Childhood traffic-related air pollution and adverse changes in subclinical atherosclerosis measures from childhood to adulthood.

BACKGROUND: Chronic exposure to air pollutants is associated with increased risk of cardiovascular disease (CVD) among adults. However, little is known about how air pollution may affect the development of subclinical atherosclerosis in younger populations. Carotid artery intima-media thickness (CIMT) is a measure of subclinical atherosclerosis that provides insight into early CVD pathogenesis. METHODS: In a pilot study of 70 participants from the Southern California Children's Health Study, we investigated CIMT progression from childhood to adulthood. Using carotid artery ultrasound images obtained at age 10 and follow-up images at age 21-22, we examined associations between childhood ambient and traffic-related air pollutants with changes in CIMT over time and attained adult CIMT using linear mixed-effects models adjusted for potential confounders. Average residential childhood exposures (i.e., birth to time of measurement at 10-11 years) were assigned for regional, ambient pollutants (ozone, nitrogen dioxide, particulate matter, interpolated from regulatory air monitoring data) and traffic-related nitrogen oxides (NOx) by road class (modeled using the CALINE4 line source dispersion model). Traffic density was calculated within a 300-m residential buffer. RESULTS: For each 1 standard deviation (SD) increase in childhood traffic-related total NOx exposure, we observed greater yearly rate of change in CIMT from childhood to adulthood (ß: 2.17 µm/yr, 95% CI: 0.78-3.56). Increases in annual rate of CIMT change from childhood to adulthood also were observed with freeway NOx exposure (ß: 2.24 µm/yr, 95% CI: 0.84-3.63) and traffic density (ß: 2.11 µm/yr, 95% CI: 0.79-3.43). Traffic exposures were also related to increases in attained CIMT in early adulthood. No associations of CIMT change or attained level were observed with ambient pollutants. CONCLUSIONS: Overall, we observed adverse changes in CIMT over time in relation to childhood traffic-related NOx exposure and traffic density in our study population. While these results must be cautiously interpreted given the limited sample size, the observed associations of traffic measures with CIMT suggest a need for future studies to more fully explore this relationship.

Near-roadway air pollution exposure and altered fatty acid oxidation among adolescents and young adults - The interplay with obesity.

BACKGROUND: Air pollution exposure has been shown to increase the risk of obesity and metabolic dysfunction in animal models and human studies. However, the metabolic pathways altered by air pollution exposure are unclear, especially in adolescents and young adults who are at a critical period in the development of cardio-metabolic diseases. OBJECTIVES: The aim of this study was to examine the associations between air pollution exposure and indices of fatty acid and amino acid metabolism. METHODS: A total of 173 young adults (18-23 years) from eight Children's Health Study (CHS) Southern California communities were examined from 2014 to 2018. Near-roadway air pollution (NRAP) exposure (freeway and non-freeway) and regional air pollution exposure (nitrogen dioxide, ozone and particulate matter) during one year before the study visit were estimated based on participants' residential addresses. Serum concentrations of 64 targeted metabolites including amino acids, acylcarnitines, non-esterified fatty acid (NEFA) and glycerol were measured in fasting serum samples. Principal component analysis of metabolites was performed to identify metabolite clusters that represent key metabolic pathways. Mixed effects models were used to analyze the associations of air pollution exposure with metabolomic principal component (PC) scores and individual metabolite concentrations adjusting for potential confounders. RESULTS: Higher lagged one-year averaged non-freeway NRAP exposure was associated with higher concentrations of NEFA oxidation byproducts and higher NEFA-related PC score (all p's ≤ 0.038). The effect sizes were larger among obese individuals (interaction p = 0.047). Among females, higher freeway NRAP exposure was also associated with a higher NEFA-related PC score (p = 0.042). Among all participants, higher freeway NRAP exposure was associated with a lower PC score for lower concentrations of short- and median-chain acylcarnitines (p = 0.044). CONCLUSIONS: Results of this study indicate that NRAP exposure is associated with altered fatty acid metabolism, which could contribute to the metabolic perturbation in obese youth.

Volcanic air pollution over the Island of Hawai'i: Emissions, dispersal, and composition. Association with respiratory symptoms and lung function in Hawai'i Island school children.

