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.

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.

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.

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.

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.

Sensitization of human melanoma cells to the cytotoxic effect of melphalan by the glutathione transferase inhibitor ethacrynic acid.

Glutathione transferases are enzymes implied in the resistance of tumor cells to bifunctional alkylating cytostatic drugs. We have investigated the effect of the glutathione transferase inhibitor by ethacrynic acid on the cytotoxicity of melphalan to a human melanoma cell line (RPMI 8322) with a high level of glutathione transferase activity. Using 1-chloro-2,4-dinitrobenzene as substrate, ethacrynic acid was shown to inhibit the activity of purified human glutathione transferases, with 50% inhibition values of 1, 10, and 15 microM for transferase mu (class mu), transferase epsilon (class alpha) and transferase pi (class pi), respectively, all of which occur in RPMI 8322 cells. Ethacrynic acid at a concentration of 20 microM, which by itself was noncytotoxic, increased the cytotoxicity of melphalan to RPMI 8322 human melanoma cells approximately 2-fold. The induction of DNA interstrand cross-links by 40 microM melphalan was increased 1.4-fold by 30 microM ethacrynic acid. These results indicate that a potentiation of the cytotoxic effect of bifunctional alkylating agents can be achieved by inhibition of glutathione transferase and that the enhanced cytotoxicity may be caused at least in part by increased formation of drug-DNA adducts.

Contribution of glutathione transferase M3-3 to 1,3-bis(2-chloroethyl)-1-nitrosourea resistance in a human non-small cell lung cancer cell line.

The glutathione transferase (GST) isoenzyme profile was determined in two human tumor cell lines, U1690 derived from a small cell lung cancer and U1810 derived from a non-small cell lung cancer. U1810 cells are 3.2-fold more resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) than are U1690 cells, a finding ascribable in part to the expression of O6-alkylguanine-DNA alkyltransferase activity in the U1810 cells. GST P1-1 and GST A1-1 were determined quantitatively by enzyme-linked immunoassay and were found to be 1.3- and 15-fold higher in the cytosol fraction of U1690 cells as compared to U1810 cells, respectively. The higher BCNU resistance in U1810 cells can, therefore, not be correlated with the expression of these isoenzymes. However, sodium dodecyl sulfate/polyacrylamide gel electrophoresis in combination with immunoblot analysis demonstrated a class Mu GST, which was identified as GST M3-3 on the basis of electrophoretic mobility and cross-reaction with anti-rat GST 3-3 antibodies. This isoenzyme was detectable in U1810 cells but not in U1690 cells. Studies with purified human GST A1-1, GST M1-1, GST M3-3, and GST P1-1 demonstrated that GST M3-3, but not the other isoenzymes, catalyzed the denitrosation of BCNU. Such inactivation of BCNU has previously been demonstrated with rat class Mu GSTs (M. T. Smith et al., Cancer Res., 49: 2621-2625, 1989) but not with any human GST. These findings suggest that GST M3-3 contributes to BCNU resistance in the U1810 cells.

Identification of a novel DNA regulatory element in the rabbit surfactant protein B (SP-B) promoter that is a target for ATF/CREB and AP-1 transcription factors.

Surfactant protein B (SP-B) is required for the maintenance of biophysical properties and physiological function of pulmonary surfactant. SP-B is expressed in a cell/tissue-specific manner by the alveolar type II and bronchiolar (Clara) epithelial cells of the lung and is developmentally and hormonally regulated. We previously identified a minimal promoter region containing -236/+39 base pairs (bp) of rabbit SP-B gene that is necessary and sufficient for high level promoter activity in NCI-H441 cells, a cell line with characteristics of Clara cells. In this study, we have characterized the functional importance of a novel DNA regulatory element, termed SP-B CRE, with the sequence TGAGGTCA in the SP-B minimal promoter. The SP-B CRE sequence shared homology to cyclic AMP responsive element (CRE) binding sequence and contained an overlapping nuclear receptor element binding half-site. Mutation of SP-B CRE into a scrambled sequence reduced promoter activity by greater than 70%, whereas mutation into a palindromic consensus CRE increased the promoter activity by 100%. Electrophoretic mobility shift assay (EMSA) and Western immunoblot analysis of affinity purified proteins interacting with SP-B CRE showed that it is a target for binding of members of the activating transcription factor (ATF)/cyclic AMP response element binding protein (CREB) family of transcription factors, such as CREB, CREM, ATF-1, ATF-2 as well as c-Jun and TTF-1. Overexpression of CREB, ATF-2 and c-Jun inhibited SP-B promoter activity in NCI-H441 cells. These data have shown that members of the ATF/CREB family of transcription factors and c-Jun play important roles in mediating the transcriptional regulation of the SP-B gene.

Self-esteem and adiposity in black and white girls: the NHLBI Growth and Health Study.

