Air Pollution and Prevalence of Bronchitic Symptoms Among Children in Taiwan

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CHEST

Original Research

S

hort-term changes in the occurrence of bronchitic

symptoms are more likely to be infl uenced by

changes in the environment, diet, or life-style risks

than by changes in the genetic pool. From a preventive

perspective, information on environmental, dietary,

and behavioral factors is crucial.

1

_{In a systematic}

Medline search, we identifi ed seven studies

concern-ing exposure to ambient air pollution on development

of bronchitic symptoms, but only two studies

2,3

focused on children with asthma, both of which

provided suggestive but inconclusive results.

In 2007, we conducted a nationwide cross-sectional

study in Taiwan, where we collected information

about bronchitic symptoms during the past 12 months

and also those important potential determinants of

allergic disease in children. In the present study, we

elaborated the associations between exposure to

urban air pollution and the prevalence of bronchitic

symptoms in schoolchildren, focusing on nitrogen

oxides (NO

₂

), carbon monoxide (CO), ozone (O

₃

),

sulfur dioxide (SO

₂

), and particles with an

aerody-namic diameter

ⱕ 2.5 m m (PM

_2.5

). Further, we

applied the two-stage hierarchical model to adjust for

confounding, to elaborate effect modifi cation on an

Background: There were limited studies concerning ambient air pollution exposure on

develop-ment of bronchitic symptoms among children. These studies provided suggestive but

inconclu-sive results.

Objectives: To assess the association between air pollutants and the prevalence of bronchitic

symptoms in the Taiwan Children Health Study.

Methods: We conducted a nationwide cross-sectional study of 5,049 Taiwanese children in 2007.

Routine air pollution monitoring data were used for sulfur dioxide (SO

2

), nitrogen dioxides (NO

2

),

ozone (O

3

), carbon monoxide (CO), and particles with an aerodynamic diameter

ⱕ 2.5 m m (PM

2.5

).

The exposure parameters were calculated using the between-community 3-year average

concen-tration. The effect estimates were presented as odds ratios (ORs) per interquartile changes for

SO

2

, NO

2

, O

3

, CO, and PM

2.5

.

Results: In the two-stage hierarchical model adjusting for confounding, the prevalence of

bron-chitic symptoms with asthma was positively associated with the between-community 3-year

aver-age concentrations of NO

2

(adjusted OR, 1.81 per 8.79 ppb; 95% CI, 1.14-2.86), and CO (OR, 1.31

per 105 ppb; 95% CI, 1.04-1.64). The prevalence of phlegm with no asthma was related to O

3

(OR,

1.32 per 8.77 ppb; 95% CI, 1.06-1.63).

Conclusions: The results suggest that long-term exposure to outdoor air pollutants, such as NO

2

,

CO, and O

3

, may increase the prevalence of bronchitic symptoms among children.

CHEST 2010; 137(

䊏):1 –9

Abbreviations: CO 5 carbon monoxide; NO 2 5 nitrogen dioxide; O 3 5 ozone; OC 5 organic carbon; OR 5 odds ratio;

PM 2.5 5 particles with an aerodynamic diameter ⱕ 2.5 m m; SO 2 5 sulfur dioxide

Air Pollution and Prevalence of Bronchitic

Symptoms Among Children in Taiwan

Bing-Fang Hwang, MS, PhD ; and Yungling Leo Lee, MD, PhD

Manuscript received November 2, 2009; revision accepted February 16, 2010.

Affi liations: From the Department of Occupational Safety and Health and Graduate Program (Dr Hwang), College of Public Health, China Medical University, Taichung; and the Institute of Preventive Medicine and Research Center for Genes (Dr Lee), Environment and Human Health, College of Public Health, National Taiwan University, Taipei, Taiwan .

Funding/Support: This study was supported by the National Science Council in Taiwan [Grants NSC 96-2314-B-039-019, 96-2314-B-006-053].

Correspondence to: Yungling Leo Lee, MD, PhD, Institute of Preventive Medicine, College of Public Health, National Taiwan University, No.17 Xu-Zhou Rd, 516R, Taipei 100, Taiwan; e-mail: leolee@ntu.edu.tw

© 2010 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians ( http://www.chestpubs.org/ site/misc/reprints.xhtml ).

DOI: 10.1378/chest.09-2600

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fl uorescence, and PM 2.5 by b -gauge. A daily (24-h) averaged

con-centration was calculated when at least 13 valid hourly values were available with not more than six successive hourly values missing and an 8-h averaged concentration was calculated when at least six valid hourly values were available. We hypothesized that long-term exposure to outdoor air pollutants based on historic routine air monitoring data from 2005 through 2007 would increase the prevalence of bronchitic symptoms among children. Exposure parameters in the present study were 3-year average (2005-2007) and the yearly deviations from the 3-year average concentrations in each municipality, calculated from the 24-h NO 2 , CO, SO 2 , PM 2.5 , and 10:00 am to 6:00 pm 8-h O 3 .