BACKGROUND: Kilauea Volcano on the Island of Hawai'i has erupted continuously since 1983, releasing approximately 300-12000metrictons per day of sulfur dioxide (SO2). SO2 interacts with water vapor to produce an acidic haze known locally as "vog". The combination of wind speed and direction, inversion layer height, and local terrain lead to heterogeneous and variable distribution of vog over the island, allowing study of respiratory effects associated with chronic vog exposure. OBJECTIVES: We characterized the distribution and composition of vog over the Island of Hawai'i, and tested the hypotheses that chronic vog exposure (SO2 and acid) is associated with increased asthma prevalence, respiratory symptoms, and reduced pulmonary function in Hawai'i Island schoolchildren. METHODS: We compiled data of volcanic emissions, wind speed, and wind direction over Hawai'i Island since 1992. Community-based researchers then measured 2- to 4-week integrated concentrations of SO2 and fine particulate mass and acidity in 4 exposure zones, from 2002 to 2005, when volcanic SO2 emissions averaged 1600metrictons per day. Concurrently, community researchers recruited schoolchildren in the 4th and 5th grades of 25 schools in the 4 vog exposure zones, to assess determinants of lung health, respiratory symptoms, and asthma prevalence. RESULTS: Environmental data suggested 4 different vog exposure zones with SO2, PM2.5, and particulate acid concentrations (mean±s.d.) as follows: 1) Low (0.3±0.2ppb, 2.5±1.2µg/m(3), 0.6±1.1nmolH+/m(3)), 2) Intermittent (1.6±1.8ppb, 2.8±1.5µg/m(3), 4.0±6.6nmolH+/m(3)), 3) Frequent (10.1±5.2ppb, 4.8±1.9µg/m(3), 4.3±6.7nmolH+/m(3)), and 4) Acid (1.2±0.4ppb, 7.2±2.3µg/m(3), 25.3±17.9nmolH+/m(3)). Participants (1957) in the 4 zones differed in race, prematurity, maternal smoking during pregnancy, environmental tobacco smoke exposure, presence of mold in the home, and physician-diagnosed asthma. Multivariable analysis showed an association between Acid vog exposure and cough and strongly suggested an association with FEV1/FVC <0.8, but not with diagnosis of asthma, or chronic persistent wheeze or bronchitis in the last 12months. CONCLUSIONS: Hawai'i Island's volcanic air pollution can be very acidic, but contains few co-contaminants originating from anthropogenic sources of air pollution. Chronic exposure to acid vog is associated with increased cough and possibly with reduced FEV1/FVC, but not with asthma or bronchitis. Further study is needed to better understand how volcanic air pollution interacts with host and environmental factors to affect respiratory symptoms, lung function, and lung growth, and to determine acute effects of episodes of increased emissions.

Association of Changes in Air Quality With Bronchitic Symptoms in Children in California, 1993-2012.

IMPORTANCE: Childhood bronchitic symptoms are significant public and clinical health problems that produce a substantial burden of disease. Ambient air pollutants are important determinants of bronchitis occurrence. OBJECTIVE: To determine whether improvements in ambient air quality in Southern California were associated with reductions in bronchitic symptoms in children. DESIGN, SETTING, AND PARTICIPANTS: A longitudinal study involving 4602 children (age range, 5-18 years) from 3 cohorts was conducted during the 1993-2001, 1996-2004, and 2003-2012 years in 8 Southern California communities. A multilevel logistic model was used to estimate the association of changes in pollution levels with bronchitic symptoms. EXPOSURES: Average concentrations of nitrogen dioxide, ozone, particulate matter with an aerodynamic diameter of less than 10 µm (PM10) and less than 2.5 µm (PM2.5). MAIN OUTCOMES AND MEASURES: Annual age-specific prevalence of bronchitic symptoms during the previous 12 months based on the parent's or child's report of a daily cough for 3 months in a row, congestion or phlegm other than when accompanied by a cold, or bronchitis. RESULTS: The 3 cohorts included a total of 4602 children (mean age at baseline, 8.0 years; 2268 girls [49.3%]; 2081 Hispanic white [45.2%]) who had data from 2 or more annual questionnaires. Among these children, 892 (19.4%) had asthma at age 10 years. For nitrogen dioxide, the odds ratio (OR) for bronchitic symptoms among children with asthma at age 10 years was 0.79 (95% CI, 0.67-0.94) for a median reduction of 4.9 ppb, with absolute decrease in prevalence of 10.1%. For ozone, the OR was 0.66 (95% CI, 0.50-0.86) for a median reduction of 3.6 ppb, with an absolute decrease in prevalence of 16.3%. For PM10, the OR was 0.61 (95% CI, 0.48-0.78) for a median reduction of 5.8 µg/m3, with an absolute decrease in prevalence of 18.7%. For PM2.5, the OR was 0.68 (95% CI, 0.53-0.86) for a median reduction of 6.8 µg/m3, with absolute decrease in prevalence of 15.4%. Among children without asthma (n = 3710), the ORs were 0.84 (95% CI, 0.76-0.92) for nitrogen dioxide; 0.85 (95% CI, 0.74-0.97) for ozone, 0.80 (95% CI, 0.70-0.92) for PM10, and 0.79 (95% CI, 0.69-0.91) for PM2.5; with absolute decrease in prevalence of 1.8% for nitrogen dioxide, 1.7% for ozone, 2.2% for PM10, and 2.3% for PM2.5. The associations were similar or slightly stronger at age 15 years. CONCLUSIONS AND RELEVANCE: Decreases in ambient pollution levels were associated with statistically significant decreases in bronchitic symptoms in children. Although the study design does not establish causality, the findings support potential benefit of air pollution reduction on asthma control.

