Objective. Parental atopy and environmental exposures are recognized risk factors for childhood asthma. However, the relative contributions of specific risk factors and the overall contributions of indoor and outdoor exposures remain unexplored. This study was undertaken to identify risk factors, estimate the population attributable risk of each exposure, and compare the data for boys versus girls for physician-diagnosed asthma in Taiwanese schoolchildren.
Methods. During a February to June 2001 cross-sectional national survey, 35 036 6- to 15-year-old schoolchildren were chosen from 22 elementary and 22 middle schools located within 1-km catchment areas of 22 air-monitoring stations in Taiwan. The main outcome measure was physician-diagnosed asthma, as reported by the parents. We investigated hereditary and indoor and outdoor environmental factors for childhood asthma by questionnaire. The adjusted prevalences of questionnaire-determined outdoor indicators were also compared with air-monitoring data.
Results. Outdoor air pollutants were associated with parent-reported perceived ambient air pollution. Physician-diagnosed asthma was reported for 8.1% of the boys (1330 of 16 441) and 5.6% of the girls (894 of 16 056). The risk of physician-diagnosed asthma was significantly associated with parental atopy and perceived ambient air pollution in both sexes. The presence of visible cockroaches (odds ratio [OR]: 1.30; 95% confidence interval [CI]: 1.07–1.59), mold on walls at home (OR: 1.20; 95% CI: 1.01–1.41), and water damage (OR: 1.33; 95% CI: 1.02–1.70) were also associated with asthma in girls; however, only visible mold on walls at home was related to asthma in boys. Mutually adjusted analytical models produced statistically significant associations between any indoor factor and asthma in girls (OR: 1.24; 95% CI: 1.00–1.56) but not in boys (OR: 1.04; 95% CI: 0.87–1.25). For all hereditary and environmental factors, the total population attributable risk was 44.31% in boys and 60.61% in girls.
Conclusions. Parental atopy contributed more to childhood asthma than indoor or outdoor environmental factors. Girls may be more susceptible to indoor factors than boys.
- environmental exposure
- parental atopy
- water damage
- air pollution
- population attributable risk
Asthma is the single most common chronic childhood disease in developed nations,1,2 and its prevalence and severity have been reported as increasing in many countries.3–6 The changing pattern of the disease has not been fully explained, in part because of an incomplete understanding of its pathogenesis. The change has been too rapid to be accounted for by changes in gene frequencies. It is also unlikely that the increase can be totally accounted for by changes in either clinical diagnostic patterns or increased recognition of asthma symptoms by the general population.7 This does, however, suggest a role for environmental exposures in the cause of this evolving epidemic.8
Many factors have been proved to be associated with the prevalence and/or attacks of asthma, including personal factors (smoking habits, genetics, age, sex, nutritional status, number of siblings, coexisting lung disease, lifestyle, allergy status, family history, and occupation) and environmental stimuli (house dust, animal danders, molds, cockroach infestation, occupational exposure, environmental tobacco smoke, indoor/outdoor air pollution, cooking fumes, aeroallergens, and climate).9–29 Both genetic and environmental factors are believed to contribute to the relationship. However, epidemiologic evidence concerning different effects in boys and girls in relationships between environmental exposures and childhood asthma was insufficient and warranted additional investigations.
The first aim of this study was to investigate the relationship between physician-diagnosed asthma and selected risk factors in a population-based sample of 6- to 15-year-old elementary- and middle-school children. Second, the prevalences of questionnaire-determined outdoor indicators in each community were compared with air-monitoring station data to see their representativeness. Finally, we estimated the population attributable risk (PAR) of each exposure category and compared the data for boys and girls.