Covariates

Information on potential confounders was obtained from the parental-administered questionnaire. The covariates in the pres-ent analyses included age, gender, parpres-ental education, family annul income, duration of breastfeeding, maternal smoking his-tory during pregnancy, environmental tobacco smoke, cock-roaches note, carpet used, home dampness and mold, and parental atopy ( Table 1 ). Parental atopy was a measure of genetic predis-position to asthma and it was defi ned as the father or mother of the index child ever having been diagnosed as having asthma, allergic rhinitis, or atopic eczema.

Statistical Methods

The association between air pollution and the prevalence of bronchitic symptoms was examined in two groups (children with

individual level, and to assess the community-level

effects of air pollution.

4,5

Materials and Methods

Data Collection and Study Population

Taiwan Children Health Study was based on a multipurpose nationwide design that focused on outdoor air pollutants as pri-mary interest. Communities of Taiwan were selected with the aim of maximizing the variability and minimizing the correlations in criteria outdoor pollutants based on historic routine air monitor-ing data. In communities with pollution patterns of interest, neighborhoods with stable, largely middle-income populations, ethnically representative of Taiwan as a whole, were identifi ed from 2004 census data.

A total of 5,804 seventh- to eighth-grade children were recruited from public schools in 14 communities covering diverse parts of Taiwan, which was representative of Taiwanese middle-school children. Written consent was obtained from parents or guardians. The questionnaire was distributed in all communities simultaneously in September, and subjects were given the forms by project staff following their pulmonary function tests and asked to complete and return them the fol-lowing day. Questionnaire responses by parents or guardians were used to categorize children’s basic information, medical history, family history, personal habits, housing characteristics, and environmental conditions. The fi nal study population was 5,052 schoolchildren (response rate, 87.0%). The study protocol was approved by the Respiratory Health Screening Steering Committee of the Taiwan Department of Health and the Insti-tutional Review Board of National Taiwan University, and it complied with the principles outlined in the Helsinki Declaration. 6

Health Outcomes

Questions on respiratory symptoms and illnesses were modi-fi ed after those used in the Children’s Health Study in Southern California. 2,7_{The outcome of interest was bronchitic symptoms.}

The bronchitic symptoms were defi ned on the basis of having any one of the following: (1) one or more episodes of bronchitis (defi ned by the question: “How many times in the past 12 months did your child have bronchitis?”), without the following symp-toms: (2) chronic cough (defi ned by a yes answer to the question “During the past 12 months, has this child had a cough fi rst thing in the morning that lasted for as long as 3 months in a row?” or to the question “During the past 12 months, has this child had a cough at other times of the day that lasted for as much as 3 months in a row?”), or (3) chronic phlegm (defi ned by a yes answer to the question: “Other than with colds, does this child usually seem congested in the chest or bring up phlegm?”). A history of asthma for each child was assessed on the basis of the answer to the question, “Has a physician ever diagnosed your child as having asthma?”

Exposure Assessment

Complete monitoring data for the air pollutants, including SO 2 ,

NO 2 , O 3 , CO, and PM 2.5 , as well as daily temperature and relative

humidity, are available for 14 EPA monitoring stations in Taiwan Children Health Study communities since 2005 ( Fig 1 ). Concen-trations of each pollutant are measured continuously and reported hourly—CO by nondispersive infrared absorption, NO 2 by

chemi-luminescence, O 3 by ultraviolet absorption, SO 2 by ultraviolet

[AQ3]

Figure 1. Locations of 14 communities in the Taiwan Children Health Study.

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the fi rst stage for the risk of bronchitic symptoms as a function of site-specifi c intercepts, j, where a j 5 1, ..., 14, and personal covari-ates. The adjusted site-specifi c intercepts and prevalence rates are related by Pj 5 e a j_{/(1 1 e} a j_{). In the second stage, these intercept}

terms representing the logit of the site-specifi c prevalence rates (Pj; j 5 1, ..., 14), adjusted for personal covariates, were regressed on each site-specifi c ambient pollutant level by using a linear “eco-logic” regression, that is, logit a j 5 a 1 Uj 1 b Zj, where Uj denotes the random departure from the general prevalence a j on the logit scale for site j and Zj denotes the ambient pollution level for site j. Thus, b can be interpreted as the log odds ratio (per interquartile changes) for each pollutant, adjusted for personal characteristics. and without asthma) to determine whether children with asthma

