 384 (14.4%) had AD, 799 (30.0%) had AR, and 336 synergistic effect with PM2.5 on asthma with ORs (95%CI) of 1.60
(12.6%) had asthma. Table 1 outlines the demographic character- (1.06–2.42) for high PM2.5 exposure without mite sensitization,
istics of the study population. Mite (43.1%) was the most common 1.75 (1.12–2.73) for low PM2.5 exposure with mite sensitization,
sensitizing aeroallergen, and milk (15.9%) was the most common and 3.06 (1.89–4.93) for high PM2.5 exposure with mite sensi-
sensitizing food allergen (Table 2). Boys had a higher mite sensi- tization, compared to the children with low PM2.5 exposure and
tization rate than girls (Table 2). The annual average PM10 was without mite sensitization (p for trend < 0.001) (Table 6). There-
48.14 ± 1.31 ␮g/m3 , followed by PM2.5 (28.81 ± 0.84 ␮g/m3 ), NO2 fore, the children who had mite sensitization and were exposed to
(23.04 ± 0.73 ppb), and SO2 (6.30 ± 0.57 ppb). The hourly average PM2.5 had an increased risk of asthma. After stratification by mite
levels of CO and O3 were 0.63 ± 0.03 ppm and 40.65 ± 1.01 ppb, sensitization, we found that mite allergens may modify the effect
respectively (Table 3). of PM10 and CO on AR and AD. However, mite sensitization did not
Mite sensitization significantly increased the risk of AD, AR, and show significant interactive effects with air pollutants on asthma,
asthma with ORs (95%CI) of 1.70 (1.37–2.12), 1.94 (1.64–2.29), and AR, or AD (Table 6).

Table 3
Meteorological factors and air pollutants in the study area in 2004–2011.

Mean ± SD Median Min Max Quartile

◦
Temperature ( C) 23.50 ± 0.29 23.47 21.58 29.10 23.33–23.64
Humidity (%) 72.11 ± 0.76 72.13 67.22 78.87 72.03–72.35
PM10 (␮g/m3 ) 48.14 ± 1.31 48.32 27.75 52.77 47.08–49.24
PM2.5 (␮g/m3 ) 28.81 ± 0.84 29.07 17.55 30.45 28.42–29.40
NO2 (ppb) 23.04 ± 0.73 23.03 16.48 26.03 22.86–23.28
SO2 (ppb) 6.30 ± 0.57 6.46 1.72 6.80 6.30–6.60
CO (ppm) 0.63 ± 0.03 0.63 0.39 0.82 0.62–0.64
O3 (ppb) 27.50 ± 0.61 27.62 23.58 31.37 27.43–27.84
8hO3 (ppb) 40.65 ± 1.01 40.84 28.49 42.40 40.58–41.19

Abbreviations: SO2 , sulfur dioxide; NO2 , nitrogen dioxide;O3 , ozone; CO, carbon monoxide; PM10 , particulate matter ≤ 10 ␮m; PM2.5 , particulate matter ≤ 2.5 ␮m; 8hO3 , 8-h
average ozone concentration.

