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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.

Background: From around 2012, the use of automated equipment for fine particulate matter (PM 2.5 ) measurement with equivalence to a reference method has become popular nationwide in Japan. This enabled us to perform a national health effect assessment employing PM 2.5 concentrations based on the standardized measurement method. We evaluated the association between non-accidental mortality and short-term exposure to PM 2.5 and coarse particulate matter (PM), with the latter estimated as the difference between suspended particulate matter and PM 2.5 , for the fiscal years 2012-2014., Methods: This was a time-stratified case-crossover study in 100 highly-populated Japanese cities. Mortality data was obtained from the Ministry of Health, Labour and Welfare. City-specific estimates of PM-mortality association were calculated by applying a conditional logistic regression analysis, and combined with a random-effects meta-analysis., Results: The respective averages of daily mean concentration were 14.6 µg/m 3 for PM 2.5 and 6.4 µg/m 3 for coarse PM. A 10 µg/m 3 increase in PM 2.5 concentrations for the average of the day of death and the previous day was associated with an increase of 1.3% (95% confidence interval (CI), 0.9-1.6%) in total non-accidental mortality. For cause-specific mortality, PM 2.5 was positively associated with cardiovascular and respiratory mortality. After adjustment for PM 2.5 , we observed a 1.4% (95% CI, 0.2-2.6%) increase in total mortality with a 10 µg/m 3 increase in coarse PM., Conclusion: The study revealed that short-term exposure to PM 2.5 had adverse effects on total non-accidental, cardiovascular, and respiratory mortality in Japan. Coarse PM exposure also increased the risk of total mortality.

Short-term health effects of ambient PM 2.5 have been established with numerous studies, but evidence in Asian countries is limited. This study aimed to investigate the short-term effects of PM 2.5 on acute health outcomes, particularly all-cause, cardiovascular, respiratory, cerebrovascular and neuropsychological outcomes. We utilized daily emergency ambulance dispatches (EAD) data from eight Japanese cities (2007-2011). Statistical analyses included two stages: (1) City-level generalized linear model with Poisson distribution; (2) Random-effects meta-analysis in pooling city-specific effect estimates. Lag patterns were explored using (1) unconstrained-distributed lags (lag 0 to lag 7) and (2) average lags (lag: 0-1, 0-3, 0-5, 0-7). In all-cause EAD, significant increases were observed in both shorter lag (lag 0: 1.24% (95% CI: 0.92, 1.56)) and average lag 0-1 (0.64% (95% CI: 0.23, 1.06)). Increases of 1.88% and 1.48% in respiratory and neuropsychological EAD outcomes, respectively, were observed at lag 0 per 10 µg/m³ increase in PM 2.5 . While respiratory outcomes demonstrated significant average effects, no significant effect was observed for cardiovascular outcomes. Meanwhile, an inverse association was observed in cerebrovascular outcomes. In this study, we observed that effects of PM 2.5 on all-cause, respiratory and neuropsychological EAD were acute, with average effects not exceeding 3 days prior to EAD onset., Competing Interests: The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, nor in the decision to publish the results.

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.

Background and Purpose: There is a strong association between ambient concentrations of particulate matter (PM) and cardiovascular disease. However, it remains unclear whether acute exposure to fine PM (PM 2.5 ) triggers ischemic stroke events and whether the timing of exposure is associated with stroke risk. We, therefore, examined the association between ambient PM 2.5 and occurrence of ischemic stroke., Methods: We analyzed data for 6885 ischemic stroke patients from a multicenter hospital-based stroke registry in Japan who were previously independent and hospitalized within 24 hours of stroke onset. Time of symptom onset was confirmed, and the association between PM (suspended PM and PM 2.5 ) and occurrence of ischemic stroke was analyzed by time-stratified case-crossover analysis., Results: Ambient PM 2.5 and suspended PM at lag days 0 to 1 were associated with subsequent occurrence of ischemic stroke (ambient temperature-adjusted odds ratio [95% confidence interval] per 10 μg/m 3 : suspended PM, 1.02 [1.00-1.05]; PM 2.5 , 1.03 [1.00-1.06]). In contrast, ambient suspended PM and PM 2.5 at lag days 2 to 3 or 4 to 6 showed no significant association with stroke occurrence. The association between PM 2.5 at lag days 0 to 1 and ischemic stroke was maintained after adjusting for other air pollutants (nitrogen dioxide, photochemical oxidants, or sulfur dioxide) or influenza epidemics and was evident in the cold season., Conclusions: These findings suggest that short-term exposure to PM 2.5 within 1 day before onset is associated with the subsequent occurrence of ischemic stroke., (© 2016 American Heart Association, Inc.)

