Sex-difference in air pollution-related acute circulatory and respiratory mortality and hospitalization.

BACKGROUND: Numerous studies have estimated adverse effects of short-term exposure to ambient air pollution on public health. Few have focused on sex-differences, and results have been inconsistent. The purpose of this study was three-fold: to identify sex-differences in air pollution-related health outcomes; to examine sex-differences by cause and season; and to examine time trends in sex-differences. METHODS: Daily data were collected on circulatory- and respiratory-related mortality (for 29 years) and cause-specific hospitalization (for 17 years) with hourly concentrations of ozone (O3), nitrogen dioxide (NO2), and fine particulate matter (PM2.5). For hospitalization, more specific causes were examined: ischemic heart disease (IHD), other heart disease (OHD), cerebrovascular disease (CEV), chronic lower respiratory diseases (CLRD), and Influenza/Pneumonia (InfPn). Generalized Poisson models were applied to 24 Canadian cities, and the city-specific estimates were combined for nationwide estimates for each sex using Bayesian hierarchical models. Finally, sex-differences were tested statistically based on their interval estimates, considering the correlation between sex-specific national estimates. RESULTS: Sex-differences were more frequently observed for hospitalization than mortality, respiratory than circulatory health outcomes, and warm than cold season. For hospitalization, males were at higher risk (M > F) for warm season (OHD and InfPn from O3; IHD from NO2; and InfPn from PM2.5), but F > M for cold season (CEV from O3 and OHD from NO2). For mortality, we found F > M only for circulatory diseases from ozone during the warm season. Among the above-mentioned sex-differences, three cases showed consistent time trends over the years: while M > F for OHD from O3 and IHD from NO2, F > M for OHD from NO2. CONCLUSIONS: We found that sex-differences in effect of ambient air pollution varied over health outcome, cause, season and time. In particular, the consistent trends (either F > M or M > F) across 17 years provide stronger evidence of sex-differences in hospitalizations, and warrant investigation in other populations.

Systematic review and meta-analysis of cohort studies of long term outdoor nitrogen dioxide exposure and mortality.

OBJECTIVE: To determine whether long term exposure to outdoor nitrogen dioxide (NO2) is associated with all-cause or cause-specific mortality. METHODS: MEDLINE, Embase, CENTRAL, Global Health and Toxline databases were searched using terms developed by a librarian. Screening, data extraction and risk of bias assessment were completed independently by two reviewers. Conflicts were resolved through consensus and/or involvement of a third reviewer. Pooling of results across studies was conducted using random effects models, heterogeneity among included studies was assessed using Cochran's Q and I2 measures, and sources of heterogeneity were evaluated using meta-regression. Sensitivity of pooled estimates to individual studies was examined and publication bias was evaluated using Funnel plots, Begg's and Egger's tests, and trim and fill. RESULTS: Seventy-nine studies based on 47 cohorts, plus one set of pooled analyses of multiple European cohorts, met inclusion criteria. There was a consistently high degree of heterogeneity. After excluding studies with probably high or high risk of bias in the confounding domain (n = 12), pooled hazard ratios (HR) indicated that long term exposure to NO2 was significantly associated with mortality from all/ natural causes (pooled HR 1.047, 95% confidence interval (CI), 1.023-1.072 per 10 ppb), cardiovascular disease (pooled HR 1.058, 95%CI 1.026-1.091), lung cancer (pooled HR 1.083, 95%CI 1.041-1.126), respiratory disease (pooled HR 1.062, 95%CI1.035-1.089), and ischemic heart disease (pooled HR 1.111, 95%CI 1.079-1.144). Pooled estimates based on multi-pollutant models were consistently smaller than those from single pollutant models and mostly non-significant. CONCLUSIONS: For all causes of death other than cerebrovascular disease, the overall quality of the evidence is moderate, and the strength of evidence is limited, while for cerebrovascular disease, overall quality is low and strength of evidence is inadequate. Important uncertainties remain, including potential confounding by co-pollutants or other concomitant exposures, and limited supporting mechanistic evidence. (PROSPERO registration number CRD42018084497).

Association between prenatal exposure to PM2.5 and the increased risk of specified infant mortality in South Korea.

