Original Contribution

The relationship of short-term air pollution and weather to ED visits for asthma in Japan

Toshikazu Abe MD^a,?, Yasuharu Tokuda MD, MPH^b, Sachiko Ohde EdM^b, Shinichi Ishimatsu MD, PhD^a, Tomohiko Nakamura EMT^c, Richard B. Birrer MD^d

^aDepartment of Emergency and Critical Care Medicine, St. Luke’s International Hospital, Tokyo 104-8560, Japan ^bClinical Practice Evaluation and Research Center, St. Luke’s Life Science Institute, Tokyo 104-0044, Japan ^cTokyo Fire Department, Tokyo 100-0004, Japan

^dDepartment of Medicine, Cornell University School of Medicine, New York, NY 10021, USA

Received 30 October 2007; revised 16 January 2008; accepted 22 January 2008

Abstract

Introduction: The incidence of asthma exacerbation has been increasing in many countries. Environmental factors may play an important role in this trend. We aimed to investigate the relationship of Weather conditions and air pollution to significant exacerbation of asthma.

Methods: The daily number of emergency department (ED) visits by ambulance for asthma was collected through records of the Tokyo Fire Department from January 1 to December 31, 2005. We also collected daily air pollution levels and meteorological data for Tokyo during the same period. Meteorological data included minimum temperature, maximum barometric pressure, maximum relative humidity, and precipitation. Measured air pollutants included sulfur dioxide, nitrogen monoxide, nitrogen oxides, suspended particulate matter, and carbon monoxide. We performed a Time series analysis using multivariable-adjusted autoregressive integrated moving average model. The analysis was conducted separately among adults and among children (b15 years old).

Results: Of a total of 643849 patients who were transported to the ED by ambulance, there were 6447 patients with exacerbation of asthma. Among adults, lower minimum temperature was significantly associated with increased transport. Among children, there were no significant associations between exacerbation of asthmas requiring emergency transport and air pollutants or meteorological factors. The highest number of transports was found on October 11, the day after the National Sports Day in Japan. Conclusions: Cold temperature is related to an increased risk of significant exacerbation of asthma in adults. Air pollution does not seem to play a major role in significant exacerbation of asthma requiring Ambulance transports to ED.

(C) 2009

Introduction

The prevalence of bronchial asthma and the incidence of asthma exacerbation have been increasing in many countries

* Corresponding author. Tel.: +81 03 3541 5151; fax: +81 03 5550 2051.

E-mail address: [email protected] (T. Abe).

[1-3]. Emergency department (ED) visits and hospital admission for asthma have also been increasing [4,5]. Factors related to exacerbation of asthma include Respiratory tract infections, individual idiosyncrasy, exercise, allergen exposure, emotional stress, obesity, food, smoking, and environmental factors [6-12]. Among these environmental factors, weather conditions and air pollution are suggested to

0735-6757/$ - see front matter (C) 2009 doi:10.1016/j.ajem.2008.01.013

play an important role in the increased trend for exacerbation of asthma [12-15].

Several studies have indicated positive associations between ED visits for asthma and various weather factors, including Low Temperature, heavy precipitation, higher baro- metric pressure, and a rapid decrease from higher to lower barometric pressure [15-17]. In contrast, other studies have suggested no association between ED visits for asthma and several weather conditions [12,18].

Several studies have also investigated the relationship between levels of air pollutants and exacerbation of asthma. One study has indicated positive associations between ED visits for asthma and levels of air pollutants, including nitrogen oxides (NO_x), carbon monoxide (CO), and particu- late matter with a diameter of 10 um or less (PM10), among children, but not among adults [13]. Other studies have identified positive associations between ED visits for asthma and levels of ozone [14] and sulfur dioxide (SO₂) [19]. In contrast, another study has suggested a negative correlation between ED visits for asthma and ozone concentrations [15]. Time series analyses have been increasingly used in epidemiological research. Since the early 1970s, time series methods, in particular autoregressive integrated moving average (ARIMA) models, which have the ability to cope with stochastic dependence of consecutive data, have become well established in the commercial and industrial fields [20-22]. Therefore, in this study, we aimed to investigate the relationship between exacerbation of asthma and weather conditions as well as air pollutants, by controlling the autocorrelations of time series data, based

on ARIMA model.

