Ambient air pollutants are associated with morning serum cortisol in overweight and obese Latino youth in Los Angeles.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA)-axis dysfunction has been associated with a variety of mental health and cardio-metabolic disorders. While causal models of HPA-axis dysregulation have been largely focused on either pre-existing health conditions or psychosocial stress factors, recent evidence suggests a possible role for central nervous system activation via air pollutants, such as nitrogen dioxide (NO2), ozone (O3) and particulate matter (PM). Therefore, in an observational study of Latino youth, we investigated if monthly ambient NO2, O3, and PM with aerodynamic diameter ≤ 2.5 (PM2.5) exposure were associated with morning serum cortisol levels. METHODS: In this cross-sectional study, morning serum cortisol level was assessed after a supervised overnight fast in 203 overweight and obese Latino children and adolescents (female/male: 88/115; mean age: 11.1 ± 1.7 years; pre-pubertal/pubertal/post-pubertal: 85/101/17; BMI z-score: 2.1 ± 0.4). Cumulative concentrations of NO2, O3 and PM2.5 were spatially interpolated at the residential addresses based on measurements from community monitors up to 12 months prior to testing. Single and multi-pollutant linear effects models were used to test the cumulative monthly lag effects of NO2, O3, and PM2.5 on morning serum cortisol levels after adjusting for age, sex, seasonality, social position, pubertal status, and body fat percent by DEXA. RESULTS: Single and multi-pollutant models showed that higher O3 exposure (derived from maximum 8-h exposure windows) in the prior 1-7 months was associated with higher serum morning cortisol (p < 0.05) and longer term PM2.5 exposure (4-10 months) was associated with lower serum morning cortisol levels (p < 0.05). Stratification by pubertal status showed associations in pre-pubertal children compared to pubertal and post-pubertal children. Single, but not multi-pollutant, models showed that higher NO2 over the 4-10 month exposure period associated with lower morning serum cortisol (p < 0.05). CONCLUSIONS: Chronic ambient NO2, O3 and PM2.5 differentially associate with HPA-axis dysfunction, a mechanism that may serve as an explanatory pathway in the relationship between ambient air pollution and metabolic health of youth living in polluted urban environments. Further research that uncovers how ambient air pollutants may differentially contribute to HPA-axis dysfunction are warranted.

Effects of air pollution exposure on glucose metabolism in Los Angeles minority children.

OBJECTIVES: Growing evidence indicates that ambient (AAP: NO2 , PM2.5 and O3 ) and traffic-related air pollutants (TRAP) contribute to metabolic disease risk in adults; however, few studies have examined these relationships in children. METHODS: Metabolic profiling was performed in 429 overweight and obese African-American and Latino youth living in urban Los Angeles, California. This cross-sectional study estimated individual residential air pollution exposure and used linear regression to examine relationships between air pollution and metabolic outcomes. RESULTS: AAP and TRAP exposure were associated with adverse effects on glucose metabolism independent of body fat percent. PM2.5 was associated with 25.0% higher fasting insulin (p < 0.001), 8.3% lower insulin sensitivity (p < 0.001), 14.7% higher acute insulin response to glucose (p = 0.001) and 1.7% higher fasting glucose (p < 0.001). Similar associations were observed for increased NO2 exposure. TRAP from non-freeway roads was associated with 12.1% higher insulin (p < 0.001), 6.9% lower insulin sensitivity (p = 0.02), 10.8% higher acute insulin response to glucose (p = 0.003) and 0.7% higher fasting glucose (p = 0.047). CONCLUSIONS: Elevated air pollution exposure was associated with a metabolic profile that is characteristic of increased risk for type 2 diabetes. These results indicate that increased prior year exposure to air pollution may adversely affect type 2 diabetes-related pathophysiology in overweight and obese minority children.

Prenatal traffic-related air pollution exposures, cord blood adipokines and infant weight.

OBJECTIVE: Studies suggest that prenatal exposure to traffic-related air pollution (TRAP) may contribute to childhood obesity. While exact mechanisms for this association are unknown, circulating adipokines are hypothesized to contribute to early-life weight gain. METHODS: The Maternal and Child Health Study birth cohort included 136 women from the Los Angeles County + University of Southern California Medical Center. This study estimated prenatal residential TRAP exposure and used linear regression analysis to examine associations between adipokines with TRAP exposure and infant weight change (birth to 6 months). RESULTS: A one standard deviation (1-SD: 2 ppb) increase in prenatal non-freeway nitrogen oxides was associated with 33% (P = 0.01) higher leptin and 9% higher high molecular weight adiponectin levels (P = 0.07) in cord blood. Leptin levels were 71% higher in mothers who lived <75 m than those living >300 m from major roadways (P = 0.03). A 1-SD (10 ng mL-1 ) increase in leptin was associated with a significant increase in infant weight change in female infants (0.62 kg, P = 0.02) but not male infants (0.11 kg, P = 0.48). CONCLUSIONS: Higher TRAP exposures were associated with higher cord blood levels of leptin and high molecular weight adiponectin. These adipokines were associated with increased infant weight change in female infants, which may have implications for future obesity risk.

The Effects of Policy-Driven Air Quality Improvements on Children's Respiratory Health.

INTRODUCTION: Ambient air pollution causes substantial morbidity and mortality in the United States and worldwide. To reduce this burden of adverse health effects, a broad array of strategies to reduce ambient air pollution has been developed and applied over past decades to achieve substantial reductions in ambient air pollution levels. This has been especially true in California, where the improvement of air quality has been a major focus for more than 50 years. Direct links between regulatory policies, changes in ambient pollutant concentrations, and improvements in public health have not been extensively documented. Data from the Children's Health Study (CHS), a multiyear study of children's respiratory health development, offered a unique opportunity to evaluate the effects of long-term reductions in air pollution on children's health. METHODS: We assessed whether changes in ambient air quality and emissions were reflected in three important indices of children's respiratory health: lung-function growth, lung-function level, and bronchitic symptoms. To make the best use of available data, these analyses were performed across the longest chronological period and largest CHS population available for the respective lung-function or bronchitic symptoms data sets. During field study operations over the course of the CHS, children's health status was documented annually by testing lung-function performance and the completion of standardized questionnaires covering a broad range of respiratory symptoms. Air quality data for the periods of interest were obtained from community monitoring stations, which operated in collaboration with regional air monitoring networks over the 20-year study time frame. Over the 20-year sampling period, common protocols were applied to collect data across the three cohorts of children. Each cohort's data set was assessed to investigate the relationship between temporal changes in lung-function development, prevalence of bronchitic symptoms, and ambient air pollution concentrations during a similar, vulnerable adolescent growth period (age 11 to 15 years). Analyses were performed separately for particulate matter ≤10 µm in aerodynamic diameter (PM10), particulate matter ≤2.5 µm in aerodynamic diameter (PM2.5), ozone (O3), and nitrogen dioxide (NO2). Emissions data and regulatory policies were collected from the staff of state and regional regulatory agencies, modeling estimates, and archived reports. RESULTS: Emissions in the regions of California studied during the 20-year period decreased by 54% for oxides of nitrogen (NOₓ), 65% for reactive organic gases (ROG), 21% for PM2.5, and 15% for PM10. These reductions occurred despite a concurrent 22% increase in population and a 38% increase in motor vehicle miles driven during that time frame. Air quality improved over the same time frame, with reductions in NO2 and PM2.5 in virtually all of the CHS communities. Annual average NO2 decreased by about 53% (from ~41 to 19 ppb) in the highest NO2-reporting community (Upland) and by about 28% (from ~10 to 7 ppb) in one of the lowest NO2-reporting communities (Santa Maria). Reductions in annual average PM2.5 concentrations ranged from 54% (~33 to 15 µg/m³) in the community with the highest concentration (Mira Loma) to 13% (~9 to 8 µg/m³) in a community with one of the lowest concentrations (Santa Maria). Improvements in PM10 and O3 (measured during eight daytime hours, 10 AM to 6 PM) were most evident in the CHS communities that initially had the highest levels of PM and O3. Trends in annual average NO2, PM2.5, and PM10 ambient air concentrations in the communities with higher-pollution levels were generally consistent with observed trends in NOₓ, ROG, PM2.5, and PM10 emissions.Significant improvements in lung-function growth in progressive cohorts were observed as air quality improved over the study period. Improvements in four-year growth of both forced expiratory volume in the first second of exhalation (FEV1) and forced vital capacity (FVC) were associated with declining levels of NO2 (P < 0.0001), PM2.5 (P < 0.01), and PM10 (P < 0.001). These associations persisted after adjustment for important potential confounders. Further, significant improvements in lung-function growth were observed in both boys and girls and among asthmatic and non-asthmatic children. Within-community decreases in O3 exposure were not significantly associated with lung-function growth. The proportion of children with clinically low FEV1 (defined as <80% predicted) at age 15 declined significantly, from 7.9% to 3.6% across the study periods, respectively, as the air quality improved (P < 0.005). We found little evidence to suggest that improvements in lung-function development were attributable to temporal confounding.Reductions in outdoor levels of NO2, O3, PM10, and PM2.5 across the cohort years of participation were associated with significant reductions in the prevalence of bronchitic symptoms regardless of asthma status, but observed improvements were larger in children with asthma. Among asthmatic children, the reductions in prevalence of bronchitic symptoms at age 10 were 21% (P < 0.01) for NO2, 34% (P < 0.01) for O3, 39% (P < 0.01) for PM10, and 32% (P < 0.01) for PM2.5 for reductions of 4.9 ppb, 3.6 ppb, 5.8 µg/m³, and 6.8 µg/m³, respectively. Similar reductions in prevalence of bronchitic symptoms were observed at age 15 among these same asthmatic children. As in the lung-function analyses, we found little evidence that temporal confounding accounted for the observed associations of symptoms reduction with air quality improvement.The large number and breadth of regulatory activities, as well as the prolonged phase-in periods of several policy approaches to reduce emissions, precluded the close temporal linkage of specific policies with specific changes in health status. However, the combination of policies addressing motor vehicle emissions - from on-board diagnostics to emission controls, from low-sulfur fuels to vehicle smog-check recertification, and from re-formulated gasoline to the various strategies contained within the San Pedro Bay Ports Clean Air Plan (especially the Clean Truck Program) - all contributed to an impressive and substantial reduction in emissions. These reductions collectively improved local and regional air quality, and improvements in local and regional air quality were associated with improvements in respiratory health. CONCLUSIONS: This study provides evidence that multiyear improvements in air quality and emissions, primarily driven through a broad array of science-based regulatory policy initiatives, have resulted in improved public health outcomes. Our study demonstrates that improvements in air quality, brought about by science-based regulatory actions, are associated with improved respiratory health in children. These respiratory health metrics include reductions in respiratory symptoms and improvements in lung-function development in a population widely accepted to be at risk and highly vulnerable to the effects of air pollution. Our research findings underscore the importance of sustained air regulatory efforts as an effective means of achieving improved respiratory health in communities and regions affected by airborne pollution.

Living near a freeway is associated with lower bone mineral density among Mexican Americans.

UNLABELLED: We hypothesized that chronic exposures to traffic combustion products may lower bone mineral density (BMD). We found that proximity to freeways was associated with reduced BMD. Our findings suggest that traffic-related pollution may contribute to the occurrence of osteopenia and osteoporosis. INTRODUCTION: Adults residing in rural areas have been linked with higher BMD. We aimed to determine if this difference is due in part to air pollution by examining the relationships between traffic metrics and ambient air pollution with total body and pelvic BMD. METHODS: Mexican American adults (n = 1,175; mean 34 years; 72 % female) who had participated in the BetaGene study of air pollution, obesity, and insulin resistance were included in this analysis. Total body and pelvic BMD were estimated using dual-energy X-ray absorptiometry. Traffic and ambient air pollutant exposures were estimated at residences using location and ambient monitoring data. Variance component models were used to analyze the associations between residential distance to the nearest freeway and ambient air pollutants with BMD. RESULTS: Residential proximity to a freeway was associated with lower total body BMD (p-trend = 0.01) and pelvic BMD (p-trend = 0.03) after adjustment for age, sex, weight, and height. The adjusted mean total body and pelvic BMD in participants living within 500 m of a freeway were 0.02 and 0.03 g/cm(2) lower than participants living greater than 1,500 m from a freeway. These associations did not differ significantly by age, sex, or obesity status. Results were similar after further adjustment for body fat and weekly physical activity minutes. Ambient air pollutants (NO2, O3, and PM2.5) were not significantly associated with BMD. CONCLUSIONS: Traffic-related exposures in overweight and obese Mexican Americans may adversely affect BMD. Our findings indicate that long-term exposures to traffic may contribute to the occurrence of osteoporosis and its consequences.

