Figures
Abstract
Background
A nationwide asthma survey on the effects of air pollution is lacking in Taiwan. The purpose of this study was to evaluate the time trend and the relationship between air pollution and health care services for asthma in Taiwan.
Methods
Health care services for asthma and ambient air pollution data were obtained from the National Health Insurance Research database and Environmental Protection Administration from 2000 through 2009, respectively. Health care services, including those related to the outpatient and inpatient visits were compared according to the concentration of air pollutants.
Results
The number of asthma-patient visits to health-care facilities continue to increase in Taiwan. Relative to the respective lowest quartile of air pollutants, the adjusted relative risks (RRs) of the outpatient visits in the highest quartile were 1.10 (P-trend = 0.013) for carbon monoxide (CO), 1.10 (P-trend = 0.015) for nitrogen dioxide (NO2), and 1.20 (P-trend <0.0001) for particulate matter with an aerodynamic diameter ≦10µm (PM10) in the child group (aged 0–18). For adults aged 19–44, the RRs of outpatient visits were 1.13 (P-trend = 0.078) for CO, 1.17 (P-trend = 0.002) for NO2, and 1.13 (P-trend <0.0001) for PM10. For adults aged 45–64, the RRs of outpatient visits were 1.15 (P-trend = 0.003) for CO, 1.19 (P-trend = 0.0002) for NO2, and 1.10 (P-trend = 0.001) for PM10. For the elderly (aged≥ 65), the RRs of outpatient visits in were 1.12 (P-trend = 0.003) for NO2 and 1.10 (P-trend = 0.006) for PM10. For inpatient visits, the RRs across quartiles of CO level were 1.00, 1.70, 1.92, and 1.86 (P-trend = 0.0001) in the child group. There were no significant linear associations between inpatient visits and air pollutants in other groups.
Citation: Pan H-H, Chen C-T, Sun H-L, Ku M-S, Liao P-F, Lu K-H, et al. (2014) Comparison of the Effects of Air Pollution on Outpatient and Inpatient Visits for Asthma: A Population-Based Study in Taiwan. PLoS ONE 9(5): e96190. https://doi.org/10.1371/journal.pone.0096190
Editor: Stephania Ann Cormier, University of Tennessee Health Science Center, United States of America
Received: November 26, 2013; Accepted: April 3, 2014; Published: May 1, 2014
Copyright: © 2014 Pan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Asthma is a common chronic inflammatory respiratory disease that affects 300 million people of all ages and all ethnic backgrounds and accounts for about 1 in every 250 deaths worldwide [1]. In Taiwan, the prevalence of asthma increased from 5.07% in 1985 to 11.9% in 2007 [2], [3]. The risk factors for asthma include many external determinants such as mites, dust, mold, indoor and outdoor air pollution, and season variations [4]–[6]. Although air pollution has not been shown as the sole cause of respiratory illnesses, there is evidence that air pollution episodes lead to respiratory irritation, increased use of asthma medications and hospitalizations [7], [8]. Traffic and industry-related pollutants, nitrogen dioxide (NO2) and carbon monoxide (CO), were associated with asthma hospitalizations and outpatient visits [9], [10]. Elevated levels of ozone (O3), sulfur dioxide (SO2) and particulate matter with an aerodynamic diameter ≦10µm (PM10) were reported to be related with increased asthma emergency room visits and admissions [11]–[13]. It has been reported that the rise in air pollution has increased respiratory and cardiovascular complications leading to elevated risk of death [14].
If air pollution is responsible for the observed enhanced respiratory complications and mortality, one would also expect to see an impact on clinic visits, outpatient visits, emergency department (ED) visits and hospitalization rates for asthma. However, there are no data regarding a population based survey with seasonal and air pollutants in asthma outpatient and inpatient visits in Taiwan. The objective of this study was to assess asthma-related outpatient and inpatient patterns of visits in different age groups based on the National Health Insurance Research Database (NHIRD) in Taiwan, and to compare the association with utilization of health care services and concentrations of air pollutants.
