Person:

Zanobetti, Antonella

Background: Extremes of temperature are associated with short-term increases in daily mortality. Objectives: We set out to identify subpopulations and mortality causes with increased susceptibility to temperature extremes. Methods: We conducted a case-only analysis using daily mortality and hourly weather data from 50 U.S. cities for the period 1989–2000, covering a total of 7,789,655 deaths. We used distributions of daily minimum and maximum temperature in each city to define extremely hot days (≥ 99th percentile) and extremely cold days (≤ 1st percentile), respectively. For each (hypothesized) effect modifier, a city-specific logistic regression model was fitted and an overall estimate calculated in a subsequent meta-analysis. Results: Older subjects [odds ratio (OR) = 1.020; 95% confidence interval (CI), 1.005–1.034], diabetics (OR = 1.035; 95% CI, 1.010–1.062), blacks (OR = 1.037; 95% CI, 1.016–1.059), and those dying outside a hospital (OR = 1.066; 95% CI, 1.036–1.098) were more susceptible to extreme heat, with some differences observed between those dying from a cardiovascular disease and other decedents. Cardiovascular deaths (OR = 1.053; 95% CI, 1.036–1.070), and especially cardiac arrest deaths (OR =1.137; 95% CI, 1.051–1.230), showed a greater relative increase on extremely cold days, whereas the increase in heat-related mortality was marginally higher for those with coexisting atrial fibrillation (OR = 1.059; 95% CI, 0.996–1.125). Conclusions: In this study we identified several subpopulations and mortality causes particularly susceptible to temperature extremes. This knowledge may contribute to establishing health programs that would better protect the vulnerable.

Studies on acute effects of particulate matter (PM) air pollution show significant variability in exposure-effect relations among cities. Recent studies have shown an influence of ventilation on personal/indoor-outdoor relations and stronger associations of adverse effects with combustion-related particles. We evaluated whether differences in prevalence of air conditioning (AC) and/or the contribution of different sources to total PM(10) emissions could partly explain the observed variability in exposure-effect relations. We used regression coefficients of the relation between PM(10) and hospital admissions for chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD), and pneumonia from a recent study in 14 U.S. cities. We obtained data on the prevalence of AC from the 1993 American Housing Survey and data on PM(10) emissions by source category, vehicle miles traveled (VMT), and population density from the U.S. EPA. We analyzed data using meta-regression techniques. PM(10) regression coefficients for CVD and COPD decreased significantly with increasing percentage of homes with central AC when cities were stratified by whether their PM(10) concentrations peaked in winter or non-winter months. PM(10) coefficients for CVD increased significantly with increasing percentage of PM(10) emission from highway vehicles, highway diesels, oil combustion, metal processing, decreasing percentage of PM(10) emission from fugitive dust, and increasing population density and VMT/mile(2). In multivariate analysis, only percentage of PM(subscript)10(/subscript) from highway vehicles/diesels and oil combustion remained significant. For COPD and pneumonia, associations were less significant but the patterns of the associations were similar to that for CVD. The results suggest that air conditioning and proportion of especially traffic-related particles significantly modify the effect of PM(10) on hospital admissions, especially for CVD.

Introduction: Ambient particulate pollution and traffic have been linked to myocardial infarction and cardiac death risk. Possible mechanisms include autonomic cardiac dysfunction. Methods: In a repeated-measures study of 46 patients 43–75 years of age, we investigated associations of central-site ambient particulate pollution, including black carbon (BC) (a marker for regional and local traffic), and report of traffic exposure with changes in half-hourly averaged heart rate variability (HRV), a marker of autonomic function measured by 24-hr Holter electrocardiogram monitoring. Each patient was observed up to four times within 1 year after a percutaneous intervention for myocardial infarction, acute coronary syndrome without infarction, or stable coronary artery disease (4,955 half-hour observations). For each half-hour period, diary data defined whether the patient was home or not home, or in traffic. Results: A decrease in high frequency (HF; an HRV marker of vagal tone) of −16.4% [95% confidence interval (CI), −20.7 to −11.8%] was associated with an interquartile range of 0.3-μg/m3 increase in prior 5-day averaged ambient BC. Decreases in HF were independently associated both with the previous 2-hr averaged BC (−10.4%; 95% CI, −15.4 to −5.2%) and with being in traffic in the previous 2 hr (−38.5%; 95% CI, −57.4 to −11.1%). We also observed independent responses for particulate air matter with aerodynamic diameter ≤ 2.5 μm and for gases (ozone or nitrogen dioxide). Conclusion: After hospitalization for coronary artery disease, both particulate pollution and being in traffic, a marker of stress and pollution, were associated with decreased HRV.