Parental stress increases body mass index trajectory in pre-adolescents.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Rates of childhood obesity have increased since the mid-1970s. Research into behavioural determinants has focused on physical inactivity and unhealthy diets. Cross-sectional studies indicate an association between psychological stress experienced by parents and obesity in pre-adolescents. WHAT THIS STUDY ADDS: We provide evidence of a prospective association between parental psychological stress and increased weight gain in pre-adolescents. Family-level support for those experiencing chronic stress might help promote healthy diet and exercise behaviours in children. OBJECTIVE: We examined the impact of parental psychological stress on body mass index (BMI) in pre-adolescent children over 4 years of follow-up. METHODS: We included 4078 children aged 5-10 years (90% were between 5.5 and 7.5 years) at study entry (2002-2003) in the Children's Health Study, a prospective cohort study in southern California. A multi-level linear model simultaneously examined the effect of parental stress at study entry on the attained BMI at age 10 and the slope of change across annual measures of BMI during follow-up, controlled for the child's age and sex. BMI was calculated based on objective measurements of height and weight by trained technicians following a standardized procedure. RESULTS: A two standard deviation increase in parental stress at study entry was associated with an increase in predicted BMI attained by age 10 of 0.287 kg m(-2) (95% confidence interval 0.016-0.558; a 2% increase at this age for a participant of average attained BMI). The same increase in parental stress was also associated with an increased trajectory of weight gain over follow-up, with the slope of change in BMI increased by 0.054 kg m(-2) (95% confidence interval 0.007-0.100; a 7% increase in the slope of change for a participant of average BMI trajectory). CONCLUSIONS: We prospectively demonstrated a small effect of parental stress on BMI at age 10 and weight gain earlier in life than reported previously. Interventions to address the burden of childhood obesity should address the role of parental stress in children.

HLA-DQ strikes again: genome-wide association study further confirms HLA-DQ in the diagnosis of asthma among adults.

BACKGROUND: Asthma is a common chronic respiratory disease in children and adults. An important genetic component to asthma susceptibility has long been recognized, most recently through the identification of several genes (e.g., ORMDL3, PDE4D, HLA-DQ, and TLE4) via genome-wide association studies. OBJECTIVE: To identify genetic variants associated with asthma affection status using genome-wide association data. METHODS: We describe results from a genome-wide association study on asthma performed in 3855 subjects using a panel of 455 089 single nucleotide polymorphisms (SNPs). RESULT: The genome-wide association study resulted in the prioritization of 33 variants for immediate follow-up in a multi-staged replication effort. Of these, a common polymorphism (rs9272346) localizing to within 1 Kb of HLA-DQA1 (chromosome 6p21.3) was associated with asthma in adults (P-value = 2.2E-08) with consistent evidence in the more heterogeneous group of adults and children (P-value = 1.0E-04). Moreover, some genes identified in prior asthma GWAS were nominally associated with asthma in our populations. CONCLUSION: Overall, our findings further replicate the HLA-DQ region in the pathogenesis of asthma. HLA-DQA1 is the fourth member of the HLA family found to be associated with asthma, in addition to the previously identified HLA-DRA, HLA-DQB1 and HLA-DQA2.

The effect of ambient air pollution on exhaled nitric oxide in the Children's Health Study.

