Dose-response association of aerobic and muscle-strengthening physical activity with mortality: a national cohort study of 416 420 US adults.

OBJECTIVES: To investigate the dose-response association of aerobic physical activity (PA) and muscle-strengthening exercise (MSE) with all-cause mortality. METHODS: National Health Interview Survey data (1997-2014) were linked to the National Death Index through 2015, which produced a cohort of 416 420 US adults. Cox proportional-hazard models were used to estimate HRs and 95% CIs for the associations of moderate aerobic PA (MPA), vigorous aerobic PA (VPA) and MSE with mortality risk. Models controlled for age, sex, race-ethnicity, income, education, marital status, survey year, smoking status, body mass index and chronic conditions. RESULTS: Relative to those who engaged in no aerobic PA, substantial mortality risk reduction was associated with 1 hour/week of aerobic PA (HR: 0.85, 95% CI: 0.83 to 0.86) and levelled off at 3 hours/week of aerobic PA (0.73, 0.71 to 0.75). Similar results were observed for men and women and for individuals younger and older than 60 years. MSE conferred additional mortality risk reduction at 1 time/week (0.89, 0.81 to 0.97) and appeared no longer beneficial at 7 times/week (0.99, 0.94 to 1.04). CONCLUSION: The minimum effective dose of aerobic PA for significant mortality risk reduction was 1 hour/week of MPA or VPA, with additional mortality risk reduction observed up to 3 hours/week. For older adults, only small decreases in mortality risk were observed beyond this duration. Completing MSE in combination with aerobic PA conferred additional mortality risk reduction, with a minimum effective dose of 1-2 times/week.

Greenness, air pollution, and mortality risk: A U.S. cohort study of cancer patients and survivors.

BACKGROUND: Several studies suggest that living in areas of high surrounding greenness may be associated with a lower cardiopulmonary mortality risk. However, associations of greenness with specific causes of death in cancer patients and survivors has not been examined and it is unknown whether this relationship is affected by area levels of fine particulate matter air pollution (PM2.5). This study evaluated associations between greenness and PM2.5 on causes of death in a large, U.S.-based cohort of cancer patients and survivors. METHODS: Surveillance, Epidemiology and End Results (SEER) data were used to generate a cohort of 5,529,005 cancer patients and survivors from 2000 to 2016. Census-tract Normalized Difference Vegetation Index (NDVI) during May-October from 2003 to 2016 was population-weighted to act as a county-level greenness measure. County-level PM2.5 exposure was estimated from annual concentrations averaged from 1999 to 2015. Cox Proportional Hazards models were used to estimate the association between greenness, PM2.5, and cause-specific mortality while controlling for age, sex, race, and other individual and county level variables. FINDINGS: An IQR increase in greenness was associated with a decrease in cancer mortality for cancer patients (Hazard ratio of 0.94, 95% CI: 0.93-0.95), but not for cardiopulmonary mortality (0.98, 95% CI: 0.96-1.00). Inversely, an increase in 10 µg/m3 PM2.5 was associated with increased cardiopulmonary mortality (1.24, 95% CI: 1.19-1.29), but not cancer mortality (0.99, 95% CI: 0.97-1.00). Hazard ratios were robust to inclusion of PM2.5 in models with greenness and vice versa. Although exposure estimates were constant over most stratifications, greenness seemed to benefit individuals diagnosed with high survivability cancers (0.92, 95% CI: 0.90-0.95) more than those with low survivability cancers (0.98. 95% CI: 0.96-0.99). INTERPRETATION: Higher levels of greenness are associated with lower cancer mortality in cancer patients. The evidence suggests minimal confounding between greenness and PM2.5 exposures and risk of mortality.

Fine Particulate Matter Air Pollution and Mortality Risk Among US Cancer Patients and Survivors.