The International Study of Asthma and Allergies in Childhood (ISAAC) is a multinational collaborative project developed to investigate variations in childhood asthma and allergies at the population level.30 Phase I of the ISAAC study was designed to use core questionnaires to assess the prevalence and severity of asthma and other allergic diseases.30 Between February and June 2001, we modified the ISAAC protocol and conducted a national, cross-sectional, school-based phase I survey of middle- and elementary-school children. Classroom incentives but not individual incentives were used to encourage participation. The study protocol was approved by the Respiratory Health Screening Steering Committee of the Taiwan Department of Health and the Institutional Review Board at our university hospital, and it complied with the principles outlined in the Helsinki Declaration.31 The standard ISAAC-Chinese version questionnaire was taken home by students and answered by parents. The definition of “asthma” used in this study was determined by a positive response to the question, “Has a physician ever diagnosed you as having asthma?”
To compare outdoor air pollution data with questionnaire results, the study population was limited to children who attended schools located within 1 km of Taiwan Environmental Protection Agency air-monitoring stations. Complete monitoring data for the 5 criteria air pollutants sulfur dioxide (SO2), nitrogen oxides (NOx), ozone (O3), carbon monoxide (CO), and particles with an aerodynamic diameter of 10 μm or less (PM10) were available from Environmental Protection Agency monitoring stations on Taiwan’s main island since 1994. Concentrations of each pollutant were measured continuously and reported hourly—CO by nondispersive infrared absorption, NOx by chemiluminescence, O3 by ultraviolet absorption, SO2 by ultraviolet fluorescence, and PM10 by β-gauge. Twenty-two of the 875 middle schools and 22 of the 2604 elementary schools in Taiwan’s 22 counties were investigated. Stratified sampling by grade was applied in each school. We believed that our study population based on 22 different areas covering diverse parts of Taiwan was representative of Taiwanese elementary- and middle-school children.
We reviewed the English literature on the causes of asthma to identify the hereditary and environmental risk factors for childhood asthma. Our focus was residential factors that might be changed by climate and were not related directly to human behaviors. These included cockroaches, water damage, and visible mold on walls at home. Self-perceived ambient air pollution level was also answered as an outdoor factor. Parental atopy was a measure of genetic predisposition and defined by reports of the father or the mother of the index child’s ever having received a diagnosis of asthma, allergic rhinitis, or atopic eczema. To adjust for possible confounding, we also included host-related variables: the child’s age and sex, maternal smoking during pregnancy, the number of siblings at home, and the educational level of the household head. Unfortunately, neither blood samplings nor skin tests were performed in our large nationwide study design.
Previously reported analyses of ecological outcomes have demonstrated a larger inter-city variation than would be predicted by interindividual variation.9,32 We used 2-stage methods to correct for any excess between-site variability. In the first step, a regression model was used to control for parental education level. In the second step, the community-specific adjusted prevalences of parentally reported perceived ambient air pollution levels were regressed against the annual means of outdoor air pollutants in 2000; the regression used weights inversely proportional to the sum of the between-site and within-site variances. Statistical significance was set at P < .05.
We performed bivariate analyses to determine associations with physician-diagnosed asthma. All risk factor were categorized into 3 groups of factors—hereditary, indoor environmental, and outdoor environmental factors—and then we developed multiple logistic regression models to assess the relative effectiveness of each on physician-diagnosed asthma. We calculated 95% confidence intervals (CIs) for odds ratios (ORs), and those that did not include one were considered statistically significant. PARs were also calculated to estimate the contribution of various risk factors for asthma. PAR represents those cases of asthma that would be prevented if children were not exposed to specific agents or risk factors. PAR was calculated using the formula P(R − 1)/[P(R − 1) + 1], where P is the prevalence of the exposure and R is the relative risk as a result of the exposure.33
Our study surveyed 35 036 children from 22 elementary and 22 middle schools. The rate of satisfactory responses was 92.8% (16 441 boys and 16 056 girls and their parents). All subjects were between 6 and 15 years of age. Overall, 8.1% of the boys and 5.6% of the girls had physician-diagnosed asthma (Table 1). In the year 2000 in Taiwan, the national public and private elementary and middle school populations were approximately 1.48 million boys and 1.36 million girls, so these prevalences correspond to approximately 195 300 schoolchildren aged 6 to 15 years. Table 1 also shows the characteristics of study subjects. Younger subjects, higher parental education level, fewer siblings, and maternal smoking during pregnancy were found to be associated with the occurrence of childhood asthma.