are more likely to develop bronchitic symptoms. We estimated adjusted odds ratios (ORs) in a two-stage hierarchical model using logistic and ecologic model analyses. The models assume two sources of variation: the variation among subjects in the fi rst stage, part of which could be explained by the individual confounders, and the variation of air pollution between communities in the sec-ond stage, part of which could be explained by variables measured at the municipal level. In the analyses we assumed that (1) the outcome variable follows Bernoulli distribution, (2) intercept terms are random at the municipal level, and (3) all the explanatory variables are fi xed effects. A logistic regression model was fi tted in

Table 1— Distribution of Bronchitic Symptoms, Demographics, and Other Characteristics in Patients With/Without History of Asthma Characteristic Asthma (N 5 376 ) No Asthma (N 5 4,676) x 2 No. % No. % Bronchitis 81 21.5 205 4.4 181.1 ( P , .001) Chronic phlegm 53 14.1 164 3.5 96.6 ( P , .001) Chronic cough 52 13.8 119 2.5 134.5 ( P , .001) Bronchitic symptoms 137 36.4 429 9.2 253.1 ( P , .001) Age, y 2.51 ( P 5 .29) 12 255 67.8 2,971 63.5 13 98 26.1 1,361 29.1 14 23 6.1 344 7.4 Sex 5.14 ( P , .05) Male 202 53.7 2,245 48.0 Female 174 46.3 2,431 52.0 Parental education, y a _{1.92 ( P 5 .38)} , 8 65 17.4 841 18.1 8-11 244 65.4 3,111 67.1 ⱖ 12 64 17.2 686 14.8

Family annual income a _{5.16 ( P 5 .08)}

Low 111 32.0 1,651 38.1

Medium 187 53.9 2,174 50.2

High 49 14.1 505 11.7

Environmental tobacco smoke a _{0.41 ( P 5 .52)}

Yes 188 50.4 2,267 48.8

No 185 49.6 2,375 51.2

Maternal smoking during pregnancy a _{4.58 ( P 5 .03)}

Yes 22 5.9 174 3.7

No 353 94.1 4,472 96.3

Cockroaches 0.02 ( P 5 .88)

Yes 331 89.5 4,137 89.4

No 39 10.5 493 10.6

Any home dampness and mold 5.15 ( P = .02)

Yes 147 39.1 2,569 54.9 No 229 60.9 2,107 45.1 Duration of breastfeeding, mo a _{0.67 ( P 5 .88)} 0 188 50.7 2,430 52.8 1-2 143 38.5 1,714 37.3 3-5 22 5.9 246 5.3 ⱖ 6 18 4.9 209 4.5 Carpet used a _{1.12 ( P 5 .29)} Yes 33 8.8 503 10.8 No 340 91.2 4,151 89.2 Pet 0.03 ( P 5 .86) Yes 222 59.0 2,743 58.7 No 154 41.0 1,933 41.3 Parental atopy 53.4 ( P , .001) Yes 160 42.6 1,170 25.0 No 216 57.4 3,506 75.0

a_{Number of subjects does not add up to total number because data were missing.}

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Air Pollution and Bronchitic Symptoms

In the one-pollutant model, the prevalence of

bron-chitic symptoms with asthma was related to NO

₂

lev-els (adjusted OR 1.81 per 8.79 ppb change; 95% CI,

1.14-2.86). With the addition of SO

₂

(adjusted OR

1.76; 95% CI, 0.99-3.14), PM

_2.5

(adjusted OR, 2.01;

95% CI, 1.20-3.36), or O

₃

(adjusted OR, 1.79; 95%

CI, 1.12-2.85), the effect estimate for NO

₂

remained

signifi cant ( Table 6 ). The adjusted OR for 105 ppb

change in CO was 1.31 (95% CI, 1.04-1.64) and the

estimates changed little when a second pollutant was

added. The adjusted odds ratio for 1.31 ppb change in

SO

₂

alone was 1.17 (95% CI, 0.97-1.40), but inclusion

of O

₃

increased the effect estimate substantially

(adjusted OR, 1.26; 95% CI, 1.03-1.53), whereas

addi-tion of CO (adjusted OR, 1.11; 95% CI, 0.92-1.34)

and NO

₂

(adjusted OR, 1.02; 95% CI, 0.81-1.28) had

little infl uence. The prevalence of bronchitic

symp-toms with asthma was weak or not related to PM

_2.5

concentrations in any combination of air pollutants.

