Air pollution and DNA methylation: interaction by psychological factors in the VA Normative Aging Study

DNA methylation is a potential pathway linking air pollution to disease. Studies indicate that psychological functioning modifies the association between pollution and morbidity. The authors estimated the association of DNA methylation with ambient particulate matter less than 2.5 μm in diameter (PM(2.5)) and black carbon, using mixed models. DNA methylation of the inducible nitric oxide synthase gene, iNOS, and the glucocorticoid receptor gene, GCR, was measured by quantitative polymerase chain reaction pyrosequencing of 1,377 blood samples from 699 elderly male participants in the VA Normative Aging Study (1999-2009). The authors also investigated whether this association was modified by psychological factors including optimism or pessimism, anxiety, and depression. iNOS methylation was decreased after acute exposure to both black carbon and PM(2.5). A 1-μg/m(3) increase in exposure to black carbon in the 4 hours preceding the clinical examination was associated with a 0.9% decrease in 5-methylcytosine (95% CI: 0.4, 1.4) in iNOS, and a 10-μg/m(3) increase in exposure to PM(2.5) was associated with a 0.6% decrease in 5-methylcytosine (95% CI: 0.03, 1.1) in iNOS. Participants with low optimism and high anxiety had associations that were 3-4 times larger than those with high optimism or low anxiety. GCR methylation was not associated with particulate air pollution exposure.     

Respiratory Health Effects of Airborne Particulate Matter: The Role of Particle Size, Composition, and Oxidative Potential-The RAPTES Project

Background: Specific characteristics of particulate matter (PM) responsible for associations with respiratory health observed in epidemiological studies are not well established. High correlations among, and differential measurement errors of, individual components contribute to this uncertainty.Objectives: We investigated which characteristics of PM have the most consistent associations with acute changes in respiratory function in healthy volunteers.Methods: We used a semiexperimental design to accurately assess exposure. We increased exposure contrast and reduced correlations among PM characteristics by exposing volunteers at five different locations: an underground train station, two traffic sites, a farm, and an urban background site. Each of the 31 participants was exposed for 5 hr while exercising intermittently, three to seven times at different locations during March-October 2009. We measured PM10, PM2.5, particle number concentrations (PNC), absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and PM oxidative potential. Lung function [FEV1 (forced expiratory volume in 1 sec), FVC (forced vital capacity), FEF25-75 (forced expiratory flow at 25-75% of vital capacity), and PEF (peak expiratory flow)] and fractional exhaled nitric oxide (FENO) were measured before and at three time points after exposure. Data were analyzed with mixed linear regression.Results: An interquartile increase in PNC (33,000 particles/cm3) was associated with an 11% [95% confidence interval (CI): 5, 17%] and 12% (95% CI: 6, 17%) FENO increase over baseline immediately and at 2 hr postexposure, respectively. A 7% (95% CI: 0.5, 14%) increase persisted until the following morning. These associations were robust and insensitive to adjustment for other pollutants. Similarly consistent associations were seen between FVC and FEV1 with PNC, NO2 (nitrogen dioxide), and NOx (nitrogen oxides).Conclusions: Changes in PNC, NO2, and NOx were associated with evidence of acute airway inflammation (i.e., FENO) and impaired lung function. PM mass concentration and PM10 oxidative potential were not predictive of the observed acute responses.     

