Investigating the dose-response relation between air pollution and total mortality in the APHEA-2 multicity project

Background: Several recent studies have reported significant health effects of air pollution even at low levels of air pollutants, but in most of these studies linear non-threshold relations were assumed.     

On being new to an insurance plan: health care use associated with the first years in a health insurance plan

BACKGROUND We wanted to compare health care utilization and costs in the first year of being in a health insurance plan with those of subsequent years.     

Abortion and the risk of breast cancer: A case-control study in greece

We have examined the association between induced or spontaneous abortion and breast cancer risk in Greece. In a hospital-based case-control study in Athens, 820 patients with confirmed breast cancer were compared with 795 orthopedic patient controls and 753 healthy visitor controls, matched to cases by age and interviewer. Logistic regression was used to analyze the data, controlling for demographic, reproductive and nutritional variables. Odds ratio (OR) patterns were similar for the 2 control series, which were therefore combined to increase precision of the estimates. The risk for breast cancer was not increased for women who had a history of abortion, compared to nulliparous women with no history of abortion. Thus ORs and 95% confidence intervals were for nulliparous women with spontaneous abortion, 1.17 (0.64–2.13); for nulliparous women with induced abortion, 0.98 (0.56–1.73); for parous women with no abortion, 0.56 (0.31–1.01); for parous women with spontaneous abortion, 0.61 (0.33–1.14) and for parous women with induced abortion, 0.99 (0.56–1.74). When the analysis was restricted to parous women, using parous women with no history of abortion as the baseline, ORs and 95% confidence intervals were for induced abortion before first full-term pregnancy, 2.06 (1.45–2.90); for induced abortion after first full-term pregnancy, 1.59 (1.24–2.04) and for spontaneous abortion, 1.10 (0.82–1.40). Our findings suggest that an interrupted pregnancy does not impart the long-term protective effect of a full-term pregnancy attributable to terminal differentiation. © 1995 Wiley-Liss, Inc.     

Endothelial nitric oxide synthase gene polymorphisms in recurrent spontaneous abortions

OBJECTIVE: The risk of miscarriage is enhanced by a variety of genetic and environmental factors. Previous studies indicated an association between endothelial nitric oxide synthase (eNOS) activity, and implantation and maintenance of pregnancy, but it is rather controversial whether polymorphisms of the gene encoding for eNOS are associated with recurrent spontaneous abortions (RSA). The aim of our study was to determine whether the 27 bp intron 4 repeat polymorphism (4VNTR) and a Glu298Asp missense mutation encoded by exon 7 of the eNOS gene are associated with an increased risk for recurrent spontaneous abortions (RSA), in the Greek population. METHODS: A total of 126 women who had at least three unexplained spontaneous abortions before 20 weeks of gestation, with the same partner, were included in the study group. The control group consistent of 130 women with at least two live childbirths and without history of abortions. All patients and controls were investigated for the two polymorphisms. To genotype the cohorts we used the PCR-RFLPs method. RESULTS: The observed frequencies of bb, ba, aa genotypes of the VNTR, in intron 4, polymorphism were 0.75, 0.24, 0.01, respectively, for the patient group and 0.73, 0.24, 0.03, respectively, for the control group. The observed frequencies of GG, GT, TT of the Glu298Asp polymorphism were 0.42, 0.45, 0.13, respectively, for the patient group and 0.47, 0.45, 0.08, respectively, for the control group. Statistical analysis of the results indicates no significant difference between the two groups, for both the two studied polymorphisms. CONCLUSION: Our results do not show any influence of the two polymorphisms, VNTR in intron 4 and Glu298Asp of the eNOS gene, on early pregnancy.     

The temporal pattern of mortality responses to air pollution: a multicity assessment of mortality displacement.

