The temporal pattern of respiratory and heart disease mortality in response to air pollution

Short-term changes in ambient particulate matter with aerodynamic diameters < 10 micro m (PM10) have been associated with short-term fluctuations in mortality or morbidity in many studies. In this study, we tested whether those deaths are just advanced by a few days or weeks using a multicity hierarchical modeling approach for all-cause, respiratory, and cardiovascular deaths, for all ages and stratifying by age groups, within the APHEA-2 (Air Pollution and Health: A European Approach) project. We fit a Poisson regression and used an unconstrained distributed lag to model the effect of PM10 exposure on deaths up to 40 days after the exposure. In baseline models using PM10 the day of and day before the death, we found that the overall PM10 effect (per 10 micro g/m3) was 0.74% [95% confidence interval (95% CI), -0.17 to 1.66] for respiratory deaths and 0.69% (95% CI, 0.31-1.08) for cardiovascular deaths. In unrestricted distributed lag models, the effect estimates increased to 4.2% (95% CI, 1.08-7.42) for respiratory deaths and to 1.97% (95% CI, 1.38-2.55) for cardiovascular deaths. Our study confirms that most of the effect of air pollution is not simply advanced by a few weeks and that effects persist for more than a month after exposure. The effect size estimate for PM10 doubles when we considered longer-term effects for all deaths and for cardiovascular deaths and becomes five times higher for respiratory deaths. We found similar effects when stratifying by age groups. These larger effects are important for risk assessment.     

Determinants of Physician Discussion Regarding Tobacco and Alcohol Abuse

The U.S. Preventive Services Task Force recommends that clinicians screen adults for tobacco and alcohol abuse and provide appropriate interventions. This study employed direct observation and interactional analysis of medical visits to investigate factors associated with physician discussion of tobacco and alcohol use with patients. New adult patients were randomly assigned to primary care at a university medical center. Videotapes of the visits were analyzed using the Davis observation code. Regression equations related discussions of substance use (alcohol and other substances), smoking, and health promotion to patient health status, depression, age, education, income, gender, alcohol abuse, and current smoking. Patients reporting better physical health were more likely to have their physicians employ a practice style emphasizing addiction behaviors (p = .0186). Substance use (p = .0117) and health promotion counseling (p = .0130) occurred more frequently with younger patients. Physicians discussed substance use (p = < .0001) and addiction (p < .0001) more often with male patients. Problem drinkers were more likely to have physicians address their substance use (p = .0069) and focus on addiction behaviors (p = .0017). Physicians adopted an addiction-oriented practice style (p < .0001), addressing substance use (p = .0009) and smoking (p < .0001), more often with patients who smoked. Physicians appear more apt to discuss these behavioral risk factors with healthier, younger, male patients who abuse tobacco and alcohol.     

Associations between Fine and Coarse Particles and Mortality in Mediterranean Cities: Results from the MED-PARTICLES Project

Background: Few studies have investigated the independent health effects of different size fractions of particulate matter (PM) in multiple locations, especially in Europe.Objectives: We estimated the short-term effects of PM with aerodynamic diameter ≤ 10 μm (PM₁₀), ≤ 2.5 μm (PM_2.5), and between 2.5 and 10 μm (PM_2.5–10) on all-cause, cardiovascular, and respiratory mortality in 10 European Mediterranean metropolitan areas within the MED-PARTICLES project.Methods: We analyzed data from each city using Poisson regression models, and combined city-specific estimates to derive overall effect estimates. We evaluated the sensitivity of our estimates to co-pollutant exposures and city-specific model choice, and investigated effect modification by age, sex, and season. We applied distributed lag and threshold models to investigate temporal patterns of associations.Results: A 10-μg/m³ increase in PM_2.5 was associated with a 0.55% (95% CI: 0.27, 0.84%) increase in all-cause mortality (0–1 day cumulative lag), and a 1.91% increase (95% CI: 0.71, 3.12%) in respiratory mortality (0–5 day lag). In general, associations were stronger for cardiovascular and respiratory mortality than all-cause mortality, during warm versus cold months, and among those ≥ 75 versus < 75 years of age. Associations with PM_2.5–10 were positive but not statistically significant in most analyses, whereas associations with PM₁₀ seemed to be driven by PM_2.5.Conclusions: We found evidence of adverse effects of PM_2.5 on mortality outcomes in the European Mediterranean region. Associations with PM_2.5–10 were positive but smaller in magnitude. Associations were stronger for respiratory mortality when cumulative exposures were lagged over 0–5 days, and were modified by season and age.     