Background: Several studies have shown cross-sectional associations between long term exposure to particulate air pollution and survival in general population or convenience cohorts. Less is known about susceptibility, or year to year changes in exposure. We investigated whether particles were associated with survival in a cohort of persons with COPD in 34 US cities, eliminating the usual cross-sectional exposure and treating PM10 as a within city time varying exposure. Methods: Using hospital discharge data, we constructed a cohort of persons discharged alive with chronic obstructive pulmonary disease using Medicare data between 1985 and 1999. 12-month averages of PM10 were merged to the individual annual follow up in each city. We applied Cox's proportional hazard regression model in each city, with adjustment for individual risk factors. Results: We found significant associations in the survival analyses for single year and multiple lag exposures, with a hazard ratio for mortality for an increase of 10 μg/m3 PM10 over the previous 4 years of 1.22 (95% CI: 1.17–1.27). Conclusion: Persons discharged alive for COPD have substantial mortality risks associated with exposure to particles. The risk is evident for exposure in the previous year, and higher in a 4 year distributed lag model. These risks are significantly greater than seen in time series analyses.

We carried out time-series analyses in 12 U.S. cities to estimate both the acute effects and the lagged influence of weather on respiratory and cardiovascular disease (CVD) deaths. We fit generalized additive Poisson regressions for each city using nonparametric smooth functions to control for long time trend, season, and barometric pressure. We also controlled for day of the week. We estimated the effect and the lag structure of both temperature and humidity based on a distributed lag model. In cold cities, both high and low temperatures were associated with increased CVD deaths. In general, the effect of cold temperatures persisted for days, whereas the effect of high temperatures was restricted to the day of the death or the day before. For myocardial infarctions (MI), the effect of hot days was twice as large as the cold-day effect, whereas for all CVD deaths the hot-day effect was five times smaller than the cold-day effect. The effect of hot days included some harvesting, because we observed a deficit of deaths a few days later, which we did not observe for the cold-day effect. In hot cities, neither hot nor cold temperatures had much effect on CVD or pneumonia deaths. However, for MI and chronic obstructive pulmonary disease deaths, we observed lagged effects of hot temperatures (lags 4-6 and lags 3 and 4, respectively). We saw no clear pattern for the effect of humidity. In hierarchical models, greater variance of summer and winter temperature was associated with larger effects for hot and cold days, respectively, on respiratory deaths.

Introduction: Systemic inflammation may be one of the mechanisms mediating the association between ambient air pollution and cardiovascular morbidity and mortality. Interleukin-6 (IL-6) and fibrinogen are biomarkers of systemic inflammation that are independent risk factors for cardiovascular disease. Objective: We investigated the association between ambient air pollution and systemic inflammation using baseline measurements of IL-6 and fibrinogen from controlled human exposure studies. Methods: In this retrospective analysis we used repeated-measures data in 45 nonsmoking subjects. Hourly and daily moving averages were calculated for ozone, nitrogen dioxide, sulfur dioxide, and particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5). Linear mixed-model regression determined the effects of the pollutants on systemic IL-6 and fibrinogen. Effect modification by season was considered. Results: We observed a positive association between IL-6 and O3 [0.31 SD per O3 interquartile range (IQR); 95% confidence interval (CI), 0.08–0.54] and between IL-6 and SO2 (0.25 SD per SO2 IQR; 95% CI, 0.06–0.43). We observed the strongest effects using 4-day moving averages. Responses to pollutants varied by season and tended to be higher in the summer, particularly for O3 and PM2.5. Fibrinogen was not associated with pollution. Conclusions: This study demonstrates a significant association between ambient pollutant levels and baseline levels of systemic IL-6. These findings have potential implications for controlled human exposure studies. Future research should consider whether ambient pollution exposure before chamber exposure modifies IL-6 response.

Background: Ozone has been associated with daily mortality, mainly in the summer period. Despite the ample literature on adaptation of inflammatory and pulmonary responses to ozone, and the link, in cohort studies, between lung function and mortality risk there has been little done to date to examine the question of adaptation in the acute mortality risk associated with ambient ozone. Methods: We applied a case-crossover design in 48 US cities to examine the ozone effect by season, by month and by age groups, particularly focusing on whether there was an adaptation effect. Results: We found that the same day ozone effect was highest in summer with a 0.5% (95% CI: 0.38, 0.62) increase in total mortality for 10 ppb increase in 8-hr ozone, whilst the effect decrease to null in autumn and winter. We found higher effects in the months May- July with a 0.46% (95% CI: 0.24, 0.68) increase in total mortality for 10 ppb increase in ozone in June, and a 0.65% (95% CI: 0.47, 0.82) increase in mortality during July. The effect decreased in August and became null in September. We found similar effects from the age group 51–60 up to age 80 and a lower effect in 80 years and older. Conclusion: The mortality effects of ozone appear diminished later in the ozone season, reaching the null effect previously reported in winter by September. More work should address this issue and examine the biological mechanism of adaptation.

