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1.  Traffic exposure and incident venous thromboembolism in the Atherosclerosis Risk in Communities (ARIC) Study 
Summary
Background
Two recent case-control studies in Italy reported that long-term exposure to particulate air pollution or living near major traffic roads was associated with an increased risk of deep vein thrombosis (DVT). No prospective evidence exists about long-term traffic-related air pollution and incident venous thromboembolism (VTE).
Objectives
To examine the association between long-term traffic exposure and incident VTE in a population-based prospective cohort study.
Methods
We studied 13,143 middle-aged men and women in the Atherosclerosis Risk in Communities Study without history of DVT or pulmonary embolus (PE) at baseline examination (1987-1989). Geographical Information System (GIS)-mapped traffic density and distance to major roads in the four study communities served as measures of traffic exposure. We examined the association between traffic exposure and incident VTE using proportional hazards regression models.
Results
405 subjects developed VTE through 2005. Traffic density was not significantly associated with VTE. Relative to those in the lowest quartile of traffic density, the adjusted hazard ratios across increasing quartiles were 1.18 (95%CI 0.88-1.57), 0.99 (95%CI 0.74-1.34) and 1.14 (95%CI 0.86-1.51) (p for trend across quartiles = 0.64). For residents living within 150 meters of major roads compared to subjects living further away, the adjusted hazard ratio was 1.16 (95%CI 0.95-1.42, p=0.14).
Conclusions
This first prospective study in the general population does not support an association between air pollution exposure or traffic proximity and risk of DVT. More data may be needed to clarify whether traffic or air pollution influences the risk of VTE.
doi:10.1111/j.1538-7836.2011.04210.x
PMCID: PMC3071427  PMID: 21255249
traffic exposure; VTE; air pollution; cohort
2.  Exposure to Particulate Air Pollution and Risk of Deep Vein Thrombosis 
Archives of internal medicine  2008;168(9):920-927.
Background
Particulate air pollution has been linked to heart disease and stroke, possibly resulting from enhanced coagulation and arterial thrombosis. Whether particulate air pollution exposure is related to venous thrombosis is unknown.
Methods
We examined the association of exposure to particulate matter of less than 10 µm in aerodynamic diameter (PM10) with DVT risk in 870 patients and 1210 controls from Lombardia Region, Italy examined between 1995–2005. We estimated exposure to particulate matter of less than 10 µm in aerodynamic diameter (PM10) in the year before DVT diagnosis (cases) or examination (controls) through area-specific average levels obtained from ambient monitors.
Results
Higher average PM10 level in the year before the examination was associated with shortened Prothrombin Time (PT) in DVT cases (beta=−0.12; 95% CI −0.23, 0.00; p=0.04) and controls (beta=-0.06; 95% CI −0.11, 0.00, p=0.04). Each PM10 increase of 10 µg/m3 was associated with a 70% increase in DVT risk (OR=1.70; 95% CI, 1.30–2.23; p=0.0001) in models adjusting for clinical and environmental covariates. The exposure-response relationship was approximately linear over the observed PM10 range. The association between PM10 and DVT was weaker in women (OR=1.40; 95% CI, 1.02–1.92; p=0.02 for the interaction between PM10 and sex), particularly in those using oral contraceptives or hormone replacement therapy (OR=0.97; 95% CI 0.58–1.61; p=0.048 for the interaction between PM10 and hormone use).
Conclusions
Long-term exposure to particulate air pollution is associated with altered coagulation function and DVT risk. Other risk factors for DVT may modulate the effect of particulate air pollution.
doi:10.1001/archinte.168.9.920
PMCID: PMC3093962  PMID: 18474755
3.  An Economic Evaluation of Venous Thromboembolism Prophylaxis Strategies in Critically Ill Trauma Patients at Risk of Bleeding 
PLoS Medicine  2009;6(6):e1000098.
Using decision analysis, Henry Stelfox and colleagues estimate the cost-effectiveness of three venous thromboembolism prophylaxis strategies in patients with severe traumatic injuries who were also at risk for bleeding complications.
Background
Critically ill trauma patients with severe injuries are at high risk for venous thromboembolism (VTE) and bleeding simultaneously. Currently, the optimal VTE prophylaxis strategy is unknown for trauma patients with a contraindication to pharmacological prophylaxis because of a risk of bleeding.
Methods and Findings
Using decision analysis, we estimated the cost effectiveness of three VTE prophylaxis strategies—pneumatic compression devices (PCDs) and expectant management alone, serial Doppler ultrasound (SDU) screening, and prophylactic insertion of a vena cava filter (VCF)—in trauma patients admitted to an intensive care unit (ICU) with severe injuries who were believed to have a contraindication to pharmacological prophylaxis for up to two weeks because of a risk of major bleeding. Data on the probability of deep vein thrombosis (DVT) and pulmonary embolism (PE), and on the effectiveness of the prophylactic strategies, were taken from observational and randomized controlled studies. The probabilities of in-hospital death, ICU and hospital discharge rates, and resource use were taken from a population-based cohort of trauma patients with severe injuries (injury severity scores >12) admitted to the ICU of a regional trauma centre. The incidence of DVT at 12 weeks was similar for the PCD (14.9%) and SDU (15.0%) strategies, but higher for the VCF (25.7%) strategy. Conversely, the incidence of PE at 12 weeks was highest in the PCD strategy (2.9%), followed by the SDU (1.5%) and VCF (0.3%) strategies. Expected mortality and quality-adjusted life years were nearly identical for all three management strategies. Expected health care costs at 12 weeks were Can$55,831 for the PCD strategy, Can$55,334 for the SDU screening strategy, and Can$57,377 for the VCF strategy, with similar trends noted over a lifetime analysis.
Conclusions
The attributable mortality due to PE in trauma patients with severe injuries is low relative to other causes of mortality. Prophylactic placement of VCF in patients at high risk of VTE who cannot receive pharmacological prophylaxis is expensive and associated with an increased risk of DVT. Compared to the other strategies, SDU screening was associated with better clinical outcomes and lower costs.
Please see later in the article for Editors' Summary
Editors' Summary
Background
For patients who have been seriously injured in an accident or a violent attack (trauma patients), venous thromboembolism (VTE)—the formation of blood clots that limit the flow of blood through the veins—is a frequent and potentially fatal complication. The commonest form of VTE is deep vein thrombosis (DVT). “Distal” DVTs (clots that form in deep veins below the knee) affect about half of patients with severe trauma; “proximal” DVTs (clots that form above the knee) develop in one in five trauma patients. DVTs cause pain and swelling in the affected leg and can leave patients with a painful condition called post-thrombotic syndrome. Worse still, part of the clot can break off and travel to the lungs where it can cause a life-threatening pulmonary embolism (PE). Distal DVTs rarely embolize but, if untreated, half of patients who present with a proximal DVT will develop a PE, and 2%–3% of them will die as a result.
Why Was This Study Done?
VTE is usually prevented by using heparin, a drug that stops blood clotting, but clinicians treating critically ill trauma patients have a dilemma. Many of these patients are at high risk of serious bleeding complications so cannot be given heparin to prevent VTE. Nonpharmacological ways to prevent VTE include the use of pneumatic compression devices to keep the blood moving in the legs (clots often form in patients confined to bed because of the sluggish blood flow in their legs), repeated screening for blood clots using Doppler ultrasound, and the insertion of a “vena cava filter” into the vein that takes blood from the legs to the heart. This last device catches blood clots before they reach the lungs but increases the risk of DVT. Unfortunately, no-one knows which VTE prevention strategy works best in trauma patients who cannot be given heparin. In this study, therefore, the researchers use decision analysis (the systematic evaluation of the most important factors affecting a decision) to estimate the costs and likely clinical outcomes of these strategies.