For an available indicator of asthma exacerbation, we used the number of ambulance transports to the ED for exacerbation of asthma in the entire metropolitan area of Tokyo. Daily data for ambulance transports to the ED for asthma were analyzed to capture the frequency of significant exacerbation of asthma because ambulance-transported patients usually have more severe symptoms and are at higher risk of hospital admission or tracheal intubation than ambulatory patients with asthma [23,24].

Methods and materials

Study population

We conducted the study in Tokyo, the capital prefecture of Japan, with a population of approximately 12 million in 2005, a land area of 2187 km², and a temperate climate. As a prefectural institution, the Tokyo Fire Department organizes a 1-tiered system covering the whole prefecture, with basic life support ambulances based at 80 fire stations through- out the prefecture. Although emergency care services are somewhat fragmented between private and public hospitals in the competition for patients in a given area, patients are

free to seek an emergency medical service regardless of private or public hospitals. In addition, ambulance services are free of charge in Japan, and this policy seems to encourage liberal use of ambulance among Japanese people. Ambulances are usually staffed with nonphysician emer- gency medical technicians. Using a follow-up collection of diagnostic information provided by emergency physicians, ambulance staffs keep a digitalized record of the diagnosis of all patients transported to hospital EDs, along with careful protection for confidentiality of patients. Prior ethical approval from the institutional review board of St Luke’s International Hospital was obtained.

Data collection

We reviewed all patients transported to hospital EDs of Tokyo during a 1-year period from January 1 to December 31, 2005. Of these patients, we identified patients with asthma using follow-up diagnostic data provided by emergency physicians. The diagnosis of asthma was based on the clinical history and physical examination by emergency physicians. In this study, patients 15 years or older were defined as adults, and those 14 years or younger were defined as children. Data collection was involved with the digitalized registry data of transported patients in the Tokyo Fire Department.

We collected demographic data for each patient with exacerbation of asthma. Data were collected for the daily number of ambulance transports to ED for asthma in the entire metropolitan area of Tokyo. We also collected daily meteorological data for Tokyo from the Japan Meteorologi- cal Agency during the same period. Daily meteorological data included minimum temperature (in ?C), maximum baro- metric pressure (in hectopascal [hPa]), maximum relative humidity (in percent), and precipitation (in millimeters). For temperature, the daily minimum level was used for the analysis because previous studies have shown an association between exacerbations of asthma and the minimum tem- perature [15,25,26]. For barometric pressure, the daily maximum level was used for the analysis because a previous study has shown an association between exacerbations of asthma and the maximum barometric pressure [15]. For relative humidity, the daily maximum level was used for the analysis because a previous study has investigated the possible association between exacerbations of asthma and the maximum humidity, although the authors reported that there was no significant relationship [14].

The 4 seasons in Tokyo were defined by the Japanese meteorological classification: spring (March through May), summer (June through August), autumn (September through November), and winter (December through February).

We also collected data on air pollution levels of Tokyo in official publications from the Ministry of the Environment, Government of Japan. Daily data of air pollutants included SO₂ (in pbb), nitrogen monoxide (NO; in ppb), NO_x (in ppb), suspended particulate matter (SPM; in ug/m³), and CO (x0.1 in parts per million). Daily continuous monitoring

was performed for these pollutants at 22 monitoring points in Tokyo, and data of the metropolitan central point (Chuo City) were used for the analysis. Because the levels of pollutants fluctuate during a day and previous studies reported the association between exacerbations of asthma and the increased levels of air pollutants [13,14,27], the highest values of pollutants in each single day were used for the analysis.

