Childhood Asthma in Beijing, China: A Population-based Case-Control Study

Tongzhang Zheng1, Shiru Niu2, Baoyu Lu2, Xiu’e Fan2, Fengying Sun2, Jinping Wang2, Yawei Zhang1, Bing Zhang3, Patricia Owens1, Lanying Hao4, Yingdong Li4 and Brian Leaderer1

1 Department of Epidemiology and Public Health, Yale School of Medicine, New Haven, CT.
2 Union School of Public Health, Chinese Academy of Preventive Medicine, Beijing, People’s Republic of China.
3 Department of Epidemiology and Biostatistics, McGill University, Montreal, Canada.
4 Shunyi County Public Health and Antiepidemic Station, Beijing, People’s Republic of China.

Received for publication December 21, 2001; accepted for publication June 11, 2002.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
China is the most populous country in the world. Few studies, however, have been conducted there to investigate the risk factors for childhood asthma. A population-based case-control study was conducted in Shunyi County, People’s Republic of China, in January 1999 and March 2001 to investigate the issue. An increased risk of childhood asthma was associated with smoking by relatives in front of the mother while she was pregnant with the child (odds ratio (OR) = 1.3, 95% confidence interval (CI): 1.0, 1.6) and with smoking by relatives in front of the child (OR = 1.4, 95% CI: 1.1, 1.9). The risk increased with the increasing number of smokers and the total minutes of smoking by relatives in front of both the child and the mother while she was pregnant with the child. An increased risk was observed for use of coal for heating (OR = 1.5, 95% CI: 1.1, 1.9). Those who reported using coal for cooking without ventilation also had an increased risk (OR = 2.3, 95% CI: 1.5, 3.5). An increased risk was observed for those who reported having molds or fungi on the ceilings of their houses (OR = 1.8, 95% CI: 1.1, 2.9) or inside the child’s room (OR = 1.8, 95% CI: 1.0, 3.2). An increased risk was also found for those having both a dog and a cat as pets (OR = 1.5, 95% CI: 1.0, 2.3) or for finding both cockroaches and rats inside their houses (OR = 1.8, 95% CI: 1.2, 2.8).

asthma; case-control studies; child; environmental pollutants; fungi; risk factors; tobacco smoke pollution

Abbreviations: Abbreviations: CI, confidence interval; OR, odds ratio.


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Epidemiologic studies have shown that the prevalence of childhood asthma varies markedly by geographic regions worldwide (1). For example, physician-diagnosed asthma alone was reported to be as high as 24 percent in Chicago, Illinois, and 26 percent in Sydney, Australia (2, 3). Our recent survey, however, showed that the prevalence rate of lifetime asthma was 2.2 percent for schoolchildren in Shunyi County, Beijing, China, which is consistent with those found for five Chinese cities reported in the International Study of Asthma and Allergies in Childhood (1). In that study, the 12-month asthma prevalence rates for Chinese children between 13 and 14 years of age ranged from 1.5 percent to 3.5 percent based on responses to video questionnaires and from 2.5 percent to 5 percent based on responses from written questionnaires.

This change in risk was seen not only for genetically distinct populations but also for genetically similar populations living in different geographic areas (1, 4). Studies of migrant populations also show that the disease risk changed after migration and that the extent of change correlated positively with the duration of exposure to the new living environment (4).

These observations suggest that environmental factors may be largely responsible for the observed geographic patterns (5, 6). So far, a number of environmental factors have been linked to the risk of childhood asthma. These factors, although inconsistent, include indoor air contaminants (such as environmental tobacco smoke and use of gas for cooking and heating) and residential exposures to aeroallergens associated with cats, dogs, birds, dust mites, cockroaches, and molds (58).

