An Empirical Bayes Approach to Estimating the Relation of Mortality to Exposure to Particulate Matter

As part of its assessment of the health risks associated with exposure to particulate matter (PM), the U.S. Environmental Protection Agency analyzed the risks associated with current levels, and the risk reductions that might be achieved by attainment of alternative PM standards, in two locations in the United States, Philadelphia, and Los Angeles. The concentration-response function describing the relation between a health endpoint and ambient PM concentrations is an important component, and a source of substantial uncertainty, in such risk analyses. In the absence of location-specific estimates, the concentration-response functions necessary for risk assessments in Philadelphia and Los Angeles must be inferred from the available information in other locations. Although the functional form of the concentration-response relations is assumed to be the same everywhere, the value of the PM coefficient in that function may vary from one location to another. Under this model, a distribution describes the probability that the PM coefficient in a randomly selected location will lie in any range of interest. An empirical Bayes estimation technique was used to improve the estimation of location-specific concentration-response functions relating mortality to short-term exposure to particles of aerodynamic diameter less than or equal to 2.5 microm (PM-2.5), for which functions have previously been estimated in several locations. The empirical Bayes-adjusted parameter values and their SEs were used to derive an estimate of the distribution of PM-2.5 coefficients for mortality associated with short-term exposures. From this distribution, distributions of relative risks corresponding to different specified changes in PM-2.5 concentrations could be derived.     

Threshold Evaluation of Emergency Risk Communication for Health Risks Related to Hazardous Ambient Temperature

Emergency risk communication (ERC) programs that activate when the ambient temperature is expected to cross certain extreme thresholds are widely used to manage relevant public health risks. In practice, however, the effectiveness of these thresholds has rarely been examined. The goal of this study is to test if the activation criteria based on extreme temperature thresholds, both cold and heat, capture elevated health risks for all‐cause and cause‐specific mortality and morbidity in the Minneapolis‐St. Paul Metropolitan Area. A distributed lag nonlinear model (DLNM) combined with a quasi‐Poisson generalized linear model is used to derive the exposure–response functions between daily maximum heat index and mortality (1998–2014) and morbidity (emergency department visits; 2007–2014). Specific causes considered include cardiovascular, respiratory, renal diseases, and diabetes. Six extreme temperature thresholds, corresponding to 1st–3rd and 97th–99th percentiles of local exposure history, are examined. All six extreme temperature thresholds capture significantly increased relative risks for all‐cause mortality and morbidity. However, the cause‐specific analyses reveal heterogeneity. Extreme cold thresholds capture increased mortality and morbidity risks for cardiovascular and respiratory diseases and extreme heat thresholds for renal disease. Percentile‐based extreme temperature thresholds are appropriate for initiating ERC targeting the general population. Tailoring ERC by specific causes may protect some but not all individuals with health conditions exacerbated by hazardous ambient temperature exposure.     

Miscommunicating Risk,Uncertainty, and Causation: Fine Particulate Air Pollution and Mortality Risk as an Example

A recent paper in this journal (Fann et al., 2012) estimated that “about 80,000 premature mortalities would be avoided by lowering PM_2.5 levels to 5 μg/m³ nationwide” and that 2005 levels of PM_2.5 cause about 130,000 premature mortalities per year among people over age 29, with a 95% confidence interval of 51,000 to 200,000 premature mortalities per year.⁽¹⁾ These conclusions depend entirely on misinterpreting statistical coefficients describing the association between PM_2.5 and mortality rates in selected studies and models as if they were known to be valid causal coefficients. But they are not, and both the expert opinions of EPA researchers and analysis of data suggest that a true value of zero for the PM_2.5 mortality causal coefficient is not excluded by available data. Presenting continuous confidence intervals that exclude the discrete possibility of zero misrepresents what is currently known (and not known) about the hypothesized causal relation between changes in PM_2.5 levels and changes in mortality rates, suggesting greater certainty about projected health benefits than is justified.     