Please cite this article in press as: Wang, I.-J., et al., Allergens, air pollutants, and childhood allergic diseases. Int. J. Hyg. Environ. Health
(2015), http://dx.doi.org/10.1016/j.ijheh.2015.09.001
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Table 5 important role on the risk of asthma and AR. Children with mite
The association between air pollutants and allergic diseases.
sensitization were most susceptible to the adverse effects of air
Air pollutantsa Allergic diseases pollutants. In addition, exposure to PM2.5 and mite allergens had a
Asthma Allergic rhinitis Atopic dermatitis synergistic effect on the development of asthma.
OR (95% CI)b OR (95% CI) OR (95% CI)
We also found that PM2.5 , PM10 , and CO were significantly asso-
Outdoor ciated with asthma. Gehring et al. (2015) also reported that PM
PM10 1.39 (1.03–1.87)* 1.15 (0.79–1.66) 1.00 (0.70–1.44) constituents, reflecting poorly regulated non-tailpipe road traf-
PM2.5 1.45 (1.07–1.97)* 1.54 (1.03–2.32)* 1.25 (0.85–1.82)
fic emissions, may increase the risk of asthma and allergy in
NO2 1.33 (0.99–1.78) 0.95 (0.74–1.20) 1.33 (0.98–1.79)
SO2 1.10 (0.82–1.48) 1.00 (0.78–1.29) 1.24 (0.90–1.70) schoolchildren. Increased exposure to PM2.5 was associated with
CO 1.36 (1.01–1.83)* 1.02 (0.80–1.29) 1.33 (0.98–1.80) sensitization to both aero and food allergens and an increased
O3 0.68 (0.51–0.92)* 1.01 (0.76–1.34) 1.03 (0.77–1.38) risk of subsequent asthma in childhood. Moreover, the associa-
8hO3 0.79 (0.59–1.07) 1.07 (0.85–1.36) 1.22 (0.93–1.60)
tion between allergic rhinitis and PM2.5 absorbance was found to
Indoor
ETS 1.28 (1.00–1.64)* 1.26 (1.05–1.49)* 0.90 (0.72–1.13) be significant in a study from Germany (Fuertes et al., 2013). Out-
Dampness 1.10 (0.88–1.39) 0.90 (0.76–1.07) 1.03 (0.83–1.27) door environmental exposure to O3 , CO, NO, NO2 , PM10 , and SO2
Heating 0.78 (0.62–0.98)* 0.83 (0.70–0.98)* 1.02 (0.82–1.27) has been well documented to exacerbate asthma. In addition to
Abbreviations: SO2 , sulfur dioxide; NO2 , nitrogen dioxide; O3 , ozone; CO, carbon asthma exacerbation, Clark et al. observed a statistically signifi-
monoxide; PM10 , particulate matter ≤ 10 ␮m; PM2.5 , particulate matter ≤ 2.5 ␮m; cantly increased risk of asthma development with increased early
8hO3 , 8-h average ozone concentration; ETS, environmental tobacco smoke. life exposure to CO, NO, NO2 , PM10 , SO2 and black carbon and the
*
p < 0.05. proximity to the point source (Clark et al., 2010). However, we failed
a
Air pollutant levels were dichotomized into high and low exposure groups with
the cut off value of the median level; PM10 , 48.32 ␮g/m3 ; PM2.5 , 29.07 ␮g/m3 ; NO2 ,
to find significant associations between NO2 , SO2 , and O3 and aller-
23.03 ppb; SO2 , 6.46 ppb; CO, 0.63 ppm; O3 , 27.62 ppb; 8hO3 , 40.84 ppb; tempera- gic diseases. Consistent with our study, Koo et al. also reported no
ture, 23.47 ◦ C; humidity, 72.13%. The low exposure group served as the controls. association between O3 and respiratory symptoms among primary
b
Models were adjusted for age, gender, body mass index, environmental tobacco school children (Bernard et al., 2001). Different study populations,
smoke, maternal history of atopy, maternal education and nationality, duration of
study design, different levels of exposure, and constituents of air
breast feeding, duration of sleep, number of siblings, temperature, relative humidity,
and distance from the home to the air monitoring station. pollutants (gas or particle) may explain differences between stud-
ies.
The biological mechanisms by which air pollutants exert toxic
effects on asthma are not well understood. Aside from irritating
4. Discussion
the respiratory tract, Lin et al. reported that air pollutants may
cause elevated blood IgE (Donaldson et al., 2003). It is plausible that
In this study, we investigated the potential association between
PM stimulates dendritic cells and T cells to produce Th2 cytokines
air pollutants, allergen sensitization, and pediatric allergic dis-
and activate pro-inflammatory genes in a process mediated by free
eases. We found that dust mite sensitization and PM2.5 played an

Table 6
Joint effect of exposure to air pollutants and mite allergens on allergic diseases.