Materials and Methods
Database
The data were obtained from the NHIRD released by the National Health Research Institute (NHRI) in Taiwan. The National Health Insurance Program finances compulsory universal health care for 99% of all of residents of Taiwan [15]. The database contains demographic data, all health-care encounters, expenditure and dates of enrollment and withdrawal. To facilitate research, the NHRI randomly sampled a representative database of one million subjects enrolled in the National Health Insurance program in the year 2005 by a systematic sampling method. This one-million sample was validated to be representative of the entire insured population as reported by the NHRI. The identification numbers and personal information of all individuals in the NHRID were erased to protect the privacy of the individuals. This study was approved by the Institutional Review Board of the Chung-Shan Medical University Hospital, Taiwan.
Study Population
Cases of asthma were ascertained by the service claim for either outpatient or inpatient visit with a primary diagnosis of asthma (ICD-9-CM code 493.xx). Daily counts of clinic visits, outpatient visits, ED visits and hospital admissions for asthma were extracted from the medical insurance file for the period of 2000–2009. The outpatient visit was defined as a patient visit to a physician's office, clinic, or hospital outpatient department. The inpatient visits include ED visits and admissions. The analyses covered 54 municipalities, each with its own air quality monitoring station. We identified 306628 men and 315178 women who lived in municipalities with air quality monitoring stations during the study period. There were 33934 men and 34527 women with asthma. The patient's exact addresses were not available from the database. Therefore, we assumed that the municipality where a patient visit occurred was regarded as the same area where the patient was most likely exposed to air pollutants. Each asthma outpatient or inpatient visit was matched with the municipality's seasonal average pollutant concentrations. Each occurrence, limited to municipality with air quality monitoring stations, was counted as one visit. The outpatient and inpatient visits were further analyzed by seasons (spring as February, March and April; summer as May, June and July; autumn as August, September and October; winter as November, December and January) and four age groups (0–18, 19–44, 45–64 and ≥65 years).
Outdoor Air Pollution Monitoring
There were 76 air quality monitoring stations in Taiwan, established by the Environmental Protection Administration. Data from background and industrial air quality monitoring stations were excluded to avoid extreme levels of air pollutants. Finally, data from 54 air quality monitoring stations were enrolled (24 municipalities in northern, 9 municipalities in central, 19 municipalities in southern and 2 municipalities in eastern Taiwan). Complete monitoring data for the air pollutants included PM10, SO2, CO, O3, and NO2. The average seasonal concentration of each air pollutant from the Taiwan Environmental Protection Administration's air quality monitoring stations was calculated for further analysis from 2000 to 2009.
Statistical Analysis
All analyses were done by using the SAS ver. 9.3 software package (SAS Institute, Cary, NC, USA). Multivariate Poisson Regression was made in order to determine the relative risk (RR) of asthma inpatient and outpatient visits by sex, age, year and seasons. For use of health services in relation to air pollutants, the municipalities were defined as the observed units, and the level of air pollutants and counts of patient visits were collected in each municipality for each season from 2000 to 2009. As multiple visits by the same patient in a season in the municipality who lived, the count of the visits was as one visit per season. Generalized estimating equations (PROC GENMOD with repeated statement by the SAS Institute) were used to analyze of levels of pollutants by stratifying municipalities and to compare whether the inpatient and outpatient visits in those municipalities correlated with levels of pollutants. A p value <0.05 was considered statistically significant.
Results
The descriptive statistics for outpatient and inpatient visits and corresponding period and season data are shown in Table 1. Compared with women, the RRs for inpatient and outpatient visits in men were 1.31 (p<0.0001) and 1.15 (p<0.0001), respectively. Furthermore, when divided into 4 age groups, the highest RRs for inpatient and outpatient visits were among the elderly group (i.e. ≥65 years) followed by the child group (0 –18), the adults aged 45–64 group and the adult aged 19–44 group. For the period effect, there were increased outpatient visits (RR: 1.29, P<0.0001) since 2005 and inpatient visits (RR: 3.30, P<0.0001) since 2006 when compared with patient visits in 2000. The peak seasons for asthma inpatient and outpatient visits in Taiwan were spring (5.1/10,000 person-season) and winter (149.6/10,000 person-season), respectively.
