Concentration-response function for ozone and daily mortality: results from five urban and five rural U.K. populations.

BACKGROUND: Short-term exposure to ozone has been associated with increased daily mortality. The shape of the concentration-response relationship-and, in particular, if there is a threshold-is critical for estimating public health impacts. OBJECTIVE: We investigated the concentration-response relationship between daily ozone and mortality in five urban and five rural areas in the United Kingdom from 1993 to 2006. METHODS: We used Poisson regression, controlling for seasonality, temperature, and influenza, to investigate associations between daily maximum 8-hr ozone and daily all-cause mortality, assuming linear, linear-threshold, and spline models for all-year and season-specific periods. We examined sensitivity to adjustment for particles (urban areas only) and alternative temperature metrics. RESULTS: In all-year analyses, we found clear evidence for a threshold in the concentration-response relationship between ozone and all-cause mortality in London at 65 µg/m3 [95% confidence interval (CI): 58, 83] but little evidence of a threshold in other urban or rural areas. Combined linear effect estimates for all-cause mortality were comparable for urban and rural areas: 0.48% (95% CI: 0.35, 0.60) and 0.58% (95% CI: 0.36, 0.81) per 10-µg/m3 increase in ozone concentrations, respectively. Seasonal analyses suggested thresholds in both urban and rural areas for effects of ozone during summer months. CONCLUSIONS: Our results suggest that health impacts should be estimated across the whole ambient range of ozone using both threshold and nonthreshold models, and models stratified by season. Evidence of a threshold effect in London but not in other study areas requires further investigation. The public health impacts of exposure to ozone in rural areas should not be overlooked.

PM10, and children's respiratory symptoms and lung function in the PATY study.

Studies of the impact of long-term exposure to outdoor air pollution on the prevalence of respiratory symptoms and lung function in children have yielded mixed results, partly related to differences in study design, exposure assessment, confounder selection and data analysis. We assembled respiratory health and exposure data for >45,000 children from comparable cross-sectional studies in 12 countries. 11 respiratory symptoms were selected, for which comparable questions were asked. Spirometry was performed in about half of the children. Exposure to air pollution was mainly characterised by annual average concentrations of particulate matter with a 50% cut-off aerodynamic diameter of 10 µm (PM(10)) measured at fixed sites within the study areas. Positive associations were found between the average PM(10) concentration and the prevalence of phlegm (OR per 10 µg · m(-3) 1.15, 95% CI 1.02-1.30), hay fever (OR 1.20, 95% CI 0.99-1.46), bronchitis (OR 1.08, 95% CI 0.98-1.19), morning cough (OR 1.15, 95% CI 1.02-1.29) and nocturnal cough (OR 1.13, 95% CI 0.98-1.29). There were no associations with diagnosed asthma or asthma symptoms. PM(10) was not associated with lung function across all studies combined. Our study adds to the evidence that long-term exposure to outdoor air pollution, characterised by the concentration of PM(10), is associated with increased respiratory symptoms.

Parental education and lung function of children in the PATY study.

Studies of the relationships between low socio-economic status and impaired lung function were conducted mainly in Western European countries and North America. East-West differences remain unexplored. Associations between parental education and lung function were explored using data on 24,010 school-children from eight cross-sectional studies conducted in North America, Western and Eastern Europe. Parental education was defined as low and high using country-specific classifications. Country-specific estimates of effects of low parental education on volume and flow parameters were obtained using linear and logistic regression, controlling for early life and other individual risk factors. Meta-regressions were used for assessment of heterogeneity between country-specific estimates. The association between low parental education and lung function was not consistent across the countries, but showed a more pronounced inverse gradient in the Western countries. The most consistent decrease associated with low parental education was found for peak expiratory flow (PEF), ranging from -2.80 to -1.14%, with statistically significant associations in five out of eight countries. The mean odds ratio for low PEF (<75% of predicted) was 1.34 (95% CI 1.06-1.70) after all adjustments. Although social gradients were attenuated after adjusting for known risk factors, these risk factors could not completely explain the social gradient in lung function.