After adjustment for parental education level, the effects of each outdoor air pollutant on parentally reported perceived ambient air pollution levels were assessed separately and also expressed as ORs for a change by 1 standard deviation (Table 2). In the regression model in which P values were calculated, statistically significant associations were found for SO2, CO, PM10, and NOx in prevalences of any ambient air pollution and moderate to severe ambient air pollution in the 22 target communities. Relatively weak and nonsignificant associations were noted for O3. In addition, all outdoor air pollutants had relatively stronger predictive effects on the prevalence of perceived moderate to severe air pollution than on the prevalence of perceived mild to severe air pollution level (Table 2).
After adjustment for host factors such as age, parental education level, number of siblings, and maternal smoking during pregnancy, we found that parental asthma, parental allergic rhinitis/atopic eczema, and parentally reported perceived ambient air pollution were significantly related to physician-diagnosed asthma in both sexes (Table 3). Girls who lived at home with visible cockroaches were 1.30 times more likely to develop and receive a diagnosis of asthma. The presence of visible mold on walls at home (OR: 1.20; 95% CI: 1.01–1.41) and water damage (OR: 1.33; 95% CI: 1.02–1.70) were also independently associated with physician-diagnosed asthma in girls. However, asthma in boys was associated only with visible mold on walls at home (OR: 1.27; 95% CI: 1.10–1.47). Although mutually adjusted models were applied, we found that adjusted ORs and PARs were similar in boys and girls in hereditary and outdoor environmental factors (Table 3). Statistically significant associations between indoor factors—defined as visible cockroaches, water damage, or visible mold on walls at home—and physician-diagnosed asthma was noted in girls (OR: 1.24; 95% CI: 1.00–1.56) but not in boys (OR: 1.04; 95% CI: 0.87–1.25). The PAR of indoor environmental factors was >5 times higher in girls (16.68%) than in boys (3.20%). For all of the hereditary and environmental factors that we identified, the total PARs were 44.31% in the boys and 60.61% in the girls of our population.
Of the estimated 195 300 cases of physician-diagnosed asthma in 6- to 15-year-old Taiwanese elementary- and middle-school children, we estimated that >55 900 excess cases of asthma were attributable to hereditary factors—defined as parental asthma or allergic rhinitis/atopic eczema. Exposure to ambient air pollution accounted for approximately 26 500 excess cases. Indoor factors accounted for 16 500 excess cases (12 700 girls but only 3800 boys).
Our cross-sectional ISAAC questionnaire survey of 6- to 15-year-old school children in Taiwan for asthma linked to local air-monitoring data demonstrated that outdoor air pollutants were significantly associated with parentally reported perceived ambient air pollution in the areas that we studied. In addition, it showed that girls seemed more susceptible than boys to indoor factors, especially cockroaches and water damage. We also found approximately 16 500 excess cases of asthma attributable to indoor factors and 26 500 attributable to outdoor ambient air pollution. The effect of eliminating these indoor/outdoor risk factors, if they are indeed causal, would have a profound impact on hospitalization rates, clinic and emergency department visits, and medication use in children.34
Questionnaires have been used widely to assess the prevalence of asthma. Asthma was usually defined as current asthma (ie, wheezing within the past 12 months). We used lifetime prevalence of physician-diagnosed asthma as our outcome measurement in determining risk factors. Underestimating the true prevalence of asthma may occur if parental reports of physician-diagnosed asthma are used. However, our rates of 8.1% and 5.6% were similar to those found in previous questionnaire studies involving 12-year-old children in Switzerland (5.9%)35 and in Chile (8.0%)36 and in 7- to 11-year-old Asian children in the United Kingdom (6.2%).37 Higher asthma prevalence was found in children in England (13.1%)38 and Australia (23.2%).36 The causality of substantial difference could not be determined in our study design. Comparative or secular studies are warranted in future investigations.