Approximations for Estimating Change in Life Expectancy Attributable to Air Pollution in Relation to Multiple Causes of Death Using a Cause Modified Life Table

There is considerable debate as to the most appropriate metric for characterizing the mortality impacts of air pollution. Life expectancy has been advocated as an informative measure. Although the life‐table calculus is relatively straightforward, it becomes increasingly cumbersome when repeated over large numbers of geographic areas and for multiple causes of death. Two simplifying assumptions were evaluated: linearity of the relation between excess rate ratio and change in life expectancy, and additivity of cause‐specific life‐table calculations. We employed excess rate ratios linking PM_2.5 and mortality from cerebrovascular disease, chronic obstructive pulmonary disease, ischemic heart disease, and lung cancer derived from a meta‐analysis of worldwide cohort studies. As a sensitivity analysis, we employed an integrated exposure response function based on the observed risk of PM_2.5 over a wide range of concentrations from ambient exposure, indoor exposure, second‐hand smoke, and personal smoking. Impacts were estimated in relation to a change in PM_2.5 from 19.5 μg/m³ estimated for Toronto to an estimated natural background concentration of 1.8 μg/m³. Estimated changes in life expectancy varied linearly with excess rate ratios, but at higher values the relationship was more accurately represented as a nonlinear function. Changes in life expectancy attributed to specific causes of death were additive with maximum error of 10%. Results were sensitive to assumptions about the air pollution concentration below which effects on mortality were not quantified. We have demonstrated valid approximations comprising expression of change in life expectancy as a function of excess mortality and summation across multiple causes of death.     

Integrating risk assessment and life cycle assessment: a case study of insulation.

Increasing residential insulation can decrease energy consumption and provide public health benefits, given changes in emissions from fuel combustion, but also has cost implications and ancillary risks and benefits. Risk assessment or life cycle assessment can be used to calculate the net impacts and determine whether more stringent energy codes or other conservation policies would be warranted, but few analyses have combined the critical elements of both methodologies In this article, we present the first portion of a combined analysis, with the goal of estimating the net public health impacts of increasing residential insulation for new housing from current practice to the latest International Energy Conservation Code (IECC 2000). We model state-by-state residential energy savings and evaluate particulate matter less than 2.5 microm in diameter (PM2.5), NOx, and SO2 emission reductions. We use past dispersion modeling results to estimate reductions in exposure, and we apply concentration-response functions for premature mortality and selected morbidity outcomes using current epidemiological knowledge of effects of PM2.5 (primary and secondary). We find that an insulation policy shift would save 3 x 10(14) British thermal units or BTU (3 x 10(17) J) over a 10-year period, resulting in reduced emissions of 1,000 tons of PM2.5, 30,000 tons of NOx, and 40,000 tons of SO2. These emission reductions yield an estimated 60 fewer fatalities during this period, with the geographic distribution of health benefits differing from the distribution of energy savings because of differences in energy sources, population patterns, and meteorology. We discuss the methodology to be used to integrate life cycle calculations, which can ultimately yield estimates that can be compared with costs to determine the influence of external costs on benefit-cost calculations.     

Regression Versus Causation,Revisited

I recently discussed pitfalls in attempted causal inference based on reduced‐form regression models. I used as motivation a real‐world example from a paper by Dr. Sneeringer, which interpreted a reduced‐form regression analysis as implying the startling causal conclusion that “doubling of [livestock] production leads to a 7.4% increase in infant mortality.” This conclusion is based on: (A) fitting a reduced‐form regression model to aggregate (e.g., county‐level) data; and (B) (mis)interpreting a regression coefficient in this model as a causal coefficient, without performing any formal statistical tests for potential causation (such as conditional independence, Granger‐Sims, or path analysis tests). Dr. Sneeringer now adds comments that confirm and augment these deficiencies, while advocating methodological errors that, I believe, risk analysts should avoid if they want to reach logically sound, empirically valid, conclusions about cause and effect. She explains that, in addition to (A) and (B) above, she also performed other steps such as (C) manually selecting specific models and variables and (D) assuming (again, without testing) that hand‐picked surrogate variables are valid (e.g., that log‐transformed income is an adequate surrogate for poverty). In her view, these added steps imply that “critiques of A and B are not applicable” to her analysis and that therefore “a causal argument can be made” for “such a strong, robust correlation” as she believes her regression coefficient indicates. However, multiple wrongs do not create a right. Steps (C) and (D) exacerbate the problem of unjustified causal interpretation of regression coefficients, without rendering irrelevant the fact that (A) and (B) do not provide evidence of causality. This reply focuses on whether any statistical techniques can produce the silk purse of a valid causal inference from the sow's ear of a reduced‐form regression analysis of ecological data. We conclude that Dr. Sneeringer's analysis provides no valid indication that air pollution from livestock operations causes any increase in infant mortality rates. More generally, reduced‐form regression modeling of aggregate population data—no matter how it is augmented by fitting multiple models and hand‐selecting variables and transformations—is not adequate for valid causal inference about health effects caused by specific, but unmeasured, exposures.     