Maternal smoking during pregnancy and childhood obesity: results from the CESAR Study.

Childhood obesity is a worldwide public health concern. Recent studies from high income countries have demonstrated associations between maternal smoking during pregnancy and children's excess body weight. We examine associations between maternal smoking during pregnancy and children's overweight or obesity, in six countries in the less affluent Central/Eastern European region. Questionnaire data were analysed, for 8,926 singleton children aged 9-12 years. Country-specific odds ratios for effects of maternal smoking during pregnancy on being overweight, and on obesity, were estimated using logistic regression. Heterogeneity between country-specific results, and mean effects (allowing for heterogeneity) were estimated. Positive associations between maternal smoking and overweight were seen in all countries but Romania. While not individually statistically significant, the mean odds ratio was 1.26 (95% CI 1.03-1.55), with no evidence of between-country heterogeneity. Obese children were few (2.7%), and associations between obesity and maternal smoking during pregnancy were more heterogeneous, with odds ratios ranging from 0.71 (0.32-1.57) in Poland to 5.49 (2.11-14.30) in Slovakia. Between-country heterogeneity was strongly related to average persons-per-room, a possible socioeconomic indicator, with stronger associations where households were less crowded. Estimates of dose-response relationships tended to be small and non-significant, even when pooled. Our results provide evidence of a link between maternal smoking in pregnancy and childhood overweight. Associations with obesity, though strong in some countries, were less consistent. Maternal smoking may confer an addition to a child's potential for obesity, which is more likely to be realised in affluent conditions.

Geographical variation in infant mortality, stillbirth and low birth weight in Northern Ireland, 1992-2002.

BACKGROUND: Improving the health of expectant mothers and reductions in health inequalities, are repeatedly prioritised in policy reports in England and Northern Ireland. Measurement of underlying rates, and geographical variation in rates, of adverse birth outcomes are tools in monitoring these priorities. METHODS: Northern Ireland data on stillbirths, infant mortality and low birth weight (1992-2002) were linked to board (n=4), district council (n=26) and 1991 census wards (n=568). Underlying variations in rates were estimated at each geographical level, unadjusted and controlling for year, ward-level deprivation, settlement size and higher geographical levels. Impacts on geographical variation of individual social class, maternal age, multiple birth and smoking were assessed. RESULTS: There was significant variation in underlying rates of low birth weight (<2500 g) at all three geographical levels. Controlling for smoking reduced variation between wards. Geographical variation proved more robust for medium than for very low birth weight. No variation was seen between boards for other outcomes, nor between district level rates of infant mortality. Evidence was weak for variation in district rates of neonatal deaths and stillbirths, and variation in ward-level adjusted stillbirth rates was not significant. Variation in ward-level infant death rates was robust to all adjustments, with risks tripling (infant mortality) or quadrupling (neonatal mortality) between the 10th and 90th percentile. CONCLUSIONS: Strong evidence was found of geographical variation in infant mortality and low birth weight, unexplained by individual risk factors or by area-level deprivation. Geographical targeting or area-level interventions might look beyond deprivation scores, to other environmental and social factors.

Ozone, heat and mortality: acute effects in 15 British conurbations.