We assessed the effect of daily variations in ambient air pollutants on exhaled nitric oxide fraction (F(eNO)) using data from a cohort of school children with large differences in air pollutant exposures from the Children's Health Study. Based on a cohort of 2,240 school children from 13 Southern Californian communities, cumulative lagged average regression models were fitted to determine the association between F(eNO) and ambient air pollution levels from central site monitors with lags of up to 30 days prior to F(eNO) testing. Daily 24-h cumulative lagged averages of particles with a 50% cut-off aerodynamic diameter of 2.5 µm (PM2.5; over 1-8 days) and particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10; over 1-7 days), as well as 10:00-18:00 h cumulative lagged average of O3 (over 1-23 days) were significantly associated with 17.42% (p<0.01), 9.25% (p<0.05) and 14.25% (p<0.01) higher F(eNO) levels over the interquartile range of 7.5 µg·m⁻³, 12.97 µg·m⁻³ and 15.42 ppb, respectively. The effects of PM2.5, PM10 and O3 were higher in the warm season. The particulate matter effects were robust to adjustments for effects of O3 and temperature and did not vary by asthma or allergy status. In summary, short-term increases in PM2.5, PM10 and O3 were associated with airway inflammation independent of asthma and allergy status, with PM10 effects significantly higher in the warm season.

Exhaled nitric oxide, susceptibility and new-onset asthma in the Children's Health Study.

A substantial body of evidence suggests an aetiological role of inflammation, and oxidative and nitrosative stress in asthma pathogenesis. Exhaled nitric oxide fraction (F(eNO)) may provide a noninvasive marker of oxidative and nitrosative stress, and aspects of airway inflammation. We examined whether children with elevated F(eNO) are at increased risk for new-onset asthma. We prospectively followed 2,206 asthma-free children (age 7-10 yrs) who participated in the Children's Health Study. We measured F(eNO) and followed these children for 3 yrs to ascertain incident asthma cases. Cox proportional hazard models were fitted to examine the association between F(eNO) and new-onset asthma. We found that F(eNO) was associated with increased risk of new-onset asthma. Children in the highest F(eNO) quartile had more than a two-fold increased risk of new-onset asthma compared to those with the lowest quartile (hazard ratio 2.1, 95% CI 1.3-3.5). This effect did not vary with the child's history of respiratory allergic symptoms. However, the effect of elevated F(eNO) on new-onset asthma was most apparent among those without a parental history of asthma. Our results indicate that children with elevated F(eNO) are at increased risk for new-onset asthma, especially if they have no parental history of asthma.

Genetic variations in nitric oxide synthase and arginase influence exhaled nitric oxide levels in children.

BACKGROUND: Exhaled nitric oxide (FeNO) is a biomarker of airway inflammation. In the nitric oxide (NO) synthesis pathway, nitric oxide synthases (encoded by NOS1, NOS2A, and NOS3) and arginases (encoded by ARG1 and ARG2) compete for L-arginine. Although FeNO levels are higher in children with asthma/allergy, influence of these conditions on the relationships between variations in these genes and FeNO remains unknown. The aims of the study were to evaluate the role of genetic variations in nitric oxide synthases and arginases on FeNO in children and to assess the influence of asthma and respiratory allergy on these genetic associations. METHODS: Among children (6-11 years) who participated in the southern California Children's Health Study, variations in these five genetic loci were characterized by tagSNPs. FeNO was measured in two consecutive years (N = 2298 and 2515 in Years 1 and 2, respectively). Repeated measures analysis of variance was used to evaluate the associations between these genetic variants and FeNO. RESULTS: Sequence variations in the NOS2A and ARG2 loci were globally associated with FeNO (P = 0.0002 and 0.01, respectively). The ARG2 association was tagged by intronic variant rs3742879 with stronger association with FeNO in asthmatic children (P-interaction = 0.01). The association of a NOS2A promoter haplotype with FeNO varied significantly by rs3742879 genotypes and by asthma. CONCLUSION: Variants in the NO synthesis pathway genes jointly contribute to differences in FeNO concentrations. Some of these genetic influences were stronger in children with asthma. Further studies are required to confirm our findings.

TSLP polymorphisms are associated with asthma in a sex-specific fashion.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex-specific fashion. METHODS: We conducted regular and sex-stratified analyses of association between SNPs in TSLP and asthma in families of children with asthma in Costa Rica. Significant findings were replicated in whites and African-American participants in the Childhood Asthma Management Program, in African-Americans in the Genomic Research on Asthma in the African Diaspora study, in whites and Hispanics in the Children's Health Study, and in whites in the Framingham Heart Study (FHS). MAIN RESULTS: Two SNPs in TSLP (rs1837253 and rs2289276) were significantly associated with a reduced risk of asthma in combined analyses of all cohorts (P values of 2 × 10(-5) and 1 × 10(-5) , respectively). In a sex-stratified analysis, the T allele of rs1837253 was significantly associated with a reduced risk of asthma in males only (P = 3 × 10(-6) ). Alternately, the T allele of rs2289276 was significantly associated with a reduced risk of asthma in females only (P = 2 × 10(-4) ). Findings for rs2289276 were consistent in all cohorts except the FHS. CONCLUSIONS: TSLP variants are associated with asthma in a sex-specific fashion.

Obesity, waist size and prevalence of current asthma in the California Teachers Study cohort.

BACKGROUND: Obesity is a risk factor for asthma, particularly in women, but few cohort studies have evaluated abdominal obesity which reflects metabolic differences in visceral fat known to influence systemic inflammation. A study was undertaken to examine the relationship between the prevalence of asthma and measures of abdominal obesity and adult weight gain in addition to body mass index (BMI) in a large cohort of female teachers. METHODS: Prevalence odds ratios (ORs) for current asthma were calculated using multivariable linear modelling, adjusting for age, smoking and race/ethnicity. RESULTS: Of the 88 304 women in the analyses, 13% (n = 11,500) were obese (BMI > or = 30 kg/m(2)) at baseline; 1334 were extremely obese (BMI > or = 40 kg/m(2)). Compared with those of normal weight, the adjusted OR for adult-onset asthma increased from 1.40 (95% confidence interval (CI) 1.31 to 1.49) for overweight women to 3.30 (95% CI 2.85 to 3.82) for extremely obese women. Large waist circumference (>88 cm) was associated with increased asthma prevalence, even among women with a normal BMI (OR 1.37, 95% CI 1.18 to 1.59). Among obese women the OR for asthma was greater in those who were also abdominally obese than in women whose waist was < or = 88 cm (2.36 vs 1.57). Obese and overweight women were at greater risk of severe asthma episodes, measured by urgent medical visits and hospital admissions. CONCLUSIONS: This study confirms the association between excess weight and asthma severity and prevalence, and showed that a large waist was associated with increased asthma prevalence even among women considered to have normal body weight.

Ambient ozone modifies the effect of tumor necrosis factor G-308A on bronchitic symptoms among children with asthma.

BACKGROUND: Tumor necrosis factor (TNF)-alpha has a recognized role in respiratory pathophysiology. One genetic variant (G-308A) in the promoter region affecting the expression of this cytokine may contribute to airway inflammatory diseases, but the studies on bronchitic symptoms were still inconclusive. Because ozone produces oxidative stress, increased airway TNF, and inflammation, the associations of the TNF-308 polymorphism with bronchitic symptoms may vary by ambient ozone exposure. METHODS: We studied associations of TNF-308 genotype with bronchitic symptoms among asthmatic children in Children's Health Study. The association of TNF G-308A polymorphism with bronchitic symptoms was investigated and we also determined whether the associations vary with ambient ozone exposure. RESULTS: Asthmatic children with TNF-308 GG genotype had a significantly reduced risk of bronchitic symptoms with low-ozone exposure (adjusted OR: 0.53; 95% CI: 0.31-0.91). The risk was not reduced in children living in high-ozone communities (adjusted OR: 1.42; 95% CI: 0.75-2.70). This difference in genotypic effects between low- and high-ozone environments was statistically significant among asthmatics (P for interaction = 0.01), but insignificant among nonasthmatic children. CONCLUSION: Our findings suggest a role of gene-environmental interactions on the occurrence of bronchitic symptoms among children with asthma.

Glutathione-S-transferase (GST) P1, GSTM1, exercise, ozone and asthma incidence in school children.