What Did the Researchers Do and Find?
The researchers used cost and clinical data from patients admitted to a Canadian trauma center with severe head/neck and/or abdomen/pelvis injuries (patients with a high risk of bleeding complications likely to make heparin therapy dangerous for up to two weeks after the injury) to construct a Markov decision analysis model. They then fed published data on the chances of patients developing DVT or PE, and on the effectiveness of the three VTE prevention strategies, into the model to obtain estimates of the costs and clinical outcomes of the strategies at 12 weeks after the injury and over the patients' lifetime. The estimated incidence of DVT at 12 weeks was 15% for the pneumatic compression device and Doppler ultrasound strategies, but 25% for the vena cava filter strategy. By contrast, the estimated incidence of PE was 2.9% with the pneumatic compression device, 1.5% with Doppler ultrasound, but only 0.3% with the vena cava filter. The expected mortality with all three strategies was similar. Finally, the estimated health care costs per patient at 12 weeks were Can$55,334 and Can$55,831 for the Doppler ultrasound and pneumatic compression device strategies, respectively, but Can$57,377 for the vena cava filter strategy; similar trends were seen for lifetime health care costs.
What Do These Findings Mean?
As with all mathematical models, these findings depend on the data fed into the model and on the assumptions included in it. For example, because data from one Canadian trauma unit were used to construct the model, these findings may not be generalizable. Nevertheless, these findings suggest that, although VTE is common among patients with severe injuries, PE is not a major cause of death among these patients. They also suggest that the use of vena cava filters for VTE prevention in patients who cannot receive heparin should not be routinely used because it is expensive and increases the risk of DVT. Finally, these results suggest that, compared with the other strategies, serial Doppler ultrasound is associated with better clinical outcomes and lower costs.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000098.
The US National Heart Lung and Blood Institute provides information (including an animation) on deep vein thrombosis and pulmonary embolism
MedlinePlus provides links to more information about deep vein thrombosis and pulmonary embolism (in several languages)
The UK National Health Service Choices Web site has information on deep vein thrombosis and on embolism (in English and Spanish)
The Eastern Association for the Surgery of Trauma working group document Practice Management Guidelines for the Management of Venous Thromboembolism in Trauma Patients can be downloaded from the Internet
doi:10.1371/journal.pmed.1000098
PMCID: PMC2695771  PMID: 19554085
4.  Air Pollution and the Microvasculature: A Cross-Sectional Assessment of In Vivo Retinal Images in the Population-Based Multi-Ethnic Study of Atherosclerosis (MESA) 
PLoS Medicine  2010;7(11):e1000372.
Sara Adar and colleagues show that residing in locations with higher air pollution concentrations and experiencing daily increases in air pollution are associated with narrower retinal arteriolar diameters in older individuals, thus providing a link between air pollution and cardiovascular disease.
Background
Long- and short-term exposures to air pollution, especially fine particulate matter (PM2.5), have been linked to cardiovascular morbidity and mortality. One hypothesized mechanism for these associations involves microvascular effects. Retinal photography provides a novel, in vivo approach to examine the association of air pollution with changes in the human microvasculature.
Methods and Findings
Chronic and acute associations between residential air pollution concentrations and retinal vessel diameters, expressed as central retinal arteriolar equivalents (CRAE) and central retinal venular equivalents (CRVE), were examined using digital retinal images taken in Multi-Ethnic Study of Atherosclerosis (MESA) participants between 2002 and 2003. Study participants (46 to 87 years of age) were without clinical cardiovascular disease at the baseline examination (2000–2002). Long-term outdoor concentrations of PM2.5 were estimated at each participant's home for the 2 years preceding the clinical exam using a spatio-temporal model. Short-term concentrations were assigned using outdoor measurements on the day preceding the clinical exam. Residential proximity to roadways was also used as an indicator of long-term traffic exposures. All associations were examined using linear regression models adjusted for subject-specific age, sex, race/ethnicity, education, income, smoking status, alcohol use, physical activity, body mass index, family history of cardiovascular disease, diabetes status, serum cholesterol, glucose, blood pressure, emphysema, C-reactive protein, medication use, and fellow vessel diameter. Short-term associations were further controlled for weather and seasonality. Among the 4,607 participants with complete data, CRAE were found to be narrower among persons residing in regions with increased long- and short-term levels of PM2.5. These relationships were observed in a joint exposure model with −0.8 µm (95% confidence interval [CI] −1.1 to −0.5) and −0.4 µm (95% CI −0.8 to 0.1) decreases in CRAE per interquartile increases in long- (3 µg/m3) and short-term (9 µg/m3) PM2.5 levels, respectively. These reductions in CRAE are equivalent to 7- and 3-year increases in age in the same cohort. Similarly, living near a major road was also associated with a −0.7 µm decrease (95% CI −1.4 to 0.1) in CRAE. Although the chronic association with CRAE was largely influenced by differences in exposure between cities, this relationship was generally robust to control for city-level covariates and no significant differences were observed between cities. Wider CRVE were associated with living in areas of higher PM2.5 concentrations, but these findings were less robust and not supported by the presence of consistent acute associations with PM2.5.
Conclusions
Residing in regions with higher air pollution concentrations and experiencing daily increases in air pollution were each associated with narrower retinal arteriolar diameters in older individuals. These findings support the hypothesis that important vascular phenomena are associated with small increases in short-term or long-term air pollution exposures, even at current exposure levels, and further corroborate reported associations between air pollution and the development and exacerbation of clinical cardiovascular disease.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Cardiovascular disease (CVD)—disease that affects the heart and/or the blood vessels—is a common cause of illness and death among adults in developed countries. In the United States, for example, the leading cause of death is coronary heart disease, a CVD in which narrowing of the heart's arteries by atherosclerotic plaques (fatty deposits that build up with age) slows the blood supply to the heart and may eventually cause a heart attack (myocardial infarction). Other types of CVD include stroke (in which atherosclerotic plaques interrupt the brain's blood supply) and peripheral arterial disease (in which the blood supply to the limbs is blocked). Smoking, high blood pressure, high blood levels of cholesterol (a type of fat), having diabetes, being overweight, and being physically inactive all increase a person's risk of developing CVD. Treatments for CVD include lifestyle changes and taking drugs that lower blood pressure or blood cholesterol levels.
Why Was This Study Done?
Another risk factor for CVD is exposure to long-term and/or short-term air pollution. Fine particle pollution or PM2.5 is particularly strongly associated with an increased risk of CVD. PM2.5—particulate matter 2.5 µm in diameter or 1/30th the diameter of a human hair—is mainly produced by motor vehicles, power plants, and other combustion sources. Why PM2.5 increases CVD risk is not clear but one possibility is that it alters the body's microvasculature (fine blood vessels known as capillaries, arterioles, and venules), thereby impairing the blood flow through the heart and brain. In this study, the researchers use noninvasive digital retinal photography to investigate whether there is an association between air pollution and changes in the human microvasculature. The retina—a light-sensitive layer at the back of the eye that converts images into electrical messages and sends them to the brain—has a dense microvasculature. Retinal photography is used to check the retinal microvasculature for signs of potentially blinding eye diseases such as diabetic retinopathy. Previous studies have found that narrower than normal retinal arterioles and wider than normal retinal venules are associated with CVD.
What Did the Researchers Do and Find?