A cohort study of traffic-related air pollution impacts on birth outcomes

BACKGROUND: Evidence suggests that air pollution exposure adversely affects pregnancy outcomes. Few studies have examined individual-level intraurban exposure contrasts. OBJECTIVES: We evaluated the impacts of air pollution on small for gestational age (SGA) birth weight, low full-term birth weight (LBW), and preterm birth using spatiotemporal exposure metrics. METHODS: With linked administrative data, we identified 70,249 singleton births (1999-2002) with complete covariate data (sex, ethnicity, parity, birth month and year, income, education) and maternal residential history in Vancouver, British Columbia, Canada. We estimated residential exposures by month of pregnancy using nearest and inverse-distance weighting (IDW) of study area monitors [carbon monoxide, nitrogen dioxide, nitric oxide, ozone, sulfur dioxide, and particulate matter < 2.5 (PM2.5) or < 10 (PM10) microm in aerodynamic diameter], temporally adjusted land use regression (LUR) models (NO, NO2, PM2.5, black carbon), and proximity to major roads. Using logistic regression, we estimated the risk of mean (entire pregnancy, first and last month of pregnancy, first and last 3 months) air pollution concentrations on SGA (< 10th percentile), term LBW (< 2,500 g), and preterm birth. RESULTS: Residence within 50 m of highways was associated with a 26% increase in SGA [95% confidence interval (CI), 1.07-1.49] and an 11% (95% CI, 1.01-1.23) increase in LBW. Exposure to all air pollutants except O3 was associated with SGA, with similar odds ratios (ORs) for LUR and monitoring estimates (e.g., LUR: OR = 1.02; 95% CI, 1.00-1.04; IDW: OR = 1.05; 95% CI, 1.03-1.08 per 10-microg/m3 increase in NO). For preterm births, associations were observed with PM2.5 for births < 37 weeks gestation (and for other pollutants at < 30 weeks). No consistent patterns suggested exposure windows of greater relevance. CONCLUSION: Associations between traffic-related air pollution and birth outcomes were observed in a population-based cohort with relatively low ambient air pollution exposure.     

Air pollution and emergency admissions in Boston, MA

STUDY OBJECTIVE: Many studies have shown that ambient particulate air pollution (PM) is associated with increased risk of hospital admissions and deaths for cardiovascular or respiratory causes around the world. In general these have been analysed in association with PM(10) and ozone, whereas PM(2.5) is now the particle measure of greatest health and regulatory concern. And little has been published on associations of hospital admissions and PM components. DESIGN: This study analysed hospital admissions for myocardial infarction (15 578 patients), and pneumonia (24 857 patients) in associations with fine particulate air pollution, black carbon (BC), ozone, nitrogen dioxide (NO(2)), PM not from traffic, and carbon monoxide (CO) in the greater Boston area for the years 1995-1999 using a case-crossover analysis, with control days matched on temperature. MAIN RESULTS: A significant association was found between NO(2) (12.7% change (95% CI: 5.8, 18)), PM(2.5) (8.6% increase (95% CI: 1.2, 15.4)), and BC (8.3% increase (95% CI: 0.2, 15.8)) and the risk of emergency myocardial infarction hospitalisation; and between BC (11.7% increase (95% CI: 4.8, 17.4)), PM(2.5) (6.5% increase (95% CI: 1.1, 11.4)), and CO (5.5% increase (95% CI: 1.1, 9.5)) and the risk of pneumonia hospitalisation. CONCLUSIONS: The pattern of associations seen for myocardial infarction and pneumonia (strongest associations with NO(2), CO, and BC) suggests that traffic exposure is primarily responsible for the association with heart attacks.     

Personal exposures to traffic-related air pollution and acute respiratory health among Bronx schoolchildren with asthma

Background

Previous studies have reported relationships between adverse respiratory health outcomes and residential proximity to traffic pollution, but have not shown this at a personal exposure level.

Objective

We compared, among inner-city children with asthma, the associations of adverse asthma outcome incidences with increased personal exposure to particulate matter mass ≤ 2.5 μm in aerodynamic diameter (PM_2.5) air pollution versus the diesel-related carbonaceous fraction of PM_2.5.

Methods

Daily 24-hr personal samples of PM_2.5, including the elemental carbon (EC) fraction, were collected for 40 fifth-grade children with asthma at four South Bronx schools (10 children per school) during approximately 1 month each. Spirometry and symptom scores were recorded several times daily during weekdays.

Results

We found elevated same-day relative risks of wheeze [1.45; 95% confidence interval (CI), 1.03–2.04)], shortness of breath (1.41; 95% CI, 1.01–1.99), and total symptoms (1.30; 95% CI, 1.04–1.62) with an increase in personal EC, but not with personal PM_2.5 mass. We found increased risk of cough, wheeze, and total symptoms with increased 1-day lag and 2-day average personal and school-site EC. We found no significant associations with school-site PM_2.5 mass or sulfur. The EC effect estimate was robust to addition of gaseous pollutants.

