Francine Laden

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

Chronic Exposure to Fine Particles and Mortality: An Extended Follow-up of the Harvard Six Cities Study from 1974 to 2009

Background: Epidemiologic studies have reported associations between fine particles (aerodynamic diameter ≤ 2.5 µm; PM2.5) and mortality. However, concerns have been raised regarding the sensitivity of the results to model specifications, lower exposures, and averaging time. Objective: We addressed these issues using 11 additional years of follow-up of the Harvard Six Cities study, incorporating recent lower exposures. Methods: We replicated the previously applied Cox regression, and examined different time lags, the shape of the concentration–response relationship using penalized splines, and changes in the slope of the relation over time. We then conducted Poisson survival analysis with time-varying effects for smoking, sex, and education. Results: Since 2001, average PM2.5 levels, for all six cities, were < 18 µg/m3. Each increase in PM2.5 (10 µg/m3) was associated with an adjusted increased risk of all-cause mortality (PM2.5 average on previous year) of 14% [95% confidence interval (CI): 7, 22], and with 26% (95% CI: 14, 40) and 37% (95% CI: 7, 75) increases in cardiovascular and lung-cancer mortality (PM2.5 average of three previous years), respectively. The concentration–response relationship was linear down to PM2.5 concentrations of 8 µg/m3. Mortality rate ratios for PM2.5 fluctuated over time, but without clear trends despite a substantial drop in the sulfate fraction. Poisson models produced similar results. Conclusions: These results suggest that further public policy efforts that reduce fine particulate matter air pollution are likely to have continuing public health benefits.

Night Work and Risk of Breast Cancer

Background: Melatonin shows potential oncostatic activity and is acutely suppressed by light exposure. Some evidence suggests an association between night work and breast cancer risk, possibly through the melatonin pathway. Methods: In a cohort of premenopausal nurses, we prospectively studied the relation between rotating night shift work and breast cancer risk. Total number of months during which the nurses worked rotating night shifts was first assessed at baseline in 1989 and periodically updated thereafter. We used Cox proportional hazards models to calculate relative risks (RRs) and 95% confidence intervals (CIs). Results: Among 115,022 women without cancer at baseline, 1,352 developed invasive breast cancer during 12 years of follow up. Women who reported more than 20 years of rotating night shift work experienced an elevated relative risk of breast cancer compared with women who did not report any rotating night shift work (multivariate RR = 1.79; 95% CI = 1.06–3.01). There was no increase in risk associated with fewer years of rotating night work. Conclusion: Our results suggest a modestly elevated risk of breast cancer after longer periods of rotating night work. Additional studies are warranted to rule out small sample size or uncontrolled sources for confounding as alternative explanations.

Chronic Fine and Coarse Particulate Exposure, Mortality, and Coronary Heart Disease in the Nurses’ Health Study

Background The relationship of fine particulate matter < 2.5 μm in diameter (PM2.5) air pollution with mortality and cardiovascular disease is well established, with more recent long-term studies reporting larger effect sizes than earlier long-term studies. Some studies have suggested the coarse fraction, particles between 2.5 and 10 μm (PM10–2.5), may also be important. With respect to mortality and cardiovascular events, questions remain regarding the relative strength of effect sizes for chronic exposure to fine and coarse particles. Objectives We examined the relationship of chronic PM2.5 and PM10–2.5 exposures with all-cause mortality and fatal and nonfatal incident coronary heart disease (CHD), adjusting for time-varying covariates. Methods The current study included women from the Nurses’ Health Study living in metropolitan areas of the northeastern and midwestern United States. Follow-up was from 1992 to 2002. We used geographic information systems–based spatial smoothing models to estimate monthly exposures at each participant’s residence. Results We found increased risk of all-cause mortality [hazard ratio (HR), 1.26; 95% confidence interval (CI), 1.02–1.54] and fatal CHD (HR = 2.02; 95% CI, 1.07–3.78) associated with each 10-μg/m3 increase in annual PM2.5 exposure. The association between fatal CHD and PM10–2.5 was weaker. Conclusions Our findings contribute to growing evidence that chronic PM2.5 exposure is associated with risk of all-cause and cardiovascular mortality.

Outdoor particulate matter exposure and lung cancer: a systematic review and meta-analysis.