The risk of bronchitic symptoms with asthma was not

related to O

3

in the one-pollutant model (adjusted

OR, 0.80 per 8.77 ppb change; 95% CI, 0.59-1.09),

but addition of PM

_2.5

reduced the effect estimate

sub-stantially (adjusted OR, 0.64; 95% CI, 0.41-1.00), and

inclusion of other pollutants changes the effect

esti-mates a little. Furthermore, the prevalence of chronic

phlegm without asthma in the one-pollutant model

was related to O

₃

(adjusted OR, 1.32 per 8.77 ppb

change; 95% CI, 1.06-1.63). With the addition of

either NO

₂

(adjusted OR, 1.35; 95% CI, 1.07-1.69),

CO (adjusted OR, 1.37; 95% CI, 1.08-1.75), SO

₂

(adjusted OR, 1.28; 95% CI, 1.03-1.59), or PM

_2.5

(adjusted OR, 1.34; 95% CI, 1.00-1.78), the effect

estimate for O

3

remained signifi cant.

Discussion

The prevalence of bronchitic symptoms increased

according to increased 3-year average concentrations

of two pollutants, NO

₂

and CO, among children with

asthma. The prevalence of bronchitic symptoms with

asthma was weak or not related to the levels of PM

_2.5

,

SO

₂

, and O

₃

. Our results provide evidence that

chil-dren with asthma are more likely to develop

bron-chitic symptoms when exposed to the air pollutants

NO

₂

and CO. Furthermore, the prevalence of chronic

phlegm was also associated with O

₃

among children

without asthma.

Validity of Results

We used routine air pollution monitoring data as

the basis for exposure assessment. These data

reason-ably represented exposures both in the school and in

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[AQ6]

The results from the models are presented as ORs, along with their

95% CIs. The goodness of fi t was assessed with likelihood ratio tests to determine whether a variable contributed signifi cantly to the model. First, we fi tted a full model with a complete set of cova-riates. To elaborate sources of confounding, we fi tted models with different combinations of covariates and compared the effect from models with and without the covariate of interest. If the adjusted OR differed from the crude OR by . 10%, that covariate was included in the fi nal model.

We considered the effect of multiple pollutants on the preva-lence of bronchitic symptoms. The correlation between NO 2 and

CO concentrations was high (0.86), and the concentrations of PM 2.5 and SO 2 were also highly correlated (0.68). We fi rst fi tted

one-pollutant models ( Table 2 ) and then considered two-pollutant models by fi tting one (NO 2 or CO) and the other (SO 2 or PM 2.5 )

pollutant . Finally, we fi tted two-pollutant models with O 3 and

another pollutant. The two-pollutant models provide estimates of the independent effects of CO, NO 2 , SO 2 , PM 2.5 , and O 3 on the

bronchitic symptoms controlling for the second pollutant in the model ( Table 3 ). The effect of each pollutant on the risk of bron-chitic symptoms was presented as ORs per interquartile changes for SO 2 , NO 2 , O 3 , and PM 2.5 .

Results

Study Population and Prevalence

of Bronchitic Symptoms

The characteristics of the study population and the

prevalence of bronchitic symptoms with and without

asthma according to the baseline covariates are shown

in Table 1 . The prevalence of bronchitic symptoms

with and without asthma during the past 12 months

was 36.4% and 9.2%, respectively. A larger

propor-tion of subjects with asthma than subjects without

asthma were male ( x

2

_{5 5.14, P , .05) and had}

mater-nal smoking during pregnancy ( x

2

_{5 4.58, P 5 .03),}

parental atopy ( x

2

_{5 53.4, P , .001), and less}

pres-ence of any home dampness and mold ( x

2

_{5 5.15,}

P 5 .02) ( Table 1 ).

Air Pollution

The distributions of the annual mean air pollutant

concentrations in the 14 monitoring stations in the

years 2005 through 2007 are presented in Table 4 , and

the correlations between different pollutants between

communities are presented in Table 5 . The correlation

between NO

₂

and CO concentrations was high (0.86),

which refl ects the common source of gasoline-power

vehicles or natural gas power plant combustion. The

concentrations of PM

_2.5

and SO

₂

were also highly

cor-related (0.68), indicating a common source of

station-ary fuel combustion or diesel-power vehicles, although

SO

₂

concentrations were also correlated with NO

₂

(0.56). The concentration of O

₃

was negatively

corre-lated with CO (0.33), but positively correcorre-lated with

PM

_2.5

(0.73) and SO

₂

(0.37), and it was only weakly

cor-related with that of one (NO

₂

or CO) and another

(PM

_2.5

or SO

₂

) air pollutants.

