Fetuin A concentration in the second trimester amniotic fluid of fetuses with Trisomy 21 appears to be lower: phenotypic considerations

Objective: We investigated whether the concentration of the glycoprotein fetuin A is altered in the second trimester amniotic fluid of trisomy 21 pregnancies compared with euploid pregnancies. Methods. 25 pregnancies with an extra chromosome 21 were matched for maternal and gestational age with 25 pregnancies with normal karyotype. Levels of fetuin A in amniotic fluid were measured by a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results: The median concentration of fetuin A in amniotic fluid of trisomy 21 pregnancies (5.3 ng/ml) was statistically significantly lower (P value = 0.008) compared with that in euploid pregnancies (6.8 ng/mL). Conclusion: Lower levels of fetuin A in trisomy 21 may indicate an association with altered metabolic pathways in this early stage that could potentially be associated with features of the syndrome, such as growth restriction or impaired osteogenesi

The risks of acute exposure to black carbon in Southern Europe: results from the MED-PARTICLES project

While several studies have reported associations of daily exposures to PM2.5 (particles less than 2.5 µm) with mortality, few studies have examined the impact of its constituents such as black carbon (BC), which is also a significant contributor to global climate change. Methods: We assessed the association between daily concentrations of BC and total, cardiovascular and respiratory mortality in two southern Mediterranean cities. Daily averages of BC were collected for 2 years in Barcelona, Spain and Athens, Greece. We used case-crossover analysis and examined single and cumulative lags up to 3 days. Results: We observed associations between BC and all mortality measures. For a 3-day moving average, cardiovascular mortality increased by 4.5% (95% CI 0.7 to 8.5) and 2.0% (95% CI 0 to 4.0) for an interquartile change in BC in Athens and Barcelona, respectively. Considerably higher effects for respiratory mortality and for those above age 65 were observed. In addition, BC exhibited much greater toxicity per microgram than generic PM2.5. Conclusions: Our findings suggest that BC, derived in western industrialised nations primarily from diesel engines and biomass burning, poses a significant burden to public health, particularly in European cities with high-traffic density.Peer ReviewedPostprint (published version

PM2.5 and NO2 exposure errors using proxy measures, including derived personal exposure from outdoor sources: A systematic review and meta-analysis.

BACKGROUND: The use of proxy exposure estimates for PM2.5 and NO2 in air pollution studies instead of personal exposures, introduces measurement error, which can produce biased epidemiological effect estimates. Most studies consider total personal exposure as the gold standard. However, when studying the effects of ambient air pollution, personal exposure from outdoor sources is the exposure of interest. OBJECTIVES: We assessed the magnitude and variability of exposure measurement error by conducting a systematic review of the differences between personal exposures from outdoor sources and the corresponding measurements for ambient concentrations in order to increase understanding of the measurement error structures of the pollutants. DATA SOURCES AND ELIGIBILITY CRITERIA: We reviewed the literature (ISI Web of Science, Medline, 2000-2016) for English language studies (in any age group in any location (NO2) or Europe and North America (PM2.5)) that reported repeated measurements over time both for personal and ambient PM2.5 or NO2 concentrations. Only a few studies reported personal exposure from outdoor sources. We also collected data for infiltration factors and time-activity patterns of the individuals in order to estimate personal exposures from outdoor sources in every study. STUDY APPRAISAL AND SYNTHESIS METHODS: Studies using modelled rather than monitored exposures were excluded. Type of personal exposure monitor was assessed. Random effects meta-analysis was conducted to quantify exposure error as the mean difference between "true" and proxy measures. RESULTS: Thirty-two papers for PM2.5 and 24 for NO2 were identified. Outdoor sources were found to contribute 44% (range: 33-55%) of total personal exposure to PM2.5 and 74% (range: 57-88%) to NO2. Overall estimates of personal exposure (24-hour averages) from outdoor sources were 9.3 μg/m3 and 12.0 ppb for PM2.5 and NO2 respectively, while the corresponding difference between these exposures and the ambient concentrations (i.e. the measurement error) was 5.72 μg/m3 and 7.17 ppb. Our findings indicated also higher error variability for NO2 than PM2.5. Large heterogeneity was observed which was not explained sufficiently by geographical location or age group of the study sample. LIMITATIONS, CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Relying only on information available in published studies led to some limitations: the contribution of outdoor sources to total personal exposure for NO2 had to be inferred, individual variation in exposure misclassification was unavailable and instrument error could not be addressed. The larger magnitude and variability of errors for NO2 compared with PM2.5 has implications for biases in the health effect estimates of multi-pollutant epidemiological models. Results suggest that further research is needed regarding personal exposure studies and measurement error bias in epidemiological models