BACKGROUND: Because asthma has been associated with exercise and ozone exposure, an association likely mediated by oxidative stress, we hypothesised that glutathione-S-transferase (GST)P1, GSTM1, exercise and ozone exposure have interrelated effects on the pathogenesis of asthma. METHODS: Associations of the well characterised null variant of GSTM1 and four single nucleotide polymorphisms (SNPs) that characterised common variation in the GSTP1 locus with new onset asthma in a cohort of 1610 school children were examined. Children's exercise and ozone exposure were classified using participation in team sports and community annual average ozone levels, respectively. RESULTS: A two SNP model involving putatively functional variants (rs6591255, rs1695 (Ile105Va)) best captured the association between GSTP1 and asthma. The risk of asthma was lower for those with the Val allele of Ile105Val (hazard ratio (HR) 0.60, 95% CI 0.4 to 0.8) and higher for the variant allele of rs6591255 (HR 1.40, 95% CI 1.1 to 1.9). The risk of asthma increased with level of exercise among ile(105) homozygotes but not among those with at least one val(105) allele (interaction p value = 0.02). The risk was highest among ile(105) homozygotes who participated in >or=3 sports in the high ozone communities (HR 6.15, 95% CI 2.2 to 7.4). GSTM1 null was independently associated with an increased risk of asthma and showed little variation with air pollution or GSTP1 genotype. These results were consistent in two independent fourth grade cohorts recruited in 1993 and 1996. CONCLUSION: Children who inherit a val(105) variant allele may be protected from the increased risk of asthma associated with exercise, especially in high ozone communities. GSTM1 null genotype was associated with an increased risk of asthma.

Associations of FcepsilonRIbeta E237G polymorphism with wheezing in Taiwanese schoolchildren.

BACKGROUND: The beta-chain of a high-affinity IgE receptor (FcepsilonRIbeta) has been proposed as a candidate gene for atopic diseases, but previous studies have come to inconsistent conclusions. Because some air pollutants would produce oxidative stress, increase serum IgE, and trigger T-helper type 2 (Th2)-type airway inflammation, the associations of FcepsilonRIbeta polymorphism with wheezing illness may vary by their exposures and variants of oxidant defence genes. The purpose of this study was to investigate the association of FcepsilonRIbeta E237G polymorphism with wheezing illness and to determine whether these associations vary with air pollution and glutathione S-transferase (GST) P1-105 and M1 genotypes. METHODS: In 2001, we conducted a case-control study comprised of 214 children with any history of wheezing and 185 non-wheezing controls, all of whom were selected from 2558 fourth- to ninth-grade schoolchildren in southern Taiwan. We examined differences in associations with ambient air pollution and by GST genotypes. RESULTS: Compared with the FcepsilonRIbeta EE genotype, children with the G allele had a significantly reduced risk of lifetime wheezing with low-ozone exposure [adjusted odds ratio (aOR)=0.25, 95% confidence interval (CI) 0.08-0.69]. The risk was not reduced in children living in high-ozone communities (aOR=0.98, 95% CI 0.57-1.67). This difference in genotypic effects between low- and high-pollution environments was statistically significant. The reduction of the protective effect from the G allele with higher air pollution was most marked in the GSTP1-105 Ile/Val or Val/Val and GSTM1 null groups. CONCLUSION: The FcepsilonRIbeta E237G allele may have a protective role in wheezing illness among Taiwanese schoolchildren, depending on airway oxidative stress levels.

The ADRB3 Trp64Arg variant and obesity in African-American breast cancer cases.