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T

able 2

—

Adjusted Odds Ratios and 95% CIs of Bronchitic Symptoms Among Children W

ith Asthma in T wo Pollutant Models Symptom Two-Pollutant Model 1 (NO 2 1 SO 2 ) T wo-Pollutant Model 2 (NO 2 1 PM 2.5 ) T wo-Pollutant Model 3 (NO 2 1 O 3 ) T wo-Pollutant Model 4 (CO 1 SO 2 ) T wo-Pollutant Model 5 (CO 1 PM 2.5 ) T wo-Pollutant Model 6 (CO 1 O 3 ) T wo-Pollutant Model 7 (SO 2 1 O 3 ) T wo-Pollutant Model 8 (PM 2.5 1 O 3 ) NO 2 (8.79 ppb) Bronchitis 1.99 (1.02-3.87) 2.04 (1.15-3.63) 1.81 (1.06-3.10) … … … … … Chronic phlegm 1.27 (0.59-2.74) 1.51 (0.79-2.89) 1.49 (0.81-2.73) … … … … … Chronic cough 1.25 (0.49-3.23) 1.26 (0.57-2.80) 1.10 (0.58-2.07) … … … … … Bronchitic symptoms 1.76 (0.99-3.14) 2.01 (1.20-3.36) 1.79 (1.12-2.85) … … … … … CO (105 ppb) Bronchitis … … … 1.26 (0.97-1.64) 1.28 (0.99-1.65) 1.26 (0.97-1.64) … … Chronic phlegm … … … 1.17 (0.87-1.59) 1.22 (0.91-1.62) 1.20 (0.89-1.63) … … Chronic cough … … … 1.15 (0.80-1.67) 1.15 (0.81-1.65) 1.05 (0.75-1.45) … … Bronchitic symptoms … … … 1.27 (1.00-1.60) 1.31 (1.04-1.66) 1.27 (1.00-1.61) … … SO 2 (1.31 ppb) Bronchitis 0.95 (0.73-1.23) … … 1.06 (0.85-1.32) … … 1.18 (0.94-1.48) … Chronic phlegm 1.13 (0.83-1.52) … … 1.15 (0.90-1.46) … … 1.26 (0.98-1.61) … Chronic cough 0.93 (0.64-1.35) … … 0.96 (0.71-1.29) … … 1.09 (0.83-1.43) … Bronchitic symptoms 1.02 (0.81-1.28) … … 1.11 (0.92-1.34) … … 1.26 (1.03-1.53) … PM 2.5 (16.84 µg/m 3 ) Bronchitis … 0.75 (0.42-1.33) … … 0.92 (0.54-1.56) … … 1.39 (0.64-2.99) Chronic phlegm … 1.02 (0.53-1.93) … … 1.12 (0.62-2.04) … … 1.98 (0.82-4.76) Chronic cough … 0.75 (0.34-1.66) … … 0.79 (0.39-1.62) … … 1.68 (0.67-4.22) Bronchitic symptoms … 0.75 (0.46-1.24) … … 0.92 (0.58-1.44) … … 1.61 (0.83-3.10) O3 (8.77 ppb) Bronchitis … … 0.85 (0.59-1.23) … … 0.93 (0.64-1.33) 0.76 (0.52-1.12) 0.72 (0.43-1.20) Chronic phlegm … … 0.87 (0.57-1.32) … … 0.92 (0.60-1.42) 0.75 (0.48-1.17) 0.61 (0.33-1.13) Chronic cough … … 0.64 (0.42-0.99) … … 0.65 (0.42-1.02) 0.61 (0.38-0.98) 0.49 (0.26-0.93) Bronchitic symptoms … … 0.82 (0.60-1.11) … … 0.88 (0.64-1.21) 0.71 (0.51-0.98) 0.64 (0.41-1.00) T

wo-stage hierarchical analysis adjusting for age, sex, parental education, yearly income, during of breastfeeding, maternal sm

oking during pregnancy

, environmental tobacco smoke, cockroaches note

monthly

, carpet, pets, home dampness and mold, parental atopy

. CO 5 carbon monoxide; NO 2 5 nitrogen dioxide; O 3 5 ozone; OR 5 odds ratio; PM 2.5 5

particles with aerodynamic diameter 2.5

m m or less; SO 2 5 sulfur dioxide.