Table 2 Correlations of meteorological factors and air

pollutants to asthma transports to ED (N = 6447)

Measured daily variable

Adults (n = 5666)

Children (n = 781)

Correlation coefficient

P

value

Correlation coefficient

P

value

Meteorological fact

Maximum 0.207 b.001 0.135 .010

SPM, ug/m³

CO, 0.1 ppm

-0.064

0.167

.226 -0.014

.001 -0.035

.794

.506

Ozone and PM10 were not evaluated, since monitoring of these substances was not conducted at the time of this study in Japan.	barometric pressure, hPa Lowest temperature, ?C	-0.381 b.001 0.092 .080
	Maximum	-0.157	.003	0.104	.048
2.3. Statistical analysis	humidity, %
	Precipitation, mm	-0.010	.842	0.004	.944

The daily number of ED visits for exacerbation of asthma through ambulance transports was treated as a dependent variable. Independent variables were daily meteorological factors and daily air pollutants. Descriptive statistics were calculated for the demographics of patients with asthma and for meteorological factors and air pollutant levels. Pearson Correlation coefficients, as unadjusted crude analyses, were used in bivariate analysis for illustrating each relationship between one independent variable and the dependent variable one at a time, separately among adults and children. In addition, the ARIMA model was used in analyzing time series data separately among adults and children. Three main parameters were selected when fitting the ARIMA model: the order of autoregressive (p), the order of integration (d), and the order of moving average (q). Consequently, the process is called ARIMA (p, d, q). The selection of ARIMA processes was conducted using Akaike’s information criterion, which measures how well the model fits the series. A multivariable- adjusted ARIMA model was constructed for fitting the model

Table 1 Daily levels of meteorological factors and air pollutants

Table 3 ARIMA (1, 0, 1) model for ambulance transports to ED for asthma exacerbation among adults

Air pollutants
SO2, ppb	-0.047	.368	-0.086	.100
NO, ppb	0.100	.056	-0.024	.650
NOx, ppb	0.112	.032	-0.031	.557

with the generalized least squares regression by controlling autocorrelation and partial autocorrelation of time series data and by adjusting cross correlations. Lag time (lag) indicates the interval (days) from the time of significant independent variables to the time of a dependent variable in this model. The slope of the regression surface constructed by the fitted model is indicated by the ? coefficient of significant variables. A plus code of ? coefficients means a positive correlation, whereas a minus code of ? coefficients means a negative correlation. All P values were 2-sided, and P b .05 was considered statistically significant. Statistical analyses were

Measured daily Mean variable	Range	The day with extreme values
Meteorological factors
Maximum 1011.6	991.2 to	April 18
barometric	1025.1
pressure, hPa
Lowest 13.1	-0.7 to	December 19
temperature, ?C	27.9
Maximum 72.8	32 to 91	May 5, September 4
humidity, %		and 5, October 8
Precipitation, mm 4.1	0 to 74.5	July 26
Air pollutants
SO2, ppb 5.3	0 to 73	May 4
NO, ppb 90.3	2 to 463	November 28
NOx, ppb 137.4	20 to	November 28
	542
SPM, ug/m3 62.9	12 to	July 2
	283
CO, 0.1 ppm 11.5	3 to 44	December 20

Lag time		? Coefficient	SE	t Statistic	P value
Constant	NA	-26.592	47.949	-0.555	.580
Autoregression	1	0.764	0.154	4.950	b.0001
Moving average	1	0.648	0.182	3.569	b.0001
Maximum	0	0.043	0.047	0.915	.361
barometric
pressure
Lowest	0	-0.243	0.052	-4.723	b.0001
temperature
Maximum	0	0.017	0.023	0.752	.452
humidity
Precipitation	0	0.020	0.025	0.799	.425
SO2	0	0.008	0.041	0.208	.836
NO	0	0.006	0.027	0.236	.813
NOx	0	-0.017	0.026	-0.653	.514
SPM	0	0.008	0.009	0.864	.388
CO	0	0.151	0.098	1.537	.125
SE indicates standard error of ? coefficient; NA, not applicable.