Measurement error in a multi-level analysis of air pollution and health: a simulation study.

BACKGROUND: Spatio-temporal models are increasingly being used to predict exposure to ambient outdoor air pollution at high spatial resolution for inclusion in epidemiological analyses of air pollution and health. Measurement error in these predictions can nevertheless have impacts on health effect estimation. Using statistical simulation we aim to investigate the effects of such error within a multi-level model analysis of long and short-term pollutant exposure and health. METHODS: Our study was based on a theoretical sample of 1000 geographical sites within Greater London. Simulations of "true" site-specific daily mean and 5-year mean NO2 and PM10 concentrations, incorporating both temporal variation and spatial covariance, were informed by an analysis of daily measurements over the period 2009-2013 from fixed location urban background monitors in the London area. In the context of a multi-level single-pollutant Poisson regression analysis of mortality, we investigated scenarios in which we specified: the Pearson correlation between modelled and "true" data and the ratio of their variances (model versus "true") and assumed these parameters were the same spatially and temporally. RESULTS: In general, health effect estimates associated with both long and short-term exposure were biased towards the null with the level of bias increasing to over 60% as the correlation coefficient decreased from 0.9 to 0.5 and the variance ratio increased from 0.5 to 2. However, for a combination of high correlation (0.9) and small variance ratio (0.5) non-trivial bias (> 25%) away from the null was observed. Standard errors of health effect estimates, though unaffected by changes in the correlation coefficient, appeared to be attenuated for variance ratios > 1 but inflated for variance ratios < 1. CONCLUSION: While our findings suggest that in most cases modelling errors result in attenuation of the effect estimate towards the null, in some situations a non-trivial bias away from the null may occur. The magnitude and direction of bias appears to depend on the relationship between modelled and "true" data in terms of their correlation and the ratio of their variances. These factors should be taken into account when assessing the validity of modelled air pollution predictions for use in complex epidemiological models

Long-term exposure to low concentrations of air pollutants and hospitalisation for respiratory diseases:A prospective cohort study in Australia

Background: Short- and long-term spatiotemporal variation in exposure to air pollution is associated with respiratory morbidity in areas with moderate-to-high level of air pollution, but very few studies have examined whether these associations also exist in areas with low level exposure. Objectives: We assessed the association between spatial variation in long-term exposure to PM and NO and hospitalisation for all respiratory diseases, asthma, chronic obstructive pulmonary disease (COPD), and pneumonia, in older adults residing in Sydney, Australia, a city with low-level concentrations. Methods: We recorded data on hospitalisations for 100,084 participants, who were aged >45 years at entry in 2006–2009 until June 2014. Annual NO and PM concentrations were estimated for the participants’ residential addresses and Cox proportional hazards regression was used to model the association between exposure to air pollutants and first episode of hospitalisation, controlling for personal and area level covariates. We further investigated the shape of the exposure-response association and potential effect modification by age, sex, education level, smoking status, and BMI. Results: NO and PM annual mean exposure estimates were 17.5 μg·m and 4.5 μg·m respectively. NO and PM was positively, although not significantly, associated with asthma. The adjusted hazard ratio for a 1 μg·m increase in PM was 1.08, 95% confidence interval 0.89–1.30. The adjusted hazard ratio for a 5 μg·m increase in NO was 1.03, 95% confidence interval 0.88–1.19. We found no positive statistically significant associations with hospitalisation for all respiratory diseases, and pneumonia while negative associations were observed with COPD. Conclusions: We found weak positive associations of exposure to air pollution with hospitalisation for asthma while there was no evidence of an association for all respiratory diseases