Recently, attention has focused on whether particulate air pollution is a specific trigger of myocardial infarction (MI). The results of several studies of single locations assessing the effects of ambient particular matter on the risk of MI have been disparate. We used a multicity case-crossover study to examine risk of emergency hospitalization associated with fine particulate matter (PM) with aerodynamic diameter < 10 μm (PM10) for > 300,000 MIs during 1985–1999 among elderly residents of 21 U.S. cities. We used time-stratified controls matched on day of the week or on temperature to detect possible residual confounding by weather. Overall, we found a 0.65% [95% confidence interval (CI), 0.3–1.0%] increased risk of hospitalization for MI per 10 μg/m3 increase in ambient PM10 concentration. Matching on apparent temperature yielded a 0.64% increase in risk (95% CI, 0.1–1.2%). We found that the effect size for PM10 doubled for subjects with a previous admission for chronic obstructive pulmonary disease or a secondary diagnosis of pneumonia, although these differences did not achieve statistical significance. There was a weaker indication of a larger effect on males but no evidence of effect modification by age or the other diagnoses. We also found that the shape of the exposure–response relationship between MI hospitalizations and PM10 is almost linear, but with a steeper slope at levels of PM10 < 50 μg/m3. We conclude that increased concentrations of ambient PM10 are associated with increased risk of MI among the elderly.

Background: Associations between ambient temperature and cardiovascular mortality are well established. This study investigated whether inflammation could be part of the mechanism leading to temperature-related cardiovascular deaths. Methods: The study population consisted of a cohort of 673 men with mean age of 74.6 years, living in the greater Boston area. They were seen for examination roughly every 4 years, and blood samples for inflammation marker analyses were drawn in 2000-2008 (total of 1254 visits). We used a mixed effects model to estimate the associations between ambient temperature and a variety of inflammation markers (C-reactive protein, white blood cell count, soluble Vascular Cell Adhesion Molecule-1, soluble Intercellular Adhesion Molecule-1, tumor necrosis factor alpha, and interleukins -1β, -6 and -8). Random intercept for each subject and several possible confounders, including combustion-related air pollution and ozone, were used in the models. Results: We found a 0 to 1 day lagged and up to 4 weeks cumulative responses in C-reactive protein in association with temperature. We observed a 24.9% increase [95% Confidence interval (CI): 7.36, 45.2] in C-reactive protein for a 5°C decrease in the 4 weeks' moving average of temperature. We observed similar associations also between temperature and soluble Intercellular Adhesion Molecule-1 (4.52%, 95% CI: 1.05, 8.10, over 4 weeks' moving average), and between temperature and soluble Vascular Cell Adhesion Molecule-1 (6.60%, 95% CI: 1.31, 12.2 over 4 weeks' moving average). Penalized spline models showed no deviation from linearity. There were no associations between temperature and other inflammation markers. Conclusions: Cumulative exposure to decreased temperature is associated with an increase in inflammation marker levels among elderly men. This suggests that inflammation markers are part of intermediate processes, which may lead to cold-, but not heat-, related cardiovascular deaths.

Increased levels of daily ambient particle pollution have been associated with increased risk of cardiovascular morbidity. Black carbon (BC) is a measure of the traffic-related component of particles. We investigated associations between ambient pollution and ST-segment levels in a repeated-measures study including 269 observations on 24 active Boston residents 61–88 years of age, each observed up to 12 times from June through September 1999. The protocol involved continuous Holter electrocardiogram monitoring including 5 min of rest, 5 min of standing, 5 min of exercise outdoors, 5 min of recovery, and 20 cycles of paced breathing. Pollution-associated ST-depression was estimated for a 10th- to 90th-percentile change in BC. We calculated the average ST-segment level, referenced to the P-R isoelectric values, for each portion of the protocol. The mean BC level in the previous 12 hr, and the BC level 5 hr before testing, predicted ST-segment depression in most portions of the protocol, but the effect was strongest in the postexercise periods. During post-exercise rest, an elevated BC level was associated with −0.1 mm ST-segment depression (p = 0.02 for 12-hr mean BC; p = 0.001 for 5-hr BC) in continuous models. Elevated BC also predicted increased risk of ST-segment depression ≥0.5 mm among those with at least one episode of that level of ST-segment depression. Carbon monoxide was not a confounder of this association. ST-segment depression, possibly representing myocardial ischemia or inflammation, is associated with increased exposure to particles whose predominant source is traffic.