Exposure Misclassification and Threshold Concentrations in Time Series Analyses of Air Pollution Health Effects

Linear, no-threshold relationships are typically reported for time series studies of air pollution and mortality. Since regulatory standards and economic valuations typically assume some threshold level, we evaluated the fundamental question of the impact of exposure misclassification on the persistence of underlying personal-level thresholds when personal data are aggregated to the population level in the assessment of exposure-response relationships. As an example, we measured personal exposures to two particle metrics, PM2.5 and sulfate (SO4(2-)), for a sample of lung disease patients and compared these with exposures estimated from ambient measurements Previous work has shown that ambient:personal correlations for PM2.5 are much lower than for SO4(2-), suggesting that ambient PM2.5 measurements misclassify exposures to PM2.5. We then developed a method by which the measured:estimated exposure relationships for these patients were used to simulate personal exposures for a larger population and then to estimate individual-level mortality risks under different threshold assumptions. These individual risks were combined to obtain the population risk of death, thereby exhibiting the prominence (and the value) of the threshold in the relationship between risk and estimated exposure. Our results indicated that for poorly classified exposures (PM2.5 in this example) population-level thresholds were apparent at lower ambient concentrations than specified common personal thresholds, while for well-classified exposures (e.g., SO4(2-)), the apparent thresholds were similar to these underlying personal thresholds. These results demonstrate that surrogate metrics that are not highly correlated with personal exposures obscure the presence of thresholds in epidemiological studies of larger populations, while exposure indicators that are highly correlated with personal exposures can accurately reflect underlying personal thresholds.     

Estimating the National Public Health Burden Associated with Exposure to Ambient PM2.5 and Ozone

Ground‐level ozone (O₃) and fine particulate matter (PM_2.5) are associated with increased risk of mortality. We quantify the burden of modeled 2005 concentrations of O₃ and PM_2.5 on health in the United States. We use the photochemical Community Multiscale Air Quality (CMAQ) model in conjunction with ambient monitored data to create fused surfaces of summer season average 8‐hour ozone and annual mean PM_2.5 levels at a 12 km grid resolution across the continental United States. Employing spatially resolved demographic and concentration data, we assess the spatial and age distribution of air‐pollution‐related mortality and morbidity. For both PM_2.5 and O₃ we also estimate: the percentage of total deaths due to each pollutant; the reduction in life years and life expectancy; and the deaths avoided according to hypothetical air quality improvements. Using PM_2.5 and O₃ mortality risk coefficients drawn from the long‐term American Cancer Society (ACS) cohort study and National Mortality and Morbidity Air Pollution Study (NMMAPS), respectively, we estimate 130,000 PM_2.5‐related deaths and 4,700 ozone‐related deaths to result from 2005 air quality levels. Among populations aged 65–99, we estimate nearly 1.1 million life years lost from PM_2.5 exposure and approximately 36,000 life years lost from ozone exposure. Among the 10 most populous counties, the percentage of deaths attributable to PM_2.5 and ozone ranges from 3.5% in San Jose to 10% in Los Angeles. These results show that despite significant improvements in air quality in recent decades, recent levels of PM_2.5 and ozone still pose a nontrivial risk to public health.     