Short-term exposure to air pollution may be linked to negative health outcomes that require an emergency medical response. However, few studies have been undertaken on this phenomenon to date. The aim of this study therefore was to examine the association between short-term exposure to ambient suspended particulate matter (SPM) and emergency ambulance dispatches (EADs) for acute illness in Japan. Daily EAD data, daily mean SPM and meteorological data were obtained for four prefectures in the Kanto region of Japan for the period from 2007 to 2011. The area-specific association between daily EAD for acute illness and SPM was explored using generalized linear models while controlling for ambient temperature, relative humidity, seasonality, long-term trends, day of the week and public holidays. Stratified analyses were conducted to evaluate the modifying effects of age, sex and medical conditions. Area-specific estimates were combined using meta-analyses. For the total study period the mean level of SPM was 23.7μg/m(3). In general, higher SPM was associated with a significant increase in EAD for acute illness [estimated pooled relative risk (RR): 1.008, 95% CI: 1.007 to 1.010 per 10μg/m(3) increase in SPM at lag 0-1]. The effects of SPM on EAD for acute illness were significantly greater for moderate/mild medical conditions (e.g. cases that resulted in <3weeks hospitalization or no hospitalization) when compared to severe medical conditions (e.g. critical cases, and cases that led to >3weeks hospitalization or which resulted in death). Using EAD data, this study has shown the adverse health effects of ambient air pollution. This highlights the importance of reducing the level of air pollution in order to maintain population health and well-being., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Placenta praevia is an obstetric complication involving placental implantation in the lower uterine segment. Given the suggested aetiology of placenta praevia, adverse biological effects of air pollutants, such as plasma viscosity increment, endothelial dysfunction, and systemic inflammation, have the potential to induce low implantation. We explored the association between exposure to air pollutants during the pregnancy period up to implantation, and placenta praevia, in pregnant Japanese women. The outcome also included placenta accreta, which often exists in combination with placenta praevia., Methods: From the Japan Perinatal Registry Network database, we obtained data on 40,573 singleton pregnant women in western Japan (Kyushu-Okinawa Districts) between 2005 and 2010. We assigned pollutant concentrations (suspended particulate matter [SPM], ozone, nitrogen dioxide [NO2], and sulphur dioxide [SO2]), measured at the nearest monitoring station to the respective delivery hospital of each woman. A logistic regression model was used to adjust for several covariates., Results: The odds ratios (ORs) of placenta praevia per 10 units increase were 1.12 (95% confidence interval (CI)=1.01-1.23) for SPM over 0-4weeks of gestation, and 1.08 (1.00-1.16) for ozone. The association between exposure to NO2 and SO2, and praevia, was in the direction of increased risk. SPM exposure during 0-4weeks was associated with placenta accreta without praevia (OR=1.33, 95% CI=1.07-1.66). We found no association with exposure to air pollutants during 5-12weeks and the second trimester., Conclusions: Exposure to air pollutants through to implantation was positively associated with placenta praevia and accreta., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A suggestive mechanism behind the association between particulate matter and cardiovascular disease is inflammatory response. Earlier population-based studies investigating the association between particulate matter and inflammatory biological markers, in particular C-reactive protein (CRP), showed inconsistent results. In addition, evidence from the Asian population, in which CRP levels are typically lower than those observed in Western populations, was sparse. We examined the cross-sectional association between short- and long-term exposure to particulate matter and inflammatory markers, including high-sensitivity CRP (hs-CRP) and white blood cell (WBC) count, in a representative population of Japanese community dwellers (NIPPON DATA2010). We analysed data from 2360 participants (1002 men and 1358 women), aged 20 years or older, who resided in 300 randomly selected districts (222 public health centre areas) throughout Japan. We used background concentrations of suspended particulate matter (SPM, defined as particles with a 100% cut-off level at 10 μm aerodynamic diameter) and co-pollutants within the public health centre area. A logistic regression model was applied to estimate odds ratios (ORs) of elevated hs-CRP (> 0.3 mg/dl) or WBC (> 9000/μl). Since smoking is an important confounding factor, we firstly included this in the models, and additionally conducted the analyses after excluding current smokers. The one-month average concentration of SPM was positively associated with hs-CRP (OR per 10 μg/m(3) increase in SPM = 1.42, 95% confidence interval = 1.00-2.04), and high exposure to SPM on the day of blood draw was associated with increased WBC count, after excluding current smokers (OR = 1.13, 1.01-1.28). Similar association patterns were observed for ozone. In conclusion, exposure to particulate matter was associated with inflammatory markers in the general Japanese population. Systemic inflammation may play a role in the link between particulate matter and cardiovascular disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: There is no conclusive evidence of adverse health effects caused by short-term exposure to coarse particulate matter, so in this case-crossover study we looked for an association between exposure and emergency ambulance dispatches (as a proxy of acute health outcomes)., Methods: We used data on emergency ambulance dispatches in Fukuoka City, Japan between 2005 and 2010. After excluding ambulance dispatches related to external injuries and pregnancy/childbirth, we analyzed data on 176,123 dispatches. Citywide daily mean concentrations of suspended particulate matter (SPM) and fine particulate matter (PM2.5) were calculated from ambient monitoring data, and the differences between concentrations of SPM and PM2.5 were used as an exposure surrogate of coarse particulate matter. Using a conditional logistic regression model, we estimated the ambient temperature and relative humidity adjusted odds ratios (ORs) per 10 μg/m(3) increase in coarse particulate matter., Results: The average daily concentration of coarse particulate matter over the study period was 9.9 μg/m(3), representing 33% of the total concentration of SPM. Elevated concentrations of coarse particulate matter were associated with an increase in respiratory disease-related emergency ambulance dispatches for adults aged 65 years or older (9,716 dispatches, OR for lag0-1 = 1.065, 95% confidence interval = 1.023-1.109). After additional adjustment for exposure to PM2.5, we observed a statistically non-significant increased risk (OR = 1.035, 0.986-1.086)., Conclusions: We found weak evidence of adverse effects of short-term exposure to coarse particulate matter on human health.