BACKGROUND: Acute associations between mortality and ozone are largely accepted, though recent evidence is less conclusive. Evidence on ozone-heat interaction is sparse. We assess effects of ozone, heat, and their interaction, on mortality in Britain. METHODS: Acute effects of summer ozone on mortality were estimated using data from 15 conurbations in England and Wales (May-September, 1993-2003). 2-day means of daily maximum 8-h ozone were entered into case series analyses, controlling for particulate matter with aerodynamic diameter of <10 µm, natural cubic splines of temperature, and other factors. Heat effects were estimated, comparing adjusted mortality rates at 97.5th and 75th percentiles of 2-day mean temperature. A separate model employed interaction terms to assess whether ozone effects increased on 'hot days' (where 2-day mean temperature exceeded the whole-year 95th percentile). Other heat metrics, and non-linear ozone effects, were also examined. RESULTS: Adverse ozone and heat effects occurred in nearly all conurbations. The mean mortality rate ratio for heat effect across conurbations was 1.071 (1.050-1.093). The mean ozone rate ratio was 1.003 per 10 µg/m(3) ozone increase (95% CI 1.001 to 1.005). On 'hot days' the mean ozone effect reached 1.006 (1.002-1.009) per 10 µg/m(3), though ozone-heat interaction was significant in London only. On substituting maximum for mean temperature, the overall ozone effect reduced to null, though evidence remained of effects on hot days, particularly in London. An estimated ozone effect threshold was below current guidelines in 'mean temperature' models. CONCLUSION: While heat showed robust effects on summer mortality, estimates for ozone depended upon the modelling of temperature. However, there was some evidence that ozone effects were worse on hot days, whichever temperature measure was used.

Socio-economic inequalities in cerebral palsy prevalence in the United Kingdom: a register-based study.

Evidence is unclear as to whether there is a socio-economic gradient in cerebral palsy (CP) prevalence beyond what would be expected from the socio-economic gradient for low birthweight, a strong risk factor for CP. We conducted a population-based study in five regions of the UK with CP registers, to investigate the relationship between CP prevalence and socio-economic deprivation, and how it varies by region, by birthweight and by severity and type of CP. The total study population was 1 657 569 livebirths, born between 1984 and 1997. Wards of residence were classified into five quintiles according to a census-based deprivation index, from Q1 (least deprived) to Q5 (most deprived). Socio-economic gradients were modelled by Poisson regression, and region-specific estimates combined by meta-analysis. The prevalence of postneonatally acquired CP was 0.14 per 1000 livebirths overall. The mean deprivation gradient, expressed as the relative risk in the most deprived vs. the least deprived quintile, was 1.86 (95% confidence interval [95% CI 1.19, 2.88]). The prevalence of non-acquired CP was 2.22 per 1000 livebirths. For non-acquired CP the gradient was 1.16 [95% CI 1.00, 1.35]. Evidence for a socio-economic gradient was strongest for spastic bilateral cases (1.32 [95% CI 1.09, 1.59]) and cases with severe intellectual impairment (1.59 [95% CI 1.06, 2.39]). There was evidence for differences in gradient between regions. The gradient of risk of CP among normal birthweight births was not statistically significant overall (1.21 [95% CI 0.95, 1.54]), but was significant in two regions. There was non-significant evidence of a reduction in gradients over time. The reduction of the higher rates of postneonatally acquired CP in the more socioeconomically deprived areas is a clear goal for prevention. While we found evidence for a socio-economic gradient for non-acquired CP of antenatal or perinatal origin, the picture was not consistent across regions, and there was some evidence of a decline in inequalities over time. The steeper gradients in some regions for normal birthweight cases and cases with severe intellectual impairment require further investigation.

Current and future climate- and air pollution-mediated impacts on human health.

