Massimo Stafoggia

Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE)

BACKGROUND Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations. METHODS This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses. FINDINGS The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03-1·45] per 10 μg/m(3)). For PM2·5 the HR was 1·18 (0·96-1·46) per 5 μg/m(3). The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10-2·08) and 1·55 (1·05-2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99-1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95-1·07] per 20 μg/m(3)) or traffic intensity on the nearest street (HR 1·00 [0·97-1·04] per 5000 vehicles per day). INTERPRETATION Particulate matter air pollution contributes to lung cancer incidence in Europe. FUNDING European Communitys Seventh Framework Programme.

Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project

BACKGROUND Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants. METHODS We used data from 22 European cohort studies, which created a total study population of 367,251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 μm (PM2.5), less than 10 μm (PM10), and between 10 μm and 2.5 μm (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buffer. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis. FINDINGS The total study population consisted of 367,251 participants who contributed 5,118,039 person-years at risk (average follow-up 13.9 years), of whom 29,076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 μg/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I(2) p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 μg/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 μg/m(3) (1.07, 1.01-1.13). INTERPRETATION Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value. FUNDING European Communitys Seventh Framework Program (FP7/2007-2011).

Vulnerability to Heat-Related Mortality: A Multicity, Population-Based, Case-Crossover Analysis

Background: Although studies have documented increased mortality during heat waves, little information is available on the subgroups most susceptible to these effects. We evaluated the effects of summertime high temperature on daily mortality among population subgroups defined by demographic characteristics, socioeconomic status, and episodes of hospitalization for various conditions during the preceding 2 years. Methods: We studied a total of 205,019 residents of 4 Italian cities (Bologna, Milan, Rome, and Turin) age 35 or older who died during 1997–2003. The case-crossover design was applied to evaluate the association between mean apparent temperature (same and previous day) and all-cause mortality. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) of dying at 30°C (apparent temperature) relative to 20°C were estimated accounting for time, population changes, and air pollution. Results: We found an overall OR of 1.34 (CI = 1.27–1.42) at 30°C relative to 20°C. The odds ratio increased with age and was higher among women (OR = 1.45; 1.37–1.52) and among widows and widowers (1.50; 1.33–1.69). Low area-based income modestly increased the effect. Among the preexisting medical conditions investigated, effect modification was detected for previous psychiatric disorders (1.69; 1.39–2.07), depression (1.72; 1.24–2.39), heart conduction disorders (1.77; 1.38–2.27), and circulatory disorders of the brain (1.47; 1.34–1.62). Temperature-related mortality was higher among people residing in nursing homes, and a large effect was also detected for hospitalized subjects. Conclusions: Subsets of the population that are particularly vulnerable to high summer temperatures include the elderly, women, widows and widowers, those with selected medical conditions, and those staying in nursing homes and healthcare facilities.

Long-term exposure to urban air pollution and mortality in a cohort of more than a million adults in Rome.

Background: Few European studies have investigated the effects of long-term exposure to both fine particulate matter (≤ 2.5 µm; PM2.5) and nitrogen dioxide (NO2) on mortality. Objectives: We studied the association of exposure to NO2, PM2.5, and traffic indicators on cause-specific mortality to evaluate the form of the concentration–response relationship. Methods: We analyzed a population-based cohort enrolled at the 2001 Italian census with 9 years of follow-up. We selected all 1,265,058 subjects ≥ 30 years of age who had been living in Rome for at least 5 years at baseline. Residential exposures included annual NO2 (from a land use regression model) and annual PM2.5 (from a Eulerian dispersion model), as well as distance to roads with > 10,000 vehicles/day and traffic intensity. We used Cox regression models to estimate associations with cause-specific mortality adjusted for individual (sex, age, place of birth, residential history, marital status, education, occupation) and area (socioeconomic status, clustering) characteristics. Results: Long-term exposures to both NO2 and PM2.5 were associated with an increase in nonaccidental mortality [hazard ratio (HR) = 1.03 (95% CI: 1.02, 1.03) per 10-µg/m3 NO2; HR = 1.04 (95% CI: 1.03, 1.05) per 10-µg/m3 PM2.5]. The strongest association was found for ischemic heart diseases (IHD) [HR = 1.10 (95% CI: 1.06, 1.13) per 10-µg/m3 PM2.5], followed by cardiovascular diseases and lung cancer. The only association showing some deviation from linearity was that between NO2 and IHD. In a bi-pollutant model, the estimated effect of NO2 on mortality was independent of PM2.5. Conclusions: This large study strongly supports an effect of long-term exposure to NO2 and PM2.5 on mortality, especially from cardiovascular causes. The results are relevant for the next European policy decisions regarding air quality.

