Acute Effects of Air Pollution on Pulmonary Function,Airway Inflammation,and Oxidative Stress in Asthmatic Children

Background

Air pollution is associated with respiratory symptoms, lung function decrements, and hospitalizations. However, there is little information about the influence of air pollution on lung injury.

Objective

In this study we investigated acute effects of air pollution on pulmonary function and airway oxidative stress and inflammation in asthmatic children.

Methods

We studied 182 children with asthma, 9–14 years of age, for 4 weeks. Daily ambient concentrations of sulfur dioxide, nitrogen dioxide, ozone, and particulate matter ≤ 2.5 μm in aerodynamic diameter (PM_2.5) were monitored from two stations. Once a week we measured spirometry and fractional exhaled nitric oxide (Fe_NO), and determined thiobarbituric acid reactive substances (TBARS) and 8-isoprostane—two oxidative stress markers—and interleukin-6 (IL-6) in breath condensate. We tested associations using mixed-effects regression models, adjusting for confounding variables.

Results

Interquartile-range increases in 3-day average SO₂ (5.4 ppb), NO₂ (6.8 ppb), and PM_2.5 (5.4 μg/m³) were associated with decreases in forced expiratory flow between 25% and 75% of forced vital capacity, with changes being −3.1% [95% confidence interval (CI), −5.8 to −0.3], −2.8% (95% CI, −4.8 to −0.8), and −3.0% (95% CI, −4.7 to −1.2), respectively. SO₂, NO₂, and PM_2.5 were associated with increases in TBARS, with changes being 36.2% (95% CI, 15.7 to 57.2), 21.8% (95% CI, 8.2 to 36.0), and 24.8% (95% CI, 10.8 to 39.4), respectively. Risk estimates appear to be larger in children not taking corticosteroids than in children taking corticosteroids. O₃ (5.3 ppb) was not associated with health end points. Fe_NO, 8-isoprostane, and IL-6 were not associated with air pollutants.

Conclusion

Air pollution may increase airway oxidative stress and decrease small airway function of asthmatic children. Inhaled corticosteroids may reduce oxidative stress and improve airway function.     

Cadmium Alters the Biotransformation of Carcinogenic Aromatic Amines by Arylamine N-Acetyltransferase Xenobiotic-Metabolizing Enzymes: Molecular,Cellular, and in Vivo Studies

Background

Cadmium (Cd) is a carcinogenic heavy metal of environmental concern. Exposure to both Cd and carcinogenic organic compounds, such as polycyclic aromatic hydrocarbons or aromatic amines (AAs), is a common environmental problem. Human arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes that play a key role in the biotransformation of AA carcinogens. Changes in NAT activity have long been associated with variations in susceptibility to different cancers in relation with exposure to certain AAs.

Objective

We explored the possible interactions between Cd and the NAT-dependent biotransformation of carcinogenic AAs.

Methods

We exposed purified enzymes, lung epithelial cells, and mouse models to Cd and subsequently analyzed NAT-dependent metabolism of AAs.

Results

We found that Cd, at biologically relevant concentrations, impairs the NAT-dependent acetylation of carcinogenic AAs such as 2-aminofluorene (2-AF) in lung epithelial cells. NAT activity was strongly impaired in the tissues of mice exposed to Cd. Accordingly, mice exposed to Cd and 2-AF displayed altered in vivo toxicokinetics with a significant decrease (~ 50%) in acetylated 2-AF in plasma. We found that human NAT1 was rapidly and irreversibly inhibited by Cd [median inhibitory concentration (IC₅₀) ≈ 55 nM; rate inhibition constant (k_inact) = 5 × 10⁴ M⁻¹ · sec⁻¹], with results of acetyl coenzyme A (acetyl-CoA) protection assays indicating that Cd-mediated inhibition was due to the reaction of metal with the active-site cysteine residue of the enzyme. We found similar results for human NAT2, although this isoform was less sensitive to inactivation (IC₅₀ ≈ 1 μM; k_inact = 1 × 10⁴ M⁻¹ · sec⁻¹).