If exposure to indoor air pollution from tobacco smoking, natural fossil fuel use, and aeroallergens is indeed associated with the risk of childhood asthma, the mainland Chinese population would provide a unique model to study these relations. The reported risk factors of childhood asthma, based mainly on studies from developed countries, are common in the Chinese population. For example, it is reported that about 70 percent of Chinese men aged 20 or more years smoke cigarettes (9). Use of coal and gas for cooking and heating, without proper ventilation, is also common in China, particularly in the rural and suburban areas (10). However, very few studies have investigated environmental exposures as risk factors for childhood asthma in China. To investigate the risk factors for childhood asthma in the Chinese population, we conducted a population-based case-control study of childhood asthma in Shunyi County, Beijing, People’s Republic of China, in January 1999 and March 2001.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Study population
To identify cases of childhood asthma for this case-control study, we conducted a cross-sectional survey in Shunyi County, a suburban district of Beijing. Twenty-five schools were randomly selected from a total of 40 primary schools located in the county. All students aged 6–10 years, in the first to the fifth grades at each school, were invited to participate in the survey study.

In the cross-sectional phase of the study, the study staff at each school site gave each student a sealed envelope containing a questionnaire on asthma and allergic symptoms. Students were asked to take the questionnaire home for parental completion. The core questionnaire from the International Study of Asthma and Allergies in Childhood was modified for application to the study population and used to collect information on asthma and allergic symptoms. A child was considered to be asthmatic and included as a case if positive responses were made to both of the following questions: "Has a doctor ever said that your child has asthma?" and "Do you consider that your child has asthma?" A total of 403 cases were identified, and all of them participated in this case-control study.

Potential controls were children who were reported in the cross-sectional survey not to have physician-diagnosed asthma, not considered to have asthma by their parents, and not to have reported all three symptoms (wheezing, dry cough, and chest tightness) during the past 12 months. Two controls were randomly selected for each case from the same class of the school, matched by gender and age (±2 years). All 806 first selected controls participated in this case-control study.

Data collection and processing
This study was approved by the institutional review boards for human subjects at both the Chinese Academy of Preventive Medicine and the Yale School of Medicine. After obtaining parental consent, we used a standardized, structured questionnaire to collect information on tobacco smoking by the father, mother, or other relatives for two time periods, that is, when the mother was pregnant with the child and after the birth of the child; the usual type of fuel used by the family for heating and cooking; use of ventilation and air conditioning; fungi and mold on the ceilings of the house and inside the bedroom of the child; and pets and insects in the house. Other information was also collected for the study, including whether the father or mother was ever diagnosed with asthma or with allergies; if the child was born of a full-term pregnancy; the child’s birth weight; the number of months the mother breastfed the child; the ethnicity; and other background information.

Study staff checked each questionnaire for completeness and accuracy before accepting it. If the questions were incompletely answered or apparently errant, the parents were contacted by phone by the study staff for the needed information. Questionnaire data were entered into a data file and verified for accuracy. Logical checks and edits were done, and corrections were made.

Data analysis
We used both conditional and unconditional logistic regression to assess the relation between indoor air pollution and the risk of childhood asthma, reaching the same conclusion. Therefore, we present here only the results using an unconditional logistic regression model to facilitate the control of other unmatched confounders. The risk of childhood asthma associated with environmental exposures was evaluated for environmental tobacco smoking, indoor air pollution from cooking and heating, and indoor aeroallergens associated with cats, dogs, birds, dust mites, cockroaches, fungi, and mold. Odds ratios and 95 percent confidence intervals were calculated using SAS statistical software (11). The confounding factors included in the final model were gender, age, ethnicity, history of parental allergies, full-term gestation of the child, and duration of being breastfed (0, 1–12, >12 months). No other factors had a material impact on the observed association and thus were not included in the final model.


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Table 1 shows the age distribution of the cases and controls for boys and girls. About 59 percent of the cases were boys, and 41 percent of the cases were girls. Among them, 80 percent of cases were aged 9–10 years among both boys and girls.