Long term exposure to ambient air pollution and incidence of acute coronary events: prospective cohort study and meta-analysis in 11 European cohorts from the ESCAPE Project

Objectives To study the effect of long term exposure to airborne pollutants on the incidence of acute coronary events in 11 cohorts participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Design Prospective cohort studies and meta-analysis of the results. Setting Cohorts in Finland, Sweden, Denmark, Germany, and Italy. Participants 100 166 people were enrolled from 1997 to 2007 and followed for an average of 11.5 years. Participants were free from previous coronary events at baseline. Main outcome measures Modelled concentrations of particulate matter <2.5 μm (PM2.5), 2.5-10 μm (PMcoarse), and <10 μm (PM10) in aerodynamic diameter, soot (PM2.5 absorbance), nitrogen oxides, and traffic exposure at the home address based on measurements of air pollution conducted in 2008-12. Cohort specific hazard ratios for incidence of acute coronary events (myocardial infarction and unstable angina) per fixed increments of the pollutants with adjustment for sociodemographic and lifestyle risk factors, and pooled random effects meta-analytic hazard ratios. Results 5157 participants experienced incident events. A 5 μg/m3 increase in estimated annual mean PM2.5 was associated with a 13% increased risk of coronary events (hazard ratio 1.13, 95% confidence interval 0.98 to 1.30), and a 10 μg/m3 increase in estimated annual mean PM10 was associated with a 12% increased risk of coronary events (1.12, 1.01 to 1.25) with no evidence of heterogeneity between cohorts. Positive associations were detected below the current annual European limit value of 25 μg/m3 for PM2.5 (1.18, 1.01 to 1.39, for 5 μg/m3 increase in PM2.5) and below 40 μg/m3 for PM10 (1.12, 1.00 to 1.27, for 10 μg/m3 increase in PM10). Positive but non-significant associations were found with other pollutants. Conclusions Long term exposure to particulate matter is associated with incidence of coronary events, and this association persists at levels of exposure below the current European limit values.

Impact of fine and ultrafine particles on emergency hospital admissions for cardiac and respiratory diseases.

Background: Little is known about the short-term effects of ultrafine particles. Methods: We evaluated the effect of particulate matter with an aerodynamic diameter ≤10 &mgr;m (PM10), ≤2.5 &mgr;m (PM2.5), and ultrafine particles on emergency hospital admissions in Rome 2001–2005. We studied residents aged ≥35 years hospitalized for acute coronary syndrome, heart failure, lower respiratory tract infections, and chronic obstructive pulmonary disease (COPD). Information was available for factors indicating vulnerability, such as age and previous admissions for COPD. Particulate matter data were collected daily at one central fixed monitor. A case-crossover analysis was performed using a time-stratified approach. We estimated percent increases in risk per 14 &mgr;g/m3 PM10, per 10 &mgr;g/m3 PM2.5, and per 9392 particles/mL. Results: An immediate impact (lag 0) of PM2.5 on hospitalizations for acute coronary syndrome (2.3% [95% confidence interval = 0.5% to 4.2%]) and heart failure (2.4% [0.3% to 4.5%]) was found, whereas the effect on lower respiratory tract infections (2.8% [0.5% to 5.2%]) was delayed (lag 2). Particle number concentration showed an association only with admissions for heart failure (lag 0–5; 2.4% [0.2% to 4.7%]) and COPD (lag 0; 1.6% [0.0% to 3.2%]). The effects were generally stronger in the elderly and during winter. There was no clear effect modification with previous COPD. Conclusions: We found sizeable acute health effects of fine and ultrafine particles. Although differential reliability in exposure assessment, in particular of ultrafine particles, precludes a firm conclusion, the study indicates that particulate matter of different sizes tends to have diverse outcomes, with dissimilar latency between exposure and health response.

Nitrogen dioxide levels estimated from land use regression models several years apart and association with mortality in a large cohort study