BACKGROUND: Findings from previous studies on the association between exposure to fine particulate matter (PM2.5) and the risk of infant mortality were inconsistent. Thus, two main objectives of our study were to examine the association between exposure to PM2.5 and specified infant mortality and to identify critical trimesters. METHODS: We retrospectively created a birth cohort of singleton full-term infants born in South Korea between 2010 and 2015 using national birth and infant mortality data. The specified causes of infant mortality were circulatory and respiratory diseases, perinatal conditions, congenital anomalies, and sudden infant death syndrome. We performed 1:10 propensity score matching for various exposure windows: each trimester, prenatal, and postnatal (up to age 1). Conditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs), while accounting for gestational age, birth weight, maternal education level, season of birth, and regions (metropolitan areas/provinces). We also conducted sex-stratified analyses and used different matching ratios for sensitivity analyses. RESULTS: A total of 2,501,836 births and 761 deaths (0.03%) were identified in the birth cohort. We found an increased risk of infant mortality per 10 µg/m3 increase in PM2.5 exposure during the prenatal period (OR: 1.29, 95% CI: 1.07-1.55). Exposure in the 1st and 2nd trimesters was linked to an elevated risk (OR: 1.19, 95% CI: 1.02-1.37; OR: 1.21, 95% CI: 1.04-1.40). However, no association was shown in the third trimester. PM2.5 exposure in the 1st and 2nd trimesters was associated with elevated male infant mortality, but did not reach statistical significance in female infants. The use of different matching ratios did not significantly affect the results. CONCLUSION: The study findings suggest that exposure to PM2.5 could affect infant mortality differently by the timing of exposure and sex, which suggests a relation to fetal development. However, further investigations are warranted.

Correction to: Systematic review and meta-analysis of case-crossover and time-series studies of short term outdoor nitrogen dioxide exposure and ischemic heart disease morbidity.

An amendment to this paper has been published and can be accessed via the original article.

Systematic review and meta-analysis of case-crossover and time-series studies of short term outdoor nitrogen dioxide exposure and ischemic heart disease morbidity.

BACKGROUND: Nitrogen dioxide (NO2) is a pervasive urban pollutant originating primarily from vehicle emissions. Ischemic heart disease (IHD) is associated with a considerable public health burden worldwide, but whether NO2 exposure is causally related to IHD morbidity remains in question. Our objective was to determine whether short term exposure to outdoor NO2 is causally associated with IHD-related morbidity based on a synthesis of findings from case-crossover and time-series studies. METHODS: MEDLINE, Embase, CENTRAL, Global Health and Toxline databases were searched using terms developed by a librarian. Screening, data extraction and risk of bias assessment were completed independently by two reviewers. Conflicts between reviewers were resolved through consensus and/or involvement of a third reviewer. Pooling of results across studies was conducted using random effects models, heterogeneity among included studies was assessed using Cochran's Q and I2 measures, and sources of heterogeneity were evaluated using meta-regression. Sensitivity of pooled estimates to individual studies was examined using Leave One Out analysis and publication bias was evaluated using Funnel plots, Begg's and Egger's tests, and trim and fill. RESULTS: Thirty-eight case-crossover studies and 48 time-series studies were included in our analysis. NO2 was significantly associated with IHD morbidity (pooled odds ratio from case-crossover studies: 1.074 95% CI 1.052-1.097; pooled relative risk from time-series studies: 1.022 95% CI 1.016-1.029 per 10 ppb). Pooled estimates for case-crossover studies from Europe and North America were significantly lower than for studies conducted elsewhere. The high degree of heterogeneity among studies was only partially accounted for in meta-regression. There was evidence of publication bias, particularly for case-crossover studies. For both case-crossover and time-series studies, pooled estimates based on multi-pollutant models were smaller than those from single pollutant models, and those based on older populations were larger than those based on younger populations, but these differences were not statistically significant. CONCLUSIONS: We concluded that there is a likely causal relationship between short term NO2 exposure and IHD-related morbidity, but important uncertainties remain, particularly related to the contribution of co-pollutants or other concomitant exposures, and the lack of supporting evidence from toxicological and controlled human studies.

Maternal exposure to air pollution and risk of autism in children: A systematic review and meta-analysis.