Association of improved air quality with lung development in children.

BACKGROUND: Air-pollution levels have been trending downward progressively over the past several decades in southern California, as a result of the implementation of air quality-control policies. We assessed whether long-term reductions in pollution were associated with improvements in respiratory health among children. METHODS: As part of the Children's Health Study, we measured lung function annually in 2120 children from three separate cohorts corresponding to three separate calendar periods: 1994-1998, 1997-2001, and 2007-2011. Mean ages of the children within each cohort were 11 years at the beginning of the period and 15 years at the end. Linear-regression models were used to examine the relationship between declining pollution levels over time and lung-function development from 11 to 15 years of age, measured as the increases in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) during that period (referred to as 4-year growth in FEV1 and FVC). RESULTS: Over the 13 years spanned by the three cohorts, improvements in 4-year growth of both FEV1 and FVC were associated with declining levels of nitrogen dioxide (P<0.001 for FEV1 and FVC) and of particulate matter with an aerodynamic diameter of less than 2.5 µm (P= 0.008 for FEV1 and P<0.001 for FVC) and less than 10 µm (P<0.001 for FEV1 and FVC). These associations persisted after adjustment for several potential confounders. Significant improvements in lung-function development were observed in both boys and girls and in children with asthma and children without asthma. The proportions of children with clinically low FEV1 (defined as <80% of the predicted value) at 15 years of age declined significantly, from 7.9% to 6.3% to 3.6% across the three periods, as the air quality improved (P = 0.001). CONCLUSIONS: We found that long-term improvements in air quality were associated with statistically and clinically significant positive effects on lung-function growth in children. (Funded by the Health Effects Institute and others.).

Determinants of the Spatial Distributions of Elemental Carbon and Particulate Matter in Eight Southern Californian Communities.

Emerging evidence indicates that near-roadway pollution (NRP) in ambient air has adverse health effects. However, specific components of the NRP mixture responsible for these effects have not been established. A major limitation for health studies is the lack of exposure models that estimate NRP components observed in epidemiological studies over fine spatial scale of tens to hundreds of meters. In this study, exposure models were developed for fine-scale variation in biologically relevant elemental carbon (EC). Measurements of particulate matter (PM) and EC less than 2.5 µm in aerodynamic diameter (EC2.5) and of PM and EC of nanoscale size less than 0.2 µm were made at up to 29 locations in each of eight Southern California Children's Health Study communities. Regression-based prediction models were developed using a guided forward selection process to identify traffic variables and other pollutant sources, community physical characteristics and land use as predictors of PM and EC variation in each community. A combined eight-community model including only CALINE4 near-roadway dispersion-estimated vehicular emissions accounting for distance, distance-weighted traffic volume, and meteorology, explained 51% of the EC0.2 variability. Community-specific models identified additional predictors in some communities; however, in most communities the correlation between predicted concentrations from the eight-community model and observed concentrations stratified by community were similar to those for the community-specific models. EC2.5 could be predicted as well as EC0.2. EC2.5 estimated from CALINE4 and population density explained 53% of the within-community variation. Exposure prediction was further improved after accounting for between-community heterogeneity of CALINE4 effects associated with average distance to Pacific Ocean shoreline (to 61% for EC0.2) and for regional NOx pollution (to 57% for EC2.5). PM fine spatial scale variation was poorly predicted in both size fractions. In conclusion, models of exposure that include traffic measures such as CALINE4 can provide useful estimates for EC0.2 and EC2.5 on a spatial scale appropriate for health studies of NRP in selected Southern California communities.