Background: Exposure to fine particulate matter (PM2.5) air pollution has been linked to increased risk of mortality, especially cardiopulmonary and lung cancer mortality. It is unknown if cancer patients and survivors are especially vulnerable to PM2.5 air pollution exposure. This study evaluates PM2.5 exposure and risk for cancer and cardiopulmonary mortality in cohorts of US cancer patients and survivors. Methods: A primary cohort of 5 591 168 of cancer patients and a 5-year survivor cohort of 2 318 068 was constructed using Surveillance, Epidemiology, and End Results Program data from 2000 to 2016, linked with county-level estimates of long-term average concentrations of PM2.5. Cox proportional hazards models were used to estimate PM2.5-mortality hazard ratios controlling for age-sex-race combinations and individual and county-level covariables. Results: Of those who died, 26% died of noncancer causes, mostly from cardiopulmonary disease. Minimal PM2.5-mortality associations were observed for all-cause mortality (hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 1.00 to 1.03) per 10 µg/m3 increase in PM2.5. Substantial adverse PM2.5-mortality associations were observed for cardiovascular (HR = 1.32, 95% CI = 1.26 to 1.39), chronic obstructive pulmonary disease (HR = 1.10, 95% CI = 1.01 to 1.20), influenza and pneumonia (HR = 1.55, 95% CI = 1.33 to 1.80), and cardiopulmonary mortality combined (HR = 1.25, 95% CI = 1.21 to 1.30). PM2.5-cardiopulmonary mortality hazard ratio was higher for cancer patients who received chemotherapy or radiation treatments. Conclusions: Air pollution is adversely associated with cardiopulmonary mortality for cancer patients and survivors, especially those who received chemotherapy or radiation treatment. Given ubiquitous and involuntary air pollution exposures and large numbers of cancer patients and survivors, these results are of substantial clinical and public health importance.

Shape of BMI-Mortality Risk Associations: Reverse Causality and Heterogeneity in a Representative Cohort of US Adults.

OBJECTIVE: This study examines BMI-mortality associations and evaluates strategies intended to limit reverse causality. Heterogeneity in BMI-mortality risk associations across subgroups and causes of death is explored. METHODS: A cohort of 654,382 adults from the US National Health Interview Survey was constructed. Associations between unit BMI levels and mortality were estimated using Cox proportional hazards models, including and excluding the first 5 years of follow-up, with and without controls for smoking or preexisting conditions, and including and excluding ever-smokers and individuals with preexisting conditions. Stratified analyses by individual characteristics were performed. RESULTS: Addressing reverse causality led to reduced risk of mortality among those with low BMI levels (<18 kg/m2 ). Excluding ever-smokers and individuals with preexisting conditions further led to increased risk among those with high BMI levels (between 33 kg/m2 and >40 kg/m2 ) and lowered the estimated nadir risk from 27 kg/m2 to 23 kg/m2 . After excluding ever-smokers and individuals with preexisting conditions, limiting the analysis to >5 years of follow-up produced no substantive changes. Heterogeneous results were observed across individual characteristics, particularly age and causes of death. CONCLUSIONS: The exclusion of smokers and individuals with preexisting conditions alters the BMI-mortality risk association and results in a somewhat lower range of BMI with minimum mortality risk.

Fine Particulate Matter Exposure and Cancer Incidence: Analysis of SEER Cancer Registry Data from 1992-2016.

BACKGROUND: Previous research has identified an association between fine particulate matter (PM2.5) air pollution and lung cancer. Most of the evidence for this association, however, is based on research using lung cancer mortality, not incidence. Research that examines potential associations between PM2.5 and incidence of non-lung cancers is limited. OBJECTIVES: The primary purpose of this study was to evaluate the association between the incidence of cancer and exposure to PM2.5 using >8.5 million cases of cancer incidences from U.S. registries. Secondary objectives include evaluating the sensitivity of the associations to model selection, spatial control, and latency period as well as estimating the exposure-response relationship for several cancer types. METHODS: Surveillance, Epidemiology, and End Results (SEER) program data were used to calculate incidence rates for various cancer types in 607 U.S. counties. County-level PM2.5 concentrations were estimated using integrated empirical geographic regression models. Flexible semi-nonparametric regression models were used to estimate associations between PM2.5 and cancer incidence for selected cancers while controlling for important county-level covariates. Primary time-independent models using average incidence rates from 1992-2016 and average PM2.5 from 1988-2015 were estimated. In addition, time-varying models using annual incidence rates from 2002-2011 and lagged moving averages of annual estimates for PM2.5 were also estimated. RESULTS: The incidences of all cancer and lung cancer were consistently associated with PM2.5. The incident rate ratios (IRRs), per 10-µg/m3 increase in PM2.5, for all and lung cancer were 1.09 (95% CI: 1.03, 1.14) and 1.19 (95% CI: 1.09, 1.30), respectively. Less robust associations were observed with oral, rectal, liver, skin, breast, and kidney cancers. DISCUSSION: Exposure to PM2.5 air pollution contributes to lung cancer incidence and is potentially associated with non-lung cancer incidence. https://doi.org/10.1289/EHP7246.

