Michelle C. Turner

An Integrated Risk Function for Estimating the Global Burden of Disease Attributable to Ambient Fine Particulate Matter Exposure

Background: Estimating the burden of disease attributable to long-term exposure to fine particulate matter (PM2.5) in ambient air requires knowledge of both the shape and magnitude of the relative risk (RR) function. However, adequate direct evidence to identify the shape of the mortality RR functions at the high ambient concentrations observed in many places in the world is lacking. Objective: We developed RR functions over the entire global exposure range for causes of mortality in adults: ischemic heart disease (IHD), cerebrovascular disease (stroke), chronic obstructive pulmonary disease (COPD), and lung cancer (LC). We also developed RR functions for the incidence of acute lower respiratory infection (ALRI) that can be used to estimate mortality and lost-years of healthy life in children < 5 years of age. Methods: We fit an integrated exposure–response (IER) model by integrating available RR information from studies of ambient air pollution (AAP), second hand tobacco smoke, household solid cooking fuel, and active smoking (AS). AS exposures were converted to estimated annual PM2.5 exposure equivalents using inhaled doses of particle mass. We derived population attributable fractions (PAFs) for every country based on estimated worldwide ambient PM2.5 concentrations. Results: The IER model was a superior predictor of RR compared with seven other forms previously used in burden assessments. The percent PAF attributable to AAP exposure varied among countries from 2 to 41 for IHD, 1 to 43 for stroke, < 1 to 21 for COPD, < 1 to 25 for LC, and < 1 to 38 for ALRI. Conclusions: We developed a fine particulate mass–based RR model that covered the global range of exposure by integrating RR information from different combustion types that generate emissions of particulate matter. The model can be updated as new RR information becomes available. Citation: Burnett RT, Pope CA III, Ezzati M, Olives C, Lim SS, Mehta S, Shin HH, Singh G, Hubbell B, Brauer M, Anderson HR, Smith KR, Balmes JR, Bruce NG, Kan H, Laden F, Prüss-Ustün A, Turner MC, Gapstur SM, Diver WR, Cohen A. 2014. An integrated risk function for estimating the global burden of disease attributable to ambient fine particulate matter exposure. Environ Health Perspect 122:397–403; http://dx.doi.org/10.1289/ehp.1307049

Lung Cancer and Cardiovascular Disease Mortality Associated with Ambient Air Pollution and Cigarette Smoke: Shape of the Exposure–Response Relationships

Background: Lung cancer and cardiovascular disease (CVD) mortality risks increase with smoking, secondhand smoke (SHS), and exposure to fine particulate matter < 2.5 μm in diameter (PM2.5) from ambient air pollution. Recent research indicates that the exposure–response relationship for CVD is nonlinear, with a steep increase in risk at low exposures and flattening out at higher exposures. Comparable estimates of the exposure–response relationship for lung cancer are required for disease burden estimates and related public health policy assessments. Objectives: We compared exposure–response relationships of PM2.5 with lung cancer and cardiovascular mortality and considered the implications of the observed differences for efforts to estimate the disease burden of PM2.5. Methods: Prospective cohort data for 1.2 million adults were collected by the American Cancer Society as part of the Cancer Prevention Study II. We estimated relative risks (RRs) for increments of cigarette smoking, adjusting for various individual risk factors. RRs were plotted against estimated daily dose of PM2.5 from smoking along with comparison estimates for ambient air pollution and SHS. Results: For lung cancer mortality, excess risk rose nearly linearly, reaching maximum RRs > 40 among long-term heavy smokers. Excess risks for CVD mortality increased steeply at low exposure levels and leveled off at higher exposures, reaching RRs of approximately 2–3 for cigarette smoking. Conclusions: The exposure–response relationship associated with PM2.5 is qualitatively different for lung cancer versus cardiovascular mortality. At low exposure levels, cardiovascular deaths are projected to account for most of the burden of disease, whereas at high levels of PM2.5, lung cancer becomes proportionately more important.