Short-term associations between fine and coarse particulate matter and hospitalizations in Southern Europe: results from the MED-PARTICLES project

BACKGROUND: Evidence on the short-term effects of fine and coarse particles on morbidity in Europe is scarce and inconsistent. OBJECTIVES: We aimed to estimate the association between daily concentrations of fine and coarse particles with hospitalizations for cardiovascular and respiratory conditions in eight Southern European cities, within the MED-PARTICLES project. METHODS: City-specific Poisson models were fitted to estimate associations of daily concentrations of particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5), ≤ 10 μm (PM10), and their difference (PM2.5-10) with daily counts of emergency hospitalizations for cardiovascular and respiratory diseases. We derived pooled estimates from random-effects meta-analysis and evaluated the robustness of results to co-pollutant exposure adjustment and model specification. Pooled concentration-response curves were estimated using a meta-smoothing approach. RESULTS: We found significant associations between all PM fractions and cardiovascular admissions. Increases of 10 μg/m3 in PM2.5, 6.3 μg/m3 in PM2.5-10, and 14.4 μg/m3 in PM10 (lag 0-1 days) were associated with increases in cardiovascular admissions of 0.51% (95% CI: 0.12, 0.90%), 0.46% (95% CI: 0.10, 0.82%), and 0.53% (95% CI: 0.06, 1.00%), respectively. Stronger associations were estimated for respiratory hospitalizations, ranging from 1.15% (95% CI: 0.21, 2.11%) for PM10 to 1.36% (95% CI: 0.23, 2.49) for PM2.5 (lag 0-5 days). CONCLUSIONS: PM2.5 and PM2.5-10 were positively associated with cardiovascular and respiratory admissions in eight Mediterranean cities. Information on the short-term effects of different PM fractions on morbidity in Southern Europe will be useful to inform European policies on air quality standards.This research was supported by the European Union under the grant agreement LIFE+ ENV/IT/327.S

Short-term associations between particle oxidative potential and daily mortality and hospital admissions in London.

BACKGROUND: Particulate matter (PM) from traffic and other sources has been associated with adverse health effects. One unifying theory is that PM, whatever its source, acts on the human body via its capacity to cause damaging oxidation reactions related to its content of pro-oxidants components. Few epidemiological studies have investigated particle oxidative potential (OP) and health. We conducted a time series analysis to assess associations between daily particle OP measures and numbers of deaths and hospital admissions for cardiovascular and respiratory diseases. METHODS: During 2011 and 2012 particles with an aerodynamic diameter less than 2.5 and 10μm (PM2.5 and PM10 respectively) were collected daily on Partisol filters located at an urban background monitoring station in Central London. Particulate OP was assessed based on the capacity of the particles to oxidize ascorbate (OP(AA)) and glutathione (OP(GSH)) from a simple chemical model reflecting the antioxidant composition of human respiratory tract lining fluid. Particulate OP, expressed as % loss of antioxidant per μg of PM, was then multiplied by the daily concentrations of PM to derive the daily OP of PM mass concentrations (% loss per m(3)). Daily numbers of deaths and age- and cause-specific hospital admissions in London were obtained from national registries. Poisson regression accounting for seasonality and meteorology was used to estimate the percentage change in risk of death or admission associated with an interquartile increment in particle OP. RESULTS: We found little evidence for adverse associations between OP(AA) and OP(GSH) and mortality. Associations with cardiovascular admissions were generally positive in younger adults and negative in older adults with confidence intervals including 0%. For respiratory admissions there was a trend, from positive to negative associations, with increasing age although confidence intervals generally included 0%. CONCLUSIONS: Our study, the first to analyse daily particle OP measures and mortality and admissions in a large population over two years, found little evidence to support the hypothesis that short-term exposure to particle OP is associated with adverse health effects. Further studies with improved exposure assessment and longer time series are required to confirm or reject the role of particle OP in triggering exacerbations of disease