BACKGROUND: We describe a project to quantify the burden of heat and ozone on mortality in the UK, both for the present-day and under future emission scenarios. METHODS: Mortality burdens attributable to heat and ozone exposure are estimated by combination of climate-chemistry modelling and epidemiological risk assessment. Weather forecasting models (WRF) are used to simulate the driving meteorology for the EMEP4UK chemistry transport model at 5 km by 5 km horizontal resolution across the UK; the coupled WRF-EMEP4UK model is used to simulate daily surface temperature and ozone concentrations for the years 2003, 2005 and 2006, and for future emission scenarios. The outputs of these models are combined with evidence on the ozone-mortality and heat-mortality relationships derived from epidemiological analyses (time series regressions) of daily mortality in 15 UK conurbations, 1993-2003, to quantify present-day health burdens. RESULTS: During the August 2003 heatwave period, elevated ozone concentrations > 200 microg m-3 were measured at sites in London and elsewhere. This and other ozone photochemical episodes cause breaches of the UK air quality objective for ozone. Simulations performed with WRF-EMEP4UK reproduce the August 2003 heatwave temperatures and ozone concentrations. There remains day-to-day variability in the high ozone concentrations during the heatwave period, which on some days may be explained by ozone import from the European continent.Preliminary calculations using extended time series of spatially-resolved WRF-EMEP4UK model output suggest that in the summers (May to September) of 2003, 2005 & 2006 over 6000 deaths were attributable to ozone and around 5000 to heat in England and Wales. The regional variation in these deaths appears greater for heat-related than for ozone-related burdens.Changes in UK health burdens due to a range of future emission scenarios will be quantified. These future emissions scenarios span a range of possible futures from assuming current air quality legislation is fully implemented, to a more optimistic case with maximum feasible reductions, through to a more pessimistic case with continued strong economic growth and minimal implementation of air quality legislation. CONCLUSION: Elevated surface ozone concentrations during the 2003 heatwave period led to exceedences of the current UK air quality objective standards. A coupled climate-chemistry model is able to reproduce these temperature and ozone extremes. By combining model simulations of surface temperature and ozone with ozone-heat-mortality relationships derived from an epidemiological regression model, we estimate present-day and future health burdens across the UK. Future air quality legislation may need to consider the risk of increases in future heatwaves.

International study of temperature, heat and urban mortality: the 'ISOTHURM' project.

BACKGROUND: This study describes heat- and cold-related mortality in 12 urban populations in low- and middle-income countries, thereby extending knowledge of how diverse populations, in non-OECD countries, respond to temperature extremes. METHODS: The cities were: Delhi, Monterrey, Mexico City, Chiang Mai, Bangkok, Salvador, São Paulo, Santiago, Cape Town, Ljubljana, Bucharest and Sofia. For each city, daily mortality was examined in relation to ambient temperature using autoregressive Poisson models (2- to 5-year series) adjusted for season, relative humidity, air pollution, day of week and public holidays. RESULTS: Most cities showed a U-shaped temperature-mortality relationship, with clear evidence of increasing death rates at colder temperatures in all cities except Ljubljana, Salvador and Delhi and with increasing heat in all cities except Chiang Mai and Cape Town. Estimates of the temperature threshold below which cold-related mortality began to increase ranged from 15 degrees C to 29 degrees C; the threshold for heat-related deaths ranged from 16 degrees C to 31 degrees C. Heat thresholds were generally higher in cities with warmer climates, while cold thresholds were unrelated to climate. CONCLUSIONS: Urban populations, in diverse geographic settings, experience increases in mortality due to both high and low temperatures. The effects of heat and cold vary depending on climate and non-climate factors such as the population disease profile and age structure. Although such populations will undergo some adaptation to increasing temperatures, many are likely to have substantial vulnerability to climate change. Additional research is needed to elucidate vulnerability within populations.

Self-reported never-drinkers in England 1994-2003: characteristics and trends in adults aged 18-54 years.

AIMS: This paper describes prevalences, time-trends and characteristics of self-reported never-drinkers, during the period 1994-2003, focussing particularly on white adults aged 18-54. METHODS: Data on 122,809 adults (18 + ) were obtained from the Health Survey for England (HSfE). Logistic regressions were used to estimate time trends in self-reported never-drinking, and associations between never-drinking and living alone, and educational qualification. Analyses were stratified by gender, age group and period. RESULTS: The overall proportion of white, female never-drinkers was 5.5%, rising monotonically with age. Proportions among men were much lower, with the lowest proportion (1.1%) in the 30-54 age group. Odds of never-drinking increased by 3% per year in those aged 30-54, a trend not explained by any covariates. Smaller increases were seen among those aged 18-29. Never-drinking was strongly associated with living with another adult and with lower qualification. The association with qualification increased over time among young women, and the association with living with another adult increased among men aged 30-54. CONCLUSIONS: Never-drinkers are a significant minority in England, whose prevalence rose, between 1994 and 2003, among adults aged under 55 years. The prevalence varies considerably by age, sex, and social characteristics, and the social discrepancies in never-drinking appear to be widening.