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T

able 3—

Adjusted ORs and 95% CIs of Bronchitic Symptoms Among Children W

ithout Asthma in T wo-Pollutant Models Symptom T wo-Pollutant Model 1 (NO 2 1 SO 2 ) T wo-Pollutant Model 2 (NO 2 1 PM 2.5 ) T wo-Pollutant Model 3 (NO 2 1 O 3 ) T wo-Pollutant Model 4 (CO 1 SO 2 ) T wo-Pollutant Model 5 (CO 1 PM 2.5 ) T wo-Pollutant Model 6 (CO 1 O 3 ) T wo-Pollutant Model 7 (SO 2 1 O 3 ) T wo-Pollutant Model 8 (PM 2.5 1 O 3 ) NO 2 (8.79 ppb) Bronchitis 1.11 (0.76-1.63) 1.05 (0.78-1.42) 0.98 (0.71-1.35) … … … … … Chronic phlegm 0.83 (0.54-1.28) 0.91 (0.62-1.32) 1.12 (0.80-1.58) … … … … … Chronic cough 1.49 (0.94-2.35) 1.29 (0.86-1.94) 1.27 (0.87-1.86) … … … … … Bronchitic symptoms 1.06 (0.88-1.10) 1.06 (0.82-1.39) 1.06 (0.83-1.34) … … … … … CO (105 ppb) Bronchitis … … … 1.05 (0.90-1.22) 1.04 (0.90-1.21) 1.02 (0.87-1.20) … … Chronic phlegm … … … 0.93 (0.78-1.11) 0.94 (0.79-1.12) 1.06 (0.89-1.26) … … Chronic cough … … … 1.16 (0.97-1.39) 1.16 (0.97-1.38) 1.18 (0.98-1.42) … … Bronchitic symptoms … … … 1.02 (0.90-1.15) 1.02 (0.90-1.15) 1.04 (0.91-1.17) … … SO 2 (1.31 ppb) Bronchitis 0.93 (0.80-1.07) … … 0.94 (0.83-1.06) … … 0.95 (0.83-1.09) … Chronic phlegm 1.14 (0.98-1.33) … … 1.11 (0.98-1.26) … … 1.04 (0.93-1.18) … Chronic cough 0.90 (0.76-1.07) … … 0.96 (0.83-1.10) … … 0.98 (0.84-1.14) … Bronchitic symptoms 0.99 (0.88-1.10) … … 1.00 (0.91-1.10) … … 0.99 (0.90-1.27) … PM 2.5 (16.84 µg/m 3 ) Bronchitis … 0.83 (0.63-1.10) … … 0.82 (0.62-1.10) … … 0.73 (0.49-1.10) Chronic phlegm … 1.35 (0.95-1.90) … … 1.32 (0.96-1.81) … … 0.97 (0.64-1.47) Chronic cough … 0.95 (0.64-1.39) … … 1.01 (0.71-1.44) … … 1.05 (0.63-1.76) Bronchitic symptoms … 0.95 (0.74-1.22) … … 0.97 (0.77-1.23) … … 0.85 (0.62-1.15) O 3 (8.77 ppb) Bronchitis … … 0.96 (0.79-1.18) … … 0.97 (0.79-1.21) 0.99 (0.80-1.23) 1.13 (0.86-1.47) Chronic phlegm … … 1.35 (1.07-1.69) … … 1.37 (1.08-1.75) 1.28 (1.03-1.59) 1.34 (1.00-1.78) Chronic cough … … 1.02 (0.80-1.32) … … 1.07 (0.82-1.39) 1.02 (0.79-1.32) 0.98 (0.69-1.39) Bronchitic symptoms … … 1.07 (0.91-1.25) … … 1.08 (0.91-1.28) 1.07 (0.90-1.27) 1.15 (0.93-1.43) T

wo-stage hierarchical analysis adjusting for age, sex, parental education, yearly income, during of breastfeeding, maternal sm

oking during pregnancy

, environmental tobacco smoke, cockroaches note

monthly

, carpet, pets, home dampness and mold, parental atopy

. See T

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diesel-powered motor. NO

2

, CO, and PM

2.5

are

com-monly from both types of emissions. In the present

study, NO

2

and CO concentrations were highly

cor-related and SO

2

and PM

2.5

concentrations were also

correlated. In the modeling, we were able to control

for one pollutant (SO

2

or PM

2.5

) at a time as a

poten-tial confounder when assessing the effect of the other

pollutant (NO

2

or CO) and vice versa .

Synthesis With Previous Knowledge

In the present study, we found an 80% increase in

the prevalence of bronchitic symptoms per 8.79 ppb

increase in NO

2

and a 30% increased prevalence of

bronchitic symptoms per 105 ppb increase in CO

exposure among children with asthma. In addition,

we showed a 30% increased prevalence of chronic

phlegm per 8.77 ppb in O

3

among children without

asthma.