Short-term effects of particulate matter on mortality during forest fires in Southern Europe: results of the MED-PARTICLES Project

An association between occurrence of wildfires and mortality in the exposed population has been observed in several studies with controversial results for cause-specific mortality. In the Mediterranean area, forest fires usually occur during spring-summer, they overlap with Saharan outbreaks, are associated with increased temperature and their health effects are probably due to an increase in particulate matter. We analysed the effects of wildfires and particulate matter (PM10) on mortality in 10 southern European cities in Spain, France, Italy and Greece (2003-2010), using satellite data for exposure assessment and Poisson regression models, simulating a case-crossover approach. We found that smoky days were associated with increased cardiovascular mortality (lag 0-5, 6.29%, 95% CIs 1.00 to 11.85). When the effect of PM10 (per 10 µg/m(3)) was evaluated, there was an increase in natural mortality (0.49%), cardiovascular mortality (0.65%) and respiratory mortality (2.13%) on smoke-free days, but PM10-related mortality was higher on smoky days (natural mortality up to 1.10% and respiratory mortality up to 3.90%) with a suggestion of effect modification for cardiovascular mortality (3.42%, p value for effect modification 0.055), controlling for Saharan dust advections. Smoke is associated with increased cardiovascular mortality in urban residents, and PM10 on smoky days has a larger effect on cardiovascular and respiratory mortality than on other days.Peer ReviewedPostprint (published version

Estimating the Exposure–Response Relationships between Particulate Matter and Mortality within the APHEA Multicity Project

Several studies have reported significant health effects of air pollution even at low levels of air pollutants, but in most of theses studies linear nonthreshold relations were assumed. We investigated the exposure–response association between ambient particles and mortality in the 22 European cities participating in the APHEA (Air Pollution and Health—A European Approach) project, which is the largest available European database. We estimated the exposure–response curves using regression spline models with two knots and then combined the individual city estimates of the spline to get an overall exposure–response relationship. To further explore the heterogeneity in the observed city-specific exposure–response associations, we investigated several city descriptive variables as potential effect modifiers that could alter the shape of the curve. We conclude that the association between ambient particles and mortality in the cities included in the present analysis, and in the range of the pollutant common in all analyzed cities, could be adequately estimated using the linear model. Our results confirm those previously reported in Europe and the United States. The heterogeneity found in the different city-specific relations reflects real effect modification, which can be explained partly by factors characterizing the air pollution mix, climate, and the health of the population

Short-Term Effects of Carbon Monoxide on Mortality: An Analysis within the APHEA Project

Objectives: We investigated the short-term effects of carbon monoxide on total and cardiovascular mortality in 19 European cities participating in the APHEA-2 (Air Pollution and Health: A European Approach) project. Methods: We examined the association using hierarchical models implemented in two stages. In the first stage, data from each city were analyzed separately, whereas in the second stage the city-specific air pollution estimates were regressed on city-specific covariates to obtain overall estimates and to explore sources of possible heterogeneity. We evaluated the sensitivity of our results by applying different degrees of smoothing for seasonality control in the city-specific analysis. Results: We found significant associations of CO with total and cardiovascular mortality. A 1-mg/m$^3$ increase in the 2-day mean of CO levels was associated with a 1.20% [95% confidence interval (CI), 0.63–1.77%] increase in total deaths and a 1.25% (95% CI, 0.30–2.21%) increase in cardiovascular deaths. There was indication of confounding with black smoke and nitrogen dioxide, but the pollutant-adjusted effect of CO on mortality remained at least marginally statistically significant. The effect of CO on total and cardiovascular mortality was observed mainly in western and southern European cities and was larger when the standardized mortality rate was lower. Conclusions: The results of this large study are consistent with an independent effect of CO on mortality. The heterogeneity found in the effect estimates among cities may be explained partly by specific city characteristics