The researchers used digital retinal photography to measure the diameters of retinal blood vessels in the participants of the Multi-Ethnic Study of Atherosclerosis (MESA). This study is investigating CVD progression in people aged 45–84 years of various ethnic backgrounds who had no CVD symptoms when they enrolled in the study in 2000–2002. The researchers modeled the long-term outdoor concentration of PM2.5 at each participant's house for the 2-year period preceding the retinal examination (which was done between 2002 and 2003) using data on PM2.5 levels collected by regulatory monitoring stations as well as study-specific air samples collected outside of the homes and in the communities of study participants. Outdoor PM2.5 measurements taken the day before the examination provided short-term PM2.5 levels. Among the 4,607 MESA participants who had complete data, retinal arteriolar diameters were narrowed among those who lived in regions with increased long- and short-term PM2.5 levels. Specifically, an increase in long-term PM2.5 concentrations of 3 µg/m3 was associated with a 0.8 µm decrease in arteriolar diameter, a reduction equivalent to that seen for a 7-year increase in age in this group of people. Living near a major road, another indicator of long-term exposure to PM2.5 pollution, was also associated with narrowed arterioles. Finally, increased retinal venular diameters were weakly associated with long-term high PM2.5 concentrations.
What Do These Findings Mean?
These findings indicate that living in areas with long-term air pollution or being exposed to short-term air pollution is associated with narrowing of the retinal arterioles in older individuals. They also show that widening of retinal venules is associated with long-term (but not short-term) PM2.5 pollution. Together, these findings support the hypothesis that long- and short-term air pollution increases CVD risk through effects on the microvasculature. However, they do not prove that PM2.5 is the constituent of air pollution that drives microvascular changes—these findings could reflect the toxicity of another pollutant or the pollution mixture as a whole. Importantly, these findings show that microvascular changes can occur at the PM2.5 levels that commonly occur in developed countries, which are well below those seen in developing countries. Worryingly, they also suggest that the deleterious cardiovascular effects of air pollution could occur at levels below existing regulatory standards.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/ 10.1371/journal.pmed.1000372.
The American Heart Association provides information for patients and caregivers on all aspects of cardiovascular disease (in several languages), including information on air pollution, heart disease, and stroke
The US Centers for Disease Control and Prevention has information on heart disease and on stroke
Information is available from the British Heart Foundation on cardiovascular disease
The UK National Health Service Choices website provides information for patients and caregivers about cardiovascular disease
MedlinePlus provides links to other sources of information on heart disease and on vascular disease (in English and Spanish)
The AIRNow site provides information about US air quality and about air pollution and health
The Air Quality Archive has up-to-date information about air pollution in the UK and information about the health effects of air pollution
The US Environmental Protection Agency has information on PM2.5
The following Web sites contain information available on the MESA and MESA Air studies
doi:10.1371/journal.pmed.1000372
PMCID: PMC2994677  PMID: 21152417
5.  Traffic exposure and lung function in adults: the Atherosclerosis Risk in Communities study 
Thorax  2007;62(10):873-879.
Background
Traffic exposure is a major contributor to ambient air pollution for people living close to busy roads. The relationship between traffic exposure and lung function remains inconclusive in adults.
Methods
We conducted a cross-sectional study to investigate the association between traffic exposure and lung function in the Atherosclerosis Risk in Communities (ARIC) study, a community-based cohort of 15,792 middle-aged men and women. Traffic density and distance to major roads were used as measures of traffic exposure.
Results
After controlling for potential confounders including demographic factors, personal and neighborhood level socioeconomic characteristics, cigarette smoking, and background air pollution, higher traffic density was significantly associated with lower forced expiratory volume at 1s (FEV1) and forced vital capacity (FVC) in females. Relative to the lowest quartile of traffic density, the adjusted differences across increasing quartiles were 5.1, −15.4 and −21.5ml for FEV1 (p value of linear trend across the quartiles =0.041), and 1.2, −23.4 and −34.8ml for FVC (p trend =0.010). Using distance from major roads as a simpler index of traffic related air pollution exposure, the FEV1 was −15.7ml (95%CI −34.4ml, 2.9ml) lower and the FVC was −24.2ml (95%CI −46.2ml, −2.3ml) lower for women living within 150 meters compared to subjects living further away. We did not find a significant effect of traffic density or distance to major roads on lung function among men. The FEV1/FVC ratio was not significantly associated with traffic exposure in either gender.
Conclusions
This is the largest published study of traffic exposure and pulmonary function in adults to date. These results add to growing evidence that chronic exposure to traffic-related air pollution may adversely affect respiratory health.
doi:10.1136/thx.2006.073015
PMCID: PMC2094260  PMID: 17442705
air pollution; traffic; pulmonary function; FEV1; FVC
6.  Hypertension and Exposure to Noise Near Airports: the HYENA Study 
Environmental Health Perspectives  2007;116(3):329-333.
Background
An increasing number of people are exposed to aircraft and road traffic noise. Hypertension is an important risk factor for cardiovascular disease, and even a small contribution in risk from environmental factors may have a major impact on public health.
Objectives
The HYENA (Hypertension and Exposure to Noise near Airports) study aimed to assess the relations between noise from aircraft or road traffic near airports and the risk of hypertension.
Methods
We measured blood pressure and collected data on health, socioeconomic, and lifestyle factors, including diet and physical activity, via questionnaire at home visits for 4,861 persons 45–70 years of age, who had lived at least 5 years near any of six major European airports. We assessed noise exposure using detailed models with a resolution of 1 dB (5 dB for United Kingdom road traffic noise), and a spatial resolution of 250 × 250 m for aircraft and 10 × 10 m for road traffic noise.
Results
We found significant exposure–response relationships between night-time aircraft as well as average daily road traffic noise exposure and risk of hypertension after adjustment for major confounders. For night-time aircraft noise, a 10-dB increase in exposure was associated with an odds ratio (OR) of 1.14 [95% confidence interval (CI), 1.01–1.29]. The exposure–response relationships were similar for road traffic noise and stronger for men with an OR of 1.54 (95% CI, 0.99–2.40) in the highest exposure category (> 65 dB; ptrend = 0.008).
Conclusions
Our results indicate excess risks of hypertension related to long-term noise exposure, primarily for night-time aircraft noise and daily average road traffic noise.
doi:10.1289/ehp.10775
PMCID: PMC2265027  PMID: 18335099
aircraft; blood pressure; hypertension; noise; road traffic
7.  Prescription Medicines and the Risk of Road Traffic Crashes: A French Registry-Based Study 
PLoS Medicine  2010;7(11):e1000366.
Using three nationwide databases in France, Ludivine Orriols, Emmanuel Lagarde, and colleagues provide evidence that prescribed medicines contribute to the risk of experiencing a road traffic crash.
Background
In recent decades, increased attention has been focused on the impact of disabilities and medicinal drug use on road safety. The aim of our study was to investigate the association between prescription medicines and the risk of road traffic crashes, and estimate the attributable fraction.
Methods and Findings
We extracted and matched data from three French nationwide databases: the national health care insurance database, police reports, and the national police database of injurious crashes. Drivers identified by their national health care number involved in an injurious crash in France, between July 2005 and May 2008, were included in the study. Medicines were grouped according to the four risk levels of the French classification system (from 0 [no risk] to 3 [high risk]). We included 72,685 drivers involved in injurious crashes. Users of level 2 (odds ratio [OR]  = 1.31 [1.24–1.40]) and level 3 (OR  = 1.25 [1.12–1.40]) prescription medicines were at higher risk of being responsible for a crash. The association remained after adjustment for the presence of a long-term chronic disease. The fraction of road traffic crashes attributable to levels 2 and 3 medications was 3.3% [2.7%–3.9%]. A within-person case-crossover analysis showed that drivers were more likely to be exposed to level 3 medications on the crash day than on a control day, 30 days earlier (OR  = 1.15 [1.05–1.27]).