Air Pollution and Mortality: Quantification and Valuation of Years of Life Lost

To analyze the loss of life expectancy (LLE) due to air pollution and the associated social cost, a dynamic model was developed that took into account the decrease of risk after the termination of an exposure to pollution. A key parameter was the time constant for the decrease of risk, for which estimates from studies of smoking were used. A sensitivity analysis showed that the precise value of the time constant(s) was not critical for the resulting LLE. An interesting aspect of the model was that the relation between population total LLE and PM2.5 concentration was numerically almost indistinguishable from a straight line, even though the functional dependence was nonlinear. This essentially linear behavior implies that the detailed history of a change in concentration does not matter, except for the effects of discounting. This model was used to correct the data of the largest study of chronic mortality for variations in past exposure, performed by Pope et al. in 1995; the correction factor was shown to depend on assumptions about the relative toxicity of the components of PM2.5. In the European Union, an increment of 1 microg/m3 of PM2.5 for 1 year implies an average LLE of 0.22 days per person. With regard to the social cost of an air pollution pulse, it was found that for typical discount rates (3% to 8% real) the cost was reduced by a factor of about 0.4 to 0.6 relative to the case with zero discount rate, if the value of a life year was taken as given; if the value of a life year was calculated from the "value of statistical life" by assuming the latter as a series of discounted annual values, the cost varied by at most +/-20% relative to the case with zero discount rate. To assess the uncertainties, this study also examined how the LLE depended on the demographics (mortality and age pyramid) of a population, and how it would change if the relative risk varied with age, in the manner suggested by smoking studies. These points were found to have a relatively small effect (compared to the epidemiological uncertainties) on the calculated LLE.     

Development of the PEARLS model (Particulate Exposure from Ambient to Regional Lung by Subgroup) and use of Monte Carlo simulation to predict internal exposure to 2.5 in Toronto.

Air pollution is a current and growing concern for Canadians, and there is evidence that ambient levels that meet current exposure standards may be associated with mortality and morbidity in Toronto, Canada. Evaluating exposure is an important step in understanding the relationship between particulate matter (PM) exposure and health outcomes. This report describes the PEARLS model (Particulate Exposure from Ambient to Regional Lung by Subgroup), which predicts exposure distributions for 11 age-gender population subgroups in Toronto to PM2.5 (PM with a median aerodynamic diameter of 2.5 microm or less) using Monte Carlo simulation techniques. The model uses physiological and activity pattern characteristics of each subgroup to determine region-specific lung exposure to PM2.5, which is defined as the mass of PM2.5 deposited per unit time to each of five lung regions (two extrathoracic, bronchial, bronchiolar, and alveolar). The modeling results predict that children, toddlers, and infants have the broadest distributions of exposure, and the greatest chance of experiencing extreme exposures in the alveolar region of the lung. Importance analysis indicates that the most influential model variables are air exchange rate into indoor environments, time spent outdoors, and time spent at high activity levels. Additionally, a "critical point" was defined and introduced to the PEARLS to investigate the effects of possible threshold-pathogenic phenomena on subgroup exposure patterns. The analysis indicates that the subgroups initially predicted to be most highly exposed were likely to have the highest proportion of their population exposed above the critical point. Substantial exposures above the critical point were predicted in all subgroups for ambient concentrations of PM2.5 commonly observed in Toronto after continuous exposure of 24 hours or more.     

Finely Resolved On‐Road PM2.5 and Estimated Premature Mortality in Central North Carolina

To quantify the on‐road PM_2.5‐related premature mortality at a national scale, previous approaches to estimate concentrations at a 12‐km × 12‐km or larger grid cell resolution may not fully characterize concentration hotspots that occur near roadways and thus the areas of highest risk. Spatially resolved concentration estimates from on‐road emissions to capture these hotspots may improve characterization of the associated risk, but are rarely used for estimating premature mortality. In this study, we compared the on‐road PM_2.5‐related premature mortality in central North Carolina with two different concentration estimation approaches—(i) using the Community Multiscale Air Quality (CMAQ) model to model concentration at a coarser resolution of a 36‐km × 36‐km grid resolution, and (ii) using a hybrid of a Gaussian dispersion model, CMAQ, and a space–time interpolation technique to provide annual average PM_2.5 concentrations at a Census‐block level (～105,000 Census blocks). The hybrid modeling approach estimated 24% more on‐road PM_2.5‐related premature mortality than CMAQ. The major difference is from the primary on‐road PM_2.5 where the hybrid approach estimated 2.5 times more primary on‐road PM_2.5‐related premature mortality than CMAQ due to predicted exposure hotspots near roadways that coincide with high population areas. The results show that 72% of primary on‐road PM_2.5 premature mortality occurs within 1,000 m from roadways where 50% of the total population resides, highlighting the importance to characterize near‐road primary PM_2.5 and suggesting that previous studies may have underestimated premature mortality due to PM_2.5 from traffic‐related emissions.     