Younger subjects and boys had a higher rate of physician-diagnosed asthma, which was consistent with other studies,8,9,12,14,21,34,35 and the level of parental education and number of siblings were associated with the occurrence of childhood asthma. Parents with a higher education level and fewer children were more anxious about the specific health condition of their children; therefore, these children would be more likely to receive a diagnosis of asthma. Moreover, the level of exposure to allergens was actually lower at higher socioeconomic levels or in smaller families, which would result in the protection effect for their children and make them more susceptible to specific allergens at an older age.10,11 Because all of these factors were potential confounders in risk factors analyses, they were controlled as covariates. Although not statically significant, maternal smoking during pregnancy was also a positive predictor of asthma in our population, which was consistent with the finding in a recent report from the Avon Longitudinal Study of Pregnancy and Childhood.12 We also treated it as a confounder, which was adjusted in the following multiple regression analysis.
Daily cigarette consumption in families and incense burning at home showed negative effects to the occurrence of childhood asthma (Table 1), which were consistent with recent international studies.13,14 The possible explanation could be that cigarette smoking and incense use might be reduced by families with children with atopic diseases. Exposure to tobacco or incense might also provide protective effects for childhood asthma through selection mechanisms, especially in cross-sectional study. Unlike tobacco or incense exposures, the indoor environmental factors that we chose, including cockroaches, water damage, and visible mold on walls at home, would not be changed easily on human behaviors and would not show negative effects to asthma (Table 1). Pet ownership has been a potential risk factor for asthma. However, considering that asthmatic families tended to avoid pet raising15,16 and that our cross-sectional design did not allow for delineation of cause and outcome between pet raising and asthma, this question was not inquired about in this investigation. We decided not to include them as indoor factors or covariates because inclusion of these factors might have given significant associations, but they would have been difficult to interpret for causality.
The ecologic exposure assessment had many advantages in our study. The density of elementary and middle schools in Taiwan is very high, and almost all of the surveyed children attended schools within 1 km of their homes. Monitoring stations located near the schools were also likely to be near the students’ homes and thus provided good indicators for both school and home exposure. A preliminary Taiwanese study suggested that parental ranking of the air pollution level was a good predictor for childhood asthma,17 which also demonstrated an apparent dose-response relationship. We also proved that the questionnaire-determined perceived ambient air pollution level was associated with outdoor air pollutants, and the association was stronger when more severe air pollution level was reported (Table 2). NOx have been proved to be acute respiratory irritants in animal and controlled human exposure studies.18 Although never known to be a respiratory irritant, SO2 is known to induce respiratory symptoms.19 In fact, both had aversive odors and showed relative stronger effects in our results. O3 had a weaker effect on the questionnaire-determined perceived ambient air pollution. One possible explanation considered was that it was formed at some distance from emission sources and scavenged in downtown areas by nitrogen monoxide from motor vehicle exhaust.39 O3, known as a secondary air pollutant, was dependent on other air pollutants and therefore showed a relatively weak and nonsignificant association.