PURPOSE: Obesity is assumed to have a negative impact on self-esteem because of the associated social stigmatization in Western society. Studies of the psychological effect of obesity in children are inconclusive and limited, particularly pertaining to minority populations. Most studies have assessed global rather than domain-specific measures of self-esteem and hence, may have lacked specificity to detect impairment of certain aspects of self-esteem most closely associated with obesity. The purpose of this study is to examine the effect of adiposity and other environmental factors on measures of perceived competence and self-adequacy in 2205 black and white girls aged 9-10 years. METHODS: Domain-specific measures of self-esteem were studied by race and degree of adiposity, using Harter's "Self-Perception Profile for Children". Three Harter scales deemed more relevant to obesity (social acceptance (SA), physical appearance (PA), and global self-worth (GSW)) were selected for univariate and multivariate linear regression models to examine relationships between self-esteem level and adiposity (measured by the sum of triceps, subscapular, and suprailiac skinfolds (SSF)), race, pubertal maturation, and parental education. The relationship between adiposity and Harter scores was further examined with LOESS curves and also by comparing the mean scores of each quintile of SSF by race, as well as inter-quintile differences within race. RESULTS: Adiposity in general impacted negatively on the scores of all three selected Harter scales. There was also racial variation in the relationship between the scores and adiposity, with the magnitude of the effect somewhat less in black girls. White girls exhibited a significant inverse relationship between SSF and SA scores while, in striking contrast, there was no variation in scores in black girls across all ranges of adiposity. Although there was a significant inverse relationship between adiposity and PA and GSW in both groups, the slope was steeper in white girls, particularly at higher ranges of SSF. Non-linearity in the relationship between SSF and the scores was seen in SA and PA scales. CONCLUSIONS: The present study demonstrated a significant negative association between adiposity and the level of self-esteem in girls as young as 9 to 10 years. There were also intriguing racial differences in the selected domains of esteem. These results may help better understand cultural differences regarding the psychological impact of obesity and could be used to formulate appropriate strategies for public health policy.

Air pollution and daily hospital admissions in metropolitan Los Angeles.

We used daily time-series analysis to evaluate associations between ambient carbon monoxide, nitrogen dioxide, particulate matter [less than and equal to] 10 microm in aerodynamic diameter (PM(10)), or ozone concentrations, and hospital admissions for cardiopulmonary illnesses in metropolitan Los Angeles during 1992-1995. We performed Poisson regressions for the entire patient population and for subgroups defined by season, region, or personal characteristics, allowing for effects of temporal variation, weather, and autocorrelation. CO showed the most consistently significant (p<0.05) relationships to cardiovascular admissions. A wintertime 25th-75th percentile increase in CO (1.1-2.2 ppm) predicted an increase of 4% in cardiovascular admissions. NO(2), and, to a lesser extent, PM(10) tracked CO and showed similar associations with cardiovascular disease, but O(3) was negatively or nonsignificantly associated. No significant demographic differences were found, although increased cardiovascular effects were suggested in diabetics, in whites and blacks (relative to Hispanics and Asians), and in persons older than 65 years of age. Pulmonary disease admissions associated more with NO(2) and PM(10) than with CO. Pulmonary effects were generally smaller than cardiovascular effects and were more sensitive to the choice of model. We conclude that in Los Angeles, atmospheric stagnation with high primary (CO/NO(2)/PM(10)) pollution, most common in autumn/winter, increases the risk of hospitalization for cardiopulmonary illness. Summer photochemical pollution (high O(3)) apparently presents less risk.

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.

A meta-analysis of 61 sperm count studies revisited.

OBJECTIVE: To re-examine data on sperm counts over time from 61 studies from around the world. DESIGN: Parametric analyses and flexible nonlinear models of the relation between sperm counts and time. MAIN OUTCOME MEASURE(S): Mean sperm concentrations per milliliter and regression coefficients for possible trends of concentrations over time. RESULT(S): A significant decline was found only in U.S. studies. CONCLUSION(S): Studies from specific sites have found declines in sperm counts, but a world-wide decline has not been demonstrated. Rigorous assessment of statistical models should be done before conclusions are drawn. Flexible smoothing models are a useful addition to currently available analytic methods.

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.

Educational intervention to control cockroach allergen exposure in the homes of hispanic children in Los Angeles: results of the La Casa study.

BACKGROUND: Cockroach allergy is common among inner city children with asthma, and exposure to cockroach allergen is associated with more severe disease. However, there has been little evaluation of educational approaches for controlling cockroach infestations and reducing allergen exposure. OBJECTIVE: An educational intervention to reduce cockroach allergen exposure in the homes of Hispanic children in Los Angeles was implemented and evaluated. METHODS: Caretakers of 150 children with asthma were randomly assigned to an in-home intervention or comparison group. In the intervention group, peer health educators trained the caretaker to control cockroaches by reducing harbourage and access to food and by applying boric acid, and to reduce allergen exposure by cleaning. Allergen impermeable covers were placed on the child's mattress and pillows. Knowledge, reported and observed behaviour, cockroach counts, and cockroach allergen (Bla g 1) in dust samples from the kitchen and the child's bedding were assessed at study entry and at follow-up 4 months later. RESULTS: There was improvement in knowledge and in observed and reported behaviour hypothesized to be associated with cockroach control. The geometric mean cockroach number in the intervention homes at the follow-up visit was 60% lower than in the non-intervention homes (95% confidence interval (CI) 14%, 81%). Geometric mean total cockroach allergen collected from the child's bedding was 64% lower in the intervention group (95% CI 12%, 85%). In homes with heavier initial cockroach infestation, there was a larger reduction in total kitchen dust allergen and concentration associated with the intervention than in homes with fewer initial cockroaches. CONCLUSIONS: We conclude that reduction in number of cockroaches and in total allergen in bedding dust can be achieved by caretakers of asthmatic children following a single home educational intervention by peer educators.

Inactivation of the genotoxic aldehyde acrolein by human glutathione transferases of classes alpha, mu, and pi.

Acrolein, a genotoxic aldehyde released in the metabolic activation of the cytostatic drug cyclophosphamide, is inactivated by glutathione transferases either by conjugation with reduced glutathione or by covalent binding to the enzymes in the absence of glutathione. The catalytic efficiency (kcat/Km) with acrolein as a substrate was determined for representatives of the three classes Alpha, Mu, and Pi of human glutathione transferases. Transferase pi exhibited the highest and transferase epsilon the lowest catalytic efficiencies, respectively. As measured by the kcat/Km value, acrolein ranks among the most active substrates known for transferase pi. The irreversible binding of acrolein to the enzymes was monitored as the inactivation of the enzyme activity. Transferase pi reacted significantly more rapidly with acrolein than did transferases mu and epsilon.

Characterization of rabbit SP-B promoter region responsive to downregulation by tumor necrosis factor-alpha.

Surfactant protein B (SP-B) is essential for the maintenance of biophysical properties and physiological function of pulmonary surfactant. Tumor necrosis factor-alpha (TNF-alpha), an important mediator of lung inflammation, inhibits surfactant phospholipid and surfactant protein synthesis in the lung. In the present study, we investigated the TNF-alpha inhibition of rabbit SP-B promoter activity in a human lung adenocarcinoma cell line (NCI-H441). Deletion experiments indicated that the TNF-alpha response elements are located within -236 bp of SP-B 5'-flanking DNA. The TNF-alpha response region contained binding sites for nuclear factor-kappa B (NF-kappa B), Sp1/Sp3, thyroid transcription factor (TTF)-1, and hepatocyte nuclear factor (HNF)-3 transcription factors. Inhibitors of NF-kappa B activation such as dexamethasone and N-tosyl-L-phenylalanine chloromethyl ketone and mutation of the NF-kappa B element did not reverse TNF-alpha inhibition of SP-B promoter, indicating that TNF-alpha inhibition of SP-B promoter activity occurs independently of NF-kappa B activation. TNF-alpha treatment decreased the binding activities of TTF-1 and HNF-3 elements without altering the nuclear levels of TTF-1 and HNF-3 alpha proteins. Pretreatment of cells with okadaic acid reversed TNF-alpha inhibition of SP-B promoter activity. Taken together these data indicated that in NCI-H441 cells 1) TNF-alpha inhibition of SP-B promoter activity may be caused by decreased binding activities of TTF-1 and HNF-3 elements, 2) the decreased binding activities of TTF-1 and HNF-3 alpha are not due to decreased nuclear levels of the proteins, and 3) okadaic acid-sensitive phosphatases may be involved in mediating TNF-alpha inhibition of SP-B promoter activity.

Identification of functional TTF-1 and Sp1/Sp3 sites in the upstream promoter region of rabbit SP-B gene.

Surfactant protein B (SP-B) is essential for the maintenance of biophysical properties and physiological function of pulmonary surfactant. SP-B mRNA is expressed in a cell type-restricted manner in alveolar type II and bronchiolar (Clara) epithelial cells of the lung and is developmentally induced. In NCI-H441 cells, a lung cell line with characteristics of Clara cells, a minimal promoter region comprising -236 to +39 nucleotides supports high-level expression of chloramphenicol acetyltransferase reporter activity. In the present investigation, we characterized the upstream promoter region, -236 to -140 nucleotides, that is essential for promoter activity. Deletion mapping identified two segments, -236 to -170 and -170 to -140 nucleotides, that are important for promoter activity. Mutational analysis and gel mobility shift experiments identified thyroid transcription factor-1, Sp1, and Sp3 as important trans-acting factors that bind to sequences in the upstream promoter region. Our data suggest that SP-B promoter activity is dependent on interactions between factors bound to upstream and downstream regions of the promoter.