Fig. 1 Daily ambulance transports to ED for asthma exacerbation among adults. Red line indicates the observed number; blue line indicates the fitted estimate.

performed using SPSS 15.0J with TRENDS system (SPSS- Japan, Tokyo, Japan).

Results

Of a total of 643849 patients who were transported to hospitals by ambulances in Tokyo during the 1-year study period, there were 6447 patients with exacerbation of asthma (1.0% of all patients). The mean (SD) age of patients with asthma was 49.8 (25.2) years. Of these, 47.2% were women and 52.8% were men; 5666 (87.9%) were adults and 781

(12.1%) were children. There were 2940 (45.6%) patients who were admitted to hospital wards. The mean number of daily ambulance transports to ED for asthma in Tokyo was

17.7 patients. Table 1 presents the daily levels of meteor- ological factors and air pollutants.

Regarding the number of ambulance transports to ED for exacerbation of asthma on the days with extreme values for each meteorological factor, the day with the highest barometric pressure (1025 hPa) was April 18. On that day, the number of transports was 19. The day with the heaviest precipitation (74.5 mm) was July 26. On that day, the number of transports was 20. In contrast, the day with the lowest temperature (-0.7?C) was December 19, and on that day, the number of transports was 26.

The maximum number of daily ambulance transports to ED for asthma was 40, which occurred on October 11, followed by 33 on November 21. October 11 was the day after

October 10, the National Sports Day (one of the national holidays in Japan). On October 10 (National Sports Day), Japanese people are encouraged to do any sports outside. On October 10, 2005, maximum barometric pressure was 1019 hPa; lowest temperature, 17.1?C; maximum humidity, 89%; precipitation, 19 mm; SO₂, 0 ppb; NO, 12 ppb; NO_x,

46 ppb; SPM, 25 ug/m³; and CO, 0.6 ppm. On October 11, 2005, maximum barometric pressure was 1019 hPa; lowest temperature, 17.1?C; maximum humidity, 88%; precipita- tion, 3 mm; SO₂, 1 ppb; NO, 36 ppb; NO_x, 66 ppb; SPM, 31 ug/m³; and CO, 0.6 ppm. The minimum number of asthma transports was 7 on September 2 and 7. Seasonal mean numbers of the transports were 19.1 (winter), 17.9 (spring),

14.7 (summer), and 19.0 (autumn). Thus, the greatest number of transports was seen in the winter season, whereas the lowest number of transports was noted in the summer.

Regarding the number of ambulance transports to the ED for exacerbation of asthma on the days with the highest values of each air pollutant, the day with the highest SO₂ (73 ppb) was May 4. On that day, the number of transports was 20. On the day with the highest NO (463 ppb) and the highest NO_x (542 ppb) (November 28), the number of transports was 26. On the day with the highest SPM (283 ug/m³) (July 2), the number of transports was 15. On the day with the highest CO (4.4 ppm) (December 20), the number of transports was 25.

Table 2 shows the bivariate Pearson correlation coeffi- cients relating meteorological factors and air pollutants to the number of ambulance transports for exacerbation of asthma, as the unadjusted crude results. For adults, significant

Lag time		? Coefficient	SE	t Statistic	P value
Constant	NA	-10.752	17.206	-0.625	.532
Autoregression	1	0.934	0.031	29.784	b.0001
Moving average	1	0.761	0.058	13.022	b.0001
Maximum	0	0.012	0.017	0.736	.462
barometric
pressure
Lowest	0	-0.007	0.029	-0.226	.821
temperature
Maximum	0	0.010	0.008	1.206	.229
humidity
Precipitation	0	-0.004	0.008	-0.495	.621
SO2	0	-0.004	0.014	-0.319	.750
NO	0	0.000	0.009	0.050	.960
NOx	0	-0.003	0.009	-0.274	.784
SPM	0	-0.001	0.003	-0.465	.642
CO	0	0.019	0.034	0.549	.583
SE indicates standard error of ? coefficient; NA, not applicable.