Conclusion
The use of prescription medicines is associated with a substantial number of road traffic crashes in France. In light of the results, warning messages appear to be relevant for level 2 and 3 medications and questionable for level 1 medications. A follow-up study is needed to evaluate the impact of the warning labeling system on road traffic crash prevention.
Please see later in the article for the Editors' Summary
Editors' Summary
About 1.3 million people die each year on the world's road. 90% of road traffic deaths occur in developing countries, with pedestrians, cyclists, and users of two-wheel vehicles (scooters, motorbikes) the most vulnerable road users. Although the use of prescribed benzodiazepines has already been documented to be associated with road traffic accidents in industrialized countries, the effects of other medicines have not been well studied or have inconsistent results (for example opioids and antidepressant medications). In the European Union, it is mandatory for pharmaceutical companies to provide data about the effect of a medicine on ability to drive. In France, a multidisciplinary group of experts was appointed to classify all medicines into four levels of risk (from level 0, no or negligible risk, to level 3, major risk), in terms of their effect on driving performances. In 2006, the International Council on Alcohol, Drugs and Traffic Safety proposed a classification list similar to the French classification system.
Why Was This Study Done? There is a pressing need to understand the association between prescribed medicines and the risk of road traffic crashes and also to have a more accurate picture of the fraction of road traffic crashes that are attributable to the use of prescribed medicines. This large French study aimed to advance knowledge in this important area.
What Did the Researchers Do and Find? The researchers used three data sources to find the information they needed: the national health care insurance database (which covers the whole French population and includes data on reimbursed prescription medicines), police reports, and the national police database of injurious road traffic crashes. Drivers involved in road traffic crashes (identified by their national healthcare number) between July 2005 and May 2008 were included in the study. The researchers used a statistical model to conduct a responsibility analysis, which determined factors associated with each driver responsible for the road traffic crash and each driver who was not responsible (controls). In addition, the researchers compared medicine exposure during a period immediately before the crash (case period) with exposure during an earlier period (control period) for each driver involved in a crash. The researchers retrieved data on reimbursed medicines, dispensed within six months of the road traffic crash, by linking included drivers to the national health care insurance database using their national ID, gender, and date of birth and grouped all prescribed medicines according to the four risk levels of the French classification system.
During the study period, 72,685 drivers involved in injurious road traffic crashes were included. The researchers found that drivers who had been prescribed level 2 and level 3 medicines were at higher risk (odds ratio 1.31 and OR 1.25, respectively) of being responsible for the road traffic crash, an association that remained after the researchers adjusted for the presence of chronic diseases. Furthermore, the researchers found that the fraction of road traffic crashes attributable to the use of (prescriptions for) level 2 and 3 medicines was 3.3% and that drivers were more likely to be exposed to level 3 medicines on the day of the road traffic crash than on a control day.
What Do These Findings Mean? This study provides strong evidence for the contribution of medicines to the risk of experiencing a road traffic crash. The French drug risk classification scheme seems accurate for medicines classified as levels 2 and 3 of risk for road traffic crashes. The effect on driving abilities of level 2 medicines depends both on the pharmacodynamics of the drug and on individual susceptibility, whereas for level 3 medicines, the pharmacodynamic effect seems to be predominant. The effects of level 1 medicines seem to be so dependent on individual susceptibility that effects on driving abilities are rare, which raises questions about the relevance of the labels for these medicines. However, some limitations with the study methodology might affect the interpretation of these findings. For example, the researchers used dispensing dates for medications as a surrogate for ingestion and were not able to check for noncompliance.
However, this study provides some of the strongest evidence to date of the need for health care workers to provide patients with proper information on the potential effect of any medicine that they are prescribed (or take) on their driving abilities.
Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000366.The World Health Organization (WHO) provides information on road traffic accidentsTwo Web sites provide information for drivers about drugs that could affect their ability to driveThe US National Institute on Drug Abuse of the National Institutes of Health has an information sheet on drugged driving
doi:10.1371/journal.pmed.1000366
PMCID: PMC2981588  PMID: 21125020
8.  Air pollution and health risks due to vehicle traffic 
Traffic congestion increases vehicle emissions and degrades ambient air quality, and recent studies have shown excess morbidity and mortality for drivers, commuters and individuals living near major roadways. Presently, our understanding of the air pollution impacts from congestion on roads is very limited. This study demonstrates an approach to characterize risks of traffic for on- and near-road populations. Simulation modeling was used to estimate on- and near-road NO2 concentrations and health risks for freeway and arterial scenarios attributable to traffic for different traffic volumes during rush hour periods. The modeling used emission factors from two different models (Comprehensive Modal Emissions Model and Motor Vehicle Emissions Factor Model version 6.2), an empirical traffic speed–volume relationship, the California Line Source Dispersion Model, an empirical NO2–NOx relationship, estimated travel time changes during congestion, and concentration–response relationships from the literature, which give emergency doctor visits, hospital admissions and mortality attributed to NO2 exposure. An incremental analysis, which expresses the change in health risks for small increases in traffic volume, showed non-linear effects. For a freeway, “U” shaped trends of incremental risks were predicted for on-road populations, and incremental risks are flat at low traffic volumes for near-road populations. For an arterial road, incremental risks increased sharply for both on- and near-road populations as traffic increased. These patterns result from changes in emission factors, the NO2–NOx relationship, the travel delay for the on-road population, and the extended duration of rush hour for the near-road population. This study suggests that health risks from congestion are potentially significant, and that additional traffic can significantly increase risks, depending on the type of road and other factors. Further, evaluations of risk associated with congestion must consider travel time, the duration of rush-hour, congestion-specific emission estimates, and uncertainties.
doi:10.1016/j.scitotenv.2013.01.074
PMCID: PMC4243514  PMID: 23500830
Congestion; Morbidity; Mortality; NO2; Risk assessment; Traffic-related air pollution
9.  Socioeconomic Position and Low Birth Weight among Mothers Exposed to Traffic-Related Air Pollution 
PLoS ONE  2014;9(11):e113900.
Background
Atmospheric pollution is a major public health concern. It can affect placental function and restricts fetal growth. However, scientific knowledge remains too limited to make inferences regarding causal associations between maternal exposure to air pollution and adverse effects on pregnancy. This study evaluated the association between low birth weight (LBW) and maternal exposure during pregnancy to traffic related air pollutants (TRAP) in São Paulo, Brazil.
Methods and findings
Analysis included 5,772 cases of term-LBW (<2,500 g) and 5,814 controls matched by sex and month of birth selected from the birth registration system. Mothers’ addresses were geocoded to estimate exposure according to 3 indicators: distance from home to heavy traffic roads, distance-weighted traffic density (DWTD) and levels of particulate matter ≤10 µg/m3 estimated through land use regression (LUR-PM10). Final models were evaluated using multiple logistic regression adjusting for birth, maternal and pregnancy characteristics. We found decreased odds in the risk of LBW associated with DWTD and LUR-PM10 in the highest quartiles of exposure with a significant linear trend of decrease in risk. The analysis with distance from heavy traffic roads was less consistent. It was also observed that mothers with higher education and neighborhood-level income were potentially more exposed to TRAP.
Conclusions
This study found an unexpected decreased risk of LBW associated with traffic related air pollution. Mothers with advantaged socioeconomic position (SEP) although residing in areas of higher vehicular traffic might not in fact be more expose to air pollution. It can also be that the protection against LBW arising from a better SEP is stronger than the effect of exposure to air pollution, and this exposure may not be sufficient to increase the risk of LBW for these mothers.
doi:10.1371/journal.pone.0113900
PMCID: PMC4245223  PMID: 25426640
10.  Road Traffic and Childhood Leukemia: The ESCALE Study (SFCE) 
Environmental Health Perspectives  2010;119(4):566-572.