Acute effects of ambient ozone on mortality in Europe and North America: results from the APHENA study

The “Air Pollution and Health: A Combined European and North American Approach” (APHENA) project is a collaborative analysis of multi-city time-series data on the association between air pollution and adverse health outcomes. The main objective of APHENA was to examine the coherence of findings of time-series studies relating short-term fluctuations in air pollution levels to mortality and morbidity in 125 cities in Europe, the US, and Canada. Multi-city time-series analysis was conducted using a two-stage approach. We used Poisson regression models controlling for overdispersion with either penalized or natural splines to adjust for seasonality. Hierarchical models were used to obtain an overall estimate of excess mortality associated with ozone and to assess potential effect modification. Potential effect modifiers were city-level characteristics related to exposure to other ambient air pollutants, weather, socioeconomic status, and the vulnerability of the population. Regionally pooled risk estimates from Europe and the US were similar; those from Canada were substantially higher. The pooled estimated excess relative risk associated with a 10 μg/m³ increase in 1 h daily maximum O₃ was 0.26 % (95 % CI, 0.15 %, 0.37 %). Across regions, there was little consistent indication of effect modification by age or other effect modifiers considered in the analysis. The findings from APHENA on the effects of O₃ on mortality in the general population were comparable with previously reported results and relatively robust to the method of data analysis. Overall, there was no indication of strong effect modification by age or ecologic variables considered in the analysis.     

Obesity and the use of health care services

OBJECTIVE: This study investigated differences in the use of health care services and associated costs between obese and nonobese patients. RESEARCH METHODS AND PROCEDURES: New adult patients (N = 509) were randomly assigned to primary care physicians at a university medical center. Their use of medical services and related charges was monitored for 1 year. Data collected included sociodemographics, self-reported health status using the Medical Outcomes Study Short Form-36, evaluation for depression using the Beck Depression Index, and measured height and weight to calculate BMI. RESULTS: Obese patients included a significantly higher percentage of women and had higher mean age, lower mean education, lower mean health status, and higher mean Beck Depression Index scores. Obese patients had a significantly higher mean number of visits to both primary care (p = 0.0005) and specialty care clinics (p = 0.0006), and a higher mean number of diagnostic services (p < 0.0001). Obese patients also had significantly higher primary care (p = 0.0058), specialty clinic (p = 0.0062), emergency department (p = 0.0484), hospitalization (p = 0.0485), diagnostic services (p = 0.0021), and total charges (p = 0.0033). Controlling for health status, depression, age, education, income, and sex, obesity was significantly related to the use of primary care (p = 0.0364) and diagnostic services (p = 0.0075). There was no statistically significant relationship between obesity and medical expenditures in any of the five categories or for total charges. DISCUSSION: Obesity is a chronic condition requiring long-term management, with an emphasis on prevention. If this critical health issue is not appropriately addressed, the prevalence of obesity and obesity-related diseases will continue to grow, resulting in escalating use of health care services.     

Air pollution and inflammatory response in myocardial infarction survivors: gene-environment interactions in a high-risk group

Ambient air pollution has been associated with an increased risk of hospital admission and mortality in potentially susceptible subpopulations, including myocardial infarction (MI) survivors. The multicenter epidemiological study described in this report was set up to study the role of air pollution in eliciting inflammation in MI survivors in six European cities, Helsinki, Stockholm, Augsburg, Rome, Barcelona, and Athens. Outcomes of interest are plasma concentrations of the proinflammatory cytokine interleukin 6 (IL-6) and the acute-phase proteins C-reactive protein (CRP) and fibrinogen. In addition, the study was designed to assess the role of candidate gene polymorphisms hypothesized to lead to a modification of the short-term effects of ambient air pollution. In total, 1003 MI survivors were recruited and assessed with at least 2 repeated clinic visits without any signs of infections. In total, 5813 blood samples were collected, equivalent to an average of 5.8 repeated clinic visits per subject (97% of the scheduled 6 repeated visits). Subjects across the six cities varied with respect to risk factor profiles. Most of the subjects were nonsmokers, but light smokers were included in Rome, Barcelona, and Athens. Substantial inter- and intraindividual variability was observed for IL-6 and CRP. The study will permit assessing the role of cardiovascular disease risk factors, including ambient air pollution and genetic polymorphisms in candidate genes, in determining the inter- and the intraindividual variability in plasma IL-6, CRP, and fibrinogen concentrations in MI survivors.     

Modification of the Interleukin-6 Response to Air Pollution by Interleukin-6 and Fibrinogen Polymorphisms

Background

Evidence suggests that cardiovascular effects of air pollution are mediated by inflammation and that air pollution can induce genetic expression of the interleukin-6 gene (IL6).

Objectives

We investigated whether IL6 and fibrinogen gene variants can affect plasma IL-6 responses to air pollution in patients with cardiovascular disease.