Table 2 shows the RRs of outpatient health service use with respect to exposure to air pollutants in the four age groups following adjustments for sex, period and quartiles of air pollutants by the generalized estimating equations model. Relative to the respective lowest quartile of air pollutants, the adjusted RRs of the outpatient visits in the highest quartile were 1.10 (95% CI: 1.04, 1.16; P-trend = 0.013) for CO, 1.10 (95% CI: 1.01, 1.18; P-trend = 0.015) for NO2, 0.94 (95% CI: 0.88, 0.99; P-trend = 0.016) for O3, and 1.20 (95% CI:1.13, 1.27; P-trend <0.0001) for PM10 in the child group. For adults aged 19–44, the adjusted RRs of the outpatient visits were 1.13 (95% CI: 1.03, 1.23; P-trend = 0.078) for CO, 1.17 (95% CI: 1.05, 1.31; P-trend = 0.002) for NO2, 0.88 (95% CI: 0.83, 0.94; P-trend<0.0001) for O3, and 1.13 (95% CI: 1.05, 1.21; P-trend <0.0001) for PM10. The adjusted RRs of the outpatient visits in the adults aged 45–64 were 1.15 (95% CI: 1.05, 1.26; P-trend = 0.003) for CO, 1.19 (95% CI: 1.08, 1.30; P-trend = 0.0002) for NO2, 0.93 (95% CI: 0.89, 0.98; P-trend = 0.028) for O3, and 1.10 (95% CI: 1.02, 1.18; P-trend = 0.001) for PM10. The adjusted RRs for the elderly outpatient visits across quartiles of air pollutant level were 1.00, 1.02, 1.07, and 1.12 (P-trend = 0.003) for NO2 and 1.00, 1.04, 1.06, 1.10 (P-trend = 0.006) for PM10. There was no significant association between SO2 and outpatient visits in any group.
The use of inpatient health services in relation to levels of air pollutants by different age groups is shown in Table 3. The adjusted RRs for the child inpatient visits across quartiles of CO level were 1.00, 1.70, 1.92, and 1.86 (P-trend = 0.0001) after multivariate adjustment by sex, year and other air pollutants. There were no significant linear associations between inpatient visits and air pollutants in other age groups.
The use of inpatient health services increased with time as shown in Fig 1. In general, there were trends of increasing asthma outpatient visits in the children's group (Fig. 1A & B). In 2003, there was an outbreak of Severe Acute Respiratory Syndrome (SARS) in Hong Kong and nearly became a pandemic event [16]. During this period, inpatient visits dramatically decreased in all age groups. After the SARS outbreak, the rates of inpatient visits have increased with time since 2006, especially in the child and the elderly groups (Fig 1C & D).
SARS, Severe Acute Respiratory Syndrome.
Discussion
Among patients with asthma, air pollutant exposure causes increased asthma morbidity. Little is known about changes over time in air pollutant exposure among patients with asthma in a national sample. During the study period, the inpatient and outpatient visits by men were higher than in women. The peak seasons of asthma inpatient and outpatient visits for the total population were spring and winter, respectively. The inpatient and outpatient visits of asthmatics have not reached a plateau and have continued to increase. Inpatient visits for asthma increased with increased levels of CO in children but not for any pollutants in adults in the present study. Our study found that CO, NO2 and PM10 had significant estimated associations on outpatient visits due to asthma and children are more susceptible than other age groups.
Health care visits only illustrate a small percentage and most severe inpatients of the total impacts of air pollution. Our study used the count of health care visits from NHRI databases as the measure of morbidity in the population. Clinic visits, outpatient visits, ED visits and admissions are types of health care service, but also possessed of potentially important disparities [17], [18]. Because asthma is a chronic disease, patients with asthma were taught to deal with their symptoms and discomfort of an asthma attack [19], [20]. When the concentrations of air pollutants rise, patients with asthma may have treated symptoms by themselves or visited neighborhood clinics and hospital outpatient departments for medical treatment. Subsequently, if patients did not receive any treatment or if the condition was deteriorated or ineffective after an outpatient visit, they would then visit hospital emergency departments for assistance. This may explain why there was no increased risk for inpatient visits for adults with increasing levels of air pollutants.