View this table:
[in this window]
[in a new window]
 
TABLE 1. Age distribution of the cases and controls by gender, Beijing, People’s Republic of China, 1999–2001
 
As shown in table 2, an increased risk of childhood asthma was associated with smoking by relatives, when in front of the mother while she was pregnant (odds ratio (OR) = 1.3, 95 percent confidence interval (CI): 1.0, 1.6) and when relatives smoked in front of the child (OR = 1.4, 95 percent CI: 1.1, 1.9). The risk increased when the number of smokers and the total minutes of smoking increased. The odds ratios were 3.3 (95 percent CI: 1.9, 5.9) for those with more than three relatives who smoked in front of the pregnant women carrying the study subjects and 1.4 (95 percent CI: 1.1, 2.0) for smoking more than 30 minutes per day by relatives in front of the pregnant women. An increased risk was also observed for those with more than three relatives who smoked in front of the child (OR = 2.6, 95 percent CI: 1.5, 4.4). Smoking more than 30 minutes per day by relatives while with study subjects also resulted in a significantly increased risk of childhood asthma (OR = 1.7, 95 percent CI: 1.2, 2.3). In 1.2 percent (n = 5) of the cases and 0.6 percent (n = 5) of the controls, mothers smoked while pregnant, and in 3.2 percent (n = 13) of the cases and 1.6 percent (n = 13) of the controls, mothers smoked in front of the child.


View this table:
[in this window]
[in a new window]
 
TABLE 2. Risk of childhood asthma associated with passive smoking, Beijing, People’s Republic of China, 1999–2001
 
A significantly increased risk of childhood asthma was associated with the use of coal for heating (OR = 1.5, 95 percent CI: 1.1, 1.9). Those who reported using coal for cooking without ventilation had a significantly increased risk (OR = 2.3, 95 percent CI: 1.5, 3.5) (table 3). Use of gas/electricity for cooking without ventilation also showed an increased risk compared with the risk with ventilation (OR = 1.4, 95 percent CI: 1.1, 1.9). Use of air conditioning was not associated with an increased risk in this study.


View this table:
[in this window]
[in a new window]
 
TABLE 3. Risk of childhood asthma from indoor air pollution, Beijing, People’s Republic of China, 1999–2001
 
Table 4 shows the risk of childhood asthma associated with various indoor aeroallergens. An increased risk of childhood asthma was observed for those who reported having molds or fungi on the ceilings of their houses (OR = 1.8, 95 percent CI: 1.1, 2.9) and inside the child’s room (OR = 1.8, 95 percent CI: 1.0, 3.2). Having both a dog and cat as pets was associated with an increased risk (OR = 1.5, 95 percent CI: 1.0, 2.3). Those reporting both cockroaches and rats inside their houses also experienced an increased risk (OR = 1.8, 95 percent CI: 1.2, 2.8).


View this table:
[in this window]
[in a new window]
 
TABLE 4. Risk of childhood asthma and indoor aeroallergens, Beijing, People’s Republic of China, 1999–2001
 

    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
This is the first population-based case-control study designed specifically to investigate environmental exposures as risk factors for childhood asthma in a suburban Chinese population. In this study, we found that a number of environmental exposures may have a significant impact on the risk of childhood asthma, including environmental tobacco smoking, indoor air pollution from coal burning for cooking and heating, and exposure to indoor aeroallergens (molds or fungi, pets, and insects).

Regarding the relation between passive smoking and risk of childhood asthma, a recent review of 60 studies conducted mainly in Western populations through 1997 reported pooled odds ratios of 1.2 (95 percent CI: 1.1, 1.3) for either parent’s smoking from cross-sectional studies and 1.4 (95 percent CI: 1.2, 1.6) from case-control studies, as well as an odds ratio of 1.5 (95 percent CI: 1.3, 1.7) for both parents’ smoking (12). In our study, we found not only an increased risk of childhood asthma associated with exposure to environmental tobacco smoke but also that this increase appears to be dose dependent. Our result would further strengthen the hypothesis that passive smoking is associated with the risk of asthma in younger children (12). Studies have shown that smoking products, such as carbon monoxide and cotinine, that enter the bloodstream of the mother could cross into the fetus through the placenta with a diffusion gradient (12), and that both intrauterine and extrauterine smoke exposure is associated with a significant reduction in postbirth pulmonary function in infants (13).