Assessment of Interindividual and Geographic Variability in Human Exposure to Fine Particulate Matter in Environmental Tobacco Smoke

Environmental tobacco smoke (ETS) is a major contributor to indoor human exposures to fine particulate matter of 2.5 μm or smaller (PM_2.5). The Stochastic Human Exposure and Dose Simulation for Particulate Matter (SHEDS‐PM) Model developed by the U.S. Environmental Protection Agency estimates distributions of outdoor and indoor PM_2.5 exposure for a specified population based on ambient concentrations and indoor emissions sources. A critical assessment was conducted of the methodology and data used in SHEDS‐PM for estimation of indoor exposure to ETS. For the residential microenvironment, SHEDS uses a mass‐balance approach, which is comparable to best practices. The default inputs in SHEDS‐PM were reviewed and more recent and extensive data sources were identified. Sensitivity analysis was used to determine which inputs should be prioritized for updating. Data regarding the proportion of smokers and “other smokers” and cigarette emission rate were found to be important. SHEDS‐PM does not currently account for in‐vehicle ETS exposure; however, in‐vehicle ETS‐related PM_2.5 levels can exceed those in residential microenvironments by a factor of 10 or more. Therefore, a mass‐balance‐based methodology for estimating in‐vehicle ETS PM_2.5 concentration is evaluated. Recommendations are made regarding updating of input data and algorithms related to ETS exposure in the SHEDS‐PM model. Interindividual variability for ETS exposure was quantified. Geographic variability in ETS exposure was quantified based on the varying prevalence of smokers in five selected locations in the United States.     

Bounds in Competing Risks Models and the War on Cancer

In 1971, President Nixon declared war on cancer. Thirty years later, many declared this war a failure: the age‐adjusted mortality rate from cancer in 2000 was essentially the same as in the early 1970s. Meanwhile the age‐adjusted mortality rate from cardiovascular disease fell dramatically. Since the causes that underlie cancer and cardiovascular disease are likely dependent, the decline in mortality rates from cardiovascular disease may partially explain the lack of progress in cancer mortality. Because competing risks models (used to model mortality from multiple causes) are fundamentally unidentified, it is difficult to estimate cancer trends. We derive bounds for aspects of the underlying distributions without assuming that the underlying risks are independent. We then estimate changes in cancer and cardiovascular mortality since 1970. The bounds for the change in duration until death for either cause are fairly tight and suggest much larger improvements in cancer than previously estimated.     

Peak Exposures in Epidemiologic Studies and Cancer Risks: Considerations for Regulatory Risk Assessment

We review approaches for characterizing “peak” exposures in epidemiologic studies and methods for incorporating peak exposure metrics in dose–response assessments that contribute to risk assessment. The focus was on potential etiologic relations between environmental chemical exposures and cancer risks. We searched the epidemiologic literature on environmental chemicals classified as carcinogens in which cancer risks were described in relation to “peak” exposures. These articles were evaluated to identify some of the challenges associated with defining and describing cancer risks in relation to peak exposures. We found that definitions of peak exposure varied considerably across studies. Of nine chemical agents included in our review of peak exposure, six had epidemiologic data used by the U.S. Environmental Protection Agency (US EPA) in dose–response assessments to derive inhalation unit risk values. These were benzene, formaldehyde, styrene, trichloroethylene, acrylonitrile, and ethylene oxide. All derived unit risks relied on cumulative exposure for dose–response estimation and none, to our knowledge, considered peak exposure metrics. This is not surprising, given the historical linear no‐threshold default model (generally based on cumulative exposure) used in regulatory risk assessments. With newly proposed US EPA rule language, fuller consideration of alternative exposure and dose–response metrics will be supported. “Peak” exposure has not been consistently defined and rarely has been evaluated in epidemiologic studies of cancer risks. We recommend developing uniform definitions of “peak” exposure to facilitate fuller evaluation of dose response for environmental chemicals and cancer risks, especially where mechanistic understanding indicates that the dose response is unlikely linear and that short‐term high‐intensity exposures increase risk.     