Conclusion

Adverse health associations were strongest with personal measures of EC exposure, suggesting that the diesel “soot” fraction of PM_2.5 is most responsible for pollution-related asthma exacerbations among children living near roadways. Studies that rely on exposure to PM mass may underestimate PM health impacts.     

Air pollution and cardiovascular events at labor and delivery: a case-crossover analysis

PurposeIn this case-crossover study, we investigated the odds of having a labor/delivery with cardiovascular event (i.e., ischemic heart disease, stroke, heart failure, cardiac arrest/failure, and other or unspecified cardiovascular events) associated with acute exposure to common air pollutants.MethodsWe selected 680 women with singleton pregnancy and cardiovascular events at labor/delivery from 12 U.S. clinical sites (2002–2008). Exposures to six criteria air pollutants, six particulate constituents, and 26 air toxics were obtained using modified Community Multiscale Air Quality models. Conditional logistic regression models calculated the odds ratio (OR) and 95% confidence intervals (CI) comparing exposures during the day of delivery, the week before delivery, and each of the days of the week before delivery to two control periods before and after.ResultsAn interquartile range increase in particulate matter (PM) ≤2.5 microns and nitric oxide exposures during the week before delivery was associated with an 11% (OR 1.11, 95% CI: 1.01–1.23) and 21% (OR 1.21, 95% CI: 1.04–1.42) increased cardiovascular events odds, respectively. These pollutants, sulfur dioxide, carbon monoxide, PM ≤ 10 microns, and some PM constituents showed associations with event odds for days 0, 1, 5, and 6 before delivery. Inverse associations were observed for O₃ and some PM constituents as well as air toxics.ConclusionsCardiovascular events at labor/delivery merit more attention in relation to air pollution.     

Acute respiratory inflammation in children and black carbon in ambient air before and during the 2008 Beijing Olympics

Background: Epidemiologic evidence for a causative association between black carbon (BC) and health outcomes is limited.Objectives: We estimated associations and exposure–response relationships between acute respiratory inflammation in schoolchildren and concentrations of BC and particulate matter with an aerodynamic diameter of ≤ 2.5 μm (PM_2.5) in ambient air before and during the air pollution intervention for the 2008 Beijing Olympics.Methods: We measured exhaled nitric oxide (eNO) as an acute respiratory inflammation biomarker and hourly mean air pollutant concentrations to estimate BC and PM_2.5 exposure. We used 1,581 valid observations of 36 subjects over five visits in 2 years to estimate associations of eNO with BC and PM_2.5 according to generalized estimating equations with polynomial distributed-lag models, controlling for body mass index, asthma, temperature, and relative humidity. We also assessed the relative importance of BC and PM_2.5 with two-pollutant models.Results: Air pollution concentrations and eNO were clearly lower during the 2008 Olympics. BC and PM_2.5 concentrations averaged over 0–24 hr were strongly associated with eNO, which increased by 16.6% [95% confidence interval (CI), 14.1–19.2%] and 18.7% (95% CI, 15.0–22.5%) per interquartile range (IQR) increase in BC (4.0 μg/m³) and PM_2.5 (149 μg/m³), respectively. In the two-pollutant model, estimated effects of BC were robust, but associations between PM_2.5 and eNO decreased with adjustment for BC. We found that eNO was associated with IQR increases in hourly BC concentrations up to 10 hr after exposure, consistent with effects primarily in the first hours after exposure.Conclusions: Recent exposure to BC was associated with acute respiratory inflammation in schoolchildren in Beijing. Lower air pollution levels during the 2008 Olympics also were associated with reduced eNO.     

Air pollution and bronchitic symptoms in Southern California children with asthma.

