Preventing carbon monoxide poisoning in the Hudson River Tunnel in 1921: recounting history.

The New York Bridge and Tunnel Commission began planning for a tunnel beneath the lower Hudson river to connect Manhattan to New Jersey in 1919. At 8,300 feet, it would be the longest tunnel for passenger vehicles in the world. A team of engineers and physiologists at the Yale University Bureau of Mines Experiment Station was tasked with calculating the ventilation requirements that would provide safety from exposure to automobile exhaust carbon monoxide (CO) while balancing the cost of providing ventilation. As the level of ambient CO which was comfortably tolerated was not precisely defined, they performed human exposures breathing from 100 to 1,000 ppm CO, first on themselves and subsequently on Yale medical students. Their findings continue to provide a basis for carbon monoxide alarm requirements a century later.

Association Between Traffic Count and Cardiovascular Mortality: A Prospective Cohort Study in Taiwan.

BACKGROUND: Exposure to traffic-related pollution is positively associated with cardiovascular diseases (CVD), but little is known about how different sources of traffic pollution (eg, gasoline-powered cars, diesel-engine vehicles) contribute to CVD. Therefore, we evaluated the association between exposure to different types of engine exhaust and CVD mortality. METHODS: We recruited 12,098 participants from REVEAL-HBV cohort in Taiwan. The CVD mortality in 2000-2014 was ascertained by the Taiwan Death Certificates. Traffic pollution sources (2005-2013) were based on information provided by the Directorate General of Highway in 2005. Exposure to PM2.5 was based on a land-use regression model. We applied Cox proportional hazard models to assess the association of traffic vehicle exposure and CVD mortality. A causal mediation analysis was applied to evaluate the mediation effect of PM2.5 on the relationship between traffic and CVD mortality. RESULTS: A total of 382 CVD mortalities were identified from 2000 to 2014. We found participants exposed to higher volumes of small car and truck exhausts had an increased CVD mortality. The adjusted hazard ratio (HR) was 1.10 for small cars (95% confidence interval [CI], 0.94-1.27; P-value = 0.23) and 1.24 for truck (95% CI, 1.03-1.51; P-value = 0.03) per one unit increment of the logarithm scale. The findings were still robust with further adjustment for different types of vehicles. A causal mediation analysis revealed PM2.5 had an over 60% mediation effect on traffic-CVD association. CONCLUSIONS: Exposure to exhaust from trucks or gasoline-powered cars is positively associated with CVD mortality, and air pollution may play a role in this association.

Postmenopausal breast cancer and occupational exposure to chemicals.

Objectives The aim of this study was to investigate if exposure to chemicals in the workplace was associated with an increased risk of postmenopausal breast cancer. Methods The study comprised women born 1923-1950 living in Malmö city, Sweden, 1991-1996, and enrolled for a prospective population cohort study. Occupational exposure to various chemicals was assessed from job-exposure matrices. An extensive set of individual data on hormonal breast cancer risk factors were collected via a baseline questionnaire and used for confounding control. First time diagnoses of invasive breast cancer were identified through the Swedish Cancer Registry until end of follow-up on 31 December 2013. Results Of 16 084 women, 1011 were diagnosed with breast cancer. Women exposed to chemicals in their occupational environment had a statistically significant increased risk [adjusted hazard ratio (HR adj) 1.26, 95% confidence interval (CI) 1.02-1.54] of breast cancer, and the risk correlated with duration of exposure. Investigation of risk in association with specific chemicals showed a non-significantly elevated risk after exposure to organic solvents. More than ten years of exposure to diesel exhaust was associated with an increased risk (HR adj1.69, 95% CI 1.01-2.82). Occupational chemical exposures account for 2% of the breast cancer cases in this population. Conclusions Occupational exposure to chemicals in general was associated with an elevated risk of breast cancer. A slight elevation of risk was seen after exposure to organic solvents. A statistically significant elevation of risk after >10 years of exposure to diesel exhaust was an unexpected finding.

Suicide deaths by gas inhalation in Toronto: An observational study of emerging methods of suicide.