Uncertain Benefits Estimates for Reductions in Fine Particle Concentrations

The Environmental Protection Agency's (EPA's) estimates of the benefits of improved air quality, especially from reduced mortality associated with reductions in fine particle concentrations, constitute the largest category of benefits from all federal regulation over the last decade. EPA develops such estimates, however, using an approach little changed since a 2002 report by the National Research Council (NRC), which was critical of EPA's methods and recommended a more comprehensive uncertainty analysis incorporating probability distributions for major sources of uncertainty. Consistent with the NRC's 2002 recommendations, we explore alternative assumptions and probability distributions for the major variables used to calculate the value of mortality benefits. For metropolitan Philadelphia, we show that uncertainty in air quality improvements and in baseline mortality have only modest effects on the distribution of estimated benefits. We analyze the effects of alternative assumptions regarding the value of reducing mortality risk, whether the toxicity is above or below the average for fine particles, and whether there is a threshold in the concentration‐response relationship, and show these assumptions all have large effects on the distribution of benefits.     

Health Effects Caused by Primary Fine Particulate Matter (PM2.5) Emitted from Buses in the Helsinki Metropolitan Area, Finland

Fine particle (PM(2.5)) emissions from traffic have been associated with premature mortality. The current work compares PM(2.5)-induced mortality in alternative public bus transportation strategies as being considered by the Helsinki Metropolitan Area Council, Finland. The current bus fleet and transportation volume is compared to four alternative hypothetical bus fleet strategies for the year 2020: (1) the current bus fleet for 2020 traffic volume, (2) modern diesel buses without particle traps, (3) diesel buses with particle traps, and (4) buses using natural gas engines. The average population PM(2.5) exposure level attributable to the bus emissions was determined for the 1996-1997 situation using PM(2.5) exposure measurements including elemental composition from the EXPOLIS-Helsinki study and similar element-based source apportionment of ambient PM(2.5) concentrations observed in the ULTRA study. Average population exposure to particles originating from the bus traffic in the year 2020 is assumed to be proportional to the bus emissions in each strategy. Associated mortality was calculated using dose-response relationships from two large cohort studies on PM(2.5) mortality from the United States. Estimated number of deaths per year (90% confidence intervals in parenthesis) associated with primary PM(2.5) emissions from buses in Helsinki Metropolitan Area in 2020 were 18 (0-55), 9 (0-27), 4 (0-14), and 3 (0-8) for the strategies 1-4, respectively. The relative differences in the associated mortalities for the alternative strategies are substantial, but the number of deaths in the lowest alternative, the gas buses, is only marginally lower than what would be achieved by diesel engines equipped with particle trap technology. The dose-response relationship and the emission factors were identified as the main sources of uncertainty in the model.     

Methods for Detecting and Estimating Population Threshold Concentrations for Air Pollution–Related Mortality with Exposure Measurement Error

The association between daily fluctuations in ambient particulate matter and daily variations in nonaccidental mortality have been extensively investigated. Although it is now widely recognized that such an association exists, the form of the concentration–response model is still in question. Linear, no threshold and linear threshold models have been most commonly examined. In this paper we considered methods to detect and estimate threshold concentrations using time series data of daily mortality rates and air pollution concentrations. Because exposure is measured with error, we also considered the influence of measurement error in distinguishing between these two completing model specifications. The methods were illustrated on a 15-year daily time series of nonaccidental mortality and particulate air pollution data in Toronto, Canada. Nonparametric smoothed representations of the association between mortality and air pollution were adequate to graphically distinguish between these two forms. Weighted nonlinear regression methods for relative risk models were adequate to give nearly unbiased estimates of threshold concentrations even under conditions of extreme exposure measurement error. The uncertainty in the threshold estimates increased with the degree of exposure error. Regression models incorporating threshold concentrations could be clearly distinguished from linear relative risk models in the presence of exposure measurement error. The assumption of a linear model given that a threshold model was the correct form usually resulted in overestimates in the number of averted premature deaths, except for low threshold concentrations and large measurement error.     

