Department of Public Health, Chiba University School of Medicine, Chiba 260-8670, Japan.
Reprint requests to: Masayuki Shima, Department of Public Health, Chiba University School of Medicine, 181 Inohana, Chuo-ku, Chiba 260-8670, Japan. E-mail: sima{at}med.m.chiba-u.ac.jp
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Abstract |
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Methods A cohort study was carried out over 3 years on 842 schoolchildren living in seven different communities in Japan. Indoor NO2 concentrations over 24 hours were measured in both winter and summer in the homes of the subjects, and a 3-year average of the outdoor NO2 concentration was determined for each community. Respiratory symptoms were evaluated every year from responses to questionnaires.
Results The prevalence of bronchitis, wheeze, and asthma significantly increased with increases of indoor NO2 concentrations among girls, but not among boys. In neither boys nor girls were there significant differences in the prevalence of respiratory symptoms among urban, suburban, and rural districts. The incidence of asthma increased among children living in areas with high concentrations of outdoor NO2. Multiple logistic regression analysis showed that a 10 parts per billion (ppb) increase of outdoor NO2 concentration was associated with an increased incidence of wheeze and asthma (odds ratios [OR] = 1.76, 95% CI : 1.043.23 and OR = 2.10, 95% CI : 1.104.75, respectively), but that no such associations were found with indoor NO2 concentration (OR = 0.73, 95% CI : 0.451.14 and OR = 0.87, 95% CI : 0.511.43, respectively).
Conclusions These findings suggest that outdoor NO2 air pollution may be particularly important for the development of wheeze and asthma among children. Indoor NO2 concentrations were associated with the prevalence of respiratory symptoms only among girls. Girls may be more susceptible to indoor air pollution than boys.
Keywords Nitrogen dioxide, air pollution, indoor environment, wheeze, asthma, cohort study
Accepted 14 March 2000
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Introduction |
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The domestic use of combustion appliances also produces high indoor concentrations of NO2.11,12 In homes with unvented cooking or heating appliances, indoor concentrations of NO2 may exceed outdoor levels.13 Therefore, in evaluating the effects of ambient air pollution on human health, several studies have assessed the indoor or personal exposure levels of NO2.14,15 Because of methodological problems, however, these studies have not sufficiently evaluated the effects of indoor air pollution.13
To evaluate the effects of environmental factors on respiratory health, we conducted a series of epidemiological surveys in schoolchildren.12,16 Indoor NO2 concentrations in the homes of these children have been detailed previously.12 The objective of this study was to investigate the association of the prevalence and incidence of respiratory symptoms in children with outdoor air pollution and indoor NO2 concentrations in their homes.
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Methods |
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The 3-year average concentrations of NO2 in 19911993, measured at ambient air monitoring stations in the vicinities of these schools, were 25.331.3 parts per billion (ppb) for the urban communities, 19.3 ppb for the suburban community, and 7.010.7 ppb for the rural communities.
Questionnaire
A survey of respiratory symptoms was conducted on all the subjects in October of each year from 1992 (fourth grade) to 1994 (sixth grade). In the first survey, a standard respiratory symptom questionnaire, the modified Japanese version of ATS-DLD-78-C,17 was sent, through the schools, to the parents of all subjects. The questionnaire covered respiratory symptoms and medical history of the children, feeding method in infancy, history of allergic diseases of the parents, and smoking habits of household members, as well as certain characteristics of the house, such as the type of heating. In the second and third surveys, we used a simple questionnaire on only respiratory symptoms and on any changes in the residential environment for the past year. These questionnaires were filled out by either parent. All incomplete questionnaires, accompanied by a request for completion, were returned to the subjects.