Background
Traffic is a source of environmental exposures, including benzene, which may be related to childhood leukemia.
Objectives
A national registry–based case–control study [ESCALE (Etude Sur les Cancers et les Leucémies de l’Enfant, Study on Environmental and Genetic Risk Factors of Childhood Cancers and Leukemia)] carried out in France was used to assess the effect of exposure to road traffic exhaust fumes on the risk of childhood leukemia.
Methods
Over the study period, 2003–2004, 763 cases and 1,681 controls < 15 years old were included, and the controls were frequency matched with the cases on age and sex. The ESCALE data were collected by a standardized telephone interview of the mothers. Various indicators of exposure to traffic and pollution were determined using the geocoded addresses at the time of diagnosis for the cases and of interview for the controls. Indicators of the distance from, and density of, main roads and traffic nitrogen dioxide (NO2) concentrations derived from traffic emission data were used. Odds ratios (ORs) were estimated using unconditional regression models adjusted for potential confounders.
Results
Acute leukemia (AL) was significantly associated with estimates of traffic NO2 concentration at the place of residence > 27.7 μg/m3 compared with NO2 concentration < 21.9 μg/m3 [OR = 1.2; confidence interval (CI), 1.0–1.5] and with the presence of a heavy-traffic road within 500 m compared with the absence of a heavy-traffic road in the same area (OR = 2.0; 95% CI, 1.0–3.6). There was a significant association between AL and a high density of heavy-traffic roads within 500 m compared with the reference category with no heavy-traffic road within 500 m (OR = 2.2; 95% CI, 1.1–4.2), with a significant positive linear trend of the association of AL with the total length of heavy-traffic road within 500m.
Conclusion
This study supports the hypothesis that living close to heavy-traffic roads may increase the risk of childhood leukemia.
doi:10.1289/ehp.1002429
PMCID: PMC3080942  PMID: 21147599
acute leukemia; benzene; children; environment; epidemiology; road traffic
11.  Prospective Analysis of Traffic Exposure as a Risk Factor for Incident Coronary Heart Disease: The Atherosclerosis Risk in Communities (ARIC) Study 
Environmental Health Perspectives  2008;116(11):1463-1468.
Background
For people living close to busy roads, traffic is a major source of air pollution. Few prospective data have been published on the effects of long-term exposure to traffic on the incidence of coronary heart disease (CHD).
Objectives
In this article, we examined the association between long-term traffic exposure and incidence of fatal and nonfatal CHD in a population-based prospective cohort study.
Methods
We studied 13,309 middle-age men and women in the Atherosclerosis Risk in Communities study, without previous CHD at enrollment, from 1987 to 1989 in four U.S. communities. Geographic information system–mapped traffic density and distance to major roads served as measures of traffic exposure. We examined the association between traffic exposure and incident CHD using proportional hazards regression models, with adjustment for background air pollution and a wide range of individual cardiovascular risk factors.
Results
Over an average of 13 years of follow-up, 976 subjects developed CHD. Relative to those in the lowest quartile of traffic density, the adjusted hazard ratio (HR) in the highest quartile was 1.32 [95% confidence interval (CI), 1.06–1.65; p-value for trend across quartiles = 0.042]. When we treated traffic density as a continuous variable, the adjusted HR per one unit increase of log-transformed density was 1.03 (95% CI, 1.01–1.05; p = 0.006). For residents living within 300 m of major roads compared with those living farther away, the adjusted HR was 1.12 (95% CI, 0.95–1.32; p = 0.189). We found little evidence of effect modification for sex, smoking status, obesity, low-density lipoprotein cholesterol level, hypertension, age, or education.
Conclusion
Higher long-term exposure to traffic is associated with incidence of CHD, independent of other risk factors. These prospective data support an effect of traffic-related air pollution on the development of CHD in middle-age persons.
doi:10.1289/ehp.11290
PMCID: PMC2592264  PMID: 19057697
air pollution; coronary disease; traffic
12.  Comparison between various indices of exposure to traffic-related air pollution and their impact on respiratory health in adults 
Objective:
To evaluate the association of different indices of traffic-related air pollution (self-report of traffic intensity, distance from busy roads from geographical information system (GIS), area-based emissions of particulate matter (PM), and estimated concentrations of nitrogen dioxide (NO2) from a land-use regression model) with respiratory health in adults.
Methods:
A sample of 9488 25–59-year-old Rome residents completed a self-administered questionnaire on respiratory health and various risk factors, including education, occupation, housing conditions, smoking, and traffic intensity in their area of residence. The study used GIS to calculate the distance between their home address and the closest high-traffic road. For each subject, PM emissions in the area of residence as well as estimated NO2 concentrations as assessed by a land-use regression model (R2 value = 0.69), were available. Generalised estimating equations (GEE) were used to analyse the association between air pollution measures and prevalence of “ever” chronic bronchitis, asthma, and rhinitis taking into account the effects of age, gender, education, smoking habits, socioeconomic position, and the correlation of variables for members of the same family.
Results:
Three hundred and ninety seven subjects (4% of the study population) reported chronic bronchitis, 472 (5%) asthma, and 1227 (13%) rhinitis. Fifteen per cent of subjects reported living in high traffic areas, 11% lived within 50 m of a high traffic road, and 28% in areas with estimated NO2 greater than 50 μg/m3. Prevalence of asthma was associated only with self-reported traffic intensity whereas no association was found for the other more objective indices. Rhinitis, on the other hand, was strongly associated with all traffic-related indicators (eg, OR = 1.13, 95% CI: 1.04 to 1.22 for 10 μg/m3 NO2), especially among non-smokers.
Conclusions:
Indices of exposure to traffic-related air pollution are consistently associated with an increased risk of rhinitis in adults, especially among non-smokers. The results for asthma are weak, possibly due to ascertainment problems.
doi:10.1136/oem.2007.037846
PMCID: PMC2771851  PMID: 18203803
13.  Impact of traffic related air pollution indicators on non-cystic fibrosis bronchiectasis mortality: a cohort analysis 
Respiratory Research  2014;15(1):108.
Background
Mortality in non-cystic fibrosis bronchiectasis (NCFB) is known to be influenced by a number of factors such as gender, age, smoking history and Pseudomonas aeruginosa, but the impact of traffic related air pollution indicators on NCFB mortality is unknown.
Methods
We followed 183 patients aged 18 to 65 years with a HRCT proven diagnosis of NCFB and typical symptoms, who had visited the outpatient clinic at the University Hospital of Leuven, Belgium, between June 2006 and October 2012. We estimated hazard ratios (HR) for mortality in relation to proximity of the home to major roads and traffic load, adjusting for relevant covariables (age, gender, disease severity, chronic macrolide use, smoking history, socioeconomic status and Pseudomonas aeruginosa colonization status).
Results
Fifteen out of the 183 included patients died during the observation period. Residential proximity to a major road was associated with the risk of dying with a HR 0.28 (CI 95% 0.10-0.77; p = 0.013) for a tenfold increase in distance to a major road. Mortality was also associated with distance-weighted traffic density within 100 meters (HR for each tenfold increase in traffic density 3.80; CI 95% 1.07-13.51; p = 0.04) and 200 meters from the patient’s home address (HR for each tenfold increase in traffic density 4.14; CI 95% 1.13-15.22; p = 0.032).
Conclusion
Traffic-related air pollution appears to increase the risk of dying in patients with NCFB.
Trial registration
The study was approved by the local ethical committee of the UZ Leuven, Belgium (ML-5028), registered at ClinicalTrial.gov (NCT01906047).
doi:10.1186/s12931-014-0108-z
PMCID: PMC4156957  PMID: 25183428
Non-cystic fibrosis bronchiectasis; Pollution; Traffic; Road; Mortality
14.  Traffic exposure and lung function in adults: the Atherosclerosis Risk in Communities study 
Thorax  2007;62(10):873-879.