In response to the increasing prevalence, mortality rates, and medical cost of asthma, the Bureau of National Health Insurance initiated a Healthcare Quality Improvement Program for patients with asthma since November, 2001 [21]. The characteristics of the program were registry development, adherence to guidelines, patient education, and nursing care management. The Bureau offered financial incentives that motivated the nurses and physicians to change their practice patterns by following clinical guidelines; thereby, the asthma care team support from healthcare organizations was able to promote and enable patients to effectively self-manage their asthma with reduced healthcare resource utilization. During the SARS outbreak, people avoided hospital visits to prevent themselves from nasocomial infection and the inpatient visit rate for asthma decreased in all age groups [22]. However, there was an increase of inpatient and outpatient visits after the SARS outbreak. The exacerbation of air pollution probably plays a role in the rising rate of asthma visits due to growing populations, increased economic activity, rise in vehicular traffic, as well as the increasing intensity and occurrence of dust storms originating in Mongolia and China [23].
There have been associations between daily ambient air pollution levels and acute exacerbations of respiratory diseases in many time-series studies [11], [12], [24]. Urban air pollution constitutes a complex mixture of several compounds. The exposure of motor vehicle air pollutants, such as NO2, CO, SO2 and PM, increases the incidence and prevalence of asthma and bronchitic symptoms [25]. CO was reported to be associated with asthma admission and ED visits [9], [26], [27]. There were associations between short-term exposure to ambient CO and risk of cardiovascular disease hospitalizations, even at low ambient CO levels [28]. Sun et al conducted a one-year observation in central Taiwan that CO played a role in acute exacerbation of asthma in children and increased the number of childhood asthma ED visits, but not in adults [29]. Villeneuve et al reported that an increase in the interquartile range of the 5-day average for CO was associated with 48% increases in the risk of an asthma ED visit for children aged 2 to 4, but the associations were less pronounced in adult aged 15 to 44 [30]. In Rome, where air pollution comes mostly from combustion products of motor vehicles, CO was associated with most of the respiratory conditions in all ages, and it remained an independent predictor in multi-pollutant analysis for all respiratory admissions [31]. In London, there were significant associations between CO and daily consultations for asthma and other lower respiratory disease in children, whereas in adults the only consistent association was with PM10 [32]. In our study, CO was also significantly associated with asthma exacerbation and inpatient visits in children. However, a direct association between CO and asthma lacks a biologically plausible mechanism [33]. It is possible that CO might be a surrogate for other noxious incomplete combustion products [34]. Unlike with children, the other major confounders in adult asthmatic patients include occupational exposures, smoking, stress, emotional factors, and systemic diseases, which may also partly explain why outdoor air pollution was not associated with inpatient visits in the adults in our study.
Coal- and oil-fired power plants and diesel- and gasoline-powered motor vehicle engines are the main sources of ambient NOx emissions [35]. In a meta-analysis study, inhalation of NO2 in the air significantly increased the development of childhood asthma and symptoms of wheezing [36]. A previous study in Taipei showed that most robust associations were found for NO2 elevation and asthma admission rates [26]. NO2 levels were associated with childhood asthma exacerbations and ED visits in Santa Clara, California [37]. In a spatiotemporal analysis of air pollution and asthma patient visits in Taipei, elevated levels of NO2 had a positive association on outpatient visits [38]. In summary, there was a linear response in outpatient visits on days with elevated NO2.