Air pollutanta Mite sensitization Asthma Allergic rhinitis Atopic dermatitis

ORb 95%CI OR 95%CI OR 95%CI

PM2.5
Low − 1 1 1
High − 1.60 (1.06,2.42) 1.39 (1.01,1.90) 1.43 (0.95,2.15)
Low + 1.75 (1.12,2.73) 1.78 (1.32,2.41) 2.33 (1.64,3.30)
High + 3.06 (1.89,4.93) 2.50 (1.75,3.58) 2.27 (1.44,3.56)
p for trend <0.001 <0.001 <0.001
p for interaction 0.756 0.966 0.137
PM10
Low − 1 1 1
High − 1.39 (0.90,2.15) 1.18 (0.86,1.61) 1.15 (0.77,1.73)
Low + 1.44 (0.95,2.18) 1.77 (1.31,2.39) 2.34 (1.66,3.30)
High + 2.64 (1.66,4.20) 2.14 (1.50,3.05) 1.80 (1.16,2.81)
p for trend <0.001 <0.001 <0.001
p for interaction 0.318 0.910 0.119
O3
Low − 1 1 1
High − 0.64 (0.44,0.92) 0.89 (0.68,1.16) 0.93 (0.66,1.31)
Low + 1.77 (1.23,2.55) 1.77 (1.32,2.37) 1.86 (1.29,2.69)
High + 1.04 (0.68,1.59) 1.63 (1.20,2.24) 1.87 (1.28,2.72)
p for trend <0.001 <0.001 <0.001
p for interaction 0.773 0.852 0.778
CO
Low − 1 1 1
High − 1.25 (0.86,1.81) 0.99 (0.76,1.29) 1.25 (0.89,1.77)
Low + 1.47 (0.98,2.21) 1.77 (1.32,2.38) 2.13 (1.50,3.03)
High + 2.39 (1.58,3.61) 1.81 (1.32,2.49) 2.19 (1.47,3.25)
p for trend <0.001 <0.001 <0.001
p for interaction 0.345 0.880 0.435
a
Air pollutant levels were dichotomized into high and low exposure groups with the cut off value of the median level; PM10 , 48.32 ␮g/m3 ; PM2.5 , 29.07 ␮g/m3 ; CO,
0.63 ppm; O3 , 27.62 ppb. The low exposure group served as the controls.
b
Models were adjusted for age, gender, body mass index, environmental tobacco smoke, maternal history of atopy, maternal education and nationality, duration of breast
feeding, duration of sleep, number of siblings, temperature, relative humidity, and distance from the home to the air monitoring station. p values were adjusted for multiple
testing.