BACKGROUND: Suicide death by gas inhalation has been the subject of global scientific interest due to a rapid increase in the use of helium and charcoal gas for suicide. These may be particularly amenable to means restriction strategies. There has been little scientific attention of this phenomenon in Canada. METHODS: A review of coroner records was conducted for all suicide deaths in Toronto (1998-2015). Deaths were categorized as due to inhalational asphyxia by compressed gas (i.e. helium or nitrogen), charcoal burning or motor vehicle exhaust, with suicide deaths by other methods as a comparator. Demographic, clinical and suicide specific differences between decedents in these four categories were compared using chi-squared or ANOVA global test of significance with additional pairwise comparisons where appropriate. Secular trends were also examined. RESULTS: Gas inhalational deaths accounted for 190 (4.7%) of all suicides in Toronto (n = 4062) over the study period and a higher proportion of males used compressed gas or motor vehicle exhaust gases than those who died by other methods (83.3% and 84.0% vs.69.7%, both p = 0.01). Comparing 1998-2003 to 2010-2015 there was a 1075% increase in deaths by helium (4 vs. 43 deaths) and a 533% increase in deaths by charcoal burning (3 vs. 16 deaths) although helium and charcoal burning deaths still accounted for only 4.2% of total suicides 2010-2015. Deaths by helium were more likely to be accompanied by the book "Final Exit" than those by non-inhalational methods (15% vs. 0.7%, p < 0.0001) while 13 of 14 people who died by charcoal burning whose ethnicity could be determined were Asian. LIMITATIONS: Ethnicity and specific details of procurement of suicide methods were not systematically available in coroner records. DISCUSSION: Suicide by inhalational asphyxia, particularly by compressed gases, has increased substantially over time in Toronto consistent with observations in other countries. Increased surveillance of these deaths, efforts to restrict access to these methods, and timely interventions including minimizing media reporting are all warranted.

Time trends in suicide rates by domestic gas or car exhaust gas inhalation in Japan, 1968-1994.

AIMS: A reduction in the carbon monoxide content of domestic gas and car exhaust gas has been associated with a decrease in gassing suicides in many western countries. In Japan, a reduction in the carbon monoxide content of domestic gas supply began in the early 1970s, and carbon monoxide emissions standards of new passenger cars were significantly strengthened in 1978. However, little is known about the impact of detoxification of these gases on gassing-related suicides in Japan. Therefore, we examined the changing patterns of suicide due to domestic gas or car exhaust gas inhalation by gender and age in Japan between 1968 and 1994. METHODS: Suicide mortality data were obtained from the Vital Statistics of Japan. In this study, age was divided into four groups: 15-24, 25-44, 45-64 and 65+ years. Method of suicide was divided into three groups: domestic gas, car exhaust gas and non-gases. We calculated method-specific age-standardised suicide rates by gender within each of the four age groups. We applied joinpoint regression to the data and quantified the observed changes. RESULTS: Suicide rates by domestic gas, regardless of gender and age, increased from 1968 to the mid-1970s and then decreased sharply. The proportion of all suicides accounted for by domestic gas was comparatively high in the mid-1970s among females aged 15-24 and 25-44 years, while for other gender-age-groups the proportion of domestic gas suicides remained small, even at the peak. For females aged 15-44 years, the decrease in domestic gas suicides appeared to cause a substantial decrease in overall suicides in this gender/age group. Car exhaust gas was a more common method for males, particularly those aged 25-64 years. Car exhaust gas suicide rates for males aged 25-64 years peaked in the mid-1980s, followed by a sharp decrease. CONCLUSIONS: A reduction in the carbon monoxide content of the domestic gas, which began in the early 1970s in Japan, was associated with a decrease in domestic gas suicides for both genders of all ages. Concerning females aged 15-44 years, a decrease in domestic gas suicides caused a substantial decrease in overall suicides in this gender/age group since the proportion of domestic gas suicides among all suicides combined was comparatively large. However, it remains uncertain whether the introduction of catalytic converters in the 1970s in Japan resulted in a reduction of suicides from car exhaust gas inhalation.

Differential toxicities of fine particulate matters from various sources.

Fine particulate matters less than 2.5 µm (PM2.5) in the ambient atmosphere are strongly associated with adverse health effects. However, it is unlikely that all fine particles are equally toxic in view of their different sizes and chemical components. Toxicity of fine particles produced from various combustion sources (diesel engine, gasoline engine, biomass burning (rice straw and pine stem burning), and coal combustion) and non-combustion sources (road dust including sea spray aerosols, ammonium sulfate, ammonium nitrate, and secondary organic aerosols (SOA)), which are known major sources of PM2.5, was determined. Multiple biological and chemical endpoints were integrated for various source-specific aerosols to derive toxicity scores for particles originating from different sources. The highest toxicity score was obtained for diesel engine exhaust particles, followed by gasoline engine exhaust particles, biomass burning particles, coal combustion particles, and road dust, suggesting that traffic plays the most critical role in enhancing the toxic effects of fine particles. The toxicity ranking of fine particles produced from various sources can be used to better understand the adverse health effects caused by different fine particle types in the ambient atmosphere, and to provide practical management of fine particles beyond what can be achieved only using PM mass which is the current regulation standard.