In Taiwan, cockroaches and dust mites are the 2 prevalent allergens for individuals with asthma. In our preliminary study,20 sensitization to cockroach allergens and house dust mites, rather than cat or dog dander, was also associated with lower pulmonary functions. We found the risk of visible cockroaches at home greater for girls than for boys. A German study21 demonstrated that water-related damage at home was associated with the amount of house dust-mite antigen in the dust vacuumed from the children’s mattresses. Waegemaekers et al22 assessed the risk of asthma related to residential dampness stratified by sex and found a greater risk in women (OR: 4.16) than in men (OR: 1.15), which was consistent with our result. A recent case-control study in Finland23 found a relatively stronger effect between workplace mold and asthma development in women (OR: 1.67) than in men (OR: 1.26). A cohort study of schoolchildren in Japan24 found a significant association between the prevalence of respiratory symptoms and indoor nitrogen dioxide in girls but not in boys. A Swedish study,25 however, reported an essentially similar risk of asthma related to visible mold growth among men (OR: 2.7) and women (OR: 2.0). Pershagen et al26 also suggested that environmental exposure did not differ between boys and girls. Our results showed associations between asthma and visible mold at home after adjustment for covariates in both sexes. When we estimated the effect of having any indoor environmental exposure for physician-diagnosed asthma, a statistically significant association was noted in girls but not in boys. After controlling for hereditary and outdoor environmental factors, the significant and relatively stronger effects still showed in girls but not in boys. The mechanism of such female-led susceptibility is not known and warrants additional study. One reason considered was that girls might have more extensive exposures because they are relatively inactive and spend more time at home and, therefore, are more influenced by the indoor environment.
A family history of allergic diseases was associated with an increased risk of asthma, suggesting that genetic factors play a central role in the development of asthma.27–29 Some genetic markers could impose susceptibility to the effects of environmental factors in childhood.27 A recent Malaysian cross-sectional study28 found that parental asthma was also the strongest determinant of asthma development in children. In a twin study from Denmark,29 73% of the variation in liability to childhood asthma was explained by genetic factors, which suggested that a family history of asthma was stronger than other risk factors. Our study demonstrated that paternal and maternal asthma were stronger risk factors for childhood asthma in both sexes than were allergic rhinitis and atopic eczema in parents (Table 3). Children with a parent carrying any atopic disease were also found to have a higher probability of developing asthma in later life than those who lived at home with indoor or outdoor factors. In the mutually adjusted models, hereditary factors—defined as parental asthma or allergic rhinitis/atopic eczema—also possessed the highest attributable risks, which were consistent with 55 900 excess cases annually in Taiwan.
It is difficult to target asthma prevention efforts. Fewer than half (49%) of the children with asthma in our analysis had a parental history of atopy, and only 13.8% of those boys and 9.9% of those girls had physician-diagnosed asthma. If interventions target only families with a history of atopy, then more than half of the children who will receive a diagnosis of asthma between the ages of 6 and 15 years will be neglected, and only approximately 12% will potentially benefit. Indoor/outdoor environmental exposures showed relatively small but substantial effects on childhood asthma in our study. However, it seems easier to eliminate such exposures on a national scale than to attempt to counter hereditary factors. Additional research is necessary to prove that the elimination of indoor/outdoor exposures will result in lower rates of childhood asthma.
Our study has some limitations. This was a study of asthma prevalence in schoolchildren between 6 and 15 years of age, not of asthma incidence40; for example, a small number of families relocated, and some of the factors that we studied might have affected asthma prevalence through effects on disease duration rather than disease incidence. Bias could also be introduced if differential changes of environmental exposures showed. However, our findings were of interest and truly existed, regardless of whether the observed associations were caused by effects from incidence or duration. In fact, if factors were found to be associated with asthma prevalence, then they were of major interest in themselves, irrespective of whether the etiologic mechanism involved increases in disease incidence or duration.