Methods

We repeatedly determined plasma IL-6 in 955 myocardial infarction survivors from six European cities (n = 5,539). We conducted city-specific analyses using additive mixed models adjusting for patient characteristics, time trend, and weather to assess the impact of air pollutants on plasma IL-6. We pooled city-specific estimates using meta-analysis methodology. We selected three IL6 single-nucleotide polymorphisms (SNPs) and one SNP each from the fibrinogen α-chain gene (FGA) and β-chain gene (FGB) for gene–environment analyses.

Results

We found the most consistent modifications for variants in IL6 rs2069832 and FBG rs1800790 after exposure to carbon monoxide (CO; 24-hr average; p-values for interaction, 0.034 and 0.019, respectively). Nitrogen dioxide effects were consistently modified, but p-values for interaction were larger (0.09 and 0.19, respectively). The strongest effects were seen 6–11 hr after exposure, when, for example, the overall effect of a 2.2% increase in IL-6 per 0.64 mg/m³ CO was modified to a 10% (95% confidence interval, 4.6–16%) increase in IL-6 (p-value for interaction = 0.002) for minor homozygotes of FGB rs1800790.

Conclusions

The effect of gaseous traffic-related air pollution on inflammation may be stronger in genetic subpopulations with ischemic heart disease. This information could offer an opportunity to identify postinfarction patients who would benefit more than others from a cleaner environment and antiinflammatory treatment.     

Using spatio-temporal land use regression models to address spatial variation in air pollution concentrations in time series studies

Time series studies are used to assess the effects of short-term exposures to PM₁₀ and NO₂ on mortality using an integrated pollutant series taken to characterize exposure over a large area. We propose using spatio-temporal land use regression (LUR) models by smaller geographical sectors within an area of interest to account for spatial variability in these studies. Based on model-estimated time series, we conducted a case-crossover analysis for each sub-sector within two larger areas of interest (Athens and Thessaloniki, Greece) separately to investigate heterogeneity and provide combined results if appropriate. As sensitivity analysis, we compared the case-crossover method to classical time series analysis and also to using fixed site measurements only. For PM₁₀ exposures in Athens, we found consistent adverse effects which were larger when using spatio-temporal LUR modeled concentrations (total mortality RR 2.55 and 95% CI ? 0.30 to 5.39) compared to measurements (RR 0.36 and 95% CI ? 0.21 to 0.93). For NO₂, we found a similar magnitude in the effects, when using measurements from fixed sites (RR 0.81 and 95% CI 0.39 to 1.22) and modeled levels (RR 0.71 and 95% CI 0.14 to 1.28). Analysis by geographical sector did not add information over a unified analysis for the whole area. The effect estimates using classical Poisson regression time series yielded consistently smaller size effects compared to the case-crossover method. Our analysis demonstrates the potential of using spatio-temporal models in time series analysis for short-term air pollution effects to account for spatial variability in addition to the temporal.     

Maternal age,parity, and pregnancy estrogens

Total estrogens (TE), estradiol (E2), estriol (E3), and human placental lactogen (hPL) were determined by radioimmunoassay in the blood of 126 pregnant women during their 26th and 31st weeks of pregnancy and the results were studied in relation to maternal age and parity. Total estrogens and E2 were lowest among the youngest women (<20 years) and highest among women aged 20–24 years, whereas older women (25 + years) had, on the average, intermediate values. For E3 the pattern was qualitatively similar to that of TE and E2 but less striking, and no maternal age pattern was evident with respect to hPL. Within maternal age groups, TE and E2 were higher among women in the first, than among those in their second, full-term pregnancy; the difference was about seven percent for TE (P=0.14) and about 14 percent for E2 (P=0.05). No parity patterns were evident with respect to E3 and hPL. There were fairly strong correlations between the determinations of the same hormone in the same woman during the 26th and 31st weeks of pregnancy; Pearson correlation coefficients were 0.60 for TE, 0.78 for E2, 0.60 for E3, and 0.72 for hPL. Since the risk of breast cancer increases apparently monotonically with maternal age at birth, the present data are equivocal with respect to the hypothesis linking levels of pregnancy estrogens to risk of breast cancer in the offspring. However, the data are compatible with hypotheses linking excessive pregnancy-estrogen exposure to conditions more common among first-born individuals, including testicular cancer and cryptorchidism.Drs Panagiotopoulou, Katsouyanni, Petridou, Garas, and Tzonou are from the Department of Hygiene and Epidemiology, University of AThens Medical School, Greece, and Dr Trichopoulos, to whom correspondence should be addressed, is from the Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. This study was supported by a grant from the Greek Ministry of Youth.