Transcriptional profiling of human bronchial epithelial cell BEAS-2B exposed to diesel and biomass ultrafine particles.

BACKGROUND: Emissions from diesel vehicles and biomass burning are the principal sources of primary ultrafine particles (UFP). The exposure to UFP has been associated to cardiovascular and pulmonary diseases, including lung cancer. Although many aspects of the toxicology of ambient particulate matter (PM) have been unraveled, the molecular mechanisms activated in human cells by the exposure to UFP are still poorly understood. Here, we present an RNA-seq time-course experiment (five time point after single dose exposure) used to investigate the differential and temporal changes induced in the gene expression of human bronchial epithelial cells (BEAS-2B) by the exposure to UFP generated from diesel and biomass combustion. A combination of different bioinformatics tools (EdgeR, next-maSigPro and reactome FI app-Cytoscape and prioritization strategies) facilitated the analyses the temporal transcriptional pattern, functional gene set enrichment and gene networks related to cellular response to UFP particles. RESULTS: The bioinformatics analysis of transcriptional data reveals that the two different UFP induce, since the earliest time points, different transcriptional dynamics resulting in the activation of specific genes. The functional enrichment of differentially expressed genes indicates that the exposure to diesel UFP induces the activation of genes involved in TNFα signaling via NF-kB and inflammatory response, and hypoxia. Conversely, the exposure to ultrafine particles from biomass determines less distinct modifications of the gene expression profiles. Diesel UFP exposure induces the secretion of biomarkers associated to inflammation (CCXL2, EPGN, GREM1, IL1A, IL1B, IL6, IL24, EREG, VEGF) and transcription factors (as NFE2L2, MAFF, HES1, FOSL1, TGIF1) relevant for cardiovascular and lung disease. By means of network reconstruction, four genes (STAT3, HIF1a, NFKB1, KRAS) have emerged as major regulators of transcriptional response of bronchial epithelial cells exposed to diesel exhaust. CONCLUSIONS: Overall, this work highlights modifications of the transcriptional landscape in human bronchial cells exposed to UFP and sheds new lights on possible mechanisms by means of which UFP acts as a carcinogen and harmful factor for human health.

Exposure to Traffic Emissions and Fine Particulate Matter and Computed Tomography Measures of the Lung and Airways.

BACKGROUND: Exposure to ambient air pollution has been associated with lower lung function in adults, but few studies have investigated associations with radiographic lung and airway measures. METHODS: We ascertained lung volume, mass, density, visual emphysema, airway size, and airway wall area by computed tomography (CT) among 2,545 nonsmoking Framingham CT substudy participants. We examined associations of home distance to major road and PM2.5 (2008 average from a spatiotemporal model using satellite data) with these outcomes using linear and logistic regression models adjusted for age, sex, height, weight, census tract median household value and population density, education, pack-years of smoking, household tobacco exposure, cohort, and date. We tested for differential susceptibility by sex, smoking status (former vs. never), and cohort. RESULTS: The mean participant age was 60.1 years (standard deviation 11.9 years). Median PM2.5 level was 9.7 µg/m (interquartile range, 1.6). Living <100 m from a major road was associated with a 108 ml (95% CI = 8, 207) higher lung volume compared with ≥400 m away. There was also a log-linear association between proximity to road and higher lung volume. There were no convincing associations of proximity to major road or PM2.5 with the other pulmonary CT measures. In subgroup analyses, road proximity was associated with lower lung density among men and higher odds of emphysema among former smokers. CONCLUSIONS: Living near a major road was associated with higher average lung volume, but otherwise, we found no association between ambient pollution and radiographic measures of emphysema or airway disease.

Understanding and Improving Arterial Roads to Support Public Health and Transportation Goals.