Epidemiologic Evidence of Relationships Between Reproductive and Child Health Outcomes and Environmental Chemical Contaminants

This review summarizes the level of epidemiologic evidence for relationships between prenatal and/or early life exposure to environmental chemical contaminants and fetal, child, and adult health. Discussion focuses on fetal loss, intrauterine growth restriction, preterm birth, birth defects, respiratory and other childhood diseases, neuropsychological deficits, premature or delayed sexual maturation, and certain adult cancers linked to fetal or childhood exposures. Environmental exposures considered here include chemical toxicants in air, water, soil/house dust and foods (including human breast milk), and consumer products. Reports reviewed here included original epidemiologic studies (with at least basic descriptions of methods and results), literature reviews, expert group reports, meta-analyses, and pooled analyses. Levels of evidence for causal relationships were categorized as sufficient, limited, or inadequate according to predefined criteria. There was sufficient epidemiological evidence for causal relationships between several adverse pregnancy or child health outcomes and prenatal or childhood exposure to environmental chemical contaminants. These included prenatal high-level methylmercury (CH3Hg) exposure (delayed developmental milestones and cognitive, motor, auditory, and visual deficits), high-level prenatal exposure to polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and related toxicants (neonatal tooth abnormalities, cognitive and motor deficits), maternal active smoking (delayed conception, preterm birth, fetal growth deficit [FGD] and sudden infant death syndrome [SIDS]) and prenatal environmental tobacco smoke (ETS) exposure (preterm birth), low-level childhood lead exposure (cognitive deficits and renal tubular damage), high-level childhood CH3Hg exposure (visual deficits), high-level childhood exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (chloracne), childhood ETS exposure (SIDS, new-onset asthma, increased asthma severity, lung and middle ear infections, and adult breast and lung cancer), childhood exposure to biomass smoke (lung infections), and childhood exposure to outdoor air pollutants (increased asthma severity). Evidence for some proven relationships came from investigation of relatively small numbers of children with high-dose prenatal or early childhood exposures, e.g., CH3Hg poisoning episodes in Japan and Iraq. In contrast, consensus on a causal relationship between incident asthma and ETS exposure came only recently after many studies and prolonged debate. There were many relationships supported by limited epidemiologic evidence, ranging from several studies with fairly consistent findings and evidence of dose-response relationships to those where 20 or more studies provided inconsistent or otherwise less than convincing evidence of an association. The latter included childhood cancer and parental or childhood exposures to pesticides. In most cases, relationships supported by inadequate epidemiologic evidence reflect scarcity of evidence as opposed to strong evidence of no effect. This summary points to three main needs: (1) Where relationships between child health and environmental exposures are supported by sufficient evidence of causal relationships, there is a need for (a) policies and programs to minimize population exposures and (b) population-based biomonitoring to track exposure levels, i.e., through ongoing or periodic surveys with measurements of contaminant levels in blood, urine and other samples. (2) For relationships supported by limited evidence, there is a need for targeted research and policy options ranging from ongoing evaluation of evidence to proactive actions. (3) There is a great need for population-based, multidisciplinary and collaborative research on the many relationships supported by inadequate evidence, as these represent major knowledge gaps. Expert groups faced with evaluating epidemiologic evidence of potential causal relationships repeatedly encounter problems in summarizing the available data. A major driver for undertaking such summaries is the need to compensate for the limited sample sizes of individual epidemiologic studies. Sample size limitations are major obstacles to exploration of prenatal, paternal, and childhood exposures during specific time windows, exposure intensity, exposure–exposure or exposure–gene interactions, and relatively rare health outcomes such as childhood cancer. Such research needs call for investments in research infrastructure, including human resources and methods development (standardized protocols, biomarker research, validated exposure metrics, reference analytic laboratories). These are needed to generate research findings that can be compared and subjected to pooled analyses aimed at knowledge synthesis.

Long-term Ambient Fine Particulate Matter Air Pollution and Lung Cancer in a Large Cohort of Never-Smokers

RATIONALE There is compelling evidence that acute and chronic exposure to ambient fine particulate matter (PM(2.5)) air pollution increases cardiopulmonary mortality. However, the role of PM(2.5) in the etiology of lung cancer is less clear, particularly at concentrations that prevail in developed countries and in never-smokers. OBJECTIVES This study examined the association between mean long-term ambient PM(2.5) concentrations and lung cancer mortality among 188,699 lifelong never-smokers drawn from the nearly 1.2 million Cancer Prevention Study-II participants enrolled by the American Cancer Society in 1982 and followed prospectively through 2008. METHODS Mean metropolitan statistical area PM(2.5) concentrations were determined for each participant based on central monitoring data. Cox proportional hazards regression models were used to estimate multivariate adjusted hazard ratios and 95% confidence intervals for lung cancer mortality in relation to PM(2.5). MEASUREMENTS AND MAIN RESULTS A total of 1,100 lung cancer deaths were observed during the 26-year follow-up period. Each 10 μg/m(3) increase in PM(2.5) concentrations was associated with a 15-27% increase in lung cancer mortality. The association between PM(2.5) and lung cancer mortality was similar in men and women and across categories of attained age and educational attainment, but was stronger in those with a normal body mass index and a history of chronic lung disease at enrollment (P < 0.05). CONCLUSIONS The present findings strengthen the evidence that ambient concentrations of PM(2.5) measured in recent decades are associated with small but measurable increases in lung cancer mortality.