Associations of children's lung function with ambient air pollution: joint effects of regional and near-roadway pollutants.

BACKGROUND: Previous studies have reported adverse effects of either regional or near-roadway air pollution (NRAP) on lung function. However, there has been little study of the joint effects of these exposures. OBJECTIVES: To assess the joint effects of NRAP and regional pollutants on childhood lung function in the Children's Health Study. METHODS: Lung function was measured on 1811 children from eight Southern Californian communities. NRAP exposure was assessed based on (1) residential distance to the nearest freeway or major road and (2) estimated near-roadway contributions to residential nitrogen dioxide (NO2), nitric oxide (NO) and total nitrogen oxides (NOx). Exposure to regional ozone (O3), NO2, particulate matter with aerodynamic diameter <10 µm (PM10) and 2.5 µm (PM2.5) was measured continuously at community monitors. RESULTS: An increase in near-roadway NOx of 17.9 ppb (2 SD) was associated with deficits of 1.6% in forced vital capacity (FVC) (p=0.005) and 1.1% in forced expiratory volume in 1 s (FEV1) (p=0.048). Effects were observed in all communities and were similar for NO2 and NO. Residential proximity to a freeway was associated with a reduction in FVC. Lung function deficits of 2-3% were associated with regional PM10 and PM2.5 (FVC and FEV1) and with O3 (FEV1), but not NO2 across the range of exposure between communities. Associations with regional pollution and NRAP were independent in models adjusted for each. The effects of NRAP were not modified by regional pollutant concentrations. CONCLUSIONS: The results indicate that NRAP and regional air pollution have independent adverse effects on childhood lung function.

Development of a regional-scale pollen emission and transport modeling framework for investigating the impact of climate change on allergic airway disease.

Exposure to bioaerosol allergens such as pollen can cause exacerbations of allergenic airway disease (AAD) in sensitive populations, and thus cause serious public health problems. Assessing these health impacts by linking the airborne pollen levels, concentrations of respirable allergenic material, and human allergenic response under current and future climate conditions is a key step toward developing preventive and adaptive actions. To that end, a regional-scale pollen emission and transport modeling framework was developed that treats allergenic pollens as non-reactive tracers within the WRF/CMAQ air-quality modeling system. The Simulator of the Timing and Magnitude of Pollen Season (STaMPS) model was used to generate a daily pollen pool that can then be emitted into the atmosphere by wind. The STaMPS is driven by species-specific meteorological (temperature and/or precipitation) threshold conditions and is designed to be flexible with respect to its representation of vegetation species and plant functional types (PFTs). The hourly pollen emission flux was parameterized by considering the pollen pool, friction velocity, and wind threshold values. The dry deposition velocity of each species of pollen was estimated based on pollen grain size and density. An evaluation of the pollen modeling framework was conducted for southern California for the period from March to June 2010. This period coincided with observations by the University of Southern California's Children's Health Study (CHS), which included O3, PM2.5, and pollen count, as well as measurements of exhaled nitric oxide in study participants. Two nesting domains with horizontal resolutions of 12 km and 4 km were constructed, and six representative allergenic pollen genera were included: birch tree, walnut tree, mulberry tree, olive tree, oak tree, and brome grasses. Under the current parameterization scheme, the modeling framework tends to underestimate walnut and peak oak pollen concentrations, and tends to overestimate grass pollen concentrations. The model shows reasonable agreement with observed birch, olive, and mulberry tree pollen concentrations. Sensitivity studies suggest that the estimation of the pollen pool is a major source of uncertainty for simulated pollen concentrations. Achieving agreement between emission modeling and observed pattern of pollen releases is the key for successful pollen concentration simulations.

Predictors of intra-community variation in air quality.