Arterials are types of roads designed to carry high volumes of motorized traffic. They are an integral part of transportation systems worldwide and exposure to them is ubiquitous, especially in urban areas. Arterials provide access to diverse commercial and cultural resources, which can positively influence community health by supporting social cohesion as well as economic and cultural opportunities. They can negatively influence health via safety issues, noise, air pollution, and lack of economic development. The aims of public health and transportation partially overlap; efforts to improve arterials can meet goals of both professions. Two trends in arterial design show promise. First, transportation professionals increasingly define the performance of arterials via metrics accounting for pedestrians, cyclists, transit riders, and nearby residents in addition to motor vehicle users. Second, applying traffic engineering and design can generate safety, air quality, and livability benefits, but we need evidence to support these interventions. We describe the importance of arterials (including exposures, health behaviors, effects on equity, and resulting health outcomes) and make the case for public health collaborations with the transportation sector.

Impacts and mitigation of excess diesel-related NOx emissions in 11 major vehicle markets.

Vehicle emissions contribute to fine particulate matter (PM2.5) and tropospheric ozone air pollution, affecting human health, crop yields and climate worldwide. On-road diesel vehicles produce approximately 20 per cent of global anthropogenic emissions of nitrogen oxides (NOx), which are key PM2.5 and ozone precursors. Regulated NOx emission limits in leading markets have been progressively tightened, but current diesel vehicles emit far more NOx under real-world operating conditions than during laboratory certification testing. Here we show that across 11 markets, representing approximately 80 per cent of global diesel vehicle sales, nearly one-third of on-road heavy-duty diesel vehicle emissions and over half of on-road light-duty diesel vehicle emissions are in excess of certification limits. These excess emissions (totalling 4.6 million tons) are associated with about 38,000 PM2.5- and ozone-related premature deaths globally in 2015, including about 10 per cent of all ozone-related premature deaths in the 28 European Union member states. Heavy-duty vehicles are the dominant contributor to excess diesel NOx emissions and associated health impacts in almost all regions. Adopting and enforcing next-generation standards (more stringent than Euro 6/VI) could nearly eliminate real-world diesel-related NOx emissions in these markets, avoiding approximately 174,000 global PM2.5- and ozone-related premature deaths in 2040. Most of these benefits can be achieved by implementing Euro VI standards where they have not yet been adopted for heavy-duty vehicles.

Cough and expiration reflexes elicited by inhaled irritant gases are intensified in ovalbumin-sensitized mice.

This study was designed to determine the effect of active sensitization with ovalbumin (Ova) on cough responses to inhaled irritant gases in mice. Conscious mice moved freely in a recording chamber, while the pressure change in the chamber and audio and video signals of the mouse movements were recorded simultaneously to measure the frequencies of cough reflex (CR) and expiration reflex (ER). To further verify the accuracy of cough analysis, the intrapleural pressure was also recorded by a telemetry sensor surgically implanted in the intrapleural space in a subgroup of mice. During the irritant gas inhalation challenge, sulfur dioxide (SO2; 200 and 400 ppm) or ammonia (NH3; 0.1% and 0.2%) was drawn into the chamber at a constant flow rate for 8 min. Ova sensitization and sham sensitization with vehicle (Veh) were performed over a 25-day period in separate groups of mice. Our results showed that 1) both SO2 and NH3 inhalation challenges increased CR and ER frequencies in a concentration-dependent manner before Ova sensitization; 2) the baseline CR frequency was significantly elevated after Ova sensitization, accompanied by pronounced airway inflammation; and 3) Ova sensitization also markedly augmented the responses of CR and ER to both SO2 and NH3 inhalation challenges; in sharp contrast, the cough responses did not change after sham sensitization in the Veh group. In conclusion, Ova sensitization caused distinct and lingering increases in baseline cough frequency, and also intensified both CR and ER responses to inhaled irritant gases, which probably resulted from an allergic inflammation-induced hypersensitivity of airway sensory nerves.

Absence of multiplicative interactions between occupational lung carcinogens and tobacco smoking: a systematic review involving asbestos, crystalline silica and diesel engine exhaust emissions.