Our study also for the first time observed an increased risk of childhood asthma associated with the use of coal stoves for cooking and heating in this mainlander Chinese population. For those who did not use a fan while cooking with coal, an odds ratio of 2.3 (95 percent CI: 1.5, 3.5) was observed. In China, epidemiologic studies have linked the concentrations of polycyclic aromatic hydrocarbon carcinogens (particularly benzo[a]pyrene) in indoor air from coal burning to lung cancer mortality (14). Two other studies from mainland China have also linked the use of coal stoves to respiratory symptoms. A study by Xu and Wang (10) reported that people who were living in households where coal stoves were used for both cooking and heating had an increased risk of respiratory symptoms (including coughing, phlegm, bouts with shortness of breath, wheezing, and wheezing with shortness of breath). Another study by Qing et al. (15) from China reported that indoor use of coal stoves was significantly associated with an increased risk of coughing, phlegm, and bronchitis.

In Beijing, coal and gas are the major household fuels used for cooking and heating. Several studies from China support a potentially higher risk of childhood asthma associated with the use of coal for cooking and heating. The study by Xu and Wang (10) found that households using coal for cooking had a substantially higher particulate concentration than those using gas for cooking. Several other studies from China (1517) also showed that indoor coal combustion for cooking and heating is the major source of indoor air pollution in China, and that use of coal stoves in households produced significantly higher pollutants than use of natural gas stoves. For example, the study by Qing et al. (15) reported that the estimated indoor concentrations of inhalable particulates, SO2, and carbon monoxide were 708 µg/m3, 436 µg/m3, and 6.55 mg/m3, respectively, for children living in households using coal stoves, which are significantly higher levels than those found in households using gas stoves (247 µg/m3, 185 µg/m3, and 4.17 mg/m3, respectively).

In a study of the association between skin test reactivity and methods of cooking and heating in homes in West Germany, von Mutius et al. (18) reported that the prevalence of atopy and hay fever was significantly higher among children living in homes with gas ovens and oil furnaces compared with the prevalence among children living in homes where coal or wood was used for heating or cooking. In another study of the use of domestic gas appliances and risk of respiratory symptoms, Jarvis et al. (19) reported that women who used mainly gas for cooking had an increased risk of asthma attacks (OR = 2.6), wheeze (OR = 2.1), and waking with shortness of breath (OR = 2.3). Beckett et al. (20) reported a trend, although insignificant, for an independent association of gas stove use by Puerto Rican Hispanics and the presence of an asthmatic child. A study among Seattle, Washington, schoolchildren by Maier et al. (21), however, found no increased risk of asthma or wheezing with the use of gas, wood, or kerosene stoves.

Epidemiologic studies have linked exposure to various indoor aeroallergens to the risk of developing and severity of asthma, as reviewed by Leaderer and Beckett (5, 6). Among the most common indoor aeroallergens found in homes are those from fungi, cats, dogs, cockroaches, and house dust mites. Birds and rodents are other sources of indoor aeroallergens. In our study, we found an 80 percent significantly increased risk of childhood asthma for those who reported having molds or fungi on the ceilings of their houses or inside the child’s room. It is suggested that fungi may play a role in asthma in several ways (22), including via fungal allergen exposure that leads to sensitization, releasing irritants that may enhance the potential for sensitization and allergen-induced symptoms.

Having both a dog and cat as pets is associated with a significantly increased risk of childhood asthma. Those who reported finding both cockroaches and rats inside their houses also experienced an increased risk of childhood asthma. It is concluded that, although it is currently unknown whether or not an association exists between exposure to dog, cat, rodent, and cockroach allergens and the development of asthma, there is sufficient evidence of a causal relation between cat, dog, rodent, and cockroach allergen exposures and exacerbation of asthma in individuals specifically sensitized to dogs, cats, rodents, and cockroaches (22).

Several advantages and disadvantages must be considered in interpreting the results from our study. A major advantage of the study is that the cases were identified from a large population-based survey and that all the cases identified from the survey and the selected controls participated in the study. Second, this is one of only a few studies that have systematically examined environmental exposures as risk factors for childhood asthma in the mainland Chinese population, where the prevalence of childhood asthma is reported to be low, compared with Western populations. Although a number of environmental factors have been linked to the risk of asthma, this information came mainly from studies of Western populations. Therefore, our study provides important information regarding risk profiles for childhood asthma in the mainland Chinese population.