Background
Traffic exposure is a major contributor to ambient air pollution for people living close to busy roads. The relationship between traffic exposure and lung function remains inconclusive in adults.
Methods
A cross‐sectional study was conducted to investigate the association between traffic exposure and lung function in the Atherosclerosis Risk in Communities (ARIC) study, a community based cohort of 15 792 middle aged men and women. Traffic density and distance to major roads were used as measures of traffic exposure.
Results
After controlling for potential confounders including demographic factors, personal and neighbourhood level socioeconomic characteristics, cigarette smoking and background air pollution, higher traffic density was significantly associated with lower forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in women. Relative to the lowest quartile of traffic density, the adjusted differences across increasing quartiles were 5.1, −15.4 and −21.5 ml for FEV1 (p value of linear trend across the quartiles = 0.041) and 1.2, −23.4 and −34.8 ml for FVC (p trend = 0.010). Using distance from major roads as a simpler index of traffic related air pollution exposure, the FEV1 was −15.7 ml (95% CI −34.4 to 2.9) lower and the FVC was −24.2 ml (95% CI −46.2 to −2.3) lower for women living within 150 m compared with subjects living further away. There was no significant effect of traffic density or distance to major roads on lung function in men. The FEV1/FVC ratio was not significantly associated with traffic exposure in either men or women.
Conclusions
This is the largest published study of traffic exposure and pulmonary function in adults to date. These results add to growing evidence that chronic exposure to traffic related air pollution may adversely affect respiratory health.
doi:10.1136/thx.2006.073015
PMCID: PMC2094260  PMID: 17442705
15.  A Comparison of Exposure Metrics for Traffic-Related Air Pollutants: Application to Epidemiology Studies in Detroit, Michigan 
Vehicles are major sources of air pollutant emissions, and individuals living near large roads endure high exposures and health risks associated with traffic-related air pollutants. Air pollution epidemiology, health risk, environmental justice, and transportation planning studies would all benefit from an improved understanding of the key information and metrics needed to assess exposures, as well as the strengths and limitations of alternate exposure metrics. This study develops and evaluates several metrics for characterizing exposure to traffic-related air pollutants for the 218 residential locations of participants in the NEXUS epidemiology study conducted in Detroit (MI, USA). Exposure metrics included proximity to major roads, traffic volume, vehicle mix, traffic density, vehicle exhaust emissions density, and pollutant concentrations predicted by dispersion models. Results presented for each metric include comparisons of exposure distributions, spatial variability, intraclass correlation, concordance and discordance rates, and overall strengths and limitations. While showing some agreement, the simple categorical and proximity classifications (e.g., high diesel/low diesel traffic roads and distance from major roads) do not reflect the range and overlap of exposures seen in the other metrics. Information provided by the traffic density metric, defined as the number of kilometers traveled (VKT) per day within a 300 m buffer around each home, was reasonably consistent with the more sophisticated metrics. Dispersion modeling provided spatially- and temporally-resolved concentrations, along with apportionments that separated concentrations due to traffic emissions and other sources. While several of the exposure metrics showed broad agreement, including traffic density, emissions density and modeled concentrations, these alternatives still produced exposure classifications that differed for a substantial fraction of study participants, e.g., from 20% to 50% of homes, depending on the metric, would be incorrectly classified into “low”, “medium” or “high” traffic exposure classes. These and other results suggest the potential for exposure misclassification and the need for refined and validated exposure metrics. While data and computational demands for dispersion modeling of traffic emissions are non-trivial concerns, once established, dispersion modeling systems can provide exposure information for both on- and near-road environments that would benefit future traffic-related assessments.
doi:10.3390/ijerph110909553
PMCID: PMC4199035  PMID: 25226412
air pollution; dispersion modeling; epidemiology; exhaust; exposure misclassification; PM2.5; traffic; vehicle
16.  Heavy vehicle traffic is related to wheeze among schoolchildren: a population-based study in an area with low traffic flows 
Environmental Health  2011;10:91.
Background
An association between traffic air pollution and respiratory symptoms among children has been reported. However, the effects of traffic air pollution on asthma and wheeze have been very sparsely studied in areas with low traffic intensity in cold climate with poor dispersion. We evaluated the impact of vehicle traffic on childhood asthma and wheeze by objective exposure assessment.
Methods
As a part of the Obstructive Lung Disease in Northern Sweden (OLIN) studies, a questionnaire was sent to the families of all children attending first or second grade in Luleå (72,000 inhabitants) in Northern Sweden in 2006. The age of the children was 7-8 years and the participation rate was 98% (n = 1357). Skin prick tests were performed in 1224 (89%) children. The home addresses were given geographical coordinates and traffic counts were obtained from the local traffic authorities. A proximity model of average daily traffic and average daily heavy vehicle traffic within 200 meters from each participant's home address was used. The associations between traffic exposure and asthma and wheeze, respectively, were analysed in an adjusted multiple logistic regression model.
Results
Exposure to high traffic flows was uncommon in the study area; only 15% of the children lived within 200 meters from a road with a traffic flow of ≥8000 vehicles per day. Living closer than 200 meters from a road with ≥500 heavy vehicles daily was associated with current wheeze, odds ratio 1.7 (confidence interval 1.0-2.7). A dose-response relation was indicated. An increased risk of asthma was also seen, however not significant, odds ratio 1.5 (confidence interval 0.8-2.9). Stratified analyses revealed that the effect of traffic exposure was restricted to the non-sensitized phenotype of asthma and wheeze. The agreement between self-reported traffic exposure and objective measurements of exposure was moderate.
Conclusions
This study showed that already at low levels of exposure, vehicle traffic is related to an increased risk of wheeze among children. Thus, the global burden of traffic air pollution may be underestimated.
doi:10.1186/1476-069X-10-91
PMCID: PMC3206415  PMID: 21995638
17.  Incidence of Deep Vein Thrombosis after Major Lower Limb Orthopedic Surgery: Analysis of a Nationwide Claim Registry 
Yonsei Medical Journal  2014;56(1):139-145.
Purpose
We aimed to evaluate the nationwide incidence and risk factors for symptomatic deep vein thrombosis (DVT) after major lower limb orthopedic surgeries.
Materials and Methods
The Korean Health Insurance Review and Assessment Service database was used to retrospectively identify International Classification of Disease-10 codes for DVT and operation codes representing hip arthroplasty, knee arthroplasty, and hip fracture surgeries. The age- and gender-adjusted annual incidence of DVT, rates of major lower limb orthopedic surgeries, and the postoperative incidence of DVT according to the surgical procedure were assessed.
Results
The age- and gender-adjusted annual incidence of DVT was 70.67 per 100000 persons/year. Compared to patients aged <49 years, the relative risk of DVT was five times higher in patients aged 50-69 and 10 times higher in patients aged >70 years (p<0.001). Females showed a greater relative risk for DVT than males (1.08; p<0.001). The incidence of postoperative DVT, according to the type of surgery, was significantly greater for knee replacement arthroplasty than for other forms of surgery (p<0.002). The relative risk of postoperative DVT was higher in females in knee replacement arthroplasty (1.47) and hip fracture surgery (2.25) groups, although relatively lower in those who underwent hip replacement arthroplasty (0.97).