BACKGROUND: Tobacco smoking is the main cause of lung cancer, but it is not the sole causal factor. Significant proportions of workers are smokers and exposed to occupational lung carcinogens. This study aims to systematically review the statistical interaction between occupational lung carcinogens and tobacco smoking, in particular asbestos, crystalline silica and diesel engine exhaust emissions. METHODS: Articles were identified using Scopus, PubMed, and Web of Science, and were limited to those published in English or French, without limitation of time. The reference list of selected studies was reviewed to identify other relevant papers. One reviewer selected the articles based on the inclusion and exclusion criteria. Two reviewers checked the eligibility of articles to be included in the systematic review. Data were extracted by one reviewer and revised by two other reviewers. Cohorts and case-control studies were analyzed separately. The risk of bias was evaluated for each study based on the outcome. The results of the interaction between the tobacco smoking and each carcinogen was evaluated and reported separately. RESULTS: Fifteen original studies were included for asbestos-smoking interaction, seven for silica-smoking interaction and two for diesel-smoking interaction. The results suggested the absence of multiplicative interaction between the three occupational lung carcinogens and smoking. There is no enough evidence from the literature to conclude for the additive interaction. We believe there is a limited risk of publication bias as several studies reporting negative results were published. CONCLUSION: There are no multiplicative interactions between tobacco smoking and occupational lung carcinogens, in particular asbestos, crystalline silica and diesel engine exhaust emissions. Even though, specific programs should be developed and promoted to reduce concomitantly the exposure to occupational lung carcinogens and tobacco smoking.

Diesel exhaust alters the response of cultured primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD) to non-typeable Haemophilus influenzae.

BACKGROUND: Exacerbations constitute a major cause of morbidity and mortality in patients suffering from chronic obstructive pulmonary disease (COPD). Both bacterial infections, such as those with non-typeable Haemophilus influenzae (NTHi), and exposures to diesel engine emissions are known to contribute to exacerbations in COPD patients. However, the effect of diesel exhaust (DE) exposure on the epithelial response to microbial stimulation is incompletely understood, and possible differences in the response to DE of epithelial cells from COPD patients and controls have not been studied. METHODS: Primary bronchial epithelial cells (PBEC) were obtained from age-matched COPD patients (n = 7) and controls (n = 5). PBEC were cultured at the air-liquid interface (ALI) to achieve mucociliary differentiation. ALI-PBECs were apically exposed for 1 h to a stream of freshly generated whole DE or air. Exposure was followed by 3 h incubation in presence or absence of UV-inactivated NTHi before analysis of epithelial gene expression. RESULTS: DE alone induced an increase in markers of oxidative stress (HMOX1, 50-100-fold) and of the integrated stress response (CHOP, 1.5-2-fold and GADD34, 1.5-fold) in cells from both COPD patients and controls. Exposure of COPD cultures to DE followed by NTHi caused an additive increase in GADD34 expression (up to 3-fold). Importantly, DE caused an inhibition of the NTHi-induced expression of the antimicrobial peptide S100A7, and of the chaperone protein HSP5A/BiP. CONCLUSIONS: Our findings show that DE exposure of differentiated primary airway epithelial cells causes activation of the gene expression of HMOX1 and markers of integrated stress response to a similar extent in cells from COPD donors and controls. Furthermore, DE further increased the NTHi-induced expression of GADD34, indicating a possible enhancement of the integrated stress response. DE reduced the NTHi-induced expression of S100A7. These data suggest that DE exposure may cause adverse health effects in part by decreasing host defense against infection and by modulating stress responses.

Long-term exposure to diesel engine exhaust induced lung function decline in a cross sectional study.

To clarify the effects of lung function following exposure to diesel engine exhaust (DEE), we recruited 137 diesel engine testing workers exposed to DEE and 127 non-DEE-exposed workers as study subjects. We performed lung function tests and measured cytokinesis-block micronucleus (CBMN) cytome index and levels of urinary polycyclic aromatic hydrocarbons (PAHs) metabolites. There was a significant decrease of forced expiratory volume in 1 second (FEV1), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/ FVC), maximal mid expiratory flow curve (MMF), forced expiratory flow at 50% of FVC (FEF50%), and forced expiratory flow at 75% of FVC (FEF75%) in the DEE-exposed workers than non-DEE-exposed workers (all p<0.05). Among all study subjects, the decreases of FEF75% were associated with the increasing levels of PAHs meta-bolites (p<0.05), and there were negative correlations between FEV1, FEV1/FVC, MMF, FEF50%, and FEF75% with CBMN cytome index (all p<0.05). Our results show that long-term exposure to DEE can induce lung function decline which shows mainly obstructive changes and influence of small airways function. The decreased lung function is associated with internal dosage of DEE exposure, and accompany with the increasing CBMN cytome index.