Conclusions

Our data suggest that Cd can alter the metabolism of carcinogenic AAs through the impairment of the NAT-dependent pathway, which may have important toxicological consequences.     

Protective Role of Interleukin-10 in Ozone-Induced Pulmonary Inflammation

Background

The mechanisms underlying ozone (O₃)-induced pulmonary inflammation remain unclear. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators.

Objectives

We investigated the molecular mechanisms underlying interleuken-10 (IL-10)–mediated attenuation of O₃-induced pulmonary inflammation in mice.

Methods

Il10-deficient (Il10^−/−) and wild-type (Il10^+/+) mice were exposed to 0.3 ppm O₃ or filtered air for 24, 48, or 72 hr. Immediately after exposure, differential cell counts and total protein (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid (BALF). mRNA and protein levels of cellular mediators were determined from lung homogenates. We also used global mRNA expression analyses of lung tissue with Ingenuity Pathway Analysis to identify patterns of gene expression through which IL-10 modifies O₃-induced inflammation.

Results

Mean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in Il10^−/− mice than in Il10^+/+ mice after exposure to O₃ at all time points tested. O₃-enhanced nuclear NF-κB translocation was elevated in the lungs of Il10^−/− compared with Il10^+/+ mice. Gene expression analyses revealed several IL-10–dependent and O₃-dependent mediators, including macrophage inflammatory protein 2, cathepsin E, and serum amyloid A3.

Conclusions

Results indicate that IL-10 protects against O₃-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several genetic targets through which IL-10 may modulate the innate and adaptive immune response. These novel mechanisms of protection against the pathogenesis of O₃-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals.     

Association of Heart Rate Variability in Taxi Drivers with Marked Changes in Particulate Air Pollution in Beijing in 2008

Background

Heart rate variability (HRV), a marker of cardiac autonomic function, has been associated with particulate matter (PM) air pollution, especially in older patients and those with cardiovascular diseases. However, the effect of PM exposure on cardiac autonomic function in young, healthy adults has received less attention.

Objectives

We evaluated the relationship between exposure to traffic-related PM with an aerodynamic diameter ≤ 2.5 μm (PM_2.5) and HRV in a highly exposed panel of taxi drivers.

Methods

Continuous measurements of personal exposure to PM_2.5 and ambulatory electrocardiogram monitoring were conducted on 11 young healthy taxi drivers for a 12-hr work shift during their work time (0900–2100 hr) before, during, and after the Beijing 2008 Olympic Games. Mixed-effects regression models were used to estimate associations between PM_2.5 exposure and percent changes in 5-min HRV indices after combining data from the three time periods and controlling for potentially confounding variables.

Results

Personal exposures of taxi drivers to PM_2.5 changed markedly across the three time periods. The standard deviation of normal-to-normal (SDNN) intervals decreased by 2.2% [95% confidence interval (CI), −3.8% to −0.6%] with an interquartile range (IQR; 69.5 μg/m³) increase in the 30-min PM_2.5 moving average, whereas the low-frequency and high-frequency powers decreased by 4.2% (95% CI, −9.0% to 0.8%) and 6.2% (95% CI, −10.7% to −1.5%), respectively, in association with an IQR increase in the 2-hr PM_2.5 moving average.

Conclusions

Marked changes in traffic-related PM_2.5 exposure were associated with altered cardiac autonomic function in young healthy adults.     

Correlations between Prenatal Exposure to Perfluorinated Chemicals and Reduced Fetal Growth

Background

Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are man-made, ubiquitous, and persistent contaminants in the environment, wildlife, and humans. Although recent studies have shown that these chemicals interfere with fetal growth in humans, the results are inconsistent.

Objectives

Our goal was to investigate the correlation between relatively low levels of PFOS and PFOA in maternal serum and birth weight and birth size.

Methods

We conducted a hospital-based prospective cohort study between July 2002 and October 2005 in Sapporo, Japan. A total of 428 women and their infants were involved in the study. We obtained characteristics of the mothers and infants from self-administered questionnaire surveys and from medical records. We analyzed maternal serum samples for PFOS and PFOA by liquid chromatography–tandem mass spectrometry (LC/MS/MS).