BACKGROUND Particulate matter (PM) in outdoor air pollution was recently designated a Group I carcinogen by the International Agency for Research on Cancer (IARC). This determination was based on the evidence regarding the relationship of PM2.5 and PM10 to lung cancer risk; however, the IARC evaluation did not include a quantitative summary of the evidence. OBJECTIVE Our goal was to provide a systematic review and quantitative summary of the evidence regarding the relationship between PM and lung cancer. METHODS We conducted meta-analyses of studies examining the relationship of exposure to PM2.5 and PM10 with lung cancer incidence and mortality. In total, 18 studies met our inclusion criteria and provided the information necessary to estimate the change in lung cancer risk per 10-μg/m3 increase in exposure to PM. We used random-effects analyses to allow between-study variability to contribute to meta-estimates. RESULTS The meta-relative risk for lung cancer associated with PM2.5 was 1.09 (95% CI: 1.04, 1.14). The meta-relative risk of lung cancer associated with PM10 was similar, but less precise: 1.08 (95% CI: 1.00, 1.17). Estimates were robust to restriction to studies that considered potential confounders, as well as subanalyses by exposure assessment method. Analyses by smoking status showed that lung cancer risk associated with PM2.5 was greatest for former smokers [1.44 (95% CI: 1.04, 1.22)], followed by never-smokers [1.18 (95% CI: 1.00, 1.39)], and then current smokers [1.06 (95% CI: 0.97, 1.15)]. In addition, meta-estimates for adenocarcinoma associated with PM2.5 and PM10 were 1.40 (95% CI: 1.07, 1.83) and 1.29 (95% CI: 1.02, 1.63), respectively. CONCLUSION The results of these analyses, and the decision of the IARC Working Group to classify PM and outdoor air pollution as carcinogenic (Group 1), further justify efforts to reduce exposures to air pollutants that can arise from many sources.

PM source apportionment and health effects: 1. Intercomparison of source apportionment results

During the past three decades, receptor models have been used to identify and apportion ambient concentrations to sources. A number of groups are employing these methods to provide input into air quality management planning. A workshop has explored the use of resolved source contributions in health effects models. Multiple groups have analyzed particulate composition data sets from Washington, DC and Phoenix, AZ. Similar source profiles were extracted from these data sets by the investigators using different factor analysis methods. There was good agreement among the major resolved source types. Crustal (soil), sulfate, oil, and salt were the sources that were most unambiguously identified (generally highest correlation across the sites). Traffic and vegetative burning showed considerable variability among the results with variability in the ability of the methods to partition the motor vehicle contributions between gasoline and diesel vehicles. However, if the total motor vehicle contributions are estimated, good correspondence was obtained among the results. The source impacts were especially similar across various analyses for the larger mass contributors (e.g., in Washington, secondary sulfate SE=7% and 11% for traffic; in Phoenix, secondary sulfate SE=17% and 7% for traffic). Especially important for time-series health effects assessment, the source-specific impacts were found to be highly correlated across analysis methods/researchers for the major components (e.g., mean analysis to analysis correlation, r>0.9 for traffic and secondary sulfates in Phoenix and for traffic and secondary nitrates in Washington. The sulfate mean r value is >0.75 in Washington.). Overall, although these intercomparisons suggest areas where further research is needed (e.g., better division of traffic emissions between diesel and gasoline vehicles), they provide support the contention that PM2.5 mass source apportionment results are consistent across users and methods, and that todays source apportionment methods are robust enough for application to PM2.5 health effects assessments.

Lung Cancer in Railroad Workers Exposed to Diesel Exhaust

Diesel exhaust has been suspected to be a lung carcinogen. The assessment of this lung cancer risk has been limited by lack of studies of exposed workers followed for many years. In this study, we assessed lung cancer mortality in 54,973 U.S. railroad workers between 1959 and 1996 (38 years). By 1959, the U.S. railroad industry had largely converted from coal-fired to diesel-powered locomotives. We obtained work histories from the U.S. Railroad Retirement Board, and ascertained mortality using Railroad Retirement Board, Social Security, and Health Care Financing Administration records. Cause of death was obtained from the National Death Index and death certificates. There were 43,593 total deaths including 4,351 lung cancer deaths. Adjusting for a healthy worker survivor effect and age, railroad workers in jobs associated with operating trains had a relative risk of lung cancer mortality of 1.40 (95% confidence interval, 1.30–1.51). Lung cancer mortality did not increase with increasing years of work in these jobs. Lung cancer mortality was elevated in jobs associated with work on trains powered by diesel locomotives. Although a contribution from exposure to coal combustion products before 1959 cannot be excluded, these results suggest that exposure to diesel exhaust contributed to lung cancer mortality in this cohort.