Conclusion
Among major lower limb surgeries, advanced age, female gender, and undergoing a knee replacement arthroplasty were found to be risk factors for developing postoperative DVT. These findings further emphasize the need for orthopedic surgeons to consider the development of DVT after surgery in high-risk patients.
doi:10.3349/ymj.2015.56.1.139
PMCID: PMC4276747  PMID: 25510757
Deep vein thrombosis; incidence; hip arthroplasty; knee arthroplasty; hip fracture surgery
18.  Long-term air pollution exposure and living close to busy roads are associated with COPD in women 
Respiratory Research  2005;6(1):152.
Background
Lung function and exacerbations of chronic obstructive pulmonary disease (COPD) have been associated with short-term exposure to air pollution. However, the effect of long-term exposure to particulate matter from industry and traffic on COPD as defined by lung function has not been evaluated so far. Our study was designed to investigate the influence of long-term exposure to air pollution on respiratory symptoms and pulmonary function in 55-year-old women. We especially focused on COPD as defined by GOLD criteria and additionally compared the effects of air pollution on respiratory symptoms by questionnaire data and by lung function measurements.
Methods
In consecutive cross sectional studies conducted between 1985–1994, we investigated 4757 women living in the Rhine-Ruhr Basin of Germany. NO2 and PM10 exposure was assessed by measurements done in an 8 km grid, and traffic exposure by distance from the residential address to the nearest major road using Geographic Information System data. Lung function was determined and COPD was defined by using the GOLD criteria. Chronic respiratory symptoms and possible confounders were defined by questionnaire data. Linear and logistic regressions, including random effects were used to account for confounding and clustering on city level.
Results
The prevalence of COPD (GOLD stages 1–4) was 4.5%. COPD and pulmonary function were strongest affected by PM10 and traffic related exposure. A 7 μg/m3 increase in five year means of PM10 (interquartile range) was associated with a 5.1% (95% CI 2.5%–7.7%) decrease in FEV1, a 3.7% (95% CI 1.8%–5.5%) decrease in FVC and an odds ratio (OR) of 1.33 (95% CI 1.03–1.72) for COPD. Women living less than 100 m from a busy road also had a significantly decreased lung function and COPD was 1.79 times more likely (95% CI 1.06–3.02) than for those living farther away. Chronic symptoms as based on questionnaire information showed effects in the same direction, but less pronounced.
Conclusion
Chronic exposure to PM10, NO2 and living near a major road might increase the risk of developing COPD and can have a detrimental effect on lung function.
doi:10.1186/1465-9921-6-152
PMCID: PMC1352358  PMID: 16372913
19.  Exposure to Traffic Pollution and Increased Risk of Rheumatoid Arthritis 
Environmental Health Perspectives  2009;117(7):1065-1069.
Background
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that affects approximately 1% of the adult population, and to date, genetic factors explain < 50% of the risk. Particulate air pollution, especially of traffic origin, has been linked to systemic inflammation in many studies.
Objectives
We examined the association of distance to road, a marker of traffic pollution exposure, and incidence of RA in a prospective cohort study.
Methods
We studied 90,297 U.S. women in the Nurses’ Health Study. We used a geographic information system to determine distance to road at the residence in 2000 as a measure of traffic exposure. Using Cox proportional hazard models, we examined the association of distance to road and incident RA (1976–2004) with adjustment for a large number of potential confounders.
Results
In models adjusted for age, calendar year, race, cigarette smoking, parity, lactation, menopausal status and hormone use, oral contraceptive use, body mass index, physical activity, and census-tract-level median income and house value, we observed an elevated risk of RA [hazard ratio (HR) = 1.31; 95% confidence interval (CI), 0.98–1.74] in women living within 50 m of a road, compared with those women living 200 m or farther away. We also observed this association in analyses among nonsmokers (HR = 1.62; 95% CI, 1.04–2.52), nonsmokers with rheumatoid factor (RF)-negative RA (HR = 1.77; 95% CI, 0.93–3.38), and nonsmokers with RF-positive RA (HR = 1.51; 95% CI, 0.82–2.77). We saw no elevations in risk in women living 50–200 m from the road.
Conclusions
The observed association between exposure to traffic pollution and RA suggests that pollution from traffic in adulthood may be a newly identified environmental risk factor for RA.
doi:10.1289/ehp.0800503
PMCID: PMC2717131  PMID: 19654914
air pollution; prospective study; rheumatoid arthritis; roadway proximity; traffic
20.  Residential Traffic and Children’s Respiratory Health 
Environmental Health Perspectives  2008;116(9):1274-1279.
Background
Living near traffic has been associated with asthma and other respiratory symptoms. Most studies, however, have been conducted in areas with high background levels of ambient air pollution, making it challenging to isolate an independent effect of traffic. Additionally, most investigations have used surrogates of exposure, and few have measured traffic pollutants directly as part of the study.
Objective
We conducted a cross-sectional study of current asthma and other respiratory symptoms in children (n = 1,080) living at varying distances from high-traffic roads in the San Francisco Bay Area, California, a highly urbanized region characterized by good regional air quality due to coastal breezes.
Methods
We obtained health information and home environmental factors by parental questionnaire. We assessed exposure with several measures of residential proximity to traffic calculated using geographic information systems, including traffic within a given radius and distance to major roads. We also measured traffic-related pollutants (nitrogen oxides and nitrogen dioxide) for a subset of households to determine how well traffic metrics correlated with measured traffic pollutants.
Results
Using multivariate logistic regression analyses, we found associations between current asthma and residential proximity to traffic. For several traffic metrics, children whose residences were in the highest quintile of exposure had approximately twice the adjusted odds of current asthma (i.e., asthma episode in the preceeding 12 months) compared with children whose residences were within the lowest quintile. The highest risks were among those living within 75 m of a freeway/highway. Most traffic metrics correlated moderately well with actual pollutant measurements.
Conclusion
Our findings provide evidence that even in an area with good regional air quality, proximity to traffic is associated with adverse respiratory health effects in children.
doi:10.1289/ehp.10735
PMCID: PMC2535634  PMID: 18795175
air pollution; asthma; bronchitis; children; respiratory health; traffic
21.  Proximity of the home to roads and the risk of wheeze in an Ethiopian population 
Background: There is widespread public concern that exposure to road vehicle traffic pollution causes asthma, but epidemiological studies in developed countries have not generally confirmed a strong effect and may have underestimated the risk as a result of relatively high and widespread exposure to traffic in everyday life.
Aims: To investigate the effect of living close to a traffic bearing road on the risk of wheezing in Jimma, Ethiopia where road traffic is generally low and restricted to a limited network of roads.
Methods: Data have been previously collected on respiratory symptoms, allergic sensitisation, and numerous demographic and lifestyle factors in a systematic sample of inhabitants of Jimma town. In 2003 the homes of these people were retraced; the shortest distance to the nearest surfaced road, and traffic flows on these roads were measured.
Results: Distance measurements were collected for 7609 (80%) individuals. The overall prevalence of wheeze was similar in those living within 150 m of a road compared to those living further away (3.9% v 3.7%), but among the 3592 individuals living within 150 m, the risk of wheeze increased significantly in linear relation to proximity to the road (adjusted odds ratio = 1.17 per 30 m proximity, 95% CI 1.01 to 1.36). This relation was stronger, though not significantly so, for roads with above median traffic flows.
Conclusion: These findings indicate that living in close proximity to road vehicle traffic is associated with an increased risk of wheeze, but that other environmental factors are also likely to be important.
doi:10.1136/oem.2004.017228
PMCID: PMC1741025  PMID: 15901884
22.  Prediction and analysis of near-road concentrations using a reduced-form emission/dispersion model 
Environmental Health  2010;9:29.