Results

After adjusting for confounding factors, PFOS levels negatively correlated with birth weight [per log₁₀ unit: β = −148.8 g; 95% confidence interval (CI), −297.0 to −0.5 g]. In addition, analyses stratified by sex revealed that PFOS levels negatively correlated with birth weight only in female infants (per log₁₀ unit: β = −269.4 g; 95% CI, −465.7 to −73.0 g). However, we observed no correlation between PFOA levels and birth weight.

Conclusion

Our results indicate that in utero exposure to relatively low levels of PFOS was negatively correlated with birth weight.     

Commuters’ Exposure to Particulate Matter Air Pollution Is Affected by Mode of Transport,Fuel Type,and Route

Background

Commuters are exposed to high concentrations of air pollutants, but little quantitative information is currently available on differences in exposure between different modes of transport, routes, and fuel types.

Objectives

The aim of our study was to assess differences in commuters’ exposure to traffic-related air pollution related to transport mode, route, and fuel type.

Methods

We measured particle number counts (PNCs) and concentrations of PM_2.5 (particulate matter ≤ 2.5 μm in aerodynamic diameter), PM₁₀, and soot between June 2007 and June 2008 on 47 weekdays, from 0800 to 1000 hours, in diesel and electric buses, gasoline- and diesel-fueled cars, and along two bicycle routes with different traffic intensities in Arnhem, the Netherlands. In addition, each-day measurements were taken at an urban background location.

Results

We found that median PNC exposures were highest in diesel buses (38,500 particles/cm³) and for cyclists along the high-traffic intensity route (46,600 particles/cm³) and lowest in electric buses (29,200 particles/cm³). Median PM₁₀ exposure was highest from diesel buses (47 μg/m³) and lowest along the high- and low-traffic bicycle routes (39 and 37 μg/m³). The median soot exposure was highest in gasoline-fueled cars (9.0 × 10⁻⁵/m), diesel cars (7.9 × 10⁻⁵/m), and diesel buses (7.4 × 10⁻⁵/m) and lowest along the low-traffic bicycle route (4.9 × 10⁻⁵/m). Because the minute ventilation (volume of air per minute) of cyclists, which we estimated from measured heart rates, was twice the minute ventilation of car and bus passengers, we calculated that the inhaled air pollution doses were highest for cyclists. With the exception of PM₁₀, we found that inhaled air pollution doses were lowest for electric bus passengers.

Conclusions

Commuters’ rush hour exposures were significantly influenced by mode of transport, route, and fuel type.     

Long-Term Inhalation Exposure to Nickel Nanoparticles Exacerbated Atherosclerosis in a Susceptible Mouse Model

Background

Because associations have been reported between inhaled ambient ultrafine particles and increased risk of cardiopulmonary disease, it has been suggested that inhaled engineered nanoparticles (NPs) may also induce adverse effects on the cardiovascular system.

Objective

We examined the long-term cardiovascular effects of inhaled nickel hydroxide NPs (nano-NH) using a sensitive mouse model.

Methods

Hyperlipidemic, apoprotein E-deficient (ApoE^−/−) mice were exposed to nano-NH at either 0 or 79 μg Ni/m³, via a whole-body inhalation system, for 5 hr/day, 5 days/week, for either 1 week or 5 months. We measured various indicators of oxidative stress and inflammation in the lung and cardiovascular tissue, and we determined plaque formation on the ascending aorta.

Results

Inhaled nano-NH induced significant oxidative stress and inflammation in the pulmonary and extrapulmonary organs, indicated by up-regulated mRNA levels of certain antioxidant enzyme and inflammatory cytokine genes; increased mitochondrial DNA damage in the aorta; significant signs of inflammation in bronchoalveolar lavage fluid; changes in lung histopathology; and induction of acute-phase response. In addition, after 5-month exposures, nano-NH exacerbated the progression of atherosclerosis in ApoE^−/− mice.