Previous studies have not yielded consistent results concerning associations between O3 and SO2 and asthma admissions. SO2 was least frequently mentioned in the correlation with asthma hospitalization rate. Most previous studies have not shown a significant effect of SO2 on asthma hospitalization rates supporting our findings [29], [39]. O3 is a highly reactive gas and induces bronchial inflammation, constriction of the airways and decreased lung function [40]. Long-term exposure to outdoor O3 increases the prevalence of bronchitic symptoms among children [41]. O3 levels have been previously reported to be associated with asthma admission and ED visits [11], [24], [38]. In contrast, asthma exacerbations were not associated with O3 levels in North America [42]. Daily general-practice consultations for respiratory conditions were unrelated to O3 in London [32] and Taiwan [43].
PM10 is a heterogeneous mixture of small solid or liquid particles with varying compositions in the atmosphere. There were no consistent results concerning associations between PM10 and asthma admissions. Some studies reported that PM10 was significantly associated with asthma admissions [8], [39], other studies reported a lack of association between PM10 and asthma admission [27]. In our study, levels of PM10 were associated with outpatient visits for asthma, but not associated with admissions. Hwang and Chan used data obtained from clinic records and environmental monitoring stations in Taiwan and reported that PM10 had an impact on outpatient visits [43]. This was consistent with our findings.
Most of the previous studies are cross-sectional and have focused air pollutants on short-term, regional area and respiratory system diseases [8], [29], [38]. We conducted a nationwide asthma survey on the effects of air pollution in Taiwan and evaluated the association between different air pollutants and outpatient and inpatient visits. One of the strengths of the present study is the use of a computerized database, which is population-based and is highly representative. Because we enrolled all patients diagnosed with asthma from 2000 to 2009, we can rule out the possibility of selection bias. Since the data were obtained from a historical database, which collects all information, recall bias was avoided. Besides, we analyzed levels of pollutants at different municipalities and compared whether the inpatient and outpatient visits in those municipalities correlated with levels of pollutants. Thus this study directly associated the patient visits with the levels of pollutants in those municipalities. As multiple visits by the same patient would lead to misinterpretation of the data, we used the statistic method to reduce bias.
There were still several limitations of the present study. First, although we adjusted for several potential confounders in the statistical analysis, a number of possible confounding variables, including family history of atopy, dietary habits, physical activity, occupational exposures, smoking habits, stress and emotional factors, which are associated with asthma were not included in our database. Second, we were unable to ask patients for severity of asthma because of de-identifcation. Third, self-treatment with over-the-counter medications or alternative health services was not included in the database. These data also do not include the number of asthmatic subjects who had respiratory problems but did not search for health service. Therefore, the extent of the issue may have been considerably underestimated. Fourth, potentially inaccurate data in the records could lead to possible mis-classification.
In conclusion, the present study provides evidence that exposure to the outdoor air pollutant, CO, exerted adverse effects on health and increases in the child admission. Our study also showed a linear association between NO2, CO, and PM10 and outpatient visits. It is an important public health policy to monitor air quality and warn the public about atmospheric factors that could be associated with increased risks of asthma.
Acknowledgments
This study is based on data from the National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health and managed by National Health Research Institutes. The descriptions or conclusions herein do not represent the viewpoints of the Bureau of National Health Insurance, Department of Health or National Health Research Institutes.
Author Contributions
Conceived and designed the experiments: K.H. Lue HHP CTC. Performed the experiments: JYH JYP. Analyzed the data: K.H. Lue HLS JNS. Wrote the paper: HHP CTC. Reviewed the manuscript and gave input to the final version: HLS MSK PFL K.H. Lu JNS.
References
- 1. Masoli M, Fabian D, Holt S, Beasley R (2004) The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 59: 469–478.
- 2. Hsieh KH, Shen JJ (1988) Prevalence of childhood asthma in Taipei, Taiwan, and other Asian Pacific countries. J Asthma 25: 73–82.
- 3. Hwang CY, Chen YJ, Lin MW, Chen TJ, Chu SY, et al. (2010) Prevalence of atopic dermatitis, allergic rhinitis and asthma in Taiwan: a national study 2000 to 2007. Acta Derm Venereol 90: 589–594.
- 4. Han YY, Lee YL, Guo YL (2009) Indoor environmental risk factors and seasonal variation of childhood asthma. Pediatr Allergy Immunol 20: 748–756.