Background: Evidence of an association between fine particulate matter (PM2.5) and morbidity is limited in Asia. We used a case-crossover design to evaluate the association between short-term exposure to PM2.5 and emergency ambulance dispatches (as a proxy of acute health outcomes), and to calculate the extent to which a 10 μg/m(3) decrease in PM2.5 concentrations would reduce the number of ambulance dispatches., Methods: We used data on emergency ambulance dispatches in Fukuoka City, Japan between 2005 and 2010. Emergency ambulance services are publicly funded and cover the entire city. After excluding ambulance dispatches related to external injuries and pregnancy/childbirth, we analysed data on the remaining 176 123 dispatches. We also collected records of daily concentrations of PM2.5 from one ambient air pollution monitoring station. ORs per 10 μg/m(3) increase in PM2.5 were estimated using conditional logistic regression controlled for ambient temperature and relative humidity., Results: During the study period, the average daily concentration of PM2.5 was 20.3 μg/m(3). Exposure to PM2.5 was associated with emergency ambulance dispatches in general (lag0-1; OR=1.008 (95% CI 1.002 to 1.014)) and with dispatches due to respiratory diseases (lag0-1; OR=1.027 (1.007 to 1.048)). No association was observed for dispatches due to cardiovascular diseases. We estimated that a 10 μg/m(3) decrease in PM2.5 concentrations would have led to approximately 260 (estimated range=70-460) fewer ambulance dispatches in Fukuoka for 2012., Conclusions: Providing further evidence on the short-term health effects of PM2.5 exposure, we found that exposure was associated with an increased number of emergency ambulance dispatches. The effect was, however, relatively small., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: There is global concern over significant threats from a wide variety of environmental hazards to which children face. Large-scale and long-term birth cohort studies are needed for better environmental management based on sound science. The primary objective of the Japan Environment and Children's Study (JECS), a nation-wide birth cohort study that started its recruitment in January 2011, is to elucidate environmental factors that affect children's health and development., Methods/design: Approximately 100,000 expecting mothers who live in designated study areas will be recruited over a 3-year period from January 2011. Participating children will be followed until they reach 13 years of age. Exposure to environmental factors will be assessed by chemical analyses of bio-specimens (blood, cord blood, urine, breast milk, and hair), household environment measurements, and computational simulations using monitoring data (e.g. ambient air quality monitoring) as well as questionnaires. JECS' priority outcomes include reproduction/pregnancy complications, congenital anomalies, neuropsychiatric disorders, immune system disorders, and metabolic/endocrine system disorders. Genetic factors, socioeconomic status, and lifestyle factors will also be examined as covariates and potential confounders. To maximize representativeness, we adopted provider-mediated community-based recruitment., Discussion: Through JECS, chemical substances to which children are exposed during the fetal stage or early childhood will be identified. The JECS results will be translated to better risk assessment and management to provide healthy environment for next generations.