Geographic variation and localised clustering of congenital anomalies in Great Britain.

BACKGROUND: Environmental pollution as a cause of congenital anomalies is sometimes suspected because of clustering of anomalies in areas of higher exposure. This highlights questions around spatial heterogeneity (clustering) in congenital anomaly rates. If spatial variation is endemic, then any one specific cluster is less remarkable, though the presence of uncontrolled geographically clustered risk factors is suggested. If rates are relatively homogeneous across space other than around specific hazards, then evidence for these hazards causing the clusters is strengthened. We sought to estimate the extent of spatial heterogeneity in congenital anomaly rates in the United Kingdom. METHODS: The study population covered about one million births from five registers in Britain from 1991-1999. We estimated heterogeneity across four geographical levels: register area, hospital catchment, electoral ward, and enumeration district, using a negative binomial regression model. We also sought clusters using a circular scan statistic. RESULTS: Congenital anomaly rates clearly varied across register areas and hospital catchments (p < 0.001), but not below this level (p > 0.2). Adjusting for socioeconomic deprivation and maternal age made little difference to the extent of geographical variation for most congenital anomaly subtypes. The two most significant circular clusters (of four ano-rectal atresias and six congenital heart diseases) contained two or more siblings. CONCLUSION: The variation in rates between registers and hospital catchment area may have resulted in part from differences in case ascertainment, and this should be taken into account in geographical epidemiological studies of environmental exposures. The absence of evidence for variation below this level should be interpreted cautiously in view of the low power of general heterogeneity tests. Nevertheless, the data suggest that strong localised clusters in congenital anomalies are uncommon, so clusters around specific putative environmental hazards are remarkable when observed. Negative binomial models applied at successive hierarchical levels provide an approach of intermediate complexity to characterising geographical heterogeneity.

Parental smoking and children's respiratory health: independent effects of prenatal and postnatal exposure.

OBJECTIVES: Adverse effects have been reported of prenatal and/or postnatal passive exposure to smoking on children's health. Uncertainties remain about the relative importance of smoking at different periods in the child's life. We investigate this in a pooled analysis, on 53,879 children from 12 cross-sectional studies--components of the PATY study (Pollution And The Young). METHODS: Effects were estimated, within each study, of three exposures: mother smoked during pregnancy, parental smoking in the first two years, current parental smoking. Outcomes were: wheeze, asthma, "woken by wheeze", bronchitis, nocturnal cough, morning cough, "sensitivity to inhaled allergens" and hay fever. Logistic regressions were used, controlling for individual risk factors and study area. Heterogeneity between study-specific results, and mean effects (allowing for heterogeneity) were estimated using meta-analytical tools. RESULTS: There was strong evidence linking parental smoking to wheeze, asthma, bronchitis and nocturnal cough, with mean odds ratios all around 1.15, with independent effects of prenatal and postnatal exposures for most associations. CONCLUSIONS: Adverse effects of both pre- and postnatal parental smoking on children's respiratory health were confirmed. Asthma was most strongly associated with maternal smoking during pregnancy, but postnatal exposure showed independent associations with a range of other respiratory symptoms. All tobacco smoke exposure has serious consequences for children's respiratory health and needs to be reduced urgently.

Parental smoking and lung function in children: an international study.