Air quality has emerged as a key determinant of important health outcomes in children and adults. This study aims to identify factors that influence local, within-community air quality, and to build a model for traffic-related air pollution (TRP).We utilized concentrations of NO(2), NO, and total oxides of nitrogen (NO(x)), which were measured at 942 locations in 12 southern California communities. For each location, population density, elevation, land-use, and several indicators of traffic were calculated. A spatial random effects model was used to study the relationship of these predictors to each TRP.Variation in TRP was strongly correlated with traffic on nearby freeways and other major roads, and also with population density and elevation. After accounting for traffic, categories of land-use were not associated with the pollutants. Traffic had a larger relative impact in small urban (low regional pollution) communities than in large urban (high regional pollution) communities. For example, our best fitting model explained 70% of the variation in NO(x) in large urban areas and 76% in small urban areas. Compared with living at least 1,500 m from a freeway, living within 250 m of a freeway was associated with up to a 41% increase in TRP in a large urban area, and up to a 75% increase in small urban areas.Thus, traffic strongly affects local air quality in large and small urban areas, which has implications for exposure assessment and estimation of health risks.

Comparing universal kriging and land-use regression for predicting concentrations of gaseous oxides of nitrogen (NOx) for the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air).

BACKGROUND: Epidemiological studies that assess the health effects of long-term exposure to ambient air pollution are used to inform public policy. These studies rely on exposure models that use data collected from pollution monitoring sites to predict exposures at subject locations. Land use regression (LUR) and universal kriging (UK) have been suggested as potential prediction methods. We evaluate these approaches on a dataset including measurements from three seasons in Los Angeles, CA. METHODS: The measurements of gaseous oxides of nitrogen (NOx) used in this study are from a "snapshot" sampling campaign that is part of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). The measurements in Los Angeles were collected during three two-week periods in the summer, autumn, and winter, each with about 150 sites. The design included clusters of monitors on either side of busy roads to capture near-field gradients of traffic-related pollution. LUR and UK prediction models were created using geographic information system (GIS)-based covariates. Selection of covariates was based on 10-fold cross-validated (CV) R(2) and root mean square error (RMSE). Since UK requires specialized software, a computationally simpler two-step procedure was also employed to approximate fitting the UK model using readily available regression and GIS software. RESULTS: UK models consistently performed as well as or better than the analogous LUR models. The best CV R(2) values for season-specific UK models predicting log(NOx) were 0.75, 0.72, and 0.74 (CV RMSE 0.20, 0.17, and 0.15) for summer, autumn, and winter, respectively. The best CV R(2) values for season-specific LUR models predicting log(NOx) were 0.74, 0.60, and 0.67 (CV RMSE 0.20, 0.20, and 0.17). The two-stage approximation to UK also performed better than LUR and nearly as well as the full UK model with CV R(2) values 0.75, 0.70, and 0.70 (CV RMSE 0.20, 0.17, and 0.17) for summer, autumn, and winter, respectively. CONCLUSION: High quality LUR and UK prediction models for NOx in Los Angeles were developed for the three seasons based on data collected for MESA Air. In our study, UK consistently outperformed LUR. Similarly, the 2-step approach was more effective than the LUR models, with performance equal to or slightly worse than UK.

Residential traffic-related pollution exposures and exhaled nitric oxide in the children's health study.

BACKGROUND: The fractional concentration of nitric oxide in exhaled air (FeNO) potentially detects airway inflammation related to air pollution exposure. Existing studies have not yet provided conclusive evidence on the association of FeNO with traffic-related pollution (TRP). OBJECTIVES: We evaluated the association of FeNO with residential TRP exposure in a large cohort of children. METHODS: We related FeNO measured on 2,143 children (ages 7-11 years) who participated in the Southern California Children's Health Study (CHS) to five classes of metrics of residential TRP: distances to freeways and major roads; length of all and local roads within circular buffers around the home; traffic densities within buffers; annual average line source dispersion modeled nitrogen oxides (NOx) from freeways and nonfreeway roads; and predicted annual average nitrogen oxide, nitrogen dioxide, and NOx from a model based on intracommunity sampling in the CHS. RESULTS: In children with asthma, length of roads was positively associated with FeNO, with stronger associations in smaller buffers [46.7%; 95% confidence interval (CI), 14.3-88.4], 12.4% (95% CI, -8.8 to 38.4), and 4.1% (95% CI, -14.6 to 26.8) higher FeNO for 100-, 300-, and 1,000-m increases in the length of all roads in 50-, 100-, and 200-m buffers, respectively. Other TRP metrics were not significantly associated with FeNO, even though the study design was powered to detect exposures explaining as little as 0.4% of the variation in natural log-transformed FeNO (R2 = 0.004). CONCLUSION: Length of road was the only indicator of residential TRP exposure associated with airway inflammation in children with asthma, as measured by FeNO.