Conclusions

This is the first study to report long-term cardiovascular toxicity of an inhaled nanomaterial. Our results clearly demonstrate that long-term exposure to inhaled nano-NH can induce oxidative stress and inflammation, not only in the lung but also in the cardiovascular system, and that this stress and inflammation can ultimately contribute to progression of atherosclerosis in ApoE^−/− mice.     

Maternal Exposure to Nitrogen Dioxide during Pregnancy and Offspring Birth Weight: Comparison of Two Exposure Models

Background

Studies of the effects of air pollutants on birth weight often assess exposure with networks of permanent air quality monitoring stations (AQMSs), which have a poor spatial resolution.

Objective

We aimed to compare the exposure model based on the nearest AQMS and a temporally adjusted geostatistical (TAG) model with a finer spatial resolution, for use in pregnancy studies.

Methods

The AQMS and TAG exposure models were implemented in two areas surrounding medium-size cities in which 776 pregnant women were followed as part of the EDEN mother–child cohort. The exposure models were compared in terms of estimated nitrogen dioxide (NO₂) levels and of their association with birth weight.

Results

The correlations between the two estimates of exposure during the first trimester of pregnancy were r = 0.67, 0.70, and 0.83 for women living within 5, 2, and 1 km of an AQMS, respectively. Exposure patterns displayed greater spatial than temporal variations. Exposure during the first trimester of pregnancy was most strongly associated with birth weight for women living < 2 km away from an AQMS: a 10-μg/m³ increase in NO₂ exposure was associated with an adjusted difference in birth weight of −37 g [95% confidence interval (CI), −75 to 1 g] for the nearest-AQMS model and of −51 g (95% CI, −128 to 26 g) for the TAG model. The association was less strong (higher p-value) for women living within 5 or 1 km of an AQMS.

Conclusions

The two exposure models tended to give consistent results in terms of association with birth weight, despite the moderate concordance between exposure estimates.     

Particulate Air Pollution,Metabolic Syndrome,and Heart Rate Variability: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background

Cardiac autonomic dysfunction has been suggested as a possible biologic pathway for the association between fine particulate matter ≤ 2.5 μm in diameter (PM_2.5) and cardiovascular disease (CVD). We examined the associations of PM_2.5 with heart rate variability, a marker of autonomic function, and whether metabolic syndrome (MetS) modified these associations.

Methods

We used data from the Multi-Ethnic Study of Atherosclerosis to measure the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences (rMSSD) of 5,465 participants 45–84 years old who were free of CVD at the baseline examination (2000–2002). Data from the U.S. regulatory monitor network were used to estimate ambient PM_2.5 concentrations at the participants’ residences. MetS was defined as having three or more of the following criteria: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, high blood pressure, and high fasting glucose.

Results

After controlling for confounders, we found that an interquartile range (IQR) increase in 2-day average PM_2.5 (10.2 μg/m³) was associated with a 2.1% decrease in rMSSD [95% confidence interval (CI), −4.2 to 0.0] and nonsignificantly associated with a 1.8% decrease in SDNN (95% CI, −3.7 to 0.1). Associations were stronger among individuals with MetS than among those without MetS: an IQR elevation in 2-day PM_2.5 was associated with a 6.2% decrease in rMSSD (95% CI, −9.4 to −2.9) among participants with MetS, whereas almost no change was found among participants without MetS (p-interaction = 0.005). Similar effect modification was observed in SDNN (p-interaction = 0.011).

Conclusion

These findings suggest that autonomic dysfunction may be a mechanism through which PM exposure affects cardiovascular risk, especially among persons with MetS.     

Influence of Cobalamin on Arsenic Metabolism in Bangladesh

Background

Arsenic is a carcinogen to which 35 million people in Bangladesh are chronically exposed. The enzymatic transfer of methyl groups to inorganic As (iAs) generates monomethylarsonic (MMA) and dimethylarsinic acids (DMA) and facilitates urinary As (uAs) elimination. This process is dependent on one-carbon metabolism, a pathway in which folate and cobalamin have essential roles in the recruitment and transfer of methyl groups. Although DMA^V is the least toxic metabolite, increasing evidence suggests that MMA^III may be the most cytotoxic and genotoxic As intermediary metabolite.