Outdoor air pollution and cancer: An overview of the current evidence and public health recommendations.

Outdoor air pollution is a major contributor to the burden of disease worldwide. Most of the global population resides in places where air pollution levels, because of emissions from industry, power generation, transportation, and domestic burning, considerably exceed the World Health Organization's health-based air-quality guidelines. Outdoor air pollution poses an urgent worldwide public health challenge because it is ubiquitous and has numerous serious adverse human health effects, including cancer. Currently, there is substantial evidence from studies of humans and experimental animals as well as mechanistic evidence to support a causal link between outdoor (ambient) air pollution, and especially particulate matter (PM) in outdoor air, with lung cancer incidence and mortality. It is estimated that hundreds of thousands of lung cancer deaths annually worldwide are attributable to PM air pollution. Epidemiological evidence on outdoor air pollution and the risk of other types of cancer, such as bladder cancer or breast cancer, is more limited. Outdoor air pollution may also be associated with poorer cancer survival, although further research is needed. This report presents an overview of outdoor air pollutants, sources, and global levels, as well as a description of epidemiological evidence linking outdoor air pollution with cancer incidence and mortality. Biological mechanisms of air pollution-derived carcinogenesis are also described. This report concludes by summarizing public health/policy recommendations, including multilevel interventions aimed at individual, community, and regional scales. Specific roles for medical and health care communities with regard to prevention and advocacy and recommendations for further research are also described.

Cancer mortality risk, fine particulate air pollution, and smoking in a large, representative cohort of US adults.

PURPOSE: Air pollution and smoking are associated with various types of mortality, including cancer. The current study utilizes a publicly accessible, nationally representative cohort to explore relationships between fine particulate matter (PM2.5) exposure, smoking, and cancer mortality. METHODS: National Health Interview Survey and mortality follow-up data were combined to create a study population of 635,539 individuals surveyed from 1987 to 2014. A sub-cohort of 341,665 never-smokers from the full cohort was also created. Individuals were assigned modeled PM2.5 exposure based on average exposure from 1999 to 2015 at residential census tract. Cox Proportional Hazard models were utilized to estimate hazard ratios for cancer-specific mortality controlling for age, sex, race, smoking status, body mass, income, education, marital status, rural versus urban, region, and survey year. RESULTS: The risk of all cancer mortality was adversely associated with PM2.5 (per 10 µg/m3 increase) in the full cohort (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.08-1.22) and the never-smokers' cohort (HR 1.19, 95% CI 1.06-1.33). PM2.5-morality associations were observed specifically for lung, stomach, colorectal, liver, breast, cervix, and bladder, as well as Hodgkin lymphoma, non-Hodgkin lymphoma, and leukemia. The PM2.5-morality association with lung cancer in never-smokers was statistically significant adjusting for multiple comparisons. Cigarette smoking was statistically associated with mortality for many cancer types. CONCLUSIONS: Exposure to PM2.5 air pollution contributes to lung cancer mortality and may be a risk factor for other cancer types. Cigarette smoking has a larger impact on cancer mortality than PM2.5 , but is associated with similar cancer types.

Fine particulate air pollution and human mortality: 25+ years of cohort studies.

Much of the key epidemiological evidence that long-term exposure to fine particulate matter air pollution (PM2.5) contributes to increased risk of mortality comes from survival studies of cohorts of individuals. Although the first two of these studies, published in the mid-1990s, were highly controversial, much has changed in the last 25 + years. The objectives of this paper are to succinctly compile and summarize the findings of these cohort studies using meta-analytic tools and to address several of the key controversies. Independent reanalysis and substantial extended analysis of the original cohort studies have been conducted and many additional studies using a wide variety of cohorts, including cohorts constructed from public data and leveraging natural experiments have been published. Meta-analytic estimates of the mean of the distribution of effects from cohort studies that are currently available, provide substantial evidence of adverse air pollution associations with all-cause, cardiopulmonary, and lung cancer mortality.

Mortality Risk and Fine Particulate Air Pollution in a Large, Representative Cohort of U.S. Adults.

