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.

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.

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.

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.

Background: Mild hyperhomocysteinemia is independently associated with an increased risk of cardiovascular disease. Air pollution exposure induces short-term inflammatory changes that may determine hyperhomocysteinemia, particularly in the presence of a preexisting proinflammatory status such as that found in cigarette smokers. Objective: We examined the relation of air pollution levels with fasting and postmethionine-load total homocysteine (tHcy) in 1,213 normal subjects from Lombardia, Italy. Methods: We obtained hourly concentrations of particulate matter < 10 μm in aerodynamic diameter (PM({10})) and gaseous pollutants (carbon monoxide, nitrogen dioxide, sulfur dioxide, ozone) from 53 monitoring sites covering the study area. We applied generalized additive models to compute standardized regression coefficients controlled for age, sex, body mass index, smoking, alcohol, hormone use, temperature, day of the year, and long-term trends. Results: The estimated difference in tHcy associated with an interquartile increase in average PM({10}) concentrations in the 24 hr before the study was nonsignificant [0.4%; 95% confidence interval (CI), −2.4 to 3.3 for fasting; and 1.1%, 95% CI, −1.5 to 3.7 for postmethionine-load tHcy]. In smokers, 24-hr PM(_{10}) levels were associated with 6.3% (95% CI, 1.3 to 11.6; p < 0.05) and 4.9% (95% CI, 0.5 to 9.6; p < 0.05) increases in fasting and postmethionine-load tHcy, respectively, but no association was seen in nonsmokers (p-interaction = 0.005 for fasting and 0.039 for postmethionine-load tHcy). Average 24-hr O(_3) concentrations were associated with significant differences in fasting tHcy (6.7%; 95% CI, 0.9 to 12.8; p < 0.05), but no consistent associations were found when postmethionine-load tHcy and/or 7-day average O(_3) concentrations were considered. Conclusions: Air particles may interact with cigarette smoking and increase plasma homocysteine in healthy subjects.

We analyzed the influence of emissions from burning sugar cane on the respiratory system during almost 1 year in the city of Piracicaba in southeast Brazil. From April 1997 through March 1998, samples of inhalable particles were collected, separated into fine and coarse particulate mode, and analyzed for black carbon and tracer elements. At the same time, we examined daily records of children (< 13 years of age) and elderly people (> 64 years of age) admitted to the hospital because of respiratory diseases. Generalized linear models were adopted with natural cubic splines to control for season and linear terms to control for weather. Analyses were carried out for the entire period, as well as for burning and nonburning periods. Additional models were built using three factors obtained from factor analysis instead of particles or tracer elements. Increases of 10.2 μg/m3 in particles ≥ 2.5 μm/m3 aerodynamic diameter (PM2.5) and 42.9 μg/m3 in PM10 were associated with increases of 21.4% [95% confidence interval (CI), 4.3–38.5] and 31.03% (95% CI, 1.25–60.21) in child and elderly respiratory hospital admissions, respectively. When we compared periods, the effects during the burning period were much higher than the effects during nonburning period. Elements generated from sugar cane burning (factor 1) were those most associated with both child and elderly respiratory admissions. Our results show the adverse impact of sugar cane burning emissions on the health of the population, reinforcing the need for public efforts to reduce and eventually eliminate this source of air pollution.

Background: Past studies reported evidence of associations between air pollution and respiratory symptoms and morbidity for children. Few studies examined associations between air pollution and emergency room (ER) visits for wheezing, and even fewer for gastroenteric illness. We conducted a multicity analysis of the relationship between air pollution and ER visits for wheezing and gastroenteric disorder in children 0–2 years of age. Methods: We obtained ER visit records for wheezing and gastroenteric disorder from six Italian cities. A city-specific case–crossover analysis was applied to estimate effects of particulate matter (PM), nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide, adjusting for immediate and delayed effects of temperature. Lagged effects of air pollutants up to 6 prior days were examined. The city-specific results were combined using a random-effect meta-analysis. Results: CO and SO2 were most strongly associated with wheezing, with a 2.7% increase [95% confidence interval (CI), 0.5–4.9] for a 1.04-μg/m3 increase in 7-day average CO and a 3.4% (95% CI, 1.5–5.3) increase for an 8.0-μg/m3 increase in SO2. Positive associations were also found for PM with aerodynamic diameter ≤ 10 μg and NO2. We found a significant association between the 3-day moving average CO and gastroenteric disorders [3.8% increase (95% CI, 1.0–6.8)]. When data were stratified by season, the associations were stronger in summer for wheezing and in winter for gastroenteric disorders. Conclusion: Air pollution is associated with triggering of wheezing and gastroenteric disorders in children 0–2 years of age; more work is needed to understand the mechanisms to help prevent wheezing in children.