The association of air pollution with the prevalence of chronic lower respiratory tract symptoms among children with a history of asthma or related symptoms was examined in a cross-sectional study. Parents of a total of 3,676 fourth, seventh, and tenth graders from classrooms in 12 communities in Southern California completed questionnaires that characterized the children's histories of respiratory illness and associated risk factors. The prevalences of bronchitis, chronic phlegm, and chronic cough were investigated among children with a history of asthma, wheeze without diagnosed asthma, and neither wheeze nor asthma. Average ambient annual exposure to ozone, particulate matter (PM(10) and PM(2.5); [less than/equal to] 10 microm and < 2.5 microm in aerodynamic diameter, respectively), acid vapor, and nitrogen dioxide (NO(2)) was estimated from monitoring stations in each community. Positive associations between air pollution and bronchitis and phlegm were observed only among children with asthma. As PM(10) increased across communities, there was a corresponding increase in the risk per interquartile range of bronchitis [odds ratio (OR) 1.4/19 microg/m(3); 95% confidence interval (CI), 1.1-1.8). Increased prevalence of phlegm was significantly associated with increasing exposure to all ambient pollutants except ozone. The strongest association was for NO(2), based on relative risk per interquartile range in the 12 communities (OR 2.7/24 ppb; CI, 1.4-5.3). The results suggest that children with a prior diagnosis of asthma are more likely to develop persistent lower respiratory tract symptoms when exposed to air pollution in Southern California.     

Association of expired nitric oxide with occupational particulate exposure

Particulate air pollution has been associated with adverse respiratory health effects. This study assessed the utility of expired nitric oxide to detect acute airway responses to metal-containing fine particulates. Using a repeated-measures study design, we investigated the association between the fractional concentration of expired nitric oxide (F(E)NO) and exposure to particulate matter with an aerodynamic mass median diameter of less than or equal to 2.5 micro m (PM(2.5)) in boilermakers exposed to residual oil fly ash and metal fumes. Subjects were monitored for 5 days during boiler repair overhauls in 1999 (n = 20) or 2000 (n = 14). The Wilcoxon median baseline F(E)NO was 10.6 ppb [95% confidence interval (CI): 9.1, 12.7] in 1999 and 7.4 ppb (95% CI: 6.7, 8.0) in 2000. The Wilcoxon median PM(2.5) 8-hr time-weighted average was 0.56 mg/m(3) (95% CI: 0.37, 0.93) in 1999 and 0.86 mg/m(3) (95% CI: 0.65, 1.07) in 2000. F(E)NO levels during the work week were significantly lower than baseline F(E)NO in 1999 (p < 0.001). A significant inverse exposure-response relationship between log-transformed F(E)NO and the previous workday's PM(2.5) concentration was found in 1999, after adjusting for smoking status, age, and sampling year. With each 1 mg/m(3) incremental increase in PM(2.5) exposure, log F(E)NO decreased by 0.24 (95% CI: -0.38, -0.10) in 1999. The lack of an exposure-response relationship between PM(2.5) exposure and F(E)NO in 2000 could be attributable to exposure misclassification resulting from the use of respirators. In conclusion, occupational exposure to metal-containing fine particulates was associated with significant decreases in F(E)NO in a survey of workers with limited respirator usage.     

Exhaled nitric oxide in children with asthma and short-term PM2.5 exposure in Seattle

The objective of this study was to evaluate associations between short-term (hourly) exposures to particulate matter with aerodynamic diameters < 2.5 microm (PM2.5) and the fractional concentration of nitric oxide in exhaled breath (FE(NO) in children with asthma participating in an intensive panel study in Seattle, Washington. The exposure data were collected with tapered element oscillation microbalance (TEOM) PM2.5 monitors operated by the local air agency at three sites in the Seattle area. FE(NO) is a marker of airway inflammation and is elevated in individuals with asthma. Previously, we reported that offline measurements of FE(NO) are associated with 24-hr average PM2.5 in a panel of 19 children with asthma in Seattle. In the present study using the same children, we used a polynomial distributed lag model to assess the association between hourly lags in PM2.5 exposure and FE(NO) levels. Our model controlled for age, ambient NO levels, temperature, relative humidity, and modification by use of inhaled corticosteroids. We found that FE(NO) was associated with hourly averages of PM2.5 up to 10-12 hr after exposure. The sum of the coefficients for the lag times associated with PM2.5 in the distributed lag model was 7.0 ppm FE(NO). The single-lag-model FE(NO) effect was 6.9 [95% confidence interval (CI), 3.4 to 10.6 ppb] for a 1-hr lag, 6.3 (95% CI, 2.6 to 9.9 ppb ) for a 4-hr lag, and 0.5 (95% CI, -1.1 to 2.1 ppb) for an 8-hr lag. These data provide new information concerning the lag structure between PM2.5 exposure and a respiratory health outcome in children with asthma.     

