Hwashin H. Shin

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

Differences in blood pressure and vascular responses associated with ambient fine particulate matter exposures measured at the personal versus community level.

Background Higher ambient fine particulate matter (PM2.5) levels can be associated with increased blood pressure and vascular dysfunction. Objectives To determine the differential effects on blood pressure and vascular function of daily changes in community ambient- versus personal-level PM2.5 measurements. Methods Cardiovascular outcomes included vascular tone and function and blood pressure measured in 65 non-smoking subjects. PM2.5 exposure metrics included 24 h integrated personal- (by vest monitors) and community-based ambient levels measured for up to 5 consecutive days (357 observations). Associations between community- and personal-level PM2.5 exposures with alterations in cardiovascular outcomes were assessed by linear mixed models. Results Mean daily personal and community measures of PM2.5 were 21.9±24.8 and 15.4±7.5 μg/m3, respectively. Community PM2.5 levels were not associated with cardiovascular outcomes. However, a 10 μg/m3 increase in total personal-level PM2.5 exposure (TPE) was associated with systolic blood pressure elevation (+1.41 mm Hg; lag day 1, p<0.001) and trends towards vasoconstriction in subsets of individuals (0.08 mm; lag day 2 among subjects with low secondhand smoke exposure, p=0.07). TPE and secondhand smoke were associated with elevated systolic blood pressure on lag day 1. Flow-mediated dilatation was not associated with any exposure. Conclusions Exposure to higher personal-level PM2.5 during routine daily activity measured with low-bias and minimally-confounded personal monitors was associated with modest increases in systolic blood pressure and trends towards arterial vasoconstriction. Comparable elevations in community PM2.5 levels were not related to these outcomes, suggesting that specific components within personal and background ambient PM2.5 may elicit differing cardiovascular responses.

Within- and between-city contrasts in nitrogen dioxide and mortality in 10 Canadian cities; a subset of the Canadian Census Health and Environment Cohort (CanCHEC)

The independent and joint effects of within- and between-city contrasts in air pollution on mortality have been investigated rarely. To examine the differential effects of between- versus within-city contrasts in pollution exposure, we used both ambient measurements and land use regression models to assess associations with mortality and exposure to nitrogen dioxide (NO2) among ~735,600 adults in 10 of the largest Canadian cities. We estimated exposure contrasts partitioned into within- and between-city contrasts, and the sum of these as overall exposures, for every year from 1984 to 2006. Residential histories allowed us to follow subjects annually during the study period. We calculated hazard ratios (HRs) adjusted for many personal and contextual variables. In fully-adjusted, random-effects models, we found positive associations between overall NO2 exposures and mortality from non-accidental causes (HR per 5 p.p.b.: 1.05; 95% confidence interval (CI): 1.03–1.07), cardiovascular disease (HR per 5 p.p.b.: 1.04; 95% CI: 1.01–1.06), ischaemic heart disease (HR per 5 p.p.b.: 1.05; 95% CI: 1.02–1.08) and respiratory disease (HR per 5 p.p.b.: 1.04; 95% CI: 0.99–1.08), but not from cerebrovascular disease (HR per 5 p.p.b.: 1.01; 95% CI: 0.96–1.06). We found that most of these associations were determined by within-city contrasts, as opposed to by between-city contrasts in NO2. Our results suggest that variation in NO2 concentrations within a city may represent a more toxic mixture of pollution than variation between cities.

Indirect adjustment for multiple missing variables applicable to environmental epidemiology

OBJECTIVES Develop statistical methods for survival models to indirectly adjust hazard ratios of environmental exposures for missing risk factors. METHODS A partitioned regression approach for linear models is applied to time to event survival analyses of cohort study data. Information on the correlation between observed and missing risk factors is obtained from ancillary data sources such as national health surveys. The relationship between the missing risk factors and survival is obtained from previously published studies. We first evaluated the methodology using simulations, by considering the Weibull survival distribution for a proportional hazards regression model with varied baseline functions, correlations between an adjusted variable and an adjustment variable as well as selected censoring rates. Then we illustrate the method in a large, representative Canadian cohort of the association between concentrations of ambient fine particulate matter and mortality from ischemic heart disease. RESULTS Indirect adjustment for cigarette smoking habits and obesity increased the fine particulate matter-ischemic heart disease association by 3%-123%, depending on the number of variables considered in the adjustment model due to the negative correlation between these two risk factors and ambient air pollution concentrations in Canada. The simulations suggested that the method yielded small relative bias (<40%) for most cohort designs encountered in environmental epidemiology. CONCLUSIONS This method can accommodate adjustment for multiple missing risk factors simultaneously while accounting for the associations between observed and missing risk factors and between missing risk factors and health endpoints.