Background
Near-road exposures of traffic-related air pollutants have been receiving increased attention due to evidence linking emissions from high-traffic roadways to adverse health outcomes. To date, most epidemiological and risk analyses have utilized simple but crude exposure indicators, most typically proximity measures, such as the distance between freeways and residences, to represent air quality impacts from traffic. This paper derives and analyzes a simplified microscale simulation model designed to predict short- (hourly) to long-term (annual average) pollutant concentrations near roads. Sensitivity analyses and case studies are used to highlight issues in predicting near-road exposures.
Methods
Process-based simulation models using a computationally efficient reduced-form response surface structure and a minimum number of inputs integrate the major determinants of air pollution exposures: traffic volume and vehicle emissions, meteorology, and receptor location. We identify the most influential variables and then derive a set of multiplicative submodels that match predictions from "parent" models MOBILE6.2 and CALINE4. The assembled model is applied to two case studies in the Detroit, Michigan area. The first predicts carbon monoxide (CO) concentrations at a monitoring site near a freeway. The second predicts CO and PM2.5 concentrations in a dense receptor grid over a 1 km2 area around the intersection of two major roads. We analyze the spatial and temporal patterns of pollutant concentration predictions.
Results
Predicted CO concentrations showed reasonable agreement with annual average and 24-hour measurements, e.g., 59% of the 24-hr predictions were within a factor of two of observations in the warmer months when CO emissions are more consistent. The highest concentrations of both CO and PM2.5 were predicted to occur near intersections and downwind of major roads during periods of unfavorable meteorology (e.g., low wind speeds) and high emissions (e.g., weekday rush hour). The spatial and temporal variation among predicted concentrations was significant, and resulted in unusual distributional and correlation characteristics, including strong negative correlation for receptors on opposite sides of a road and the highest short-term concentrations on the "upwind" side of the road.
Conclusions
The case study findings can likely be generalized to many other locations, and they have important implications for epidemiological and other studies. The reduced-form model is intended for exposure assessment, risk assessment, epidemiological, geographical information systems, and other applications.
doi:10.1186/1476-069X-9-29
PMCID: PMC2914002  PMID: 20579353
23.  Diesel Exhaust Exposure, Wheezing and Sneezing 
The rising incidence of allergic disorders in developed countries is unexplained. Exposure to traffic related air pollutants may be an important cause of wheezing and asthma in childhood. Experimental evidence from human studies suggests that diesel exhaust particles, constituents of fine particulate matter less than 2.5 microns (PM2.5), may act to enhance IgE mediated aeroallergen sensitization and Th2 directed cytokine responses. To date, epidemiologic investigations indicate that children living in close proximity to heavily travelled roads are more likely to be atopic and wheeze. The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort study was initiated to test the hypothesis that early high exposure to traffic related air pollutants is associated with early aeroallergen sensitization and allergic respiratory phenotypes. Using an exposure cohort design, more than 700 infants born to atopic parents were recruited at age 1 living either less than 400 meters (high traffic pollutant exposure) or greater than 1,500 meters (low exposure) from a major road. Children were medically evaluated and underwent skin prick testing with aeroallergen at screening, and re-evaluated sequentially at ages 1, 2, 3, 4, and 7. In this study, both proximity and land use regression (LUR) models of traffic air pollutant exposure have been assessed. Proximity to stop and go traffic with large concentrations of bus and truck traffic predicted persistent wheezing during infancy. The LUR model estimated elemental carbon attributable to traffic (ECAT) as a proxy for diesel exhaust particulate exposure. High ECAT was significantly associated with wheezing at age 1 as well as persistent wheezing at age 3. High mold exposure predicted a well defined asthma phenotype at age 7.
doi:10.4168/aair.2012.4.4.178
PMCID: PMC3378923  PMID: 22754710
Air pollution; childhood; asthma; allergy; diesel
24.  Traffic Air Pollution and Oxidized LDL 
PLoS ONE  2011;6(1):e16200.
Background
Epidemiologic studies indirectly suggest that air pollution accelerates atherosclerosis. We hypothesized that individual exposure to particulate matter (PM) derived from fossil fuel would correlate with plasma concentrations of oxidized low-density lipoprotein (LDL), taken as a marker of atherosclerosis. We tested this hypothesis in patients with diabetes, who are at high risk for atherosclerosis.
Methodology/Principal Findings
In a cross-sectional study of non-smoking adult outpatients with diabetes we assessed individual chronic exposure to PM by measuring the area occupied by carbon in airway macrophages, collected by sputum induction and by determining the distance from the patient's residence to a major road, through geocoding. These exposure indices were regressed against plasma concentrations of oxidized LDL, von Willebrand factor and plasminogen activator inhibitor 1 (PAI-1). We could assess the carbon load of airway macrophages in 79 subjects (58 percent). Each doubling in the distance of residence from major roads was associated with a 0.027 µm2 decrease (95% confidence interval (CI): −0.048 to −0.0051) in the carbon load of airway macrophages. Independently from other covariates, we found that each increase of 0.25 µm2 [interquartile range (IQR)] in carbon load was associated with an increase of 7.3 U/L (95% CI: 1.3 to 13.3) in plasma oxidized LDL. Each doubling in distance of residence from major roads was associated with a decrease of −2.9 U/L (95% CI: −5.2 to −0.72) in oxidized LDL. Neither the carbon load of macrophages nor the distance from residence to major roads, were associated with plasma von Willebrand factor or PAI-1.
Conclusions
The observed positive association, in a susceptible group of the general population, between plasma oxidized LDL levels and either the carbon load of airway macrophages or the proximity of the subject's residence to busy roads suggests a proatherogenic effect of traffic air pollution.
doi:10.1371/journal.pone.0016200
PMCID: PMC3023773  PMID: 21283820
25.  Residential exposure to motor vehicle emissions and the risk of wheezing among 7-8 year-old schoolchildren: a city-wide cross-sectional study in Nicosia, Cyprus 
Environmental Health  2010;9:28.
Background
Several studies have reported associations between respiratory outcomes in children and a range of self-reported, administrative or geographical indicators of traffic pollution. First-time investigation into the frequency of asthmatic symptoms among 7-8 year-old Cypriot children in 1999-2000 showed increased prevalence in the capital Nicosia compared to other areas. Geographical differences on an island the size of Cyprus may reflect environmental and/or lifestyle factors. This study investigates the relationship between self-reported symptoms and residential exposure to motor vehicle emissions among Nicosia schoolchildren.
Methods
The addresses of children in the metropolitan area of Nicosia who participated in the original survey (N = 1,735) were geo-coded and the level of exposure of each child was assessed using distance- and emission-based indicators (i.e. estimated levels of particulate matter and nitrogen oxides emissions due to motor vehicles on main roads around the residence). Odds ratios of wheezing and asthma diagnosis in relation to levels of exposure were estimated in logistic regression models adjusting for person-based factors, co-morbidity and intra-school clustering.
Results
We found an increased risk of wheezing at distances less than 50 m from a main road and/or only among those experiencing the highest levels of exposure. The strongest effect estimates were observed when exposure was defined in terms of the cumulative burden at all roads around the residence. Adjusted odds ratios for current wheezing were 2.33 (95% CI 1.27, 4.30) amongst the quartile of participants exposed to the highest levels of PM at all roads 50 m of their residence and 2.14 (95% CI 1.05, 4.35) for NOx, with no effect at intermediate levels of exposure. While the direction of effect was apparent at longer distances, differences were generally not statistically significant.
Conclusions
Children experiencing the highest burden of emissions in Nicosia seem to be at a higher risk of reporting asthmatic symptoms. Due to the small number of children residing at close proximity to main roads and lack of evidence of risk at intermediate levels of exposure or longer distances, the observed pattern alone does not explain the generally higher prevalence observed in urban Nicosia compared to other areas.
doi:10.1186/1476-069X-9-28
PMCID: PMC2904737  PMID: 20565827

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