One of the potential limitations is that there were no medical examinations of children or reviews of medical records for confirmation of childhood asthma; all data were derived from the reports of parents. Asthma in this study was defined as a positive response to the questions, "Has a doctor ever said that your child has asthma?" and "Do you consider that your child has asthma?" Therefore, misclassification of disease status is possible. However, misclassification is unlikely differential, and nondifferential misclassification would cause an underestimation of the association between various exposures and asthma risk. It should be noted that there is no universal standard for the diagnosis of childhood asthma and that the majority of epidemiologic studies of childhood asthma, including studies from Western populations (1, 3, 20, 2326), relied upon the reports of parents. Early studies (27, 28) show that assessment of childhood respiratory symptoms by questionnaire is accurate and reproducible and that about 94–96 percent of the school-age children with asthma could be identified by parental reporting. Further, it has been suggested that exclusive dependence on physician reporting may result in significant underreporting of childhood asthma (28).

Another potential limitation is the use of questionnaires to collect information regarding environmental exposures, including environmental tobacco smoking, indoor air pollution from heating and cooking, and indoor aeroallergen exposures. This would have undoubtedly introduced misclassification of exposure. Lack of detailed information regarding exposures (such as yearly or monthly coal consumption and type of coal used) limits the study’s ability to quantitatively measure the relation between coal use and risk of childhood asthma. Because of the retrospective nature of the study, differential recall of past exposure by participants is possible and, therefore, may be responsible for the observed association between indoor pollution and an increased risk of childhood asthma. However, unlike that of city residents, the community awareness of childhood asthma and indoor air pollution of those living in rural and suburban areas of China is still low, and it is unlikely that differential recall of past exposure is a major explanation for the observed associations.

In conclusion, this population-based case-control study was designed specifically to examine environmental risk factors for childhood asthma in a suburban Chinese population. In this study, we found an increased risk of childhood asthma associated with environmental tobacco smoke, and the risk was dose dependent. Unlike studies from Western populations, we also found an increased risk of childhood asthma associated with indoor air pollution from coal burning for heating and cooking. Exposure to various indoor aeroallergens is associated with an increased risk of childhood asthma. This study demonstrates that environmental exposures may have a significant impact on the risk of childhood asthma in this suburban Chinese population.


    ACKNOWLEDGMENTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
This study was supported by grants ESO7456 and ESO5410 from the National Institute of Environmental Health Sciences and partly supported by a grant from the Procter & Gamble Company.


    NOTES
 
Reprint requests to Dr. Tongzhang Zheng, 129 Church Street, Suite 700, New Haven, CT 06510 (e-mail: tongzhang.zheng{at}yale.edu). Back