Multi-Stage Model Estimates of Lung Cancer Risk from Exposure to Diesel Exhaust, Based on a U.S. Railroad Worker Cohort

A California Environmental Protection Agency (Cal/EPA) report concluded that a reasonable and likely explanation for the increased lung cancer rates in numerous epidemiological studies is a causal association between diesel exhaust exposure and lung cancer. A version of the present analysis, based on a retrospective study of a U.S. railroad worker cohort, provided the Cal/EPA report with some of its estimates of lung cancer risk associated with diesel exhaust. The individual data for that cohort study furnish information on age, employment, and mortality for 56,000 workers over 22 years. Related studies provide information on exposure concentrations. Other analyses of the original cohort data reported finding no relation between measures of diesel exhaust and lung cancer mortality, while a Health Effects Institute report found the data unsuitable for quantitative risk assessment. None of those three works used multistage models, which this article uses in finding a likely quantitative, positive relations between lung cancer and diesel exhaust. A seven-stage model that has the last or next-to-last stage sensitive to diesel exhaust provides best estimates of increase in annual mortality rate due to each unit of concentration, for bracketing assumptions on exposure. Using relative increases of risk and multiplying by the background lung cancer mortality rates for California, the 95% upper confidence limit of the 70-year unit risks for lung cancer is estimated to be in the range 2.1 x 10(-4) (microg/m3)(-1) to 5.5 x 10(-4) (microg/m3)(-1). These risks constitute the low end of those in the Cal/EPA report and are below those reported by previous investigators whose estimates were positive using human data.     

Improving Causal Inferences in Risk Analysis

Recent headlines and scientific articles projecting significant human health benefits from changes in exposures too often depend on unvalidated subjective expert judgments and modeling assumptions, especially about the causal interpretation of statistical associations. Some of these assessments are demonstrably biased toward false positives and inflated effects estimates. More objective, data‐driven methods of causal analysis are available to risk analysts. These can help to reduce bias and increase the credibility and realism of health effects risk assessments and causal claims. For example, quasi‐experimental designs and analysis allow alternative (noncausal) explanations for associations to be tested, and refuted if appropriate. Panel data studies examine empirical relations between changes in hypothesized causes and effects. Intervention and change‐point analyses identify effects (e.g., significant changes in health effects time series) and estimate their sizes. Granger causality tests, conditional independence tests, and counterfactual causality models test whether a hypothesized cause helps to predict its presumed effects, and quantify exposure‐specific contributions to response rates in differently exposed groups, even in the presence of confounders. Causal graph models let causal mechanistic hypotheses be tested and refined using biomarker data. These methods can potentially revolutionize the study of exposure‐induced health effects, helping to overcome pervasive false‐positive biases and move the health risk assessment scientific community toward more accurate assessments of the impacts of exposures and interventions on public health.     

Estimates of the Health Risk Reductions Associated with Attainment of Alternative Particulate Matter Standards in Two U.S. Cities

As part of its periodic re-evaluation of particulate matter (PM) standards, the U.S. Environmental Protection Agency estimated the health risk reductions associated with attainment of alternative PM standards in two locations in the United States with relatively complete air quality data: Philadelphia and Los Angeles. PM standards at the time of the analysis were defined for particles of aerodynamic diameter less than or equal to 10 microm, denoted as PM-10. The risk analyses estimated the risk reductions that would be associated with changing from attainment of the PM-10 standards then in place to attainment of alternative standards using an indicator measuring fine particles, defined as those particles of aerodynamic diameter less than or equal to 2.5 microm and denoted as PM-2.5. Annual average PM-2.5 standards of 12.5, 15, and 20 microg/m3 were considered in various combinations with daily PM-2.5 standards of 50 and 65 microg/m3. Attainment of a standard or set of standards was simulated by a proportional rollback of "as is" daily PM concentrations to daily PM concentrations that would just meet the standard(s). The predicted reductions in the incidence of health effects varied from zero, for those alternative standards already being met, to substantial reductions of over 88% of all PM-associated incidence (e.g., in mortality associated with long-term exposures in Los Angeles, under attainment of an annual standard of 12.5 microg/m3). Sensitivity analyses and integrated uncertainty analyses assessed the multiple-source uncertainty surrounding estimates of risk reduction.