Although the association between particulate matter and mortality or morbidity is generally accepted, controversy remains about the importance of the association. If it is due solely to the deaths of frail individuals, which are brought forward by only a brief period of time, the public health implications of the association are fewer than if there is an increase in the number of deaths. Recently, other research has addressed the mortality displacement issue in single-city analysis. We analyzed this issue with a distributed lag model in a multicity hierarchic modeling approach, within the Air Pollution and Health: A European Approach (APHEA-2) study. We fit a Poisson regression model and a polynomial distributed lag model with up to 40 days of delay in each city. In the second stage we combined the city-specific results. We found that the overall effect of particulate matter less than 10 microM in aerodynamic diameter (PM10) per 10 microg/m3 for the fourth-degree distributed lag model is a 1.61% increase in daily deaths (95% CI = 1.02-2.20), whereas the mean of PM10 on the same day and the previous day is associated with only a 0.70% increase in deaths (95% CI = 0.43-0.97). This result is unchanged using an unconstrained distributed lag model. Our study confirms that the effects observed in daily time-series studies are not due primarily to short-term mortality displacement. The effect size estimate for airborne particles more than doubles when we consider longer-term effects, which has important implications for risk assessment.     

Understanding the link between environmental exposures and health: does the exposome promise too much?

Environmental exposures affecting human health range from complex mixtures, such as environmental tobacco smoke, ambient particulate matter air pollution and chlorination by products in drinking water, to hazardous chemicals, such as lead, and polycyclic aromatic hydrocarbons, such as benz(a)pyrene. The exposome has been proposed to complement the genome and be the totality of all environmental exposures of an individual over his or her lifetime. However, if measurements of the exposome in biological samples are the sole tool for exposure assessment there are a number of limitations. First, it has limited utility for fully capturing the impact of complex mixtures such environmental tobacco smoke or particulate matter air pollution. Second, a number of relevant environmental exposures such as noise, heat or electromagnetic fields do not have direct correlates as metabolites or protein adducts, but there is important evidence linking them with health effects. Third, functional genomic changes are likely in many instances to be both a susceptibility factor and a marker of internal doses in response to environmental exposures. Fourth, internal dose measurements of environmental exposures might have lost the distinct signature of the relevant sources. This paper emphasises the obligation of environmental epidemiology to provide robust evidence to assist timely and sufficient protection of vulnerable subgroups of populations from environmental hazards. Therefore, in applying the exposome concept to environmental health problems, a strong link with the external environment needs to be maintained.     

A case-control study of lactation and cancer of the breast.

We have examined the relation of lactation, by total duration, with breast cancer risk among pre- and post-menopausal women. In a hospital-based case-control study conducted in Athens (1989-91), involving 820 patients with confirmed breast cancer and 795 orthopaedic patient controls and 753 hospital visitor controls, logistic regression was used to analyse the data controlling for demographic, nutritional and reproductive factors, including parity and age at any birth. Among post-menopausal women, there was no association between breastfeeding and breast cancer risk, but among premenopausal women those who has breastfed for > or = 24 months had an odds ratio of 0.50 (95% confidence interval 0.23-1.41). A reduction of the odds ration was also evident among premenopausal women who had breastfed between 12 and 23 months (odds ratio 0.70; 95% confidence interval 0.34-1.60). In conjunction with several other recent reports these results support the hypothesis that breastfeeding of prolonged duration may reduce the risk of breast cancer among premenopausal women but not among post-menopausal women. The biology underlying this different effect remains unknown, and the practical implication of the finding is a marginal importance.     

Short-term effects of nitrogen dioxide on mortality: an analysis within the APHEA project.

The short-term effects of nitrogen dioxide (NO(2)) on total, cardiovascular and respiratory mortality in 30 European cities participating in the Air Pollution on Health: a European Approach (APHEA)-2 project were investigated. The association was examined using hierarchical models implemented in two stages. In the first stage, data from each city were analysed 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. A significant association of NO(2) with total, cardiovascular and respiratory mortality was found, with stronger effects on cause-specific mortality. There was evidence of confounding in respiratory mortality with black smoke and sulphur dioxide. The effect of NO(2) on total and cardiovascular mortality was observed mainly in western and southern European cities, and was larger when smoking prevalence was lower and household gas consumption was higher. The effect of NO(2) on respiratory mortality was higher in cities with a larger proportion of elderly persons in the population and higher levels of particulate matter with a 50% cut-off aerodynamic diameter of 10 mum. The results of this large study are consistent with an independent effect of nitrogen dioxide on mortality, but the role of nitrogen dioxide as a surrogate of other unmeasured pollutants cannot be completely ruled out.