Objective

We examined the associations between plasma cobalamin and uAs metabolites.

Methods

We conducted a cross-sectional study of 778 Bangladeshi adults in which we over-sampled cobalamin-deficient participants. Participants provided blood samples for the measurement of plasma cobalamin and urine specimens for As measurements.

Results

Cobalamin was inversely associated with the proportion of total uAs excreted as iAs (%iAs) [unstandardized regression coefficient (b) = –0.10; 95% confidence interval (CI), −0.17 to −0.02; p = 0.01] and positively associated with %MMA (b = 0.12; 95% CI, 0.05 to 0.20; p = 0.001). Both of these associations were stronger among folate-sufficient participants (%iAs: b = −0.17; 95% CI, −0.30 to −0.03; p = 0.02. %MMA: b = 0.20; 95% CI, 0.11 to 0.30; p < 0.0001), and the differences by folate status were statistically significant.

Conclusions

In this group of Bangladeshi adults, cobalamin appeared to facilitate the first As methylation step among folate-sufficient individuals. Given the toxicity of MMA^III, our findings suggest that in contrast to folate, cobalamin may not favorably influence As metabolism.     

Maternal Personal Exposure to Airborne Benzene and Intrauterine Growth

Background

Studies relying on outdoor pollutants measures have reported associations between air pollutants and birth weight.

Objective

Our aim was to assess the relation between maternal personal exposure to airborne benzene during pregnancy and fetal growth.

Methods

We recruited pregnant women in two French maternity hospitals in 2005–2006 as part of the EDEN mother–child cohort. A subsample of 271 nonsmoking women carried a diffusive air sampler for a week during the 27th gestational week, allowing assessment of benzene exposure. We estimated head circumference of the offspring by ultrasound measurements during the second and third trimesters of pregnancy and at birth.

Results

Median benzene exposure was 1.8 μg/m³ (5th, 95th percentiles, 0.5, 7.5 μg/m³). Log-transformed benzene exposure was associated with a gestational age–adjusted decrease of 68 g in mean birth weight [95% confidence interval (CI), −135 to −1 g] and of 1.9 mm in mean head circumference at birth (95% CI, −3.8 to 0.0 mm). It was associated with an adjusted decrease of 1.9 mm in head circumference assessed during the third trimester (95% CI, −4.0 to 0.3 mm) and of 1.5 mm in head circumference assessed at the end of the second trimester of pregnancy (95% CI, −3.1 to 0 mm).

Conclusions

Our prospective study among pregnant women is one of the first to rely on personal monitoring of exposure; a limitation is that exposure was assessed during 1 week only. Maternal benzene exposure was associated with decreases in birth weight and head circumference during pregnancy and at birth. This association could be attributable to benzene and a mixture of associated traffic-related air pollutants.     

Exposure to Polyfluoroalkyl Chemicals and Cholesterol,Body Weight,and Insulin Resistance in the General U.S. Population

Background

Polyfluoroalkyl chemicals (PFCs) are used commonly in commercial applications and are detected in humans and the environment worldwide. Concern has been raised that they may disrupt lipid and weight regulation.

Objectives

We investigated the relationship between PFC serum concentrations and lipid and weight outcomes in a large publicly available data set.

Methods

We analyzed data from the 2003–2004 National Health and Nutrition Examination Survey (NHANES) for participants 12–80 years of age. Using linear regression to control for covariates, we studied the association between serum concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) and measures of cholesterol, body size, and insulin resistance.

Results

We observed a positive association between concentrations of PFOS, PFOA, and PFNA and total and non-high-density cholesterol. We found the opposite for PFHxS. Those in the highest quartile of PFOS exposure had total cholesterol levels 13.4 mg/dL [95% confidence interval (CI), 3.8–23.0] higher than those in the lowest quartile. For PFOA, PFNA, and PFHxS, effect estimates were 9.8 (95% CI, −0.2 to 19.7), 13.9 (95% CI, 1.9–25.9), and −7.0 (95% CI, −13.2 to −0.8), respectively. A similar pattern emerged when exposures were modeled continuously. We saw little evidence of a consistent association with body size or insulin resistance.