RATIONALE: Both prenatal and postnatal passive smoking have been linked with respiratory symptoms and asthma in childhood. Their differential contributions to lung function growth in the general children's population are less clear. OBJECTIVE: To study the relative impact of pre- and postnatal exposure on respiratory functions of primary school children in a wide range of geographic settings, we analyzed flow and volume data of more than 20,000 children (aged 6-12 yr) from nine countries in Europe and North America. METHODS: Exposure information had been obtained by comparable questionnaires, and spirometry followed a protocol of the American Thoracic Society/European Respiratory Society. Linear and logistic regressions were used, controlling for individual risk factors and study area. Heterogeneity between study-specific results and mean effects were estimated using meta-analytic tools. MAIN RESULTS: Smoking during pregnancy was associated with decreases in lung function parameters between -1% (FEV1) and -6% maximal expiratory flow at 25% of vital capacity left (MEF25). A 4% lower maximal midexpiratory flow (MMEF) corresponded to a 40% increase in the risk of poor lung function (MMEF < 75% of expected). Associations with current passive smoking were weaker though still measurable, with effects ranging from -0.5% (FEV1) to -2% maximal expiratory flow (MEF50). CONCLUSIONS: Considering the high number of children exposed to maternal smoking in utero and the even higher number exposed to passive smoking after birth, this risk factor for reduced lung function growth remains a serious pediatric and public health issue.

Vulnerability to winter mortality in elderly people in Britain: population based study.

OBJECTIVE: To examine the determinants of vulnerability to winter mortality in elderly British people. DESIGN: Population based cohort study (119,389 person years of follow up). SETTING: 106 general practices from the Medical Research Council trial of assessment and management of older people in Britain. PARTICIPANTS: People aged > or = 75 years. MAIN OUTCOME MEASURES: Mortality (10,123 deaths) determined by follow up through the Office for National Statistics. RESULTS: Month to month variation accounted for 17% of annual all cause mortality, but only 7.8% after adjustment for temperature. The overall winter:non-winter rate ratio was 1.31 (95% confidence interval 1.26 to 1.36). There was little evidence that this ratio varied by geographical region, age, or any of the personal, socioeconomic, or clinical factors examined, with two exceptions: after adjustment for all major covariates the winter:non-winter ratio in women compared with men was 1.11 (1.00 to 1.23), and those with a self reported history of respiratory illness had a winter:non-winter ratio of 1.20 (1.08 to 1.34) times that of people without a history of respiratory illness. There was no evidence that socioeconomic deprivation or self reported financial worries were predictive of winter death. CONCLUSION: Except for female sex and pre-existing respiratory illness, there was little evidence for vulnerability to winter death associated with factors thought to lead to vulnerability. The lack of socioeconomic gradient suggests that policies aimed at relief of fuel poverty may need to be supplemented by additional measures to tackle the burden of excess winter deaths in elderly people.

Effect of influenza vaccination on excess deaths occurring during periods of high circulation of influenza: cohort study in elderly people.

OBJECTIVE: To estimate the protection against death provided by vaccination against influenza. DESIGN: Prospective cohort follow up supplemented by weekly national counts of influenza confirmed in the community. SETTING: Primary care. PARTICIPANTS: 24,535 patients aged over 75 years from 73 general practices in Great Britain. MAIN OUTCOME MEASURE: Death. RESULTS: In unvaccinated members of the cohort daily all cause mortality was strongly associated with an index of influenza circulating in the population (mortality ratio 1.16, 95% confidence interval 1.04 to 1.29 at 90th centile of circulating influenza). The association was strongest for respiratory deaths but was also present for cardiovascular deaths. In contrast, in vaccinated people mortality from any cause was not associated with circulating influenza. The difference in patterns between vaccinated and unvaccinated people could not easily be due to chance (P = 0.02, all causes). CONCLUSIONS: This study, using a novel and robust approach to control for confounding, provides robust evidence of a protective effect on mortality of vaccination against influenza.