Epidemiology of testicular cancer: an overview.

Testicular cancer is a rare disease, accounting for 1.1% of all malignant neoplasms in Canadian males. Despite the low overall incidence of testicular cancer, it is the most common malignancy among young men. The incidence rate of testicular cancer has been increasing since the middle of the 20th century in many western countries. However, the etiology of testicular cancer is not well understood. A search of the peer‐reviewed literature was conducted to identify important articles for review and inclusion in this overview of the epidemiology of testicular cancer. Most of the established risk factors are related to early life events, including cryptorchidism, carcinoma in situ and in utero exposure to estrogens. Occupational, lifestyle, socioeconomic and other risk factors have demonstrated mixed associations with testicular cancer. Although there are few established risk factors for testicular cancer, some appear to be related to hormonal balance at various life stages. Lifestyle and occupational exposures occurring later in life may play a role in promoting the disease, although they are not likely involved in cancer initiation. In addition to summarizing the current epidemiologic evidence on risk factors for testicular cancer, we suggest future research directions that may elucidate the etiology of testicular cancer.

Spatial Analysis of Air Pollution and Mortality in California

RATIONALE Although substantial scientific evidence suggests that chronic exposure to ambient air pollution contributes to premature mortality, uncertainties exist in the size and consistency of this association. Uncertainty may arise from inaccurate exposure assessment. OBJECTIVES To assess the associations of three types of air pollutants (fine particulate matter, ozone [O3], and nitrogen dioxide [NO2]) with the risk of mortality in a large cohort of California adults using individualized exposure assessments. METHODS For fine particulate matter and NO2, we used land use regression models to derive predicted individualized exposure at the home address. For O3, we estimated exposure with an inverse distance weighting interpolation. Standard and multilevel Cox survival models were used to assess the association between air pollution and mortality. MEASUREMENTS AND MAIN RESULTS Data for 73,711 subjects who resided in California were abstracted from the American Cancer Society Cancer Prevention II Study cohort, with baseline ascertainment of individual characteristics in 1982 and follow-up of vital status through to 2000. Exposure data were derived from government monitors. Exposure to fine particulate matter, O3, and NO2 was positively associated with ischemic heart disease mortality. NO2 (a marker for traffic pollution) and fine particulate matter were also associated with mortality from all causes combined. Only NO2 had significant positive association with lung cancer mortality. CONCLUSIONS Using the first individualized exposure assignments in this important cohort, we found positive associations of fine particulate matter, O3, and NO2 with mortality. The positive associations of NO2 suggest that traffic pollution relates to premature death.

A systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure.

Objectives We conducted a systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure. Data sources Searches of MEDLINE (1950–2009) and other electronic databases yielded 31 included studies. Data extraction Two authors independently abstracted data and assessed the quality of each study. Data synthesis Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs). There was no overall association between childhood leukemia and any paternal occupational pesticide exposure (OR = 1.09; 95% CI, 0.88–1.34); there were slightly elevated risks in subgroups of studies with low total-quality scores (OR = 1.39; 95% CI, 0.99–1.95), ill-defined exposure time windows (OR = 1.36; 95% CI, 1.00–1.85), and exposure information collected after offspring leukemia diagnosis (OR = 1.34; 95% CI, 1.05–1.70). Childhood leukemia was associated with prenatal maternal occupational pesticide exposure (OR = 2.09; 95% CI, 1.51–2.88); this association was slightly stronger for studies with high exposure-measurement-quality scores (OR = 2.45; 95% CI, 1.68–3.58), higher confounder control scores (OR = 2.38; 95% CI, 1.56–3.62), and farm-related exposures (OR = 2.44; 95% CI, 1.53–3.89). Childhood leukemia risk was also elevated for prenatal maternal occupational exposure to insecticides (OR = 2.72; 95% CI, 1.47–5.04) and herbicides (OR = 3.62; 95% CI, 1.28–10.3). Conclusions Childhood leukemia was associated with prenatal maternal occupational pesticide exposure in analyses of all studies combined and in several subgroups. Associations with paternal occupational pesticide exposure were weaker and less consistent. Research needs include improved pesticide exposure indices, continued follow-up of existing cohorts, genetic susceptibility assessment, and basic research on childhood leukemia initiation and progression.