Exploration of the Rapid Effects of Personal Fine Particulate Matter Exposure on Arterial Hemodynamics and Vascular Function during the Same Day

Background Levels of fine particulate matter [≤ 2.5 μm in aerodynamic diameter (PM2.5)] are associated with alterations in arterial hemodynamics and vascular function. However, the characteristics of the same-day exposure–response relationships remain unclear. Objectives We aimed to explore the effects of personal PM2.5 exposures within the preceding 24 hr on blood pressure (BP), heart rate (HR), brachial artery diameter (BAD), endothelial function [flow-mediated dilatation (FMD)], and nitroglycerin-mediated dilatation (NMD). Methods Fifty-one nonsmoking subjects had up to 5 consecutive days of 24-hr personal PM2.5 monitoring and daily cardiovascular (CV) measurements during summer and/or winter periods. The associations between integrated hour-long total personal PM2.5 exposure (TPE) levels (continuous nephelometry among compliant subjects with low secondhand tobacco smoke exposures; n = 30) with the CV outcomes were assessed over a 24-hr period by linear mixed models. Results We observed the strongest associations (and smallest estimation errors) between HR and TPE recorded 1–10 hr before CV measurements. The associations were not pronounced for the other time lags (11–24 hr). The associations between TPE and FMD or BAD did not show as clear a temporal pattern. However, we found some suggestion of a negative association with FMD and a positive association with BAD related to TPE just before measurement (0–2 hr). Conclusions Brief elevations in ambient TPE levels encountered during routine daily activity were associated with small increases in HR and trends toward conduit arterial vasodilatation and endothelial dysfunction within a few hours of exposure. These responses could reflect acute PM2.5-induced autonomic imbalance and may factor in the associated rapid increase in CV risk among susceptible individuals.

Can Personal Exposures to Higher Nighttime and Early Morning Temperatures Increase Blood Pressure

J Clin Hypertens (Greenwich). 2011;13:881–888. ©2011 Wiley Periodicals, Inc.

Outdoor fine particles and nonfatal strokes: systematic review and meta-analysis.

Background: Epidemiologic studies find that long- and short-term exposure to fine particles (PM2.5) is associated with adverse cardiovascular outcomes, including ischemic and hemorrhagic strokes. However, few systematic reviews or meta-analyses have synthesized these results. Methods: We reviewed epidemiologic studies that estimated the risks of nonfatal strokes attributable to ambient PM2.5. To pool risks among studies we used a random-effects model and 2 Bayesian approaches. The first Bayesian approach assumes a normal prior that allows risks to be zero, positive or negative. The second assumes a gamma prior, where risks can only be positive. This second approach is proposed when the number of studies pooled is small, and there is toxicological or clinical literature to support a causal relation. Results: We identified 20 studies suitable for quantitative meta-analysis. Evidence for publication bias is limited. The frequentist meta-analysis produced pooled risk ratios of 1.06 (95% confidence interval = 1.00–1.13) and 1.007 (1.003–1.010) for long- and short-term effects, respectively. The Bayesian meta-analysis found a posterior mean risk ratio of 1.08 (95% posterior interval = 0.96–1.26) and 1.008 (1.003–1.013) from a normal prior, and of 1.05 (1.02–1.10) and 1.008 (1.004–1.013) from a gamma prior, for long- and short-term effects, respectively, per 10 &mgr;g/m3 PM2.5. Conclusions: Sufficient evidence exists to develop a concentration-response relation for short- and long-term exposures to PM2.5 and stroke incidence. Long-term exposures to PM2.5 result in a higher risk ratio than short-term exposures, regardless of the pooling method. The evidence for short-term PM2.5-related ischemic stroke is especially strong.

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 PM2.5 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 PM2.5 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 PM2.5 from 19.5 μg/m(3) estimated for Toronto to an estimated natural background concentration of 1.8 μg/m(3) . 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.