BACKGROUND: The number of children diagnosed with autism spectrum disorder (ASD) has been increasing. Previous studies suggested potential association between pregnancy air pollution exposure and ASD. This systematic review and meta-analysis is intended to summarize the association between maternal exposure to outdoor air pollution and ASD in children by trimester based on recent studies. METHODS: A systematic literature search in 3 databases (Medline, Embase, and Web of Science) was performed using subject headings related to ASD and air pollution since 2007. Eligible studies were screened and evaluated based on predetermined criteria. For meta-analyses, the studies were grouped by air pollutant and exposure time (prenatal period and trimesters). Within-group studies were standardized by log odds ratio (OR) and then combined by three meta-analysis methods: frequentist fixed and random effects models, and Bayesian random effects model. RESULTS: Initial search identified 1564 papers, of which 25 studies remained for final analysis after duplicates and ineligible studies were removed. Of the 25 studies, 13, 14, 12, and 7 studies investigated ASD in children associated with PM2.5, PM10, NO2, and ozone, respectively. The frequentist and Bayesian random effects models resulted in different statistical significance. For prenatal period, frequentist meta-analysis returned significant pooled ORs with 95% confidence intervals, 1.06(1.01,1.11) for PM2.5 and 1.02(1.01,1.04) for NO2, whereas Bayesian meta-analysis showed similar ORs with wider 95% posterior intervals, 1.06(1.00,1.13) for PM2.5 and 1.02(1.00,1.05) for NO2. Third trimester appeared to have higher pooled ORs for PM2.5, PM10, and ozone, but patterns in the time-varying associations over the trimester were inconsistent. CONCLUSIONS: For positive association between maternal exposure to ambient air pollution and ASD in children, there is some evidence for PM2.5, weak evidence for NO2 and little evidence for PM10 and ozone. However, patterns in associations over trimesters were inconsistent among studies and among air pollutants.

Estimated public health impacts of changes in concentrations of fine particle air pollution in Canada, 2000 to 2011.

OBJECTIVES: To estimate the public health impacts of changes in fine particle air pollution in Canada between 2000 and 2011, employing nationally comprehensive exposure estimates and quantifying the impacts on life expectancy, mortality and morbidity. METHODS: We employed spatially comprehensive exposure estimates derived from satellite remote sensing to estimate the effects of actual observed changes in concentrations of fine particulate matter (PM), of median aerodynamic diameter <2.5 µm (i.e., PM2.5), from 2000 to 2011. We estimated changes in life expectancy using standard life table methods and changes in frequency of health outcomes as the product of population, baseline rate of the health outcome and the proportional change in health outcome per specified change in PM2.5 concentration. RESULTS: A population weighted average decrease in PM2.5 of nearly 25% (2.0 µg/m³) was observed between 2000 and 2011. This was estimated to result in a national population weighted average increase in life expectancy of 0.10 years (95% confidence interval 0.03-0.23; up to 0.34 years in specific census divisions) and reductions in the frequency of mortality and morbidity of up to 3.6%. Increases in PM2.5 up to 3.5 µg/m³ were observed in some census divisions, particularly in the prairies. CONCLUSION: At the national level, changes in PM2.5 concentrations between 2000 and 2011 were associated with an estimated improvement in national population weighted average life expectancy and a net reduction in mortality and morbidity. Areas that failed to improve or that worsened during this period warrant additional scrutiny to identify options for reducing PM2.5 concentrations.

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.

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.

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 µg/m 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.

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.

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.

Can personal exposures to higher nighttime and early-morning temperatures increase blood pressure?

Environmental temperatures are inversely related to BP; however, the effects of short-term temperature changes within a 24-hour period and measured with high accuracy at the personal level have not been described. Fifty-one nonsmoking patients living in the Detroit area had up to 5 consecutive days of 24-hour personal-level environmental temperature (PET) monitoring along with daily cardiovascular measurements, including BP, performed mostly between 5 pm and 7 pm during summer and/or winter periods. The associations between hour-long mean PET levels during the previous 24 hours with the outcomes were assessed by linear mixed models. Accounting for demographics, environmental factors, and monitoring compliance, systolic and diastolic BP were positively associated with several hour-long PET measurements ending from 10 to 15 hours beforehand. During this time, corresponding mostly to a period starting from between 1 am and 3 am to ending between 7 am and 9 am, an increase of 1°C was associated with a 0.81 mm Hg to 1.44 mm Hg and 0.59 mm Hg to 0.83 mm Hg elevation in systolic and diastolic BP, respectively. Modestly warmer, commonly encountered PET levels posed a clinically meaningful effect (eg, a 6.95 mm Hg systolic pressure increase per interquartile range (4.8°C) elevation at lag hour 10). Community-level outdoor ambient temperatures were not related to BP. The authors provide the first evidence that personal exposure to warmer nighttime and early-morning environmental temperatures might lead to an increase in BP during the ensuing day.

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 (PM(2.5))] 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 PM(2.5) 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 PM(2.5) monitoring and daily cardiovascular (CV) measurements during summer and/or winter periods. The associations between integrated hour-long total personal PM(2.5) 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 PM(2.5)-induced autonomic imbalance and may factor in the associated rapid increase in CV risk among susceptible individuals.

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.