Systemic effects of controlled exposure to diesel exhaust: a meta-analysis from randomized controlled trials.

INTRODUCTION: Ambient air pollution is associated with adverse cardiovascular events. This meta-analysis aimed to investigate the short-term association between air pollution and cardiovascular effects on healthy volunteers. METHODS: We searched databases to identify randomized trials with controlled human exposures to either of two models for studying ambient particulate matter: diesel-exhaust or concentrated ambient particles. Estimates of size effect were performed using standardized mean difference (SMD). Heterogeneity was assessed with I2 statistics. Outcomes were vascular function estimated by forearm blood flow (FBF), blood pressure, heart rate, and blood analysis. RESULTS: Database searches yielded 17 articles (n = 342) with sufficient information for meta-analyses. High levels of heterogeneity for the some outcomes were analyzed using random-effects model. The pooled effect estimate showed that short-term exposure to air pollution impaired FBF response from 2.7 to 2.5 mL/100 mL tissue/min (SMD 0.404; p = .006). There was an increase in 5000 platelet/mm3 following pollution exposure (SMD 0.390; p = .050) but no significant differences for other outcomes. CONCLUSION: Controlled human exposures to air pollution are associated with the surrogates of vascular dysfunction and increase in platelet count, which might be related to adverse cardiovascular events. Given the worldwide prevalence of exposure to air pollution, these findings are relevant for public health. KEY MESSAGES Controlled exposure to air pollution impairs vasomotor response, which is a surrogate for adverse cardiovascular events. This is the first meta-analysis from randomized clinical trials showing short-term association between air pollution and cardiovascular effects on healthy volunteers. Given the worldwide prevalence of exposure to air pollution, this finding is important for public health.

The 2-phase case-control design: an efficient way to use expert-time.

OBJECTIVES: The objective of this paper is to show the benefits of using a 2-phase case-control (2PCC) design in identifying dose-response relationships between cumulative occupational exposure as assessed by experts and lung cancer incidence in an actual study. METHODS: A population-based case-control study including 246 cases and 531 controls was conducted in an area with high lung cancer rates in Northeast France. Detailed occupational and personal risk factors were obtained in face-to-face interviews. Cumulative expert-based exposure scores were obtained from a subset of 215 cases and 269 controls stratified on smoking and a prior algorithmic exposure score for asbestos, crystalline silica, and polycyclic aromatic hydrocarbons (PAH) in the framework of a 2PCC design. This subset deliberately under-sampled large strata among controls but not among cases. Logistic regression models adapted to 2PCC studies were applied and corresponding computations of attributable fractions and their confidence intervals developed. RESULTS: Based on this 2PCC design, statistically significant dose-response relationships were obtained for asbestos, crystalline silica, PAH, and diesel motor exhaust. Simulations within this study showed that 2PCC studies were always more powerful than random samples. CONCLUSION: The 2PCC design may be the design of choice when resources allow only a limited number of subjects with a full expert-based exposure assessment.

The contribution of outdoor air pollution sources to premature mortality on a global scale.

Assessment of the global burden of disease is based on epidemiological cohort studies that connect premature mortality to a wide range of causes, including the long-term health impacts of ozone and fine particulate matter with a diameter smaller than 2.5 micrometres (PM2.5). It has proved difficult to quantify premature mortality related to air pollution, notably in regions where air quality is not monitored, and also because the toxicity of particles from various sources may vary. Here we use a global atmospheric chemistry model to investigate the link between premature mortality and seven emission source categories in urban and rural environments. In accord with the global burden of disease for 2010 (ref. 5), we calculate that outdoor air pollution, mostly by PM2.5, leads to 3.3 (95 per cent confidence interval 1.61-4.81) million premature deaths per year worldwide, predominantly in Asia. We primarily assume that all particles are equally toxic, but also include a sensitivity study that accounts for differential toxicity. We find that emissions from residential energy use such as heating and cooking, prevalent in India and China, have the largest impact on premature mortality globally, being even more dominant if carbonaceous particles are assumed to be most toxic. Whereas in much of the USA and in a few other countries emissions from traffic and power generation are important, in eastern USA, Europe, Russia and East Asia agricultural emissions make the largest relative contribution to PM2.5, with the estimate of overall health impact depending on assumptions regarding particle toxicity. Model projections based on a business-as-usual emission scenario indicate that the contribution of outdoor air pollution to premature mortality could double by 2050.