An overview of the association between allergy and cancer

Numerous epidemiological studies have evaluated some aspect of the association between a history of allergy and cancer occurrence. In this article, an overview of the epidemiological evidence is presented with a discussion of a number of methodological issues important in this area of study. Literature searches were conducted using the MEDLINE database from 1966 through to August 2005 to identify articles that explored a personal history of allergic disorders as a risk factor for cancer. Although it is difficult to draw conclusions between allergy and cancer at many sites because of insufficient evidence or a lack of consistency both within and among studies completed to date, strong inverse associations have been reported for pancreatic cancer and glioma, whereas lung cancer was positively associated with asthma. Additional studies are needed to confirm these finding and to address the limitations of previous studies, including the validity and reliability of exposure measures and control for confounding. Further, large prospective studies using cancer incidence would be particularly useful, including studies using biological markers of allergic status to reduce potential misclassification and to confirm the results of previous studies based on self‐report. There is also a need for further basic research to clarify a potential mechanism, should an association exist.

Relationships Between Fine Particulate Air Pollution, Cardiometabolic Disorders, and Cardiovascular Mortality

Rationale: Growing evidence suggests that long-term exposure to fine particulate matter (PM2.5) air pollution contributes to risk of cardiovascular disease (CVD) morbidity and mortality. There is uncertainty about who are most susceptible. Individuals with underlying cardiometabolic disorders, including hypertension, diabetes mellitus, and obesity, may be at greater risk. PM2.5 pollution may also contribute to cardiometabolic disorders, augmenting CVD risk. Objective: This analysis evaluates relationships between long-term PM2.5 exposure and cardiometabolic disease on risk of death from CVD and cardiometabolic conditions. Methods and Results: Data on 669 046 participants from the American Cancer Society Cancer Prevention Study II cohort were linked to modeled PM2.5 concentrations at geocoded home addresses. Cox proportional hazards regression models were used to estimate adjusted hazards ratios for death from CVD and cardiometabolic diseases based on death-certificate information. Effect modification by pre-existing cardiometabolic risk factors on the PM2.5–CVD mortality association was examined. PM2.5 exposure was associated with CVD mortality, with the hazards ratios (95% confidence interval) per 10 &mgr;g/m3 increase in PM2.5 equal to 1.12 (1.10–1.15). Deaths linked to hypertension and diabetes mellitus (mentioned on death certificate as either primary or contributing cause of death) were also associated with PM2.5. There was no consistent evidence of effect modification by cardiometabolic disease risk factors on the PM2.5–CVD mortality association. Conclusions: Pollution-induced CVD mortality risk is observed for those with and without existing cardiometabolic disorders. Long-term exposure may also contribute to the development or exacerbation of cardiometabolic disorders, increasing risk of CVD, and cardiometabolic disease mortality.

Public Perception of Population Health Risks in Canada: Health Hazards and Sources of Information

ABSTRACT A national survey of health risk perception among 1,503 Canadians was conducted in 2004. The current survey follows-up a previous national survey conducted in 1992 and documents changes in risk perception since that time and investigates new risk issues not previously examined. This article presents a description of the ratings of perceived risk of thirty specific hazards to the Canadian population, sources of information about health issues and risk, and confidence in these information sources. Of the specific hazards considered, behavioral risks such as cigarette smoking, obesity, and unprotected sex were seen to present the greatest risk to the health of Canadians. Hazards related to the social environment (e.g., homelessness, street crime, unemployment) were seen as posing moderately high health risks. Medical devices or therapies (e.g., prescription drugs, vaccines, laser eye surgery) tended to rank the lowest in terms of health risk. Women, older respondents, and those with less education reported risks as being higher than men, younger respondents, and those with more education respectively. Large geographical differences in risk perception were also observed. Participants described receiving “a lot” of information from the news media, medical doctors, and the Internet but reported the greatest amount of confidence in medical doctors, university scientists/scientific journals, and health brochures/pamphlets.