bivariate correlations were found among the number of transports and several meteorological factors and air pollu- tants, including maximum barometric pressure, lowest temp- erature, maximum humidity, NO_x, and CO. Among children, significant bivariate correlations were found among the number of transports and 2 meteorological factors, maximum barometric pressure and maximum humidity.

Table 4 ARIMA (1, 0, 1) model for ambulance transports to ED for asthma exacerbation among children

Table 3 presents the results of the fitted ARIMA (1, 0, 1) model for ambulance transports to ED for exacerbation of asthma among adults. Because the Ljung-Box Q statistic was

13.8 (df = 16; P = .612; no outliers), the model was considered to fit well to the observed data (Fig. 1). The daily lowest temperature was significantly associated with the number of transports. However, there were no significant associations between asthma transports and other meteor- ological factors. There were no significant associations between asthma transports and air pollutant levels, including SO₂, NO, NO_x, SPM, and CO.

Table 4 presents the results of the fitted ARIMA (1, 0, 1) model for ambulance transports to ED for exacerbation of asthma among children. Because the Ljung-Box Q statistic was 13.4 (df = 16; P = .644; no outliers), the model was considered to fit well to the observed data, but there were no significant associations between asthma transports and air pollutant levels nor between asthma transports and meteor- ological factors.

Discussion

Based on our time series analysis using large, population- based, and daily data for ambulance transports in one of the mega-cities of the world, lower minimum temperature is a

significant factor associated with exacerbation of asthma among adults, as suggested in a previous study [26,28]. How- ever, other meteorological factors and air pollution levels do not seem related to exacerbation of asthma among adults. No associations between these environmental factors and ambulance transports were found among asthmatic children. Many patients with asthma experience an exacerbation on exposure to Cold air. Even in a resting state, some patients with allergic asthma easily develop nasal obstruction and sneezing while moving in a cold environment. It has also been shown that airway cooling is an important trigger factor for asthma. Airway cooling enhances inflammation and thereby causes a narrowing of airways and exacerbation of asthma [29]. Furthermore, cooling of other parts of the body has also been shown to exacerbate asthma [30]. However, because the relation of the minimum temperature to exacerbations of asthma was not considered significant among children in our study, the effects of cold temperature may not contribute significantly to exacerbation of asthma among children. Other factors, such as allergen exposures and emotional stress, may play a more important role in

causing asthmatic fit among children.

Clinicians may be able to provide some advice to asthma patients in terms of being careful for the exacerbation in cold weather, as indicated by the results of this study. Some patients may receive preventive benefit from medica- tion adjustments, such as the adjustment dosages of inhaled corticosteroids based on their activity levels outside in cold temperature. This advice could be helpful especially to patients with a past history of tracheal intubation for asthma [17,28,31].

We also found that the day with the highest number of ambulance transports to the ED for exacerbation of asthma was October 11. This peak coincided with the day after October 10, the National Sports Day. This holiday was established to commemorate the opening ceremony of the 1964 Tokyo Olympics. On this holiday, Japanese people are encouraged to do some sports to promote health and well- being through actively participating in exercise. The increased number of ED visits the day after the National Sports Day could be explained by an increase in exercise- induced exacerbation and emotional stress among the asthmatics who did exercise on the sports holiday [15,17,31]. Our study has some uniqueness compared with previous studies. First, our results were based on a large population- based sample and daily consecutive data, whereas most previous studies were based on hospital-based data. Second, we used a statistical method to adjust autocorrelations and cross correlations of times series data. Previous attempts have been made to evaluate relationships between multiple environmental factors and exacerbation of asthma based on Linear regression models. However, the variables of environ- mental factors and exacerbation of asthma are usually treated as time series data with inherent autocorrelation, and it seems necessary to control the autocorrelation for exploring associations among these data. The ARIMA model, also

known as Box and Jenkins model, has the flexibility to control the autocorrelation of time series data, and its usefulness has become established in such fields as economics and environmental science [20-22].