BACKGROUND: Evidence indicates that air pollution contributes to cardiopulmonary mortality. There is ongoing debate regarding the size and shape of the pollution­mortality exposure­response relationship. There are also growing appeals for estimates of pollution­mortality relationships that use public data and are based on large, representative study cohorts. OBJECTIVES: Our goal was to evaluate fine particulate matter air pollution ([Formula: see text]) and mortality using a large cohort that is representative of the U.S. population and is based on public data. Additional objectives included exploring model sensitivity, evaluating relative effects across selected subgroups, and assessing the shape of the [Formula: see text]­mortality relationship. METHODS: National Health Interview Surveys (1986­2014), with mortality linkage through 2015, were used to create a cohort of 1,599,329 U.S. adults and a subcohort with information on smoking and body mass index (BMI) of 635,539 adults. Data were linked with modeled ambient [Formula: see text] at the census-tract level. Cox proportional hazards models were used to estimate [Formula: see text]­mortality hazard ratios for all-cause and specific causes of death while controlling for individual risk factors and regional and urban versus rural differences. Sensitivity and subgroup analyses were conducted and the shape of the [Formula: see text]­mortality relationship was explored. RESULTS: Estimated mortality hazard ratios, per [Formula: see text] long-term exposure to [Formula: see text], were 1.12 (95% CI: 1.08, 1.15) for all-cause mortality, 1.23 (95% CI: 1.17, 1.29) for cardiopulmonary mortality, and 1.12 (95% CI: 1.00, 1.26) for lung cancer mortality. In general, [Formula: see text]­mortality associations were consistently positive for all-cause and cardiopulmonary mortality across key modeling choices and across subgroups of sex, age, race-ethnicity, income, education levels, and geographic regions. DISCUSSION: This large, nationwide, representative cohort of U.S. adults provides robust evidence that long-term [Formula: see text] exposure contributes to cardiopulmonary mortality risk. The ubiquitous and involuntary nature of exposures and the broadly observed effects across subpopulations underscore the public health importance of breathing clean air. https://doi.org/10.1289/EHP4438.

Particulate matter air pollution and national and county life expectancy loss in the USA: A spatiotemporal analysis.

BACKGROUND: Exposure to fine particulate matter pollution (PM2.5) is hazardous to health. Our aim was to directly estimate the health and longevity impacts of current PM2.5 concentrations and the benefits of reductions from 1999 to 2015, nationally and at county level, for the entire contemporary population of the contiguous United States. METHODS AND FINDINGS: We used vital registration and population data with information on sex, age, cause of death, and county of residence. We used four Bayesian spatiotemporal models, with different adjustments for other determinants of mortality, to directly estimate mortality and life expectancy loss due to current PM2.5 pollution and the benefits of reductions since 1999, nationally and by county. The covariates included in the adjusted models were per capita income; percentage of population whose family income is below the poverty threshold, who are of Black or African American race, who have graduated from high school, who live in urban areas, and who are unemployed; cumulative smoking; and mean temperature and relative humidity. In the main model, which adjusted for these covariates and for unobserved county characteristics through the use of county-specific random intercepts, PM2.5 pollution in excess of the lowest observed concentration (2.8 µg/m3) was responsible for an estimated 15,612 deaths (95% credible interval 13,248-17,945) in females and 14,757 deaths (12,617-16,919) in males. These deaths would lower national life expectancy by an estimated 0.15 years (0.13-0.17) for women and 0.13 years (0.11-0.15) for men. The life expectancy loss due to PM2.5 was largest around Los Angeles and in some southern states such as Arkansas, Oklahoma, and Alabama. At any PM2.5 concentration, life expectancy loss was, on average, larger in counties with lower income and higher poverty rate than in wealthier counties. Reductions in PM2.5 since 1999 have lowered mortality in all but 14 counties where PM2.5 increased slightly. The main limitation of our study, similar to other observational studies, is that it is not guaranteed for the observed associations to be causal. We did not have annual county-level data on other important determinants of mortality, such as healthcare access and quality and diet, but these factors were adjusted for with use of county-specific random intercepts. CONCLUSIONS: According to our estimates, recent reductions in particulate matter pollution in the USA have resulted in public health benefits. Nonetheless, we estimate that current concentrations are associated with mortality impacts and loss of life expectancy, with larger impacts in counties with lower income and higher poverty rate.

Fine Particulate Matter and Respiratory Healthcare Encounters among Survivors of Childhood Cancers.