Conclusions

This exploratory cross-sectional study is consistent with other epidemiologic studies in finding a positive association between PFOS and PFOA and cholesterol, despite much lower exposures in NHANES. Results for PFNA and PFHxS are novel, emphasizing the need to study PFCs other than PFOS and PFOA.     

Polybrominated Diphenyl Ether (PBDE) Flame Retardants and Thyroid Hormone during Pregnancy

Background

Human exposure to polybrominated diphenyl ether (PBDE) flame retardants has increased exponentially over the last three decades. Animal and human studies suggest that PBDEs may disrupt thyroid function. Although thyroid hormone (TH) of maternal origin plays an essential role in normal fetal brain development, there is a paucity of human data regarding associations between exposure to PBDEs and maternal TH levels during pregnancy.

Objectives

Our goal was to determine whether PBDE serum concentrations are associated with TH levels in pregnant women.

Methods

We measured the concentration of 10 PBDE congeners, free thyroxine (T₄), total T_4, and thyroid-stimulating hormone (TSH) in 270 pregnant women around the 27th week of gestation.

Results

Serum concentrations of individual PBDE congeners with detection frequencies > 50% (BDEs 28, 47, 99, 100, and 153) and their sum (∑PBDEs) were inversely associated with TSH levels. Decreases in TSH ranged between 10.9% [95% confidence interval (CI), −20.6 to 0.0] and 18.7% (95% CI, −29.2 to −4.5) for every 10-fold increase in the concentration of individual congeners. Odds of subclinical hyperthyroidism (low TSH but normal T₄) were also significantly elevated in participants in the highest quartile of ∑PBDEs and BDEs 100 and 153 relative to those in the first quartile. Associations between PBDEs and free and total T₄ were not statistically significant. Results were not substantially altered after the removal of outliers and were independent of the method used to adjust for blood lipid levels and to express ∑PBDEs.

Conclusions

Results suggest that exposure to PBDEs is associated with lower TSH during pregnancy. Findings may have implications for maternal health and fetal development.     

Phthalates Impair Germ Cell Development in the Human Fetal Testis in Vitro without Change in Testosterone Production

Background

Several studies have described an increasing frequency of male reproductive disorders, which may have a common origin in fetal life and which are hypothesized to be caused by endocrine disruptors. Phthalate esters represent a class of environmental endocrine-active chemicals known to disrupt development of the male reproductive tract by decreasing testosterone production in the fetal rat.

Objectives

Using the organ culture system we developed previously, we investigated the effects on the development of human fetal testis of one phthalate—mono-2-ethylhexyl phthalate (MEHP)—an industrial chemical found in many products, which has been incriminated as a disruptor of male reproductive function.

Methods

Human fetal testes were recovered during the first trimester (7–12 weeks) of gestation, a critical period for testicular differentiation, and cultured for 3 days with or without MEHP in basal conditions or stimulated with luteinizing hormone (LH).

Results

Whatever the dose, MEHP treatment had no effect on basal or LH-stimulated testosterone produced by the human fetal testis in vitro, although testosterone production can be modulated in our culture system. MEHP (10⁻⁴ M) did not affect proliferation or apoptosis of Sertoli cells, but it reduced the mRNA expression of anti-Müllerian hormone. MEHP (10⁻⁴ M) reduced the number of germ cells by increasing their apoptosis, measured by the detection of caspase-3–positive germ cells, without modification of their proliferation.

Conclusions

This is the first experimental demonstration that phthalates alter the development of the germ cell lineage in humans. However, in contrast to results observed in the rat, phthalates did not affect steroidogenesis.     

Air Pollution–Related Prothrombotic Changes in Persons with Diabetes

Background

Population studies suggest that persons with diabetes are more sensitive to the effects of particulate matter (PM) air pollution. However, the biological mechanisms of a possible prothrombotic effect underlying this enhanced susceptibility remain largely unknown.

Objective

We hypothesized that exposure to PM causes prothrombotic changes in persons with diabetes, possibly via systemic inflammation.