Seven previous studies from southern California,

2,7

the eastern United States,

10,11

_Germany,

3

Switzer-land,

12

_{and Poland}

13

_{have elaborated the relationships}

between exposure to outdoor air pollutants and the

risk of bronchitic symptoms, but only two studies

2,3

focused on children with asthma. Our present study

and a southern California study

2

_{reported an increased}

risk for NO

2

, but the fi ndings are inconsistent for SO

2

,

PM

2.5

, and O

3

.

2,3

Two surveys conducted in six and 24 cities in the

eastern United States showed positive associations

between exposure to NO

2

, SO

2

, and PM

2.5

and the

prevalence of chronic cough and bronchitis.

10,11

_{In a}

cross-sectional study carried out in southern

Califor-nia, increased bronchitic symptoms were associated

the home for two reasons. The schools were chosen

to be in the vicinity of monitoring stations. Because

the density of middle schools in Taiwan is very high,

almost all children attended schools within 1 km of

their homes. In addition, the two-stage hierarchical

models took both individual-level and

community-level information into account, which would make

our results more valid.

From previous literature, we know that a high

pro-portion of outdoor air pollutants (NO

2

, CO) penetrate

indoors.

8,9

_{Most of the Taiwanese schoolchildren}

spend at least 8 h/d in the school. Air conditioning is

rare in Taiwanese classrooms. In addition,

mechani-cal fi ltration is practimechani-cally the only type of fi ltration in

Taiwanese homes during the summer, even if the

home is air conditioned. Any known or unknown

fac-tors, such as time outdoors, level of exercise, exchange,

and deposition as well as penetration of air pollutants

into the indoor microenvironments could be

attributed to the potential problem of exposure misclassifi

-cation using community-level exposure to represent

personal exposure. This is also a limitation in all

pre-vious studies assessing the effects of ambient air

pol-lution on risk of respiratory illnesses/symptoms

among children.

Assessment of the independent effects of different

pollutants is diffi cult, because urban air pollution

constitutes a complex mixture of several compounds.

Although all the measured pollutants have several

sources, NO

2

and CO are predominantly from

natu-ral gas power plant combustion, whereas the main

sources of SO

2

and PM

2.5

are stationary fossil

com-bustion processes. In addition, busy roads typically

have two types of vehicles, gasoline-powered and

Table 4— Mean and Distribution of 3-y Average Air Pollutant Concentrations Between Communities, Taiwan 2005-2007

Pollutant Mean 6 SD Minimum Maximum Interquartile Range

NO 2 , ppb 17.68 6 0.25 10.06 26.83 8.79 CO, 100 ppb 5.24 6 0.06 3.04 7.78 1.05 SO 2 , ppb 4.33 6 0.10 2.16 10.09 1.31 PM 2.5 , m g/m 3 33.38 6 0.50 19.83 51.34 16.84 O 3 , ppb 44.64 6 0.39 30.34 59.12 8.77 Temperature, °C 24 6 1.04 22.46 25.91 1.23 Relative humidity 74.0% 6 3.0% 69.0% 80.0% 4.3%

See Table 2 for expansion of abbreviations.

Table 5— Correlations of Air Pollutants Across 14 Communities

Pollutant NO 2 CO SO 2 PM 2.5 O 3 N O 2 1.00 0.86 a 0.55 a 0.37 2 0.07 CO … 1.00 0.16 0.09 2 0.33 SO 2 … … 1.00 0.68 a 0.37 PM 2.5 … … … 1.00 0.73 a O 3 … … … … 1.00

See Table 2 for expansion of abbreviations.

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symptoms with asthma was not related to the levels of

PM

_2.5

, it was likely that there was an association with

OC in PM typically present in motor vehicle exhausts

and in particular in diesel exhausts. Further studies

should assess these relationships.

Our fi ndings also suggested that the prevalence of

chronic phlegm without asthma was related to O

₃

exposure. O

₃

is a secondary pollutant in the

atmo-sphere produced from traffi c exhausts but scavenged

by direct motor vehicle emissions. O

₃

is a known

respiratory irritant and has been shown to increase

the synthesis of the allergic antibody IgE in human

beings.

16

_{It could increase sensitization to common}

allergens and infl uence the development of phlegm.

Conclusion

The present study provides additional evidence

that exposure to outdoor air pollutants increases the

prevalence of bronchitic symptoms with asthma and

without asthma in schoolchildren. The prevalence

of bronchitic symptoms with asthma was related to

NO

₂

and CO exposure. The present fi ndings also

suggest that exposure to O

₃

may increase the

preva-lence of chronic phlegm among children without

asthma.

with the levels of NO

₂

and PM

_2.5

.