OBJECTIVE: To determine if a missense change at codon 64 of ADRB3 (Trp64Arg), a candidate obesity gene, is associated with obesity and levels of subcutaneous or visceral fat in African-American breast cancer cases. Several observational studies have found that women, who are overweight or obese at the time of diagnosis, as well as those who gain weight after diagnosis, are at greater risk for breast cancer recurrence and death than non-overweight women. DESIGN: Prospective cohort of breast cancer cases. SUBJECTS: 219 African-American breast cancer patients participating in the Los Angeles component of the Health, Eating, Activity and Lifestyle Study. MEASURES: ADRB3 Trp64Arg genotype, measures of weight including body mass index (BMI), weight gain (weight 5 years before diagnosis compared with weight at 30 months after diagnosis), obesity (BMI> or =30 kg/m(2)), waist/hip circumference and visceral or subcutaneous fat were determined by magnetic resonance imaging. RESULTS: African-American women who were homozygous for the ADRB3 wild-type allele had significantly higher mean visceral fat levels than women who carried the variant (P=0.04), and were significantly more likely to be obese (odd ratios (OR)=2.1, 95% confidence interval (CI)=1.1-4.2). The association with obesity was most pronounced among women who were premenopausal (OR=4.8, 95% CI=1.3-18), who received chemotherapy for their breast cancer (OR=6.1, 95% CI=1.8-20), or who were not physically active (OR=3.9, 95% CI=1.5-9.7). CONCLUSION: The wild-type allele of the ADRB3 missense change was associated with measures of obesity in our sample of African-American women. The association was modified by menopausal status, history of chemotherapy and modest levels of physical activity. These results will need to be confirmed in an independent sample.

Association of body composition and weight history with breast cancer prognostic markers: divergent pattern for Hispanic and non-Hispanic White women.

Body composition and weight gain are breast cancer risk factors that may influence prognosis. The Health, Eating, Activity, and Lifestyle Study was designed to evaluate the relations of body composition, weight history, hormones, and lifestyle factors to prognosis for women with breast cancer. In the cross-sectional analysis of this cohort study specific to 150 Hispanic and 466 non-Hispanic White women in New Mexico diagnosed between 1996 and 1999, the authors hypothesized that obesity measures are associated with baseline prognostic markers and that these associations are modified by ethnicity. Ethnic-stratified multiple logistic regression analyses showed divergent results for a tumor size of 1.0 cm or more and, to a lesser extent, positive lymph node status. Among Hispanics, the highest quartile for body mass index (29.5 vs. <22.5 kg/m2: odds ratio (OR) = 0.16, 95% confidence interval (CI): 0.03, 0.84) and for waist circumference (> or =95.0 vs. <78.5 cm: OR = 0.09, 95% CI: 0.01, 0.78) was significantly associated with a reduced tumor size. In contrast, for overweight and obese non-Hispanic White women, there was an increased association with obesity-related measures, particularly striking for the highest quartile of waist circumference (OR = 2.76, 95% CI: 1.45, 5.26). These findings suggest that Hispanics may have a different breast cancer phenotype than non-Hispanic Whites, which associates differently with body composition and weight history.

Environmental tobacco smoke and absenteeism related to respiratory illness in schoolchildren.

Household environmental tobacco smoke (ETS) exposure accounts for substantial morbidity among young children, but the ETS-associated morbidity burden among school-age children is less well defined. Illness-related school absenteeism is a measure of a broad spectrum of adverse effects of ETS exposure in school-age children. The authors investigated the relations between ETS exposure, asthma status, and illness-related school absenteeism in a cohort of 1,932 fourth-grade schoolchildren from 12 southern California communities during January-June 1996. Incidence rates and adjusted relative risks of illness-related absences were determined by using an active surveillance system. The effects of ETS exposure on absenteeism were assessed by using stratified incidence rates and Poisson regression to adjust for sociodemographic factors. ETS exposure was associated with an increased risk of respiratory-illness-related school absences (relative risk (RR) = 1.27, 95% confidence interval (CI): 1.04, 1.56). Children living in a household with two or more smokers were at increased risk of such absences (RR = 1.75, 95% CI: 1.33, 2.30). Children's asthma status affected their response to ETS. Compared with unexposed children without asthma, children with asthma were at increased risk of respiratory-illness-related school absences when exposed to one (RR = 2.35, 95% CI: 1.49, 3.71) or two or more (RR = 4.45, 95% CI: 2.80, 7.07) household smokers. Children without asthma also had an increased risk if exposed to two or more smokers (RR = 1.44, 95% CI: 1.04, 2.00). Therefore, ETS exposure is associated with increased respiratory-related school absenteeism among children, especially those with asthma.