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 

  1. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Lancet 1998;351:1225–32.[ISI][Medline]
  2. Hu FB, Persky V, Flay BR, et al. Prevalence of asthma and wheezing in public school children: association with maternal smoking during pregnancy. Ann Allergy Asthma Immunol 1997;79:80–4.[ISI][Medline]
  3. Pearce N, Weiland S, Keil U, et al. Self-reported prevalence of asthma symptoms in children in Australia, England, Germany, and New Zealand: an international comparison using the ISAAC protocol. Eur Respir J 1993;6:1455–61.[Abstract]
  4. Leung R, Wong G, Lau J, et al. Prevalence of asthma and allergy in Hong Kong schoolchildren: an ISSAC study. Eur Respir J 1997;10:354–60.[Abstract/Free Full Text]
  5. Leaderer B, Beckett W. Epidemiologic evidence of an association between air quality and asthma. J Pharm Pharmacol 1997;49:39–44.[ISI][Medline]
  6. Leaderer B, Beckett WS. Environmental risk factors in the development and severity of asthma. In: Mohr U, ed. Relationships between respiratory disease and exposure to air pollution. Washington, DC: International Life Sciences Institute Press, 1998:15–35.
  7. Weiss ST. Environmental risk factors in childhood asthma. Clin Exp Allergy 1998;28:29–34.
  8. Boner AL, Bodini A, Piacentini GL. Environmental allergens and childhood asthma. Clin Exp Allergy 1998;28:76–81.[ISI][Medline]
  9. Niu SR, Yang GH, Chen ZM, et al. Emerging tobacco hazards in China. In: Lu R, MacKay J, Niu S, et al, eds. Tobacco: the growing epidemic. London, Great Britain: Springer-Verlag, Limited, 2000:10–13.
  10. Xu XP, Wang LH. Association of indoor and outdoor particulate level with chronic respiratory illness. Am Rev Respir Dis 1993;148:1516–22.[ISI][Medline]
  11. SAS Institute, Inc. SAS/STAT user’s guide. Version 6. Cary, NC: SAS Institute, Inc, 1990.
  12. Institute of Medicine. Exposure to environmental tobacco smoke. In: Clearing the air: asthma and indoor air exposures. Washington, DC: National Academy Press, 2000:263–97.
  13. Hopp RJ, Townley RG. Pathogenesis of asthma: genetics and epidemiology. In: Gershwin ME, Albertson TE, eds. Bronchial asthma: principles of diagnosis and treatment. 4th ed. Totowa, NJ: Humana Press, 2001:1–25.
  14. He XZ, Chen W, Liu ZY, et al. An epidemiological study of lung cancer in Xuan Wei County, China: current progress. Case-control study on lung cancer and cooking fuel. Environ Health Perspect 1991;94:9–13.[ISI][Medline]
  15. Qing YH, Yi XR, Tao Y, et al. Effects of indoor air pollution on respiratory diseases in children. Presented at the China-Japan Environmental Health Conference, Zhengzhou, China, 1992.
  16. Luo DY. Investigation of air pollution in house due to use of various fuels. Presented at the 5th International Conference on Indoor Air Quality and Climate, Toronto, Canada, 1990.
  17. Xu YL. Effects of coal and gas combustion on indoor air pollution. (In Chinese). J Environ Health 1986;3:39.
  18. von Mutius E, Martinez FD, Nicolai T. Skin test reactivity and coal burning. (Abstract). J Allergy Clin Immunol 1995;95:211.
  19. Jarvis D, Chinn S, Luczynska C, et al. Association of respiratory symptoms and lung function in young adults with use of domestic applicances. Lancet 1996;347:426–31.[ISI][Medline]
  20. Beckett WS, Belanger K, Gent JF, et al. Asthma among Puerto Rican Hispanics: a multi-ethnic comparison study of risk factors. Am J Respir Crit Care Med 1996;154:894–9.[Abstract]
  21. Maier WC, Arrighi HM, Morray B, et al. Indoor risk factors for asthma and wheezing among Seattle school children. Environ Health Perspect 1997;105:208–14.[ISI][Medline]
  22. Institute of Medicine. Indoor biologic exposures. In: Clearing the air: asthma and indoor air exposures. Washington, DC: National Academy Press, 2000:105–222.
  23. Magnus NW, Raksund P, Svidal O, et al. The prevalence of respiratory symptoms and asthma among school children in three different areas of Norway. Pediatr Allergy Immunol 1997;8:35–40.[ISI][Medline]
  24. Saraclar Y, Sekerel BE, Kalayci O, et al. Prevalence of asthma symptoms in school children in Ankara, Turkey. Respir Med 1998;92:203–7.[ISI][Medline]
  25. Persky VW, Slezak J, Contreras A, et al. Relationship of race and socioeconomic status with prevalence, severity, and symptoms of asthma in Chicago school children. Ann Allergy Asthma Immunol 1998;81:266–71.[ISI][Medline]
  26. Asthma and respiratory symptoms in 6–7 yr old Italian children: gender, latitude, urbanization and socioeconomic factors. SIDRIA (Italian Studies on Respiratory Disorders in Childhood and the Environment). Eur Respir J 1997;10:1780–6.[Abstract/Free Full Text]
  27. Brunckreef B, Groot B, Rijcken B, et al. Reproducibility of childhood respiratory symptom questions. Eur Respir J 1992;5:930–5.[Abstract]
  28. Speight ANP, Lee DA, Hey EN. Underdiagnosis and undertreatment of asthma in childhood. Br Med J 1983;286:1253–6.[ISI][Medline]