7

_{Later, a}

prospec-tive southern California study found posiprospec-tive

associa-tions between bronchitic symptoms with asthma and

NO

₂

, organic carbon (OC), and PM

_2.5

.

2

_{The risks of}

bronchitic symptoms with asthma were associated

with NO

₂

, OC, and PM

_2.5

. In a cohort study

con-ducted in Germany, the risk of bronchitic symptoms

with asthma was elevated for PM

_2.5

.

3

_{In a study}

of Swiss schoolchildren, the risk of bronchitis was

associated with NO

₂

, SO

₂

, and PM

₁₀

for the most-

compared with the least-polluted community.

12

A survey in Poland found that outdoor air pollution

level was associated with an increased risk of chronic

phlegm.

13

The possible mechanisms of NO

₂

are through

interaction with the immune system or impairment

of respiratory response to infection, which could

result in increased risk of bronchitic symptoms.

14,15

There are no plausible mechanisms through which

CO exposure would infl uence the airways and

increase the risk of bronchitic symptoms. In the

pres-ent study, it was not possible to elaborate to what

extent NO

₂

would have direct effects on children’s

airways. CO is unlikely to have any direct effects on

the airways. Our results did not show any association

between the prevalence of bronchitic symptoms with

asthma and PM

_2.5

. Although the risk of bronchitic

Table 6— Adjusted ORs and 95% CIs of Bronchitic Symptoms Among Patients With and Without Asthma in Single Pollutant Models Symptoms Asthma No Asthma OR 95% CI OR 95% CI Bronchitis (n 5 81/373) (n 5 205/4,666) NO 2 (8.79 ppb) 1.83 1.07-3.14 0.99 0.72-1.35 CO (105 ppb) 1.28 0.99-1.65 1.03 0.88-1.20 SO 2 (1.31 ppb) 1.11 0.90-1.38 0.95 0.84-1.07 PM 2.5 (16.84 m g/m 3 ) 0.96 0.57-1.62 0.83 0.62-1.11 O 3 (8.77 ppb) 0.84 0.60-1.19 0.96 0.79-1.18 Chronic phlegm (n 5 53/373) (n 5 164/4,636) NO 2 (8.79 ppb) 1.52 0.83-2.78 1.04 0.72-1.51 CO (105 ppb) 1.22 0.92-1.63 0.97 0.81-1.16 SO 2 (1.31 ppb) 1.20 0.95-1.51 1.10 0.97-1.24 PM 2.5 (16.84 m g/m 3 ) 1.17 0.65-2.11 1.30 0.94-1.79 O 3 (8.77 ppb) 0.86 0.58-1.28 1.32 1.06-1.63 Chronic cough (n 5 52/376) (n 5 119/4,676) NO 2 (8.79 ppb) 1.12 0.53-2.40 1.28 0.87-1.85 CO (105 ppb) 1.14 0.79-1.64 1.16 0.97-1.38 SO 2 (1.31 ppb) 0.98 0.73-1.33 0.98 0.85-1.13 PM 2.5 (16.84 m g/m 3 ) 0.83 0.40-1.71 1.03 0.72-1.47 O 3 (8.77 ppb) 0.65 0.42-0.99 1.01 0.79-1.28 Bronchitic symptoms (n 5 137/376) (n 5 429/4,676) NO 2 (8.79 ppb) 1.81 1.14-2.86 1.04 0.82-1.33 CO (105 ppb) 1.31 1.04-1.64 1.02 0.90-1.15 SO 2 (1.31 ppb) 1.17 0.97-1.40 1.00 0.91-1.10 PM 2.5 (16.84 m g/m 3 ) 0.99 0.63-1.57 0.98 0.78-1.23 O 3 (8.77 ppb) 0.80 0.59-1.09 1.06 0.91-1.25

Two-stage hierarchical analysis adjusting for age, sex, parental education, yearly income, during of breastfeeding, maternal smoking during pregnancy, environmental tobacco smoke, cockroaches note monthly, carpet, pets, home dampness and mold, parental atopy. See Table 2 for expansion of defi nitions.

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Acknowledgments

Author contributions: Dr Hwang: contributed to coordinating the data analysis, data interpretation, and writing the draft of this paper.

Dr Lee: contributed as the coordinator of Taiwan Children Health Study and was involved with the critical revision of the manuscript.

Financial/nonfi nancial disclosures: The authors have reported to CHEST that no potential confl icts of interest exist with any companies/organizations whose products or services may be dis-cussed in this article .

Other contributions: We thank all the fi eld workers who sup-ported data collection, the school administrators and teachers, and especially the parents and children who participated in this study.

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