Third, we constructed a model simultaneously adjusted for both weather conditions and air pollutant levels. Weather conditions may modify the air pollution [14]. For instance, cold weather and air pollution may have an added trigger effect on asthma patients. Many pollutants, such as Nitrogen dioxide, SO₂, CO, and ozone, are heavier than air; hence, they may remain suspended over the surface. Cold winter nights, especially in walled urban areas, can create a zone of stagnant air. Especially on a foggy night, these pollutants, mixed in fog, may remain stationary for long durations. When asthma patients pass through such an area, they may be affected adversely, and this effect is also known as pollution inversion [32]. In addition, it is also common to note poorer air quality in a higher-pressure environment [33]. Moreover, air pollution is dependent on rainfall precipitation. Particles in the atmosphere are readily washed out in rain, whereas pollutant gases are generally not affected much by rain [34]. Thus, if one would investigate the relationship between exacerbation of asthma and weather conditions as well as air pollution, one may need to consider a model that adjusts both weather conditions and air pollution in the analysis. Indeed, in our study, several variables were considered significant by bivariate Pearson correlation analysis (Table 2). However, this procedure is unadjusted crude analysis, and thus, we should rather rely on the results of the ARIMA models (Tables 3 and 4), which adjusted for all variables.

Our study has several limitations. First, ozone and PM10 were not included in the air pollutants measured in our study. There may be a possible relationship between increased exacerbation of asthma and increased levels of ozone [14]. Second, data were available for only 1 year in this study. Thus, we could not investigate seasonal patterns. Third, as an indicator of asthma exacerbation, we used the number of ambulance transports to the ED for exacerbation of asthma in Tokyo. Data of ambulance transports to ED for asthma may still be used as surrogate indicator for population-level time series data of Severe asthma exacerbation in Japan, where liberal access to ED is ensured for all people [35,36]. Nonetheless, air pollution may still have an effect on mild to moderate exacerbations of asthma in the ambulatory population. Our study design could not capture the data of these degrees of severity in exacerbation of asthma.

There is a growing body of literature indicating significant association between air pollution and its adverse effects on the development of respiratory systems during childhood [37,38]. Although our results showed no significant associa- tion between air pollution and exacerbation of asthma, our analysis was based on data of short-term exposure and the acute effect. Long-term exposure to air pollution may still cause adverse effects in terms of quality of chronic Asthma control [39]. Moreover, there is a number of research

reporting significant association between air pollution and its adverse effects on cardiovascular events [40,41]. Further studies are needed to investigate the influence of air pollution and weather conditions on various health-related conditions. In conclusion, cold weather is likely to be an environ- mental risk factor for significant exacerbation of asthma among adults. Exercising asthma patients may need to be careful of asthma exacerbation during cold weather. Other meteorological factors and short-term air pollution levels seem to be not associated with significant exacerbation of asthma requiring ambulance transports to ED. The day with the highest number of ambulance transports to ED for exacerbation of asthma was October 11, the day after the National Sports Day. This particularly high number of ED visits at the day after National Sports Day could be explained by an increase in exacerbation of asthma induced by exercise

and emotional stress.

Acknowledgments

The authors thank all emergency technicians, attending physicians, and residents of EDs in Tokyo, Japan. We also thank all staffs in the Tokyo Fire Department, the Japan Meteorological Agency, and the Ministry of the Environ- ment, Government of Japan, for supporting our work.

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