Some chemotherapies that treat childhood cancers have pulmonary-toxic properties that increase risk for adverse respiratory-health outcomes. PM2.5 causes similar outcomes but its effect among pulmonary compromised cancer survivors is unknown. This case-crossover study identified the PM2.5-associated odds for primary-respiratory hospitalizations and emergency department visits among childhood cancer survivors in Utah. We compared risk among chemotherapy-treated survivors to a cancer-free sample. We calculated 3-day-average PM2.5 by ZIP code and county for event and control days. Conditional logistic regression estimated odds ratios. Models were stratified by cause of admission (infection, respiratory disease, asthma), previous chemotherapy, National Ambient Air Quality Standard (NAAQS), and other variables. Results are presented per 10 µg/m³ of PM2.5. 90% of events occurred at 3-day PM2.5 averages <35.4 µg/m³, the NAAQS 24-h standard. For survivors, PM2.5 was associated with respiratory hospitalizations (OR = 1.84, 95% CI = 1.13⁻3.00) and hospitalizations from respiratory infection (OR = 2.09, 95% CI = 1.06⁻4.14). Among chemotherapy-treated survivors, the PM2.5-associated odds of respiratory hospitalization (OR = 2.03, 95% CI = 1.14⁻3.61) were significantly higher than the cancer-free sample (OR = 0.84, 95% CI = 0.57⁻1.25). This is the first study to report significant associations between PM2.5 and respiratory healthcare encounters in childhood cancer survivors. Chemotherapy-treated survivors displayed the highest odds of hospitalization due to PM2.5 exposure and their risk is significantly higher than a cancer-free sample.

Global estimates of mortality associated with long-term exposure to outdoor fine particulate matter.

Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries-the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5-10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9-8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3-4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations.

Ambient Air Pollution and Cancer Mortality in the Cancer Prevention Study II.

BACKGROUND: The International Agency for Research on Cancer classified both outdoor air pollution and airborne particulate matter as carcinogenic to humans (Group 1) for lung cancer. There may be associations with cancer at other sites; however, the epidemiological evidence is limited. OBJECTIVE: The aim of this study was to clarify whether ambient air pollution is associated with specific types of cancer other than lung cancer by examining associations of ambient air pollution with nonlung cancer death in the Cancer Prevention Study II (CPS-II). METHODS: Analysis included 623,048 CPS-II participants who were followed for 22 y (1982-2004). Modeled estimates of particulate matter with aerodynamic diameter <2.5µm (PM2.5) (1999-2004), nitrogen dioxide (NO2) (2006), and ozone (O3) (2002-2004) concentrations were linked to the participant residence at enrollment. Cox proportional hazards models were used to estimate associations per each fifth percentile-mean increment with cancer mortality at 29 anatomic sites, adjusted for individual and ecological covariates. RESULTS: We observed 43,320 nonlung cancer deaths. PM2.5 was significantly positively associated with death from cancers of the kidney {adjusted hazard ratio (HR) per 4.4 µg/m3=1.14 [95% confidence interval (CI): 1.03, 1.27]} and bladder [HR=1.13 (95% CI: 1.03, 1.23)]. NO2 was positively associated with colorectal cancer mortality [HR per 6.5 ppb=1.06 (95% CI: 1.02, 1.10). The results were similar in two-pollutant models including PM2.5 and NO2 and in three-pollutant models with O3. We observed no statistically significant positive associations with death from other types of cancer based on results from adjusted models. CONCLUSIONS: The results from this large prospective study suggest that ambient air pollution was not associated with death from most nonlung cancers, but associations with kidney, bladder, and colorectal cancer death warrant further investigation. https://doi.org/10.1289/EHP1249.

Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015.