According to the responses to the questionnaires, bronchitis was defined as any chest illness ever diagnosed as bronchitis by a physician. Wheeze was a positive response to the question Has your child had wheezing or whistling in the chest during the last 12 months? Asthma was defined as two or more episodes of wheezing accompanied by dyspnoea that had ever been given the diagnosis of asthma by a physician' and the occurrence of asthmatic attacks or the need for any medication for asthma during the past 2 years'. For children who had no previous history of wheeze or asthma in the first survey, the incidence of wheezing or asthmatic symptoms in the second or third surveys was evaluated. The definitions of wheeze and asthma were consistent across the three surveys. Children who had been diagnosed as having eczema, atopy, allergic rhinitis, or pollinosis by a physician, or who had received hyposensitization therapy, were considered to have a history of allergic diseases.
Measurements of indoor nitrogen dioxide concentration
Measurements of indoor NO2 concentrations were carried out in each subject's home on two occasions, in winter (January or February 1993) and in summer (June or July 1993). The 24-hour average concentration of indoor NO2 (ppb) was measured in the living room using badge-type samplers (Toyo Roshi, Tokyo, Japan). Details of the measurement procedure have been given elsewhere.12
For homes in which the measurement time was >22 hours and <26 hours in both seasons, the annual average of the indoor NO2 concentration was calculated as the geometrical mean of the two seasonal NO2 concentrations, according to the method described by Neas et al.14
Data analysis
The prevalence of respiratory symptoms in each survey was first compared in relation to sex, district, indoor NO2 concentration, parental smoking habits, and type of heating appliance. Annual averages of indoor NO2 concentrations were categorized in four groups: 019, 2029, 3039 and 40 ppb. The relationship between the prevalence of respiratory symptoms and indoor NO2 concentrations was estimated by Armitage's method.18
The effects of outdoor and indoor NO2 concentrations, parental smoking habits, and the use of an unvented heater in winter on the prevalence of respiratory symptoms were assessed using multiple logistic regression models, separately by sex. The models also included a history of allergic diseases, respiratory diseases under 2 years old, feeding method in infancy, and parental history of allergic diseases. The 3-year average of NO2 concentrations in 19911993, measured at the monitoring station near each school, was used as the outdoor NO2 concentration. We counted outdoor and indoor NO2 concentrations as continuous variables, and the other factors as having variables consisting of two categories.
The correlation between the incidence rate of wheeze or asthma and ambient concentration of NO2 in each community was estimated. A logistic regression model was used to evaluate the effects of various factors on the incidence of wheeze or asthma. Because wheezing symptoms arose during the study period among only 13 boys and 9 girls, and asthmatic symptoms arose among only 13 boys and 5 girls, the models combined both sexes and included sex in addition to the above factors as independent variables. All analyses were conducted using SAS software (Version 6, SAS Institute, Inc., Cary, NC).
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Results |
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The association of respiratory symptoms with outdoor and indoor NO2 concentrations was analysed using logistic regression models. The adjusted odds ratios (OR) were expressed as the effect of a 10-ppb increase in outdoor or indoor NO2 concentration in the child's home (Table 4). No significant relationship of history of allergic diseases with these environmental factors was present among either boys or girls. Among boys, neither wheeze nor asthma was associated with outdoor or indoor NO2 concentration. The factors that significantly impacted on wheeze and asthma among boys were history of allergic diseases (OR = 4.39 and 4.86, respectively) in the first survey and history of allergic diseases (OR = 2.61 and 2.98, respectively) and respiratory disease under 2 years old (OR = 2.80 and 2.94, respectively) in the second survey.
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The incidence of wheeze and asthma in the second or third surveys was evaluated among children who had no symptoms in the first survey. The incidence rates of wheeze and asthma for each community were 06.5% and 03.6%, respectively. Asthmatic symptoms tended to develop significantly with increasing outdoor NO2 concentrations (r2 = 0.783, P = 0.008, Figure 2). The logistic regression models examined the effects of various factors on incidence (Table 5
). The adjusted OR of the incidence of wheeze and asthma were 1.76 and 2.13, respectively, per 10-ppb increase in outdoor NO2 concentration; values that were significantly different from one. A history of allergic diseases was also related to a significant increase in the incidence of wheeze and asthma. Breastfeeding in infancy was related to a significant decrease in the incidence of wheeze. The effects of sex, indoor NO2, parental smoking habits, and use of unvented heaters were not significant.
