Edward L. Avol

Asthma in exercising children exposed to ozone: a cohort study

BACKGROUND Little is known about the effect of exposure to air pollution during exercise or time spent outdoors on the development of asthma. We investigated the relation between newly-diagnosed asthma and team sports in a cohort of children exposed to different concentrations and mixtures of air pollutants. METHODS 3535 children with no history of asthma were recruited from schools in 12 communities in southern California and were followed up for up to 5 years. 265 children reported a new diagnosis of asthma during follow-up. We assessed risk of asthma in children playing team sports at study entry in six communities with high daytime ozone concentrations, six with lower concentrations, and in communities with high or low concentrations of nitrogen dioxide, particulate matter, and inorganic-acid vapour. FINDINGS In communities with high ozone concentrations, the relative risk of developing asthma in children playing three or more sports was 3.3 (95% CI 1.9-5.8), compared with children playing no sports. Sports had no effect in areas of low ozone concentration (0.8, 0.4-1.6). Time spent outside was associated with a higher incidence of asthma in areas of high ozone (1.4, 1.0-2.1), but not in areas of low ozone. Exposure to pollutants other than ozone did not alter the effect of team sports. INTERPRETATION Incidence of new diagnoses of asthma is associated with heavy exercise in communities with high concentrations of ozone, thus, air pollution and outdoor exercise could contribute to the development of asthma in children.

Effect of exposure to traffic on lung development from 10 to 18 years of age: a cohort study

BACKGROUND Whether local exposure to major roadways adversely affects lung-function growth during the period of rapid lung development that takes place between 10 and 18 years of age is unknown. This study investigated the association between residential exposure to traffic and 8-year lung-function growth. METHODS In this prospective study, 3677 children (mean age 10 years [SD 0.44]) participated from 12 southern California communities that represent a wide range in regional air quality. Children were followed up for 8 years, with yearly lung-function measurements recorded. For each child, we identified several indicators of residential exposure to traffic from large roads. Regression analysis was used to establish whether 8-year growth in lung function was associated with local traffic exposure, and whether local traffic effects were independent of regional air quality. FINDINGS Children who lived within 500 m of a freeway (motorway) had substantial deficits in 8-year growth of forced expiratory volume in 1 s (FEV(1), -81 mL, p=0.01 [95% CI -143 to -18]) and maximum midexpiratory flow rate (MMEF, -127 mL/s, p=0.03 [-243 to -11), compared with children who lived at least 1500 m from a freeway. Joint models showed that both local exposure to freeways and regional air pollution had detrimental, and independent, effects on lung-function growth. Pronounced deficits in attained lung function at age 18 years were recorded for those living within 500 m of a freeway, with mean percent-predicted 97.0% for FEV1 (p=0.013, relative to >1500 m [95% CI 94.6-99.4]) and 93.4% for MMEF (p=0.006 [95% CI 89.1-97.7]). INTERPRETATION Local exposure to traffic on a freeway has adverse effects on childrens lung development, which are independent of regional air quality, and which could result in important deficits in attained lung function in later life.

Traffic, susceptibility, and childhood asthma.

Results from studies of traffic and childhood asthma have been inconsistent, but there has been little systematic evaluation of susceptible subgroups. In this study, we examined the relationship of local traffic-related exposure and asthma and wheeze in southern California school children (5–7 years of age). Lifetime history of doctor-diagnosed asthma and prevalent asthma and wheeze were evaluated by questionnaire. