Study Design and Participants' Profile in the Sub-Cohort Study in the Japan Environment and Children's Study (JECS).

BACKGROUND: The Japan Environment and Children's Study (JECS) is a nationwide birth cohort study investigating environmental effects on children's health and development. A Sub-Cohort Study has begun, conducting extended exposure and outcome measurements by targeting a subgroup randomly selected from the JECS Main Study. We report the Sub-Cohort Study methodology and participants' baseline profiles. METHODS: Of 100,148 children in the JECS Main Study, children born after April 1, 2013 who met eligibility criteria ([1] all questionnaire and medical record data from children and their mothers collected from the first trimester to 6 months of age, [2] biospecimens [except umbilical cord blood] from children and their mothers collected at first to second/third trimester and delivery) were randomly selected for each Regional Centre at regular intervals. Face-to-face assessment of neuropsychiatric development, body measurement, paediatrician's examination, blood/urine collection for clinical testing and chemical analysis, and home visits (ambient and indoor air measurement and dust collection) are conducted. Participants are followed up at 1.5 and 3 years old for home visits, and 2, 4, 6, and 8 years old for developmental/medical examination. The details of protocols after age 10 are under discussion. RESULTS: Of 10,302 selected children, 5,017 participated. The profiles of the participating mothers, fathers and children did not substantially differ between the Main Study and Sub-Cohort Study. CONCLUSION: The JECS Sub-Cohort Study offers a platform for investigating associations between environmental exposure and outcomes.

[Effect of City-Specific Characteristics on Association between Heat and Ambulance Dispatches].

OBJECTIVES: In this multicity study, we aimed to elucidate the city-specific factors affecting the association of high ambient temperature with ambulance dispatches due to acute illnesses. METHODS: We used the data of ambulance dispatches in 27 cities in Japan with more than 500,000 population excluding Tokyo, from May to September from 2012 to 2015. We included patients 20 years and older (≥20 years) and stratified them into three age groups (20-59, 60-79, and ≥80 years). We explored the city-specific pattern of the daily relative temperature (in temperature percentiles) and the risk of ambulance dispatches for each age group using a distributed lag nonlinear model and estimated the city-specific relative risks of ambulance dispatches at the 95/99 percentile temperature compared with the 77.6 percentile temperature defined as the reference temperature (Tref). Then, the estimates were combined by performing meta-analyses for each age group. We also applied meta-regression models to explore whether the city-specific characteristics modified the association of temperature with ambulance dispatches. RESULTS: The relative risks of the 95th percentile with respect to Tref were 1.14 (95% confidence interval (CI): 1.12, 1.16), 1.16 (95% CI: 1.13, 1.20), 1.13 (95% CI: 1.10, 1.16), and 1.13 (95% CI: 1.00, 1.16), for all-age (≥20) and age-stratified groups (20-59, 60-79, and ≥80 years), respectively. We observed a higher relative risk for the ≥20 years age group in the cities with higher proportions of single-elderly, single-mother, and single-father households. We also found that the relative risk for the 20-59 years age group was higher in the cities with a higher proportion of blue-collar workers. CONCLUSIONS: The present study provides insights into city-specific characteristics modifying heat-related health effects.

Fish consumption in early pregnancy and congenital gastrointestinal tract atresia in the Japan Environment and Children's Study.

Current evidence suggests that the aetiology of congenital gastrointestinal (GI) tract atresia is multifactorial, and not based solely on genetic factors. However, there are no established modifiable risk factors for congenital GI tract atresia. We used data from a Japanese nationwide birth cohort study launched in 2011, and examined whether fish consumption in early pregnancy was associated with congenital GI tract atresia. We analysed data of 89 495 women (mean age at delivery=31·2 years) who delivered singleton live births without chromosomal anomalies. Based on the results of the FFQ, we estimated the daily intake of fish and n-3 PUFA consumption in early pregnancy. We defined a composite outcome (oesophageal atresia, duodenal atresia, jejunoileal atresia and/or anorectal malformation) as congenital GI tract atresia. In this population, median fish intake was 31·9 g/d, and seventy-four cases of congenital GI tract atresia were identified. Fish consumption in early pregnancy was inversely associated with the composite outcome (multivariable-adjusted OR for the high v. low consumption category=0·5, 95 % CI 0·3, 1·0). For all the specific types of atresia, decreased OR were observed in the high consumption category, although not statistically significant. Reduced atresia occurrence was observed even beyond the US Food and Drug Administration's recommended consumption of no more than 340 g/week. Also, n-3 PUFA-rich fish and n-3 PUFA consumptions tended to be inversely associated with atresia. Fish consumption in early pregnancy may be a preventive factor for congenital GI tract atresia.