Methods

Our study included 137 nonsmoking adults with diabetes who were outpatients at the University Hospital Leuven. Recent exposure (2 hr before examination) to ambient PM was measured at the entrance of the hospital. Individual chronic exposure to PM was assessed by measuring the area occupied by carbon in airway macrophages obtained by sputum induction. Platelet function was measured ex vivo with the PFA-100 platelet function analyzer, which simulates a damaged blood vessel; we analyzed the function of platelets in primary hemostasis under high shear conditions. Total and differential blood leukocytes were counted.

Results

Independent of antiplatelet medication, an interquartile range (IQR) increase of 39.2 μg/m³ in PM₁₀ (PM with aerodynamic diameter ≤ 10 μm) concentration measured 2 hr before the clinical examination (recent exposure) was associated with a decrease of 21.1 sec [95% confidence interval (CI), − 35.3 to − 6.8] in the PFA-100 closure time (i.e., increased platelet activation) and an increase in blood leukocytes of 512 per microliter of blood (95% CI, 45.2–979). Each area increase of 0.25 μm² (IQR) in carbon load of airway macrophages (chronic exposure) was associated with an increase of 687 leukocytes per microliter of blood (95% CI, 224–1,150).

Conclusions

A relevant increase in recent PM exposure was associated with a change in platelet function toward a greater prothrombotic tendency. The magnitude of the change was about two-thirds (in the opposite direction) of the average effect of antiplatelet medication. Diabetic patients showed evidence of proinflammatory response to both recent and chronic exposure to PM air pollution.     

Triggering of Transmural Infarctions,but Not Nontransmural Infarctions,by Ambient Fine Particles

Background

Previous studies have reported increased risk of myocardial infarction (MI) after increases in ambient particulate matter (PM) air pollution concentrations in the hours and days before MI onset.

Objectives

We hypothesized that acute increases in fine PM with aerodynamic diameter ≤ 2.5 μm (PM_2.5) may be associated with increased risk of MI and that chronic obstructive pulmonary disease (COPD) and diabetes may increase susceptibility to PM_2.5. We also explored whether both transmural and nontransmural infarctions were acutely associated with ambient PM_2.5 concentrations.

Methods

We studied all hospital admissions from 2004 through 2006 for first acute MI of adult residents of New Jersey who lived within 10 km of a PM_2.5 monitoring site (n = 5,864), as well as ambient measurements of PM_2.5, nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone.

Results

Using a time-stratified case-crossover design and conditional logistic regression showed that each interquartile-range increase in PM_2.5 concentration (10.8 μg/m³) in the 24 hr before arriving at the emergency department for MI was not associated with an increased risk of MI overall but was associated with an increased risk of a transmural infarction. We found no association between the same increase in PM_2.5 and risk of a nontransmural infarction. Further, subjects with COPD appeared to be particularly susceptible, but those with diabetes were not.

Conclusions

This PM–transmural infarction association is consistent with earlier studies of PM and MI. The lack of association with nontransmural infarction suggests that future studies that investigate the triggering of MI by ambient PM_2.5 concentrations should be stratified by infarction type.     

Thyroid Hormone Levels of Pregnant Inuit Women and Their Infants Exposed to Environmental Contaminants

Background

An increasing number of studies have shown that several ubiquitous environmental contaminants possess thyroid hormone–disrupting capacities. Prenatal exposure to some of them, such as polychlorinated biphenyls (PCBs), has also been associated with adverse neurodevelopmental effects in infants.

Objectives

In this study we examined the relationship between exposure to potential thyroid hormone–disrupting toxicants and thyroid hormone status in pregnant Inuit women from Nunavik and their infants within the first year of life.

Methods

We measured thyroid hormone parameters [thyroid stimulating hormone (TSH), free thyroxine (fT₄), total triiodothyronine (T₃), thyroxine-binding globulin (TBG)] and concentrations of several contaminants [PCB-153, hydroxylated metabolites of PCBs (HO-PCBs), pentachlorophenol (PCP) and hexachlorobenzene (HCB)] in maternal plasma at delivery (n = 120), in umbilical cord plasma (n = 95), and in infant plasma at 7 months postpartum (n = 130).