- 5. Chiang CH, Wu KM, Wu CP, Yan HC, Perng WC (2005) Evaluation of risk factors for asthma in Taipei City. J Chin Med Assoc 68: 204–209.
- 6. Guo Y, Jiang F, Peng L, Zhang J, Geng F, et al. (2012) The association between cold spells and pediatric outpatient visits for asthma in Shanghai, China. PLoS One 7: e42232.
- 7. Yeh KW, Chang CJ, Huang JL (2011) The association of seasonal variations of asthma hospitalization with air pollution among children in Taiwan. Asian Pac J Allergy Immunol 29: 34–41.
- 8. Kuo HW, Lai JS, Lee MC, Tai RC, Lee MC (2002) Respiratory effects of air pollutants among asthmatics in central Taiwan. Arch Environ Health 57: 194–200.
- 9. Delamater PL, Finley AO, Banerjee S (2012) An analysis of asthma hospitalizations, air pollution, and weather conditions in Los Angeles County, California. Sci Total Environ 425: 110–118.
- 10. Wang KY, Chau TT (2013) An association between air pollution and daily outpatient visits for respiratory disease in a heavy industry area. PLoS One 8: e75220.
- 11. Wilson AM, Wake CP, Kelly T, Salloway JC (2005) Air pollution, weather, and respiratory emergency room visits in two northern New England cities: an ecological time-series study. Environ Res 97: 312–321.
- 12. Qiu H, Yu IT, Tian L, Wang X, Tse LA, et al. (2012) Effects of coarse particulate matter on emergency hospital admissions for respiratory diseases: a time-series analysis in Hong Kong. Environ Health Perspect 120: 572–576.
- 13. Cadelis G, Tourres R, Molinie J (2014) Short-term effects of the particulate pollutants contained in Saharan dust on the visits of children to the emergency department due to asthmatic conditions in Guadeloupe (French Archipelago of the Caribbean). PLoS One 9: e91136.
- 14. Wong TW, Tam WS, Yu TS, Wong AH (2002) Associations between daily mortalities from respiratory and cardiovascular diseases and air pollution in Hong Kong, China. Occup Environ Med 59: 30–35.
- 15. Lu JF, Hsiao WC (2003) Does universal health insurance make health care unaffordable? Lessons from Taiwan. Health Aff (Millwood) 22: 77–88.
- 16. Tsang KW, Ho PL, Ooi GC, Yee WK, Wang T, et al. (2003) A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med 348: 1977–1985.
- 17. Gold LS, Thompson P, Salvi S, Faruqi RA, Sullivan SD (2014) Level of asthma control and health care utilization in Asia-Pacific countries. Respir Med 108: 271–277.
- 18. Sun HL, Kao YH, Lu TH, Chou MC, Lue KH (2007) Health-care utilization and costs in Taiwanese pediatric patients with asthma. Pediatr Int 49: 48–52.
- 19. Centers for Disease Control and Prevention (2011) Vital signs: asthma prevalence, disease characteristics, and self-management education: United States, 2001—2009. MMWR Morb Mortal Wkly Rep 60: 547–552.
- 20. Weng HC (2005) Impacts of a government-sponsored outpatient-based disease management program for patients with asthma: a preliminary analysis of national data from Taiwan. Dis Manag 8: 48–58.
- 21.
Bureau of National Health Insurance (2001) A national comprehensive disease management program. Taipei: Bureau of National Health Insurance.
- 22. Huang YT, Lee YC, Hsiao CJ (2009) Hospitalization for ambulatory-care-sensitive conditions in Taiwan following the SARS outbreak: a population-based interrupted time series study. J Formos Med Assoc 108: 386–394.
- 23. Bell ML, Levy JK, Lin Z (2008) The effect of sandstorms and air pollution on cause-specific hospital admissions in Taipei, Taiwan. Occup Environ Med 65: 104–111.
- 24. Winquist A, Klein M, Tolbert P, Flanders WD, Hess J, et al. (2012) Comparison of emergency department and hospital admissions data for air pollution time-series studies. Environ Health 11: 70.