Effects of air pollution on heart rate variability: the VA normative aging study

Reduced heart rate variability (HRV), a marker of poor cardiac autonomic function, has been associated with air pollution, especially fine particulate matter [< 2.5 microm in aerodynamic diameter (PM2.5)]. We examined the relationship between HRV [standard deviation of normal-to-normal intervals (SDNN), power in high frequency (HF) and low frequency (LF), and LF:HF ratio] and ambient air pollutants in 497 men from the Normative Aging Study in greater Boston, Massachusetts, seen between November 2000 and October 2003. We examined 4-hr, 24-hr, and 48-hr moving averages of air pollution (PM2.5, particle number concentration, black carbon, ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide). Controlling for potential confounders, HF decreased 20.8% [95% confidence interval (CI), 4.6-34.2%] and LF:HF ratio increased 18.6% (95% CI, 4.1-35.2%) per SD (8 microg/m3) increase in 48-hr PM2.5. LF was reduced by 11.5% (95% CI, 0.4-21.3%) per SD (13 ppb) increment in 4-hr O3. The associations between HRV and PM2.5 and O3 were stronger in people with ischemic heart disease (IHD) and hypertension. The associations observed between SDNN and LF and PM2.5 were stronger in people with diabetes. People using calcium-channel blockers and beta-blockers had lower associations between O3 and PM2.5 with LF. No effect modification by other cardiac medications was found. Exposures to PM2.5 and O3 are associated with decreased HRV, and history of IHD, hypertension, and diabetes may confer susceptibility to autonomic dysfunction by air pollution.     

Air pollution, airway inflammation, and lung function in a cohort study of Mexico City schoolchildren

BACKGROUND: The biological mechanisms involved in inflammatory response to air pollution are not clearly understood. OBJECTIVE: In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function. METHODS: We studied a cohort of 158 asthmatic and 50 nonasthmatic school-age children, followed an average of 22 weeks. We conducted spirometric tests, measurements of fractional exhaled nitric oxide (Fe(NO)), interleukin-8 (IL-8) in nasal lavage, and pH of exhaled breath condensate every 15 days during follow-up. Data were analyzed using linear mixed-effects models. RESULTS: An increase of 17.5 microg/m(3) in the 8-hr moving average of PM(2.5) levels (interquartile range) was associated with a 1.08-ppb increase in Fe(NO) [95% confidence interval (CI), 1.01-1.16] and a 1.07-pg/mL increase in IL-8 (95% CI 0.98-1.19) in asthmatic children and a 1.16 pg/ml increase in IL-8 (95% CI, 1.00-1.36) in nonasthmatic children. The 5-day accumulated average of exposure to particulate matter <2.5 microm in aerodynamic diamter (PM(2.5)) was significantly inversely associated with forced expiratory volume in 1 sec (FEV(1)) (p=0.048) and forced vital capacity (FVC) (p=0.012) in asthmatic children and with FVC (p=0.021) in nonasthmatic children. Fe(NO) and FEV(1) were inversely associated (p=0.005) in asthmatic children. CONCLUSIONS: Exposure to PM(2.5) resulted in acute airway inflammation and decrease in lung function in both asthmatic and nonasthmatic children.     