Approach to estimating participant pollutant exposures in the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air).

Most published epidemiology studies of long-term air pollution health effects have relied on central site monitoring to investigate regional-scale differences in exposure. Few cohort studies have had sufficient data to characterize localized variations in pollution, despite the fact that large gradients can exist over small spatial scales. Similarly, previous data have generally been limited to measurements of particle mass or several of the criteria gases. The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) is an innovative investigation undertaken to link subclinical and clinical cardiovascular health effects with individual-level estimates of personal exposure to ambient-origin pollution. This project improves on prior work by implementing an extensive exposure assessment program to characterize long-term average concentrations of ambient-generated PM2.5, specific PM2.5 chemical components, and copollutants, with particular emphasis on capturing concentration gradients within cities. This paper describes exposure assessment in MESA Air, including questionnaires, community sampling, home monitoring, and personal sampling. Summary statistics describing the performance of the sampling methods are presented along with descriptive statistics of the air pollution concentrations by city.

In utero smoke exposure, glutathione S-transferase P1 haplotypes, and respiratory illness-related absence among schoolchildren.

BACKGROUND: The GSTP1 Ile105Val variant and secondhand tobacco smoke exposure have been independently associated with acute respiratory illness; however, susceptibility to in utero and secondhand tobacco smoke has yet to be examined in relation to variation across the GSTP1 locus. OBJECTIVE: The purpose of this work was to determine whether variation across the GSTP1 locus is associated with respiratory illness-related school absences and to determine whether this relationship varies by in utero and secondhand tobacco smoke exposure. METHODS: Tobacco smoke exposure status, incident respiratory-related school absence records, and DNA samples was ascertained for 1132 Hispanic and non-Hispanic white elementary school children as part of the Children's Health Study. RESULTS: Four GSTP1 single-nucleotide polymorphisms were selected that accounted for 93% of the variation across the locus. Individual single-nucleotide polymorphism analyses showed a protective effect for the minor alleles in single-nucleotide polymorphisms 1 (rs6591255), 3 (GSTP1 Ile105Val: rs1695), and 4 (rs749174) for respiratory illness. The haplotype, which includes a minor allele for single-nucleotide polymorphisms 1, 3, and 4 (h1011), was associated with a decreased risk of respiratory illness. The protective effect of GSTP1 variants was lost among individuals exposed to in utero and secondhand tobacco smoke. CONCLUSIONS: A common GSTP1 haplotype, which includes the functional Ile105Val polymorphism, was associated with respiratory-related school absences. The protection afforded by this haplotype was lost in children exposed to involuntary tobacco smoke. The paradigm of loss of genetic protection among those exposed to tobacco smoke has clinical and public health implications that warrant broader consideration in research and practice.

Exhaled nitric oxide in a population-based study of southern California schoolchildren.

BACKGROUND: Determinants of exhaled nitric oxide (FeNO) need to be understood better to maximize the value of FeNO measurement in clinical practice and research. Our aim was to identify significant predictors of FeNO in an initial cross-sectional survey of southern California schoolchildren, part of a larger longitudinal study of asthma incidence. METHODS: During one school year, we measured FeNO at 100 ml/sec flow, using a validated offline technique, in 2568 children of age 7-10 yr. We estimated online (50 ml/sec flow) FeNO using a prediction equation from a separate smaller study with adjustment for offline measurement artifacts, and analyzed its relationship to clinical and demographic characteristics. RESULTS: FeNO was lognormally distributed with geometric means ranging from 11 ppb in children without atopy or asthma to 16 ppb in children with allergic asthma. Although effects of atopy and asthma were highly significant, ranges of FeNO for children with and without those conditions overlapped substantially. FeNO was significantly higher in subjects aged > 9, compared to younger subjects. Asian-American boys showed significantly higher FeNO than children of all other sex/ethnic groups; Hispanics and African-Americans of both sexes averaged slightly higher than non-Hispanic whites. Increasing height-for-age had no significant effect, but increasing weight-for-height was associated with decreasing FeNO. CONCLUSION: FeNO measured offline is a useful biomarker for airway inflammation in large population-based studies. Further investigation of age, ethnicity, body-size, and genetic influences is needed, since they may contribute to substantial variation in FeNO.

Respiratory symptoms following wildfire smoke exposure: airway size as a susceptibility factor.

BACKGROUND: Associations between exposure to smoke during wildfire events and respiratory symptoms are well documented, but the role of airway size remains unclear. We conducted this analysis to assess whether small airway size modifies these relationships. METHODS: We analyzed data from 465 nonasthmatic 16- to 19-year-old participants in the Children's Health Study. Following an outbreak of wildfires in 2003, each student completed a questionnaire about smoke exposure, dry and wet cough, wheezing, and eye symptoms. We used log-binomial regression to evaluate associations between smoke exposure and fire-related health symptoms, and to assess modification of the associations by airway size. As a marker of airway size, we used the ratio of maximum midexpiratory flow to forced vital capacity. RESULTS: Forty percent (186 of 465) of this population (including students from 11 of 12 surveyed communities) reported the odor of wildfire smoke at home. We observed increased respiratory and eye symptoms with increasing frequency of wildfire smoke exposure. Associations between smoke exposure and having any of 4 respiratory symptoms were stronger in the lowest quartile of the lung function ratio (eg, fire smoke 6+ days: prevalence ratio: 3.8; 95% confidence interval (CI = 2.0-7.2), compared with the remaining quartiles (fire smoke 6+ days: prevalence ratio = 2.0; 1.2-3.2). Analysis of individual symptoms suggests that this interaction may be strongest for effects on wheezing. CONCLUSIONS: Small airways may serve as a marker of susceptibility to effects of wildfire smoke. Future studies should investigate the role of airway size for more common exposures and should include persons with asthma.

Relationships of online exhaled, offline exhaled, and ambient nitric oxide in an epidemiologic survey of schoolchildren.

UNLABELLED: Field measurements of exhaled nitric oxide (FeNO) and ambient nitric oxide (NO) are useful to assess both respiratory health and short-term air pollution exposure. Online real-time measurement maximizes data quality and comparability with clinical studies, but offline delayed measurement may be more practical for large epidemiological studies. To facilitate cross-comparison in larger studies, we measured FeNO and concurrent ambient NO both online and offline in 362 children at 14 schools in 8 Southern California communities. Offline breath samples were collected in bags at 100 ml/s expiratory flow with deadspace discard; online FeNO was measured at 50 ml/s. Scrubbing of ambient NO from inhaled air appeared to be nearly 100% effective online, but 50-75% effective offline. Offline samples were stored at 2-8 degrees C and analyzed 2-26 h later at a central laboratory. Offline and online FeNO showed a nearly (but not completely) linear relationship (R(2)=0.90); unadjusted means (ranges) were 10 (4-94) and 15 (3-181) p.p.b., respectively. Ambient NO concentration range was 0-212 p.p.b. Offline FeNO was positively related to ambient NO (r=0.30, P<0.0001), unlike online FeNO (r=0.09, P=0.08), indicating that ambient NO artifactually influenced offline measurements. Offline FeNO differed between schools (P<0.001); online FeNO did not (P=0.26), suggesting artifacts related to offline bag storage and transport. Artifact effects were small in comparison with between-subject variance of FeNO. An empirical statistical model predicting individual online FeNO from offline FeNO, ambient NO, and lag time before offline analysis gave R(2)=0.94. Analyses of school or age differences yielded similar results from measured or model-predicted online FeNO. CONCLUSIONS: Either online or offline measurement of exhaled NO and concurrent ambient NO can be useful in field epidemiology. Influence of ambient NO on exhaled NO should be examined carefully, particularly for offline measurements.

Traffic-related air pollution and asthma onset in children: a prospective cohort study with individual exposure measurement.