- 25. Gasana J, Dillikar D, Mendy A, Forno E, Ramos Vieira E (2012) Motor vehicle air pollution and asthma in children: a meta-analysis. Environ Res 117: 36–45.
- 26. Yang CY, Chen CC, Chen CY, Kuo HW (2007) Air pollution and hospital admissions for asthma in a subtropical city: Taipei, Taiwan. J Toxicol Environ Health A 70: 111–117.
- 27. Slaughter JC, Kim E, Sheppard L, Sullivan JH, Larson TV, et al. (2005) Association between particulate matter and emergency room visits, hospital admissions and mortality in Spokane, Washington. J Expo Anal Environ Epidemiol 15: 153–159.
- 28. Bell ML, Peng RD, Dominici F, Samet JM (2009) Emergency hospital admissions for cardiovascular diseases and ambient levels of carbon monoxide: results for 126 United States urban counties, 1999–2005. Circulation 120: 949–955.
- 29. Sun HL, Chou MC, Lue KH (2006) The relationship of air pollution to ED visits for asthma differ between children and adults. Am J Emerg Med 24: 709–713.
- 30. Villeneuve PJ, Chen L, Rowe BH, Coates F (2007) Outdoor air pollution and emergency department visits for asthma among children and adults: a case-crossover study in northern Alberta, Canada. Environ Health 6: 40.
- 31. Fusco D, Forastiere F, Michelozzi P, Spadea T, Ostro B, et al. (2001) Air pollution and hospital admissions for respiratory conditions in Rome, Italy. Eur Respir J 17: 1143–1150.
- 32. Hajat S, Haines A, Goubet SA, Atkinson RW, Anderson HR (1999) Association of air pollution with daily GP consultations for asthma and other lower respiratory conditions in London. Thorax 54: 597–605.
- 33. American Thoracic Society (1996) Health effects of outdoor air pollution. Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society. Am J Respir Crit Care Med 153: 3–50.
- 34. Norris G, YoungPong SN, Koenig JQ, Larson TV, Sheppard L, et al. (1999) An association between fine particles and asthma emergency department visits for children in Seattle. Environ Health Perspect 107: 489–493.
- 35. Trasande L, Thurston GD (2005) The role of air pollution in asthma and other pediatric morbidities. J Allergy Clin Immunol 115: 689–699.
- 36. Takenoue Y, Kaneko T, Miyamae T, Mori M, Yokota S (2012) Influence of outdoor NO2 exposure on asthma in childhood: meta-analysis. Pediatr Int 54: 762–769.
- 37. Lipsett M, Hurley S, Ostro B (1997) Air pollution and emergency room visits for asthma in Santa Clara County, California. Environ Health Perspect 105: 216–222.
- 38. Chan TC, Chen ML, Lin IF, Lee CH, Chiang PH, et al. (2009) Spatiotemporal analysis of air pollution and asthma patient visits in Taipei, Taiwan. Int J Health Geogr 8: 26.
- 39. Lin M, Stieb DM, Chen Y (2005) Coarse particulate matter and hospitalization for respiratory infections in children younger than 15 years in Toronto: a case-crossover analysis. Pediatrics 116: e235–240.
- 40. Khatri SB, Holguin FC, Ryan PB, Mannino D, Erzurum SC, et al. (2009) Association of ambient ozone exposure with airway inflammation and allergy in adults with asthma. J Asthma 46: 777–785.
- 41. Hwang BF, Lee YL (2010) Air pollution and prevalence of bronchitic symptoms among children in Taiwan. Chest 138: 956–964.
- 42. Schildcrout JS, Sheppard L, Lumley T, Slaughter JC, Koenig JQ, et al. (2006) Ambient air pollution and asthma exacerbations in children: an eight-city analysis. Am J Epidemiol 164: 505–517.
- 43. Hwang JS, Chan CC (2002) Effects of air pollution on daily clinic visits for lower respiratory tract illness. Am J Epidemiol 155: 1–10.