Isoflavone Intake in Early Pregnancy and Hypospadias in the Japan Environment and Children's Study.

OBJECTIVE: To explore the association between isoflavone intake in early pregnancy (the critical window of masculinisation) and hypospadias. Since oestrogen is likely to contribute to the differentiation of male external genitalia, dietary intake of isoflavone, which has a similar structure to human oestrogen, may be associated with the occurrence of hypospadias. However, there has been little evidence of this association. MATERIALS AND METHODS: We used data of a nationwide birth cohort study, which recruited women as early in pregnancy as possible throughout Japan between 2011 and 2014. From the response to a self-administered food-frequency questionnaire, the daily intake of genistein (as a representative for isoflavone) was estimated. Information on hypospadias cases that were diagnosed until the first month after birth was obtained from medical records. Odds ratios (ORs) of hypospadias were estimated using a logistic regression model. RESULTS: Among 41,578 mothers, who delivered singleton live male births, the median genistein intake was 15.3 mg/day, and a total of 51 cases of hypospadias were identified. Compared with mothers in the reference group (genistein intake 11th-89th percentiles), those in the low intake group (≤10th percentile) had an elevated risk of their sons having hypospadias (multivariable-adjusted OR = 2.8, 95% confidence interval = 1.4-5.8). Adverse or beneficial effects of genistein on hypospadias were not observed in the high intake group (≥90th percentile) (OR = 0.9, 95% confidence interval = 0.4-2.4). CONCLUSION: Low maternal intake of isoflavone in early pregnancy was associated with an elevated risk of hypospadias.

Questionnaire results on exposure characteristics of pregnant women participating in the Japan Environment and Children Study (JECS).

BACKGROUND: The Japan Environment and Children's Study (JECS) is a nation-wide birth cohort study investigating environmental effects on children's health and development. In this study, the exposure characteristics of the JECS participating mothers were summarized using two questionnaires administered during pregnancy. METHODS: Women were recruited during the early period of their pregnancy. We intended to administer the questionnaire during the first trimester (MT1) and the second/third trimester (MT2). The total number of registered pregnancies was 103,099. RESULTS: The response rates of the MT1 and MT2 questionnaires were 96.8% and 95.1%, respectively. The mean gestational ages (SDs) at the time of the MT1 and MT2 questionnaire responses were 16.4 (8.0) and 27.9 (6.5) weeks, respectively. The frequency of participants who reported "lifting something weighing more than 20 kg" during pregnancy was 5.3% for MT1 and 3.9% for MT2. The Cohen kappa scores ranged from 0.07 to 0.54 (median 0.31) about the occupational chemical use between MT1 and MT2 questionnaires. Most of the participants (80%) lived in either wooden detached houses or steel-frame collective housing. More than half of the questionnaire respondents answered that they had "mold growing somewhere in the house". Insect repellents and insecticides were used widely in households: about 60% used "moth repellent for clothes in the closet," whereas 32% applied "spray insecticide indoors" or "mosquito coil or an electric mosquito repellent mat." CONCLUSIONS: We summarized the exposure characteristics of the JECS participants using two maternal questionnaires during pregnancy.

Effects of high ambient temperature on ambulance dispatches in different age groups in Fukuoka, Japan.

BACKGROUND: The elderly population has been the primary target of intervention to prevent heat-related illnesses. According to the literature, the highest risks have been observed among the elderly in the temperature-mortality relationship. However, findings regarding the temperature-morbidity relationship are inconsistent. OBJECTIVES: This study aimed to examine the association of temperature with ambulance dispatches due to acute illnesses, stratified by age group. Specifically, we explored the optimum temperature, at which the relative health risks were found to be the lowest, and quantified the health risk associated with higher temperatures among different age groups. METHODS: We used the data for ambulance dispatches in Fukuoka, Japan, during May and September from 2005 to 2012. The data were grouped according to age in 20-year increments. We explored the pattern of the association of ambulance dispatches with temperature using a smoothing spline curve to identify the optimum temperature for each age group. Then, we applied a distributed lag nonlinear model to estimate the risks of the 85th-95th percentile temperature relative to the overall optimum temperature, for each age group. RESULTS: The relative risk of ambulance dispatches at the 85th and 95th percentile temperature for all ages was 1.08 [95% confidence interval (CI): 1.05, 1.12] and 1.12 (95% CI: 1.08, 1.16), respectively. In comparison, among age groups, the optimum temperature was observed as 25.0°C, 23.2°C, and 25.3°C for those aged 0-19, 60-79, and ≥80, respectively. The optimum temperature could not be determined for those aged 20-39 and 40-59. The relative risks of high temperature tended to be higher for those aged 20-39 and 40-59 than those for other age groups. CONCLUSIONS: We did not find any definite difference in the effect of high temperature on ambulance dispatches for different age groups. However, more measures should be taken for younger and middle-aged people to avoid heat-related illnesses.

Baseline Profile of Participants in the Japan Environment and Children's Study (JECS).

BACKGROUND: The Japan Environment and Children's Study (JECS), known as Ecochil-Chosa in Japan, is a nationwide birth cohort study investigating the environmental factors that might affect children's health and development. We report the baseline profiles of the participating mothers, fathers, and their children. METHODS: Fifteen Regional Centres located throughout Japan were responsible for recruiting women in early pregnancy living in their respective recruitment areas. Self-administered questionnaires and medical records were used to obtain such information as demographic factors, lifestyle, socioeconomic status, environmental exposure, medical history, and delivery information. In the period up to delivery, we collected bio-specimens, including blood, urine, hair, and umbilical cord blood. Fathers were also recruited, when accessible, and asked to fill in a questionnaire and to provide blood samples. RESULTS: The total number of pregnancies resulting in delivery was 100,778, of which 51,402 (51.0%) involved program participation by male partners. Discounting pregnancies by the same woman, the study included 95,248 unique mothers and 49,189 unique fathers. The 100,778 pregnancies involved a total of 101,779 fetuses and resulted in 100,148 live births. The coverage of children in 2013 (the number of live births registered in JECS divided by the number of all live births within the study areas) was approximately 45%. Nevertheless, the data on the characteristics of the mothers and children we studied showed marked similarity to those obtained from Japan's 2013 Vital Statistics Survey. CONCLUSIONS: Between 2011 and 2014, we established one of the largest birth cohorts in the world.

Prognostic significance of disseminated intravascular coagulation in patients with heat stroke in a nationwide registry.

PURPOSE: Heat stroke (HS) induces disseminated intravascular coagulation (DIC); however, the prognostic significance of DIC in patients with HS has not yet been fully assessed in large populations. The aim of this study was to examine the prognostic significance of DIC in patients with HS using a nationwide registry. MATERIALS AND METHODS: Data regarding HS were obtained and analyzed from three prospective, observational, multicenter HS registries (HSRs): 2010, 2012, and 2014. Univariate and multivariate analyses were performed to identify independent predictors of hospital death. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) diagnostic criteria, with a total score≥4 implying a DIC diagnosis. RESULTS: In total, 705 (median age, 68years; 501 men) were included in this study. Hospital mortality was 7.1% (50 patients). Multiple regression analysis revealed that hospital mortality was significantly associated with presence of DIC (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.09-4.27; p=0.028). Mortality worsened as the DIC score increased, and increased remarkably to approximately 10% when the DIC score was 2. CONCLUSIONS: Presence of DIC was an independent prognostic factor of hospital mortality in patients with HS. Hematological dysfunction represents potential target for specific therapies in HS.

Association between traffic-related air pollution and asthma in preschool children in a national Japanese nested case-control study.

OBJECTIVES: There has been little study on the effect of traffic-related air pollution on the incidence and persistence of asthma in preschool children. We evaluated the association of exposure to traffic-related air pollution with the incidence/persistence of asthma during the first 3 years of life using a population-based study. METHODS: A baseline survey was conducted in 1½-year-old children (n=63,266). A follow-up survey at 3 years of age (n=43,343) identified new-onset asthma cases (n=853) and persistence of asthma (n=214). In the prevalence/persistence study, the outdoor concentrations of nitrogen oxides (NOx) and elemental carbon (EC) at home during the first 1½â€…years of life were estimated by a dispersion model. In the nested case-control study, which regarded incidence of asthma as cases, the personal exposure levels were estimated by dispersion model including time-activity pattern. RESULTS: There was no statistically significant association between the incidence of asthma between age 1½ and 3 years and personal exposure levels to NOx nor EC. However, the persistence of asthmatic symptoms (between 1½ and 3  ears) was significantly associated with outdoor concentrations of NOx. ORs for the persistence of asthmatic symptoms were 6.02 (95% CI 1.51 to 23.92) for the comparison between the upper 5th and lower 25th centiles of NOx. CONCLUSIONS: While no statistically significant association was observed for the incidence of asthma, the persistence of asthmatic symptoms in preschool children was significantly associated with traffic-related air pollution. This supports its importance as a risk factor in childhood airway disease.

Patterns of Sensitization to Inhalant Allergens in Japanese Lower-Grade Schoolchildren and Related Factors.

OBJECTIVE: This study clarified sensitization patterns to house dust mite (HDM) and Japanese cedar pollen (JCP) in Japanese lower-grade schoolchildren. We also explored factors associated with allergic sensitization. METHODS: This cross-sectional study used a database from the Study on Respiratory Disease and Automobile Exhaust (SORA), a Japanese health study project. The subjects comprised 8,815 pupils aged 6-9 years. We obtained the distribution of HDM- and JCP-specific IgE, respectively, as a marker of sensitization. To determine factors associated with sensitization, we used logistic regression and calculated adjusted odds ratios (AORs) for the relative prevalence of sensitization. The cut-off point for specific IgE levels was 0.35 kU/l. RESULTS: Sensitization to HDM and JCP was detected in 51 and 39% of subjects, respectively, occurring more often in boys and at older ages. In addition, AORs of sensitization to HDM/JCP were higher in subjects with a history of bronchitis, parental asthma, parental atopic eczema and parental pollinosis. In contrast, AORs for sensitization were lower in those subjected to maternal passive smoking as well as among boys with pets. AORs of sensitization to JCP alone were lower in those with a history of otitis media, those who had been bottle milk fed, and those who were not the firstborn and who lived near a busy road. CONCLUSION: Sensitization to HDM and JCP was detected in 51 and 39% of lower-grade schoolchildren, respectively.

The Japan Environment and Children's Study (JECS): A Preliminary Report on Selected Characteristics of Approximately 10 000 Pregnant Women Recruited During the First Year of the Study.

BACKGROUND: The Japan Environment and Children's Study (JECS) is an ongoing nationwide birth cohort study launched in January 2011. In this progress report, we present data collected in the first year to summarize selected maternal and infant characteristics. METHODS: In the 15 Regional Centers located throughout Japan, the expectant mothers were recruited in early pregnancy at obstetric facilities and/or at local government offices issuing pregnancy journals. Self-administered questionnaires were distributed to the women during their first trimester and then again during the second or third trimester to obtain information on demographic factors, physical and mental health, lifestyle, occupation, environmental exposure, dwelling conditions, and socioeconomic status. Information was obtained from medical records in the first trimester and after delivery on medical history, including gravidity and related complications, parity, maternal anthropometry, and infant physical examinations. RESULTS: We collected data on a total of 9819 expectant mothers (mean age = 31.0 years) who gave birth during 2011. There were 9635 live births. The selected infant characteristics (singleton births, gestational age at birth, sex, birth weight) in the JECS population were similar to those in national survey data on the Japanese general population. CONCLUSIONS: Our final birth data will eventually be used to evaluate the national representativeness of the JECS population. We hope the JECS will provide valuable information on the impact of the environment in which our children live on their health and development.

Community trial on heat related-illness prevention behaviors and knowledge for the elderly.

This study aims to explore whether broadcasting heat health warnings (HHWs), to every household and whether the additional home delivery of bottled water labeled with messages will be effective in improving the behaviors and knowledge of elderly people to prevent heat-related illness. A community trial on heat-related-illness-prevention behaviors and knowledge for people aged between 65 and 84 years was conducted in Nagasaki, Japan. Five hundred eight subjects were selected randomly from three groups: heat health warning (HHW), HHW and water delivery (HHW+W), and control groups. Baseline and follow-up questionnaires were conducted in June and September 2012, respectively. Of the 1524 selected subjects, the 1072 that completed both questionnaires were analyzed. The HHW+W group showed improvements in nighttime AC use (p=0.047), water intake (p=0.003), cooling body (p=0.002) and reduced activities in heat (p=0.047) compared with the control, while the HHW group improved hat or parasol use (p=0.008). An additional effect of household water delivery was observed in water intake (p=0.067) and cooling body (p=0.095) behaviors. HHW and household bottled water delivery improved heat-related-illness-prevention behaviors. The results indicate that home water delivery in addition to a HHW may be needed to raise awareness of the elderly.

Association between traffic-related air pollution and development of asthma in school children: cohort study in Japan.

Air pollution is widely understood to be capable of exacerbating asthma symptoms. Here we examined the association between traffic-related air pollution and development of asthma in school children. Subjects were 10,069 school children in their first through third years of compulsory education (6-9-year old). The main outcome was incidence of asthma as determined from the questionnaire. Follow-up surveys were conducted every year up to 4 years after the end of the study. To evaluate individual level of exposure to traffic-related air pollution, we used a simulation model that accounted for exposure level both at home and at school. As surrogates of traffic-related air pollution, the estimation target was the annual average individual exposure of automobile exhaust-originating nitrogen oxides (NOx) and elemental carbon (EC). Confounding factors were adjusted using a discrete-time logistic regression model. We found a positive association between exposure to EC and incidence of asthma. The odds ratio (OR) (95% confidence interval) for asthma incidence was 1.07 (1.01-1.14) for each 0.1 µg/m(3) EC and 1.01 (0.99-1.03) for each 1 p.p.b. NOx. Traffic-related air pollution is associated with development of asthma in school children.

Characterizing the effect of summer temperature on heatstroke-related emergency ambulance dispatches in the Kanto area of Japan.

Despite rising concern on the impact of heat on human health, the risk of high summer temperature on heatstroke-related emergency dispatches is not well understood in Japan. A time-series study was conducted to examine the association between apparent temperature and daily heatstroke-related ambulance dispatches (HSAD) within the Kanto area of Japan. A total of 12,907 HSAD occurring from 2000 to 2009 in five major cities-Saitama, Chiba, Tokyo, Kawasaki, and Yokohama-were analyzed. Generalized additive models and zero-inflated Poisson regressions were used to estimate the effects of daily maximum three-hour apparent temperature (AT) on dispatch frequency from May to September, with adjustment for seasonality, long-term trend, weekends, and public holidays. Linear and non-linear exposure effects were considered. Effects on days when AT first exceeded its summer median were also investigated. City-specific estimates were combined using random effects meta-analyses. Exposure-response relationship was found to be fairly linear. Significant risk increase began from 21 °C with a combined relative risk (RR) of 1.22 (95% confidence interval, 1.03-1.44), increasing to 1.49 (1.42-1.57) at peak AT. When linear exposure was assumed, combined RR was 1.43 (1.37-1.50) per degree Celsius increment. Overall association was significant the first few times when median AT was initially exceeded in a particular warm season. More than two-thirds of these initial hot days were in June, implying the harmful effect of initial warming as the season changed. Risk increase that began early at the fairly mild perceived temperature implies the need for early precaution.

Sunlight exposure may be a risk factor of hearing impairment: a community-based study in Japanese older men and women.

BACKGROUND: Oxidative stress is an important factor in the pathology of age-related hearing loss. Recent animal studies have reported that ultraviolet radiation in sunlight is related to systemic induction of oxidative stress. Chronic sun exposure leads to photodamaged skin, which is manifested as facial skin wrinkling and hyperpigmentation. We hypothesized that sunlight exposure, as assessed by the severity of facial skin photodamage, might be associated with hearing impairment through an oxidative stress mechanism. To examine this, we performed a cross-sectional analysis by using the baseline data from a community-based cohort study of older Japanese. METHODS: A total of 805 residents (342 men and 463 women) aged 65 years or older living in Kurabuchi Town, Gunma prefecture, Japan, were examined between 2005 and 2006. Facial skin condition was quantified by image analysis of standardized facial images. Hearing impairment was defined as a failure to hear a 30-dB signal at 1 kHz and a 40-dB signal at 4 kHz in the better ear in pure-tone audiometric tests. RESULTS: In men, facial wrinkle was positively associated with hearing impairment (for highest vs lowest: multivariate-adjusted odds ratio, 2.16; 95% confidence interval, 1.00-4.66; p for trend = .01). Stratified analysis by age, educational level, smoking status, sunscreen or foundation use, and diabetes showed results similar to those for men as a whole. This association was particularly pronounced in men with the low levels of antioxidants and without occupational noise exposure. We observed no apparent association in women. CONCLUSIONS: The results support the hypothesis that chronic sun exposure is a risk factor of hearing impairment.

Population at high-risk of indoor heatstroke: the usage of cooling appliances among urban elderlies in Japan.