Traffic-related atmospheric pollutants levels during pregnancy and offspring's term birth weight: a study relying on a land-use regression exposure model

BACKGROUND: Some studies have suggested that particulate matter (PM) levels during pregnancy may be associated with birth weight. Road traffic is a major source of fine PM (PM with aero-dynamic diameter < 2.5 microm; PM(2.5)). OBJECTIVE: We determined to characterize the influence of maternal exposure to atmospheric pollutants due to road traffic and urban activities on offspring term birth weight. METHODS: Women from a birth cohort [the LISA (Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children) cohort] who delivered a non-premature baby with a birth weight > 2,500 g in Munich metropolitan area were included. We assessed PM(2.5), PM(2.5) absorbance (which depends on the blackness of PM(2.5), a marker of traffic-related air pollution), and nitrogen dioxide levels using a land-use regression model, taking into account the type and length of roads, population density, land coverage around the home address, and temporal variations in pollution during pregnancy. Using Poisson regression, we estimated prevalence ratios (PR) of birth weight < 3,000 g, adjusted for gestational duration, sex, maternal smoking, height, weight, and education. RESULTS: Exposure was defined for 1,016 births. Taking the lowest quartile of exposure during pregnancy as a reference, the PR of birth weight < 3,000 g associated with the highest quartile was 1.7 for PM(2.5) [95% confidence interval (CI), 1.2-2.7], 1.8 for PM(2.5) absorbance (95% CI, 1.1-2.7), and 1.2 for NO(2) (95% CI, 0.7-1.7). The PR associated with an increase of 1 microg/m(3) in PM(2.5) levels was 1.13 (95% CI, 1.00-1.29). CONCLUSION: Increases in PM(2.5) levels and PM(2.5) absorbance were associated with decreases in term birth weight. Traffic-related air pollutants may have adverse effects on birth weight.     

Associations between health effects and particulate matter and black carbon in subjects with respiratory disease

We measured fractional exhaled nitric oxide (FE(NO)), spirometry, blood pressure, oxygen saturation of the blood (SaO2), and pulse rate in 16 older subjects with asthma or chronic obstructive pulmonary disease (COPD) in Seattle, Washington. Data were collected daily for 12 days. We simultaneously collected PM10 and PM2.5 (particulate matter < or = 10 microm or < or = 2.5 microm, respectively) filter samples at a central outdoor site, as well as outside and inside the subjects' homes. Personal PM10 filter samples were also collected. All filters were analyzed for mass and light absorbance. We analyzed within-subject associations between health outcomes and air pollution metrics using a linear mixed-effects model with random intercept, controlling for age, ambient relative humidity, and ambient temperature. For the 7 subjects with asthma, a 10 microg/m3 increase in 24-hr average outdoor PM10 and PM2.5 was associated with a 5.9 [95% confidence interval (CI), 2.9-8.9] and 4.2 ppb (95% CI, 1.3-7.1) increase in FE(NO), respectively. A 1 microg/m3 increase in outdoor, indoor, and personal black carbon (BC) was associated with increases in FE(NO) of 2.3 ppb (95% CI, 1.1-3.6), 4.0 ppb (95% CI, 2.0-5.9), and 1.2 ppb (95% CI, 0.2-2.2), respectively. No significant association was found between PM or BC measures and changes in spirometry, blood pressure, pulse rate, or SaO2 in these subjects. Results from this study indicate that FE(NO) may be a more sensitive marker of PM exposure than traditional health outcomes and that particle-associated BC is useful for examining associations between primary combustion constituents of PM and health outcomes.     

Air pollution and exacerbation of asthma in African-American children in Los Angeles

Significant increases in asthma morbidity and mortality in the United States have occurred since the 1970s, particularly among African-Americans. Exposure to various environmental factors, including air pollutants and allergens, has been suggested as a partial explanation of these trends. To examine relations between several air pollutants and asthma exacerbation in African-Americans, we recruited a panel of 138 children in central Los Angeles. We recorded daily data on respiratory symptoms and medication use for 13 weeks and examined these data in conjunction with data on ozone (O3) nitrogen dioxide (NO2), particulate matter (PM10 and PM2.5), meteorological variables, pollens, and molds. Using generalized estimating equations, we found associations between respiratory symptom occurrence and several environmental factors. For example, new episodes of cough were associated with exposure to PM10 (OR = 1.25; 95% CI = 1.12-1.39; interquartile range [IQR] = 17 microg/m3, 24-hour average), PM2.5 (OR = 1.10; 95% CI = 1.03-1.18; IQR = 30 microg/m3, 12-hour average), NO2, and the molds Cladosporium and Alternaria, but not with exposure to O3 or pollen. The factors PM10 and O3 were associated with the use of extra asthma medication. For this population several bioaerosols and air pollutants had effects that may be clinically significant.     