The effect of dose and timing of dose on the association between airborne particles and survival.

Background Understanding the shape of the concentration–response curve for particles is important for public health, and lack of such understanding was recently cited by U.S. Environmental Protection Agency (EPA) as a reason for not tightening the standards. Similarly, the delay between changes in exposure and changes in health is also important in public health decision making. We addressed these issues using an extended follow-up of the Harvard Six Cities Study. Methods Cox proportional hazards models were fit controlling for smoking, body mass index, and other covariates. Two approaches were used. First, we used penalized splines, which fit a flexible functional form to the concentration response to examine its shape, and chose the degrees of freedom for the curve based on Akaike’s information criterion. Because the uncertainties around the resultant curve do not reflect the uncertainty in model choice, we also used model averaging as an alternative approach, where multiple models are fit explicitly and averaged, weighted by their probability of being correct given the data. We examined the lag relationship by model averaging across a range of unconstrained distributed lag models. Results We found that the concentration–response curve is linear, clearly continuing below the current U.S. standard of 15 μg/m3, and that the effects of changes in exposure on mortality are seen within two years. Conclusions Reduction in particle concentrations below U.S. EPA standards would increase life expectancy.

Perinatal Air Pollutant Exposures and Autism Spectrum Disorder in the Children of Nurses’ Health Study II Participants

Objective: Air pollution contains many toxicants known to affect neurological function and to have effects on the fetus in utero. Recent studies have reported associations between perinatal exposure to air pollutants and autism spectrum disorder (ASD) in children. We tested the hypothesis that perinatal exposure to air pollutants is associated with ASD, focusing on pollutants associated with ASD in prior studies. Methods: We estimated associations between U.S. Environmental Protection Agency–modeled levels of hazardous air pollutants at the time and place of birth and ASD in the children of participants in the Nurses’ Health Study II (325 cases, 22,101 controls). Our analyses focused on pollutants associated with ASD in prior research. We accounted for possible confounding and ascertainment bias by adjusting for family-level socioeconomic status (maternal grandparents’ education) and census tract–level socioeconomic measures (e.g., tract median income and percent college educated), as well as maternal age at birth and year of birth. We also examined possible differences in the relationship between ASD and pollutant exposures by child’s sex. Results: Perinatal exposures to the highest versus lowest quintile of diesel, lead, manganese, mercury, methylene chloride, and an overall measure of metals were significantly associated with ASD, with odds ratios ranging from 1.5 (for overall metals measure) to 2.0 (for diesel and mercury). In addition, linear trends were positive and statistically significant for these exposures (p < .05 for each). For most pollutants, associations were stronger for boys (279 cases) than for girls (46 cases) and significantly different according to sex. Conclusions: Perinatal exposure to air pollutants may increase risk for ASD. Additionally, future studies should consider sex-specific biological pathways connecting perinatal exposure to pollutants with ASD.

Exposure to Traffic Pollution and Increased Risk of Rheumatoid Arthritis

Background Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that affects approximately 1% of the adult population, and to date, genetic factors explain < 50% of the risk. Particulate air pollution, especially of traffic origin, has been linked to systemic inflammation in many studies. Objectives We examined the association of distance to road, a marker of traffic pollution exposure, and incidence of RA in a prospective cohort study. Methods We studied 90,297 U.S. women in the Nurses’ Health Study. We used a geographic information system to determine distance to road at the residence in 2000 as a measure of traffic exposure. Using Cox proportional hazard models, we examined the association of distance to road and incident RA (1976–2004) with adjustment for a large number of potential confounders. Results In models adjusted for age, calendar year, race, cigarette smoking, parity, lactation, menopausal status and hormone use, oral contraceptive use, body mass index, physical activity, and census-tract-level median income and house value, we observed an elevated risk of RA [hazard ratio (HR) = 1.31; 95% confidence interval (CI), 0.98–1.74] in women living within 50 m of a road, compared with those women living 200 m or farther away. We also observed this association in analyses among nonsmokers (HR = 1.62; 95% CI, 1.04–2.52), nonsmokers with rheumatoid factor (RF)-negative RA (HR = 1.77; 95% CI, 0.93–3.38), and nonsmokers with RF-positive RA (HR = 1.51; 95% CI, 0.82–2.77). We saw no elevations in risk in women living 50–200 m from the road. Conclusions The observed association between exposure to traffic pollution and RA suggests that pollution from traffic in adulthood may be a newly identified environmental risk factor for RA.