Results

In pregnant women, we found a positive association between HO-PCBs and T₃ concentrations (β = 0.57, p = 0.02). In umbilical cord blood, PCB-153 concentrations were negatively associated with TBG levels (β = −0.26, p = 0.01). In a subsample analysis, a negative relationship was also found between maternal PCP levels and cord fT₄ concentrations in neonates (β = −0.59, p = 0.02). No association was observed between contaminants and thyroid hormones at 7 months of age.

Conclusion

Overall, there is little evidence that the environmental contaminants analyzed in this study affect thyroid hormone status in Inuit mothers and their infants. The possibility that PCP may decrease thyroxine levels in neonates requires further investigation.     

Estimating Regional Spatial and Temporal Variability of PM2.5 Concentrations Using Satellite Data,Meteorology, and Land Use Information

Background

Studies of chronic health effects due to exposures to particulate matter with aerodynamic diameters ≤ 2.5 μm (PM_2.5) are often limited by sparse measurements. Satellite aerosol remote sensing data may be used to extend PM_2.5 ground networks to cover a much larger area.

Objectives

In this study we examined the benefits of using aerosol optical depth (AOD) retrieved by the Geostationary Operational Environmental Satellite (GOES) in conjunction with land use and meteorologic information to estimate ground-level PM_2.5 concentrations.

Methods

We developed a two-stage generalized additive model (GAM) for U.S. Environmental Protection Agency PM_2.5 concentrations in a domain centered in Massachusetts. The AOD model represents conditions when AOD retrieval is successful; the non-AOD model represents conditions when AOD is missing in the domain.

Results

The AOD model has a higher predicting power judged by adjusted R² (0.79) than does the non-AOD model (0.48). The predicted PM_2.5 concentrations by the AOD model are, on average, 0.8–0.9 μg/m³ higher than the non-AOD model predictions, with a more smooth spatial distribution, higher concentrations in rural areas, and the highest concentrations in areas other than major urban centers. Although AOD is a highly significant predictor of PM_2.5, meteorologic parameters are major contributors to the better performance of the AOD model.

Conclusions

GOES aerosol/smoke product (GASP) AOD is able to summarize a set of weather and land use conditions that stratify PM_2.5 concentrations into two different spatial patterns. Even if land use regression models do not include AOD as a predictor variable, two separate models should be fitted to account for different PM_2.5 spatial patterns related to AOD availability.     

Chronic Fine and Coarse Particulate Exposure,Mortality, and Coronary Heart Disease in the Nurses’ Health Study

Background

The relationship of fine particulate matter < 2.5 μm in diameter (PM_2.5) air pollution with mortality and cardiovascular disease is well established, with more recent long-term studies reporting larger effect sizes than earlier long-term studies. Some studies have suggested the coarse fraction, particles between 2.5 and 10 μm (PM_10–2.5), may also be important. With respect to mortality and cardiovascular events, questions remain regarding the relative strength of effect sizes for chronic exposure to fine and coarse particles.

Objectives

We examined the relationship of chronic PM_2.5 and PM_10–2.5 exposures with all-cause mortality and fatal and nonfatal incident coronary heart disease (CHD), adjusting for time-varying covariates.

Methods

The current study included women from the Nurses’ Health Study living in metropolitan areas of the northeastern and midwestern United States. Follow-up was from 1992 to 2002. We used geographic information systems–based spatial smoothing models to estimate monthly exposures at each participant’s residence.

Results

We found increased risk of all-cause mortality [hazard ratio (HR), 1.26; 95% confidence interval (CI), 1.02–1.54] and fatal CHD (HR = 2.02; 95% CI, 1.07–3.78) associated with each 10-μg/m³ increase in annual PM_2.5 exposure. The association between fatal CHD and PM_10–2.5 was weaker.

Conclusions

Our findings contribute to growing evidence that chronic PM_2.5 exposure is associated with risk of all-cause and cardiovascular mortality.