The association of expired nitric oxide with occupational particulate metal exposure

Toxicologic studies have shown that soluble transition metals in residual oil fly ash (ROFA) can induce pulmonary injury. In this study, we investigated the association between the fractional concentration of expired nitric oxide (FENO) and exposure to metal constituents of particulate matter with an aerodynamic mass median diameter < or =2.5 microm (PM2.5) in boilermakers exposed to ROFA and metal fume. Metals investigated included vanadium, chromium, manganese, nickel, copper, and lead. Subjects were monitored for 5 consecutive days during boiler repair overhauls in 1999 (n=20) and 2000 (n=14). In 1999, we found a significant inverse association between log-transformed FENO and PM2.5 metal concentrations. LogFENO changed by -0.03 (95% CI: -0.04, -0.01), -0.56 (95% CI: -0.88, -0.24), -0.09 (95% CI: -0.16, -0.02), and -0.04 (95% CI: -0.07, -0.02) per microg/m3 of PM2.5 vanadium, chromium, manganese, and nickel, respectively. In 2000, no significant associations were observed, most likely due to exposure misclassification resulting from the use of respirators. The inverse association between PM2.5 metal exposure and FENO in subjects with limited respirator usage suggests that soluble transition metals might be partially responsible for the adverse pulmonary responses seen in workers exposed to ROFA.     

Personal and ambient air pollution exposures and lung function decrements in children with asthma

BACKGROUND: Epidemiologic studies have shown associations between asthma outcomes and outdoor air pollutants such as nitrogen dioxide and particulate matter mass < 2.5 mum in diameter (PM(2.5)). Independent effects of specific pollutants have been difficult to detect because most studies have relied on highly correlated central-site measurements. OBJECTIVES: This study was designed to evaluate the relationship of daily changes in percent-predicted forced expiratory volume in 1 sec (FEV(1)) with personal and ambient air pollutant exposures. METHODS: For 10 days each, we followed 53 subjects with asthma who were 9-18 years of age and living in the Los Angeles, California, air basin. Subjects self-administered home spirometry in themorning, afternoon, and evening. We measured personal hourly PM(2.5) mass, 24-hr PM(2.5) elemental and organic carbon (EC-OC), and 24-hr NO(2), and the same 24-hr average outdoor central-site(ambient) exposures. We analyzed data with transitional mixed models controlling for personal temperature and humidity, and as-needed beta(2)-agonist inhaler use. RESULTS: FEV(1) decrements were significantly associated with increasing hourly peak and daily average personal PM(2.5), but not ambient PM(2.5). Personal NO(2) was also inversely associated with FEV(1). Ambient NO(2) was more weakly associated. We found stronger associations among 37 subjects not taking controller bronchodilators as follows: Personal EC-OC was inversely associated with morning FEV(1); for an interquartile increase of 71 mug/m(3) 1-hr maximum personal PM(2.5), overall percent-predicted FEV(1) decreased by 1.32% [95% confidence interval (CI), -2.00 to -0.65%]; and for an interquartile increase of 16.8 ppb 2-day average personal NO(2), overall percent-predicted FEV(1) decreased by 2.45% (95% CI, -3.57 to -1.33%). Associations of both personal PM(2.5) and NO(2) with FEV(1) remained when co-regressed, and both confounded ambient NO(2). CONCLUSIONS: Independent pollutant associations with lung function might be missed using ambient data alone. Different sets of causal components are suggested by independence of FEV(1) associations with personal PM(2.5) mass from associations with personal NO(2).     