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Discussion |
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In our study, the prevalence of wheeze and asthma decreased over the study period in all districts. In a British cohort, more than two-thirds of the children with a history of wheeze or asthma by age 7 experienced no attacks at age 11.21 Our subjects were observed from ages 910 to ages 1112. The remission of wheeze or asthma may be due to growth. On the other hand, some children first reported wheezing or asthmatic symptoms during the study period. The incidence rates were higher in areas with high concentrations of outdoor NO2. The relationships between outdoor NO2 and the incidence of wheeze or asthma remained significant, even after adjustment for potential confounding factors such as history of allergic diseases and indoor NO2 concentration. Respiratory symptoms were evaluated by a standardized questionnaire in the first survey, and a simple questionnaire in the second and third surveys because the latter were easy to complete. The difference in questionnaires might lead to potential bias in responses.22 However, the two questionnaires included the same questions about respiratory symptoms, and the definitions of wheeze and asthma were unified. Therefore, we have considered that misclassification due to the difference in questionnaires is minimal.
In cohort studies, a substantial number of subjects may be inevitably lost to follow-up primarily because of out-migration. Forastiere et al.23 obtained responses from 84.6% of the primary subjects after a 3.5-year interval in a cohort of children. We were able to follow up 842 children (93.0% of the subjects in the first survey) for 2 years, which satisfied the purpose of our study.
To evaluate the health effects of outdoor air pollution, the potential involvement of indoor air pollution also should be considered.1113 The use of gas cooking stoves often has been considered as a major indoor source of NO2.11,13 Several studies have shown that a gas stove in the home is a risk factor for respiratory symptoms and diseases in children,6,24 while others have failed to demonstrate such effects.25,26 In Japan, almost all homes use gas appliances for cooking, and the use of unvented heaters in winter is usually considered a source of indoor air pollution.12,16 The present study also showed that indoor NO2 concentrations were higher in homes with unvented compared to vented heaters. However, neither prevalence nor incidence of respiratory symptoms was significantly associated with type of heater.
A few studies have included measurements of NO2 in the subjects' homes. Neas et al.14 demonstrated an association between indoor NO2 concentrations and increased incidence of lower respiratory symptoms in children. Infante-Rivard25 found a dose-response relationship between personal exposure to NO2 and asthma, but NO2 measurements were conducted in only 140 children. In other studies, indoor NO2 exposure has been minimally associated with either respiratory symptoms or illnesses.26,27 Most of these studies have been conducted in only one area, and few studies have considered the potential effects of various environmental factors, including outdoor air pollution. Braun-Fahrländer et al.15 reported that NO2 measured outdoors but not indoors was associated with the duration of respiratory symptoms in children.
In this study, valid measurements of indoor NO2 concentrations were obtained in 905 homes from seven different communities in both winter and summer, although each measurement was carried out on only one day. Then, we estimated the effects of outdoor and indoor NO2 together using multiple logistic models. The relationships between the prevalence of respiratory symptoms and indoor NO2 concentration were significant among girls, but not among boys. We have previously reported that pulmonary function measurements were associated with indoor NO2 among girls only.16 Neas et al.14 found a stronger effect of indoor NO2 on respiratory symptoms among girls than among boys. In other studies, a gas stove in the home appeared to be a risk factor for respiratory illnesses, primarily among girls and young women.6,11,24 Melia et al.24 suggested that girls would be more likely to spend more time in the kitchen. Pershagen et al.6 also found an increased risk associated with a gas stove in girls only, but they suggested that environmental exposure did not differ between boys and girls, since 90% of their subjects were under 2 years. Constitutional factors linked to sex may be of importance in respiratory symptoms or diseases.