BACKGROUND: Exposure to ambient air pollution increases morbidity and mortality, and is a leading contributor to global disease burden. We explored spatial and temporal trends in mortality and burden of disease attributable to ambient air pollution from 1990 to 2015 at global, regional, and country levels. METHODS: We estimated global population-weighted mean concentrations of particle mass with aerodynamic diameter less than 2·5 µm (PM2·5) and ozone at an approximate 11 km × 11 km resolution with satellite-based estimates, chemical transport models, and ground-level measurements. Using integrated exposure-response functions for each cause of death, we estimated the relative risk of mortality from ischaemic heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, lung cancer, and lower respiratory infections from epidemiological studies using non-linear exposure-response functions spanning the global range of exposure. FINDINGS: Ambient PM2·5 was the fifth-ranking mortality risk factor in 2015. Exposure to PM2·5 caused 4·2 million (95% uncertainty interval [UI] 3·7 million to 4·8 million) deaths and 103·1 million (90·8 million 115·1 million) disability-adjusted life-years (DALYs) in 2015, representing 7·6% of total global deaths and 4·2% of global DALYs, 59% of these in east and south Asia. Deaths attributable to ambient PM2·5 increased from 3·5 million (95% UI 3·0 million to 4·0 million) in 1990 to 4·2 million (3·7 million to 4·8 million) in 2015. Exposure to ozone caused an additional 254 000 (95% UI 97 000-422 000) deaths and a loss of 4·1 million (1·6 million to 6·8 million) DALYs from chronic obstructive pulmonary disease in 2015. INTERPRETATION: Ambient air pollution contributed substantially to the global burden of disease in 2015, which increased over the past 25 years, due to population ageing, changes in non-communicable disease rates, and increasing air pollution in low-income and middle-income countries. Modest reductions in burden will occur in the most polluted countries unless PM2·5 values are decreased substantially, but there is potential for substantial health benefits from exposure reduction. FUNDING: Bill & Melinda Gates Foundation and Health Effects Institute.

Interactions between cigarette smoking and ambient PM2.5 for cardiovascular mortality.

Associations between long-term exposure to ambient fine particulate matter (PM2.5) and all-cause and cardiovascular mortality are well documented however less is known regarding possible interactions with cigarette smoking. We previously reported a supra-additive synergistic relationship between PM2.5 and cigarette smoking for lung cancer mortality. Here we examine interactions for all-cause and cardiovascular mortality among 429,406 current or never smoking participants in the prospective American Cancer Society Cancer Prevention Study-II with modeled PM2.5 concentrations. Cox proportional and additive hazards models were used to estimate mortality associations and interactions on the multiplicative and additive scales. A total of 146,495 all-cause and 64,339 cardiovascular (plus diabetes) deaths were observed. The hazard ratio (HR) (95% confidence interval (CI)) for cardiovascular mortality for high vs. low PM2.5 exposure (>14.44µg/m3 vs ≤10.59µg/m3, 75th vs 25th percentile) was 1.09 (95% CI 1.05, 1.12) in never smokers. The HR for cigarette smoking was 1.89 (95% CI 1.82, 1.96) in those with low PM2.5. The HR for both high PM2.5 and cigarette smoking was 2.08 (95% CI 2.00, 2.17). A small significant excess relative risk due to interaction (0.10; 95% CI 0.02, 0.19) was observed. Quantification of the public health burden attributed to the interaction between PM2.5 and cigarette smoking indicated a total of 32 (95% CI -6, 71) additional cardiovascular deaths per 100,000 person-years due to this interaction. In conclusion, PM2.5 was associated with all-cause and cardiovascular mortality in both smokers and never smokers, with some evidence for a small additive interaction with cigarette smoking. Reductions in cigarette smoking will result in the greatest impact on reducing all-cause and cardiovascular death at the levels of PM2.5 observed in this study. However, reductions in PM2.5 will also contribute to preventing a proportion of mortality attributed to cigarette smoking.

Comparing the Health Effects of Ambient Particulate Matter Estimated Using Ground-Based versus Remote Sensing Exposure Estimates.

BACKGROUND: Remote sensing (RS) is increasingly used for exposure assessment in epidemiological and burden of disease studies, including those investigating whether chronic exposure to ambient fine particulate matter (PM2.5) is associated with mortality. OBJECTIVES: We compared relative risk estimates of mortality from diseases of the circulatory system for PM2.5 modeled from RS with that for PM2.5 modeled using ground-level information. METHODS: We geocoded the baseline residence of 668,629 American Cancer Society Cancer Prevention Study II (CPS-II) cohort participants followed from 1982 to 2004 and assigned PM2.5 levels to all participants using seven different exposure models. Most of the exposure models were averaged for the years 2002-2004, and one RS estimate was for a longer, contemporaneous period. We used Cox proportional hazards regression to estimate relative risks (RRs) for the association of PM2.5 with circulatory mortality and ischemic heart disease. RESULTS: Estimates of mortality risk differed among exposure models. The smallest relative risk was observed for the RS estimates that excluded ground-based monitors for circulatory deaths [RR = 1.02, 95% confidence interval (CI): 1.00, 1.04 per 10 µg/m3 increment in PM2.5]. The largest relative risk was observed for the land-use regression model that included traffic information (RR = 1.14, 95% CI: 1.11, 1.17 per 10 µg/m3 increment in PM2.5). CONCLUSIONS: We found significant associations between PM2.5 and mortality in every model; however, relative risks estimated from exposure models using ground-based information were generally larger than those estimated using RS alone.