Early childhood lower respiratory illness and air pollution

BACKGROUND: Few studies of air pollutants address morbidity in preschool children. In this study we evaluated bronchitis in children from two Czech districts: Teplice, with high ambient air pollution, and Prachatice, characterized by lower exposures. OBJECTIVES: Our goal was to examine rates of lower respiratory illnesses in preschool children in relation to ambient particles and hydrocarbons. METHODS: Air monitoring for particulate matter < 2.5 microm in diameter (PM(2.5)) and polycyclic aromatic hydrocarbons (PAHs) was conducted daily, every third day, or every sixth day. Children born May 1994 through December 1998 were followed to 3 or 4.5 years of age to ascertain illness diagnoses. Mothers completed questionnaires at birth and at follow-up regarding demographic, lifestyle, reproductive, and home environmental factors. Longitudinal multivariate repeated-measures analysis was used to quantify rate ratios for bronchitis and for total lower respiratory illnesses in 1,133 children. RESULTS: After adjustment for season, temperature, and other covariates, bronchitis rates increased with rising pollutant concentrations. Below 2 years of age, increments in 30-day averages of 100 ng/m(3) PAHs and of 25 microg/m(3) PM(2.5) resulted in rate ratios (RRs) for bronchitis of 1.29 [95 % confidence interval (CI), 1.07-1.54] and 1.30 (95% CI, 1.08-1.58), respectively; from 2 to 4.5 years of age, these RRs were 1.56 (95% CI, 1.22-2.00) and 1.23 (95% CI, 0.94-1.62), respectively. CONCLUSION: Ambient PAHs and fine particles were associated with early-life susceptibility to bronchitis. Associations were stronger for longer pollutant-averaging periods and, among children > 2 years of age, for PAHs compared with fine particles. Preschool-age children may be particularly vulnerable to air pollution-induced illnesses.     

Particulate air pollution, oxidative stress genes, and heart rate variability in an elderly cohort

BACKGROUND AND OBJECTIVES: We have previously shown that reduced defenses against oxidative stress due to glutathione S-transferase M1 (GSTM1) deletion modify the effects of PM(2.5) (fine-particulate air pollution of < 2.5 microm in aerodynamic diameter) on heart rate variability (HRV) in a cross-sectional analysis of the Normative Aging Study, an elderly cohort. We have extended this to include a longitudinal analysis with more subjects and examination of the GT short tandem repeat polymorphism in the heme oxygenase-1 (HMOX-1) promoter. METHODS: HRV measurements were taken on 539 subjects. Linear mixed effects models were fit for the logarithm of HRV metrics-including standard deviation of normal-to-normal intervals (SDNN), high frequency (HF), and low frequency (LF)-and PM(2.5) concentrations in the 48 hr preceding HRV measurement, controlling for confounders and a random subject effect. RESULTS: PM(2.5) was significantly associated with SDNN (p = 0.04) and HF (p = 0.03) in all subjects. There was no association in subjects with GSTM1, whereas there was a significant association with SDNN, HF, and LF in subjects with the deletion. Similarly, there was no association with any HRV measure in subjects with the short repeat variant of HMOX-1, and significant associations in subjects with any long repeat. We found a significant three-way interaction of PM(2.5) with GSTM1 and HMOX-1 determining SDNN (p = 0.008), HF (p = 0.01) and LF (p = 0.04). In subjects with the GSTM1 deletion and the HMOX-1 long repeat, SDNN decreased by 13% [95% confidence interval (CI), -21% to -4%], HF decreased by 28% (95% CI, -43% to -9%), and LF decreased by 20% (95% CI, -35% to -3%) per 10 microg/m(3) increase in PM. CONCLUSIONS: Oxidative stress is an important pathway for the autonomic effects of particles.     

Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes

Background: Arsenic is an epigenetic toxicant and could influence fetal developmental programming.Objectives: We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes.Methods: Drinking-water and urine samples were collected when women were at ≤ 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure.Results: Mean (± SD) drinking-water arsenic concentration was 14.8 ± 36.2 μg/L (range: < 1–230 μg/L). Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52, 2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation.Conclusions: Exposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effects.