BACKGROUND: The question of whether air pollution contributes to asthma onset remains unresolved. OBJECTIVES: In this study, we assessed the association between asthma onset in children and traffic-related air pollution. METHODS: We selected a sample of 217 children from participants in the Southern California Children's Health Study, a prospective cohort designed to investigate associations between air pollution and respiratory health in children 10-18 years of age. Individual covariates and new asthma incidence (30 cases) were reported annually through questionnaires during 8 years of follow-up. Children had nitrogen dioxide monitors placed outside their home for 2 weeks in the summer and 2 weeks in the fall-winter season as a marker of traffic-related air pollution. We used multilevel Cox models to test the associations between asthma and air pollution. RESULTS: In models controlling for confounders, incident asthma was positively associated with traffic pollution, with a hazard ratio (HR) of 1.29 [95% confidence interval (CI), 1.07-1.56] across the average within-community interquartile range of 6.2 ppb in annual residential NO2. Using the total interquartile range for all measurements of 28.9 ppb increased the HR to 3.25 (95% CI, 1.35-7.85). CONCLUSIONS: In this cohort, markers of traffic-related air pollution were associated with the onset of asthma. The risks observed suggest that air pollution exposure contributes to new-onset asthma.

Glutathione S-transferase P1, maternal smoking, and asthma in children: a haplotype-based analysis.

BACKGROUND: Glutathione S-transferase P1 (GSTP1) plays a role in a spectrum of respiratory diseases; however, the effects of sequence variation across the entire locus in asthma pathogenesis have yet to be determined. OBJECTIVES: This study was designed to investigate whether sequence variations in the GSTP1 coding and promoter regions are associated with asthma and wheezing outcomes and to determine whether variants affect susceptibility to maternal smoking. METHODS: Four haplotype tagging SNPs were selected that accounted for 83% of the common haplotypic variation in GSTP1. The associations of GSTP1 variants with asthma and wheezing were assessed among white children in the Children's Health Study (CHS). RESULTS: The Ile105Val allele and a SNP in the upstream promoter region (SNP1: rs6591255, putative transcription factor 1 binding site) were associated with asthma and wheezing outcomes, an association observed in two cohorts of the CHS recruited in different years. Haplotypes that included both the promoter SNP (i.e., rs6591255) and the 105 Val variant were associated with an increased risk for asthma in non-Hispanic whites. Using SNP- and haplotype-based approaches, the effect of maternal smoking on wheezing was largest in children with the Ile105Val allele. CONCLUSIONS: Variants in both the promoter and coding regions of the GSTP1 locus may contribute to the occurrence of childhood asthma and wheezing and may increase susceptibility to adverse effects of tobacco-smoke exposure.

Microsomal epoxide hydrolase, glutathione S-transferase P1, traffic and childhood asthma.

BACKGROUND: Microsomal epoxide hydrolase (EPHX1) metabolises xenobiotics including polyaromatic hydrocarbons (PAHs). Functional variants at this locus have been associated with respiratory diseases. The effects of EPHX1 variants may depend upon exposures from tobacco smoke and traffic emissions that contain PAHs as well as variants in other enzymes in the PAH metabolic pathway such as glutathione S-transferase (GST) genes. A study was undertaken to investigate associations of variants in EPHX1, GSTM1, GSTP1 and GSTT1 with asthma and the relationships between asthma, EPHX1 metabolic phenotypes and exposure to sources of PAHs. METHODS: Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to estimate the associations of genetic variants and exposures with asthma phenotypes using data from 3124 children from the Children's Health Study. RESULTS: High EPHX1 activity was associated with an increased risk for lifetime asthma (OR 1.51, 95% CI 1.14 to 1.98) which varied by GSTP1 Ile105Val genotype and by residential proximity to major roads (p for interaction = 0.006 and 0.03, respectively). Among children with GSTP1 105Val/Val genotype, those who had high EPHX1 phenotype had a fourfold (95% CI 1.97 to 8.16) increased risk of lifetime asthma than children with low/intermediate EPHX1 phenotype. Among children living within 75 metres of a major road, those with high EPHX1 activity had a 3.2-fold (95% CI 1.75 to 6.00) higher lifetime asthma risk than those with low/intermediate activity. The results were similar for current, early persistent and late onset asthma. Children with high EPHX1 phenotype, GSTP1 Val/Val genotype who lived <75 metres from a major road were at the highest asthma risk. CONCLUSION: EPHX1 and GSTP1 variants contribute to the occurrence of childhood asthma and increase asthma susceptibility to exposures from major roads.