Outdoor NO2 exposure was also reported to be a risk factor for wheezing bronchitis in only girls.6 In our study, outdoor NO2 concentration was not significantly associated with the prevalence of respiratory symptoms in either boys or girls. The incidence of wheeze and asthma was higher among boys than girls, although the sex-related difference was not significant. Since wheeze and asthma had arisen in only a small number of our subjects, the incidence should be further evaluated in more large-scale cohort studies.
Environmental tobacco smoke (ETS) has been shown to increase the incidence of asthma and wheezing in childhood.28 However, Chinn and Rona29 found that ETS exposure was associated with wheezing but not with diagnosed asthma. In the present study, parental smoking was not related to either wheeze or asthma in children. This may be because we did not evaluate the effect of ETS exposure, but only parental smoking habits. Breastfeeding in infancy was strongly associated with a low incidence of wheeze. Wilson et al.30 showed the protective effect of breastfeeding against respiratory illness during childhood.
A history of allergic diseases was also associated with the incidence of wheeze and asthma. Half of the subjects had a history of allergic diseases, among which atopy and allergic rhinitis were dominant. In a British cohort, atopy had an influence on the incidence of wheezing during adulthood.21 No increase in allergic diseases was observed with increasing levels of air pollution in the International Study of Asthma and Allergy in Childhood (ISAAC).2,9 The comparisons between eastern and western European populations showed a higher prevalence of infectious airway diseases and a lower prevalence of allergic diseases in eastern areas with high levels of sulphur oxides and suspended particles.31,32 A recent report from Germany found no effect of air pollution on the development of allergies.33 The present study showed no difference in the prevalence of allergic diseases in relation to districts and indoor NO2 concentrations.
On the other hand, several studies using the ISAAC questionnaire have shown that air pollution from heavy traffic has adverse effects on the respiratory health of children living in urban areas.7,34,35 Traffic-related NO2 has been shown to be associated with the prevalence of asthma and respiratory symptoms in children.7,36 Our study districts in urban communities were intersected by major trunk roads, and the high NO2 concentrations were derived primarily from automobile exhaust.12 Exposure to NO2 has been assumed to influence asthma in two ways: by decreasing the threshold of allergens in the development of asthma and worsening the morbidity of existing atopy or asthma.5,37 Our findings are consistent with the latter possibility, in that the incidence of wheeze and asthma was associated with NO2 exposure and allergic diseases. Atopic children would be expected to have a greater risk of respiratory symptoms with exposure to NO2 than non-atopic children.38 Accordingly, it is possible that NO2 directly causes airway inflammation and cellular damage in the human body.39
Pilotto et al.40 suggested that repeated exposure to short-term peaks of NO2 is more important in pathogenesis than long-term exposure to lower levels of NO2. However, the NO2 monitors used in epidemiological studies can obtain only average concentrations over the measurement periods.6 In this study, outdoor NO2 levels were assessed using only 3-year average concentrations. Therefore, our results may underestimate the effects of NO2 exposure. The presence of other pollutants, such as particulates, ozone, and formaldehyde, in the outdoor and indoor environment should be also considered.4,9 Fine particles have been reported to be associated with the prevalence of bronchitis, but not with asthma.41 Outdoor NO2 concentration may act as a surrogate for the real cause of the health effects. The association between respiratory symptoms and air pollutants other than NO2 should be further evaluated.
In conclusion, this study showed that the incidence of wheeze and asthma increased among children living in areas with high concentrations of outdoor NO2. This relationship remained significant even after adjustment for various factors, such as indoor NO2 concentration. These findings suggest that air pollution, including NO2, may be particularly important for the development of wheeze and asthma in urban districts. Indoor NO2 concentrations were associated with the prevalence of respiratory symptoms among girls, but not among boys. The relationship between indoor NO2 and the incidence of wheeze or asthma was not significant either. The incidence and prognosis of respiratory symptoms should be further evaluated in a longitudinal study for many more years.
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