Please cite this article in press as: Wang, I.-J., et al., Allergens, air pollutants, and childhood allergic diseases. Int. J. Hyg. Environ. Health
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radical and oxidative stress mechanisms. In contrast, some stud-
ies have reported that exposure to diesel exhaust particles (DEPs)
did not significantly increase allergen-specific bronchial reactivity.
However, adjuvant effects of DEPs on allergic inflammation have
been reported (Riedl et al., 2012). After exposure to DEPs, elevated
expressions of inflammatory mediators have been observed in the
respiratory tract (Ghio et al., 2012). Therefore, DEPs are character-
ized by both adjuvant activity for sensitization against common
allergens and enhancing the effects of allergic symptoms in sen-
sitized patients. In addition, emerging evidence has shown that
unique gene signatures and epigenetic control of immune- and
inflammatory-based genes play important roles in the magnitude
of the impact air pollutants have on respiratory health (Alexis and
Carlsten, 2014).
After stratification by mite sensitization, the effects of PM10 and
CO only remained in those with mite sensitization. Mite sensitiza-
tion also showed a significant synergistic interaction with PM2.5
on asthma. Furthermore, the effect of air pollution from traffic
on allergic diseases was modified by mite allergen sensitization.
Exposure to TRAP during pregnancy may increase the risk of sen-
sitization to allergens among asthmatic children (Mortimer et al.,
2008). Curiously, children of dog owners were reported to be more
likely to experience bronchitis symptoms following exposure to
particulate matter than children living with a cat or no pets, sug-
gesting that exposure to mammalian proteins could enhance the
immune response to air pollution exposure (McConnell et al., 2005).
Whether air pollutants-mediated up regulation of allergy is more
likely to occur in association with mammalian proteins or those
derived from arthropods requires further investigation. Previous
studies suggest the ability of DEP to bind proteins (e.g. house dust
mite allergens), which is why it may be considered to be a poten-
tial carrier of allergens. The majority of these particles are small
enough to penetrate deep into the respiratory tree and provoke
allergic symptoms (Bernstein, 2012). DEPs have also been reported
to enhance allergen sensitization, and to differentially affect the air-
way mucosa in healthy individuals and those with asthma (Stenfors
et al., 2004). Moreover, early-life exposure to high DEP levels has
been reported to be associated with significantly increased preva-
lence of asthma among allergic children but not among non-allergic
children (Brandt et al., 2015). These findings suggest that exposure
to DEPs results in accumulation of allergen-specific TH 2/TH 17 cells
in the lungs, potentiating secondary allergen recall responses and
promoting the development of allergic asthma (Brandt et al., 2015).
Whether children with asthma are more susceptible to O3 -
induced respiratory tract injury is of great interest (Balmes, 1933).
Consistent with our study, previous study also found long term O3
exposure had protective effect on the lifetime prevalence of asthma
(Guo et al., 1999). However, some studies reported short term O3
exposure may increase asthma exacerbation frequency (Chen et al.,
2014). This may be because of the differences of long term and short
term exposure (Sheffield et al., 2015). Another reason is that high
traffic density is inversely correlated with concentrations of O3 ,
which is formed at some distance from emission sources and scav-
enged in city centers by nitrogen monoxide from vehicle exhaust
(Wjst et al., 1993). Further investigations are necessary to search
for the pathophysiological mechanisms of O3 on asthma.
There are several limitations to this study that may influence
the interpretation of the results. First, we failed to collect the dis-
tances of the subjects’ residential address to the nearest major
traffic load. Assessing exposure from air monitoring stations is
regarded to be a surrogate measurement of exposure to air pol-
lutants, which may be subject to misclassification bias. However,
a more suitable quantitative biomarker for air pollutants was not
available. Further individual monitoring of air pollutants and samp-
ling of indoor allergens are necessary to better assess exposure.
Furthermore, the study subjects were likely to be exposed to other
Please cite this article in press as: Wang, I.-J., et al., Allergens, air pollutants, and childhood allergic diseases. Int. J. Hyg. Environ. Health
(2015), http://dx.doi.org/10.1016/j.ijheh.2015.09.001
5
sources of pollutants in addition to allergens such as tobacco smoke
at home. Therefore, we adjusted for these potential confounders in
our model. Another possible limitation is recall bias with regards
the allergic diseases. We combined two specific questions in the
ISAAC questionnaire to define each allergic disease, and this has
been validated by many epidemiological studies. Recall of allergic
diseases was assessed in a subset of the study population, and con-
cordance between the parental reports and medical records was
good.
One of the strengths of this study is its inclusion of a large and
socio-demographically diverse population of children in the com-
munity, which minimizes the likelihood of selection bias and may
enhance the generality. Because of the large sample size, we were
able to control for numerous potential confounders in the statis-
tical analysis. This allowed us to perform subgroup investigations.
Moreover, our data represent exposure reasonably well as we had
information on the children’s residential history to formally assess
the lifetime exposure to air pollution. We also excluded children
who lived more than 10 km from the air monitoring stations using
a geographic information system which could reduce selection bias.
In addition, although associations between air pollutants and many
allergic diseases have been previously investigated, this is the first
study to report the joint effects of air pollutants and allergen sen-
sitization on allergic diseases.
5. Conclusion
In conclusion, exposure to both outdoor air pollutants and
indoor allergens was associated with allergic diseases in children.
Exposure to PM2.5 and mite allergens had a synergistic effect on the
development of asthma. Mite allergens may modify the effect of air
pollutants on allergic diseases, and avoiding co-exposure of indoor
allergens and outdoor air pollutants is important. These findings
provide an insight into the etiology of allergic diseases, and also
suggest that control measures to avoid allergen and air pollutant
co-exposure such as increasing ventilation of the home and living
away from busy roads may be beneficial.
6. Conflict of interest statement
None declared.
Acknowledgments
We thank the CEAS study group (Professor Mei-Lien Chen, Pau-
Chung Chen, Chen-Chang Yang, Dr. Wen-Chiuo Wu, and the related
colleagues for collecting the data).
This study was supported by grants from the National Science
Council (NSC 102-2628-B-192-001-MY3) in Taiwan and Taipei Hos-
pital, Ministry of Health and Welfare.
Appendix A. Supplementary data
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.ijheh.2015.09.
001.
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