BackgroundLand Use Regression models (LUR) are useful to estimate the spatial variability of air pollution in urban areas. Few studies have evaluated the stability of spatial contrasts in outdoor nitrogen dioxide (NO2) concentration over several years. We aimed to compare measured and estimated NO2 levels 12 years apart, the stability of the exposure estimates for members of a large cohort study, and the association of the exposure estimates with natural mortality within the cohort.MethodsWe measured NO2 at 67 locations in Rome in 1995/96 and 78 sites in 2007, over three one-week-long periods. To develop LUR models, several land-use and traffic variables were used. NO2 concentration at each residential address was estimated for a cohort of 684,000 adults. We used Cox regression to analyze the association between the two estimated exposures and mortality.ResultsThe mean NO2 measured concentrations were 45.4 μg/m3 (SD 6.9) in 1995/96 and 44.6 μg/m3 (SD 11.0) in 2007, respectively. The correlation of the two measurements was 0.79. The LUR models resulted in adjusted R2 of 0.737 and 0.704, respectively. The correlation of the predicted exposure values for cohort members was 0.96. The association of each 10 μg/m3 increase in NO2 with mortality was 6 % for 1995/96 and 4 % for 2007 LUR models. The increased risk per an inter-quartile range change was identical (4 %, 95 % CI:3–6 %) for both estimates of NO2.ConclusionsMeasured and predicted NO2 values from LUR models, from samples collected 12 years apart, had good agreement, and the exposure estimates were similarly associated with mortality in a large cohort study.

Saharan dust and associations between particulate matter and daily mortality in Rome, Italy.

Background: Outbreaks of Saharan-Sahel dust over Euro-Mediterranean areas frequently induce exceedances of the Europen Unions 24-hr standard of 50 μg/m3 for particulate matter (PM) with aerodynamic diameter ≤ than 10 μm (PM10). Objectives: We evaluated the effect of Saharan dust on the association between different PM fractions and daily mortality in Rome, Italy. Methods: In a study of 80,423 adult residents who died in Rome between 2001 and 2004, we performed a time-series analysis to explore the effects of PM2.5, PM2.5–10, and PM10 on natural, cardiac, cerebrovascular, and respiratory mortality. We defined Saharan dust days by combining light detection and ranging (LIDAR) observations and analyses from operational models. We tested a Saharan dust–PM interaction term to evaluate the hypothesis that the effects of PM, especially coarse PM (PM2.5–10), on mortality would be enhanced on dust days. Results: Interquartile range increases in PM2.5–10 (10.8 μg/m3) and PM10 (19.8 μg/m3) were associated with increased mortality due to natural, cardiac, cerebrovascular, and respiratory causes, with estimated effects ranging from 2.64% to 12.65% [95% confidence interval (CI), 1.18–25.42%] for the association between PM2.5–10 and respiratory mortality (0- to 5-day lag). Associations of PM2.5–10 with cardiac mortality were stronger on Saharan dust days (9.73%; 95% CI, 4.25–15.49%) than on dust-free days (0.86%; 95% CI, –2.47% to 4.31%; p = 0.005). Saharan dust days also modified associations between PM10 and cardiac mortality (9.55% increase; 95% CI, 3.81–15.61%; vs. dust-free days: 2.09%; 95% CI, –0.76% to 5.02%; p = 0.02). Conclusions: We found evidence of effects of PM2.5–10 and PM10 on natural and cause-specific mortality, with stronger estimated effects on cardiac mortality during Saharan dust outbreaks. Toxicological and biological effects of particles from desert sources need to be further investigated and taken into account in air quality standards.

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 (PM2.5), and between 2.5 and 10 μm (PM2.5–10) 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 PM2.5 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 PM2.5–10 were positive but not statistically significant in most analyses, whereas associations with PM10 seemed to be driven by PM2.5. Conclusions: We found evidence of adverse effects of PM2.5 on mortality outcomes in the European Mediterranean region. Associations with PM2.5–10 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.

Factors affecting in-hospital heat-related mortality: a multi-city case-crossover analysis

Background: Several studies have identified strong effects of high temperatures on mortality at population level; however, individual vulnerability factors associated with heat-related in-hospital mortality are largely unknown. The objective of the study was to evaluate heat-related in-hospital mortality using a multi-city case-crossover analysis. Methods: We studied residents of four Italian cities, aged 65+ years, who died during 1997–2004. For 94 944 individuals who died in hospital and were hospitalised two or more days before death, demographics, chronic conditions, primary diagnoses of last event and hospital wards were considered. A city-specific case-crossover analysis was performed to evaluate the association between apparent temperature and mortality. Pooled odds ratios (OR) of dying on a day with a temperature of 30°C compared to a day with a temperature of 20°C were estimated with a random-effects meta-analysis. Results: We estimated an overall OR of 1.32 (95% confidence interval: 1.25, 1.39). Age, marital status and hospital ward were important risk indicators. Patients in general medicine were at higher risk than those in high and intensive care units. A history of psychiatric disorders and cerebrovascular diseases gave a higher vulnerability. Mortality was greater among patients hospitalised for heart failure, stroke and chronic pulmonary diseases. Conclusions: In-hospital mortality is strongly associated with high temperatures. A comfortable temperature in hospitals and increased attention to vulnerable patients during heatwaves, especially in general medicine, are necessary preventive measures.