From 2003 through 2005, we compared annual mean particulate matter (PM) and nitrogen dioxide (NO₂) concentrations as measured at fixed-site monitoring stations in 6 Japanese cities with those measured inside and outside subject residences and during personal monitoring. A total of 65 households participated in indoor and outdoor residential exposure monitoring. In summer and autumn, we also performed personal monitoring of one resident of each household. On each day, personal samplers were used to collect 24-h samples of PM and NO₂ simultaneously from the fixed sites, indoor and outdoor, and from those undergoing personal monitoring. We found good correlations between the fixed-site and outdoor measurements for annual mean (average of 7-day × 4-season) concentrations of PM₂.₅, PM₁₀₋₂.₅, PM10 and NO₂ (Spearman's rank correlation coefficients (ρ) ≥ 0.75). However, the correlations between the fixed-site and indoor measurements were moderate to low. In summer and autumn, the correlations between the fixed-site and personal mean concentrations of PM₂.₅ (ρ = 0.62), PM10 (ρ = 0.58), and NO₂ (ρ = 0.70) were acceptable. However, because people spend most of their time indoors, these correlations for annual mean concentrations were not estimated to be high. Our results are important in allowing researchers to estimate the effects of resulting measurement errors of PM and NO₂., (© 2013.)

Aim: Associations between long-term exposure to particulate matter (PM) and increased cardiovascular mortality have been reported, but few studies have investigated the associated incidence of cardiovascular disease, and none involved men., Methods: We used data on 78,057 participants (37,121 men, 40,936 women) to examine the associations of long-term exposure to PM with mortality and the incidence of cardiovascular diseases. Average PM levels in the relevant area during the study period were used as an index of individual exposure to each subject. Cox models adjusted for age, sex, smoking, environmental smoking, body mass index, and alcohol consumption were used, with further adjustments for nitrogen dioxide and sulfur dioxide exposure, systolic blood pressure, total cholesterol, and diabetes mellitus., Results: Increased PM levels were associated with an increased risk of incident coronary heart disease (CHD) and myocardial infarction (MI), particularly among smokers (adjusted hazard ratio (HR) per 10 µg/m(3) increase in PM for CHD: 1.39, 95% confidence interval (CI) 1.01-1.93; for MI: 1.52, 1.08-2.13) and among women (for CHD: 1.63, 0.91-2.92; for MI: 1.99, 1.07-3.70); however, the observed positive association of PM exposure with the incidence of CHD and MI was not robust, and the association disappeared when one of the areas (Akita) was excluded. The association with CHD mortality was not statistically significant (adjusted HR per 10 µg/m(3) increase in PM: 1.11, 0.92-1.33). There was an inverse association of long-term PM exposure with stroke mortality and incidence. There was no clear association between PM levels and lung cancer mortality and incidence., Conclusions: Long-term exposure to PM might increase the risk of incident CHD in middle-aged Japanese men and women. Our findings also suggest that women and smokers are especially vulnerable to PM exposure.

Asian dust, called 'kosa' in Japan, is the long-range transport of atmospheric pollutants originating from the desert areas of China and Mongolia. Although Asian dust has a long history of appearing in Japan, it is only quite recently that there is increasing concern for its possible adverse health effects. We reviewed the epidemiologic evidence of potential health effects of Asian dust events. PubMed was used to search for the following keywords: Asian dust, yellow sand, desert dust, dust storm, sandstorm, mortality, death, morbidity, hospitalization, hospital admission, health, pulmonary and respiratory. The search was limited to the epidemiologic studies published between January 1980 and May 2009. JMEDPlus was used to search for Japanese literature. Seventeen studies were retrieved from PubMed and one study from JMEDPlus. In addition, one study was identified for reviewing from the references of another study. In total, we identified 19 epidemiologic studies (3 for mortality, 13 for hospital visits or admissions and 3 for respiratory functions or symptoms) mainly from Taiwan and Korea. There were many combinations of outcomes and lagged exposures examined, and some suggested possible associations of dust exposure with an increase in mortality and hospital visits and admissions due to cardiovascular and respiratory diseases, whereas the rest of the studies did not show statistically significant associations. The evidence from these studies was limited because exposure assessments were inadequately described and potential confounders were insufficiently controlled. Well-designed epidemiological studies are required to clarify any potential health effects of Asian dust events in Japan.