A class of non-linear exposure-response models suitable for health impact assessment applicable to large cohort studies of ambient air pollution.

The effectiveness of regulatory actions designed to improve air quality is often assessed by predicting changes in public health resulting from their implementation. Risk of premature mortality from long-term exposure to ambient air pollution is the single most important contributor to such assessments and is estimated from observational studies generally assuming a log-linear, no-threshold association between ambient concentrations and death. There has been only limited assessment of this assumption in part because of a lack of methods to estimate the shape of the exposure-response function in very large study populations. In this paper, we propose a new class of variable coefficient risk functions capable of capturing a variety of potentially non-linear associations which are suitable for health impact assessment. We construct the class by defining transformations of concentration as the product of either a linear or log-linear function of concentration multiplied by a logistic weighting function. These risk functions can be estimated using hazard regression survival models with currently available computer software and can accommodate large population-based cohorts which are increasingly being used for this purpose. We illustrate our modeling approach with two large cohort studies of long-term concentrations of ambient air pollution and mortality: the American Cancer Society Cancer Prevention Study II (CPS II) cohort and the Canadian Census Health and Environment Cohort (CanCHEC). We then estimate the number of deaths attributable to changes in fine particulate matter concentrations over the 2000 to 2010 time period in both Canada and the USA using both linear and non-linear hazard function models.

Exposure to Fine Particulate Air Pollution Is Associated With Endothelial Injury and Systemic Inflammation.

RATIONALE: Epidemiological evidence indicates that exposures to fine particulate matter air pollution (PM2.5) contribute to global burden of disease, primarily as a result of increased risk of cardiovascular morbidity and mortality. However, mechanisms by which PM2.5 exposure induces cardiovascular injury remain unclear. PM2.5-induced endothelial dysfunction and systemic inflammation have been implicated, but direct evidence is lacking. OBJECTIVE: To examine whether acute exposure to PM2.5 is associated with endothelial injury and systemic inflammation. METHODS AND RESULTS: Blood was collected from healthy, nonsmoking, young adults during 3 study periods that included episodes of elevated PM2.5 levels. Microparticles and immune cells in blood were measured by flow cytometry, and plasma cytokine/growth factors were measured using multiplexing laser beads. PM2.5 exposure was associated with the elevated levels of endothelial microparticles (annexin V+/CD41-/CD31+), including subtypes expressing arterial-, venous-, and lung-specific markers, but not microparticles expressing CD62+. These changes were accompanied by suppressed circulating levels of proangiogenic growth factors (EGF [epidermal growth factor], sCD40L [soluble CD40 ligand], PDGF [platelet-derived growth factor], RANTES [regulated on activation, normal T-cell-expressed and secreted], GROα [growth-regulated protein α], and VEGF [vascular endothelial growth factor]), and an increase in the levels of antiangiogenic (TNFα [tumor necrosis factor α], IP-10 [interferon γ-induced protein 10]), and proinflammatory cytokines (MCP-1 [monocyte chemoattractant protein 1], MIP-1α/ß [macrophage inflammatory protein 1α/ß], IL-6 [interleukin 6], and IL-1ß [interleukin 1ß]), and markers of endothelial adhesion (sICAM-1 [soluble intercellular adhesion molecule 1] and sVCAM-1 [soluble vascular cellular adhesion molecule 1]). PM2.5 exposure was also associated with an inflammatory response characterized by elevated levels of circulating CD14+, CD16+, CD4+, and CD8+, but not CD19+ cells. CONCLUSIONS: Episodic PM2.5 exposures are associated with increased endothelial cell apoptosis, an antiangiogenic plasma profile, and elevated levels of circulating monocytes and T, but not B, lymphocytes. These changes could contribute to the pathogenic sequelae of atherogenesis and acute coronary events.