Because we were unable to measure personal environmental exposures or sensitization to various allergens, such as dust mites, fungi, or cockroaches, we might have underestimated the effects of these indoor factors to childhood asthma. Outdoor environmental exposure was served only by a proxy of self-perceived air pollution level, which must be an imprecise way to measure the influence of environmental exposure. Another potential source of bias was in the interpretation of parental history for atopy/asthma as an indication of a genetic predisposition to childhood asthma. Although the importance of parental history as a predictor of disease has been demonstrated,27–29 not every child in the family inherits the allergic tendency. Therefore, in the presence of a true association, misclassification of exposure that was random with respect to other study variables would weaken the observed association rather than lead to false-positive inferences. Ecologic confounders such as urbanization and socialization actually could exist in data analysis, and there might be incomplete adjustment and residual confounding. More complete personal risk factors, however, were very difficult to obtain in such a large-scale survey. Investigators decided not to try to obtain more personal information, because it would have resulted in a lower participation rate and would have introduced greater bias in the study. The number of covariates was therefore limited, as in many other large-scale studies.
We identified a number of hereditary and indoor/outdoor environmental factors associated with physician-diagnosed asthma in Taiwanese schoolchildren. Parental atopy contributed more to childhood asthma than did indoor or outdoor environmental factors. Exposure to indoor/outdoor environmental factors increased the risk of asthma in children regardless of the coexisting hereditary factors. Girls might be more susceptible to indoor factors than boys. The present findings suggest that public health policy for eliminating certain indoor/outdoor factors are needed, which could have large effects not only on children’s health but also on medical costs in Taiwan.
This study was supported in part by grant DOH90-TD-1138 from the Taiwan Department of Health. Dr Lee was also a receipt of the Taiwan National Health Research Institute MD-PhD Predoctoral Fellowship (DD9102N).
- ↵Janson C, Chinn S, Jarvis D, Burney P. Physician diagnosed asthma and drug utilization in the European Community Health Survey. Eur Respir J.1997;10 :1795– 1802
- ↵Magnus P, Jaakkola JJK. Secular trend in the occurrence of asthma among children and young adults: critical appraisal of repeated cross sectional surveys. BMJ.1997;314 :1795– 1799
- Ng Man Kwong G, Proctor A, Billings C, et al. Increasing prevalence of asthma diagnosis and symptoms in children is confined to mild symptoms. Thorax.2001;56 :312– 314
- ↵Palmer LJ, Valinsky IJ, Pikora T, Zubrick SR, Landau LI. Environmental factors and asthma and allergy in schoolchildren from Western Australia. Eur Respir J.1999;14 :1351– 1357
- ↵Lux AL, Henderson AJ, Pocock SJ, et al. Wheeze associated with prenatal tobacco smoke exposure: a prospective, longitudinal study. Arch Dis Child.2000;83 :307– 312
- ↵Nicolai T, Illi S, von Mutius E. Effect of dampness at home in childhood on bronchial hyperreactivity in adolescence. Thorax.1998;53 :1035– 1040
- ↵Shima M, Adachi M. Effect of outdoor and indoor nitrogen dioxide on respiratory symptoms in schoolchildren. Int J Epidemiol.2000;29 :862– 870
- ↵Pershagen G, Rylander E, Norberg S, Eriksson M, Nordvall SL. Air pollution involving nitrogen dioxide exposure and wheezing bronchitis in children. Int J Epidemiol.1995;24 :1147– 1153
- ↵Quah BS, Mazidah AR, Simpson H. Risk factors for wheeze in the last 12 months in preschool children. Asia Pac J Allergy Immunol.2000;18 :73– 79
- ↵Skadhauge LR, Christensen K, Kyvik KO, Sigsgaard T. Genetic and environmental influence on asthma: a population-based study of 11, 688 Danish twin pairs. Eur Respir J.1999;13 :8– 14
- ↵Asher MI, Keil U, Anderson HR, et al. International study of asthma and allergies in childhood (ISAAC): rationale and methods. Eur Respir J.1995;8 :483– 491
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- ↵Taylor WR, Newacheck PW. Impact of childhood asthma on health. Pediatrics.1992;90 :657– 662
- ↵Pararajasingam CD, Sittampalam L, Damani P, et al. Comparison of the prevalence of asthma among Asian and European children in Southampton. Thorax.1992;47 :529– 533
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