OBJECTIVES: Heatstroke due to a heat wave during the summer is one of the commonly known health impacts of climate change in Japan. The elderly are particularly at high-risk of developing indoor heatstroke with poor prognosis. This study aims to describe the population among elderlies at high-risk of indoor heatstroke by focusing on the usage of cooling appliances. METHODS: We conducted a web-based household survey in eight urban areas during the winter season of 2011. Households with a person aged 65 and over were selected as samples from panel members of a research firm, and the oldest member of the household was queried about his/her usage of cooling appliances. The population at high-risk of indoor heatstroke is defined as the elderly staying in a room without cooling appliances, or not using the installed cooling appliances, or turning the cooling appliances on only when the room temperature is above 28 °C. RESULTS: 15.4 and 19.1 % of the elderlies living in urban areas of Japan are identified as at high-risk of indoor heatstroke during activity time and sleeping time, respectively, according to the definition of high-risk of indoor heatstroke in this study. CONCLUSIONS: These figures are not negligible since the consequences of heatstroke are grave, but its risk can be eliminated by an appropriate usage of cooling appliances. The preventive interventions are needed to protect the elderlies at high-risk of heatstroke.

[Information system of heat-disorders and prevention].

In Japan several services for providing information on heat-disorders and its prevention are available. For the information on patients of heat-disorders, National Institute for Environmental Studies (NIES) and Fire and Disaster Management Agency(FDMA) have systems for providing the information of the patients transported by ambulance cars from heat-disorders. NIES deals the data from major cities and FDMA deals the data of all Japan by prefecture. For the information on preventing heat-disorders, Japan Meteorological Agency (JMA) and NIES have systems for providing the weather information. JMA alarms when the daily maximum temperature reached or will reach to extremely high (> or = 35 degrees C) and NIES provides the WBGT(wet-bulb globe temperature) forecast for coming three days for all around Japan.

Growing concern about heatstroke this summer in Japan after Fukushima nuclear disaster.

Heat stroke management will be a major challenge following the Fukushima nuclear plant accident that occurred due to the Great East Japan Earthquake. In this article, a number of actions to meet this challenge are proposed.

Relation between temperature and suicide mortality in Japan in the presence of other confounding factors using time-series analysis with a semiparametric approach.

OBJECTIVES: The objective of this study was to assess the relation between temperature and suicide mortality in Japan using time series analysis with a semiparametric approach. METHODS: We analyzed the relation between daily fluctuations in suicide mortality and maximum temperatures for all regions in Japan over the period of time from 1972 to 1995 using a generalized additive model. The model controls for the time trend, season, selected meteorological parameters, day of the week, and holiday. Adjustment was based using penalized splines and the decision on the amount of smoothness was based on minimizing the unbiased risk estimation criterion. RESULTS: The results show that suicide mortality in Japan has a seasonal character and it varies from year to year, with the highest occurrence in April, as well as in the first part of the week, especially on Mondays and Tuesdays. As for the day of the week, there were only few suicide cases on Saturdays and holidays. We found that for all regions in Japan when temperature increased the suicide mortality increased on the same day (lag = 0). Analysis by method of suicide showed that when temperature increased mortality significantly increased only for suicide by a violent method. The pattern of the relation for other methods remained unclear. CONCLUSIONS: This study suggests that an increase in temperature has a short-term effect on suicide mortality in Japan.

Estimating mortality effects of fine particulate matter in Japan: a comparison of time-series and case-crossover analyses.

Small particles can reach alveoli without being trapped in the upper respiratory tract and may have a greater impact on health than larger particles. Given the limited knowledge on health effects of fine particulate matter (PM2.5) in Japan, the short-term effects of PM2.5 on daily mortality using the generalized additive model (GAM), generalized linear model (GLIM), and time-stratified case-crossover analysis were estimated. Daily mortality data were obtained from the Ministry of Health, Labor, and Welfare. Air pollution and meteorological data in 20 areas were obtained from the National Institute for Environmental Studies and the Japan Meteorological Agency, respectively. The three methods were compared, adjusting for meteorological variables and co-pollutants, for area-specific analyses and combined area-specific results using meta-analysis with a random-effects model. Daily mortality for elderly aged 65 and over varied from 0.5 to 127.3 by area. The 24-hr mean concentration of PM2.5 ranged from 11.8 to 22.8 microg/m3. Area-specific analyses revealed regional heterogeneity. Furthermore, combined results showed that a 10-microg/m3 increase in PM2.5 for the single-pollutant model at lag1 was associated with a 0.53, 0.77, and 0.88% increase in all-cause mortality for the GAM, GLIM, and case-crossover analysis, respectively. These findings provide robust evidence for the short-term effects of air pollutants on daily mortality in Japan and suggest that differences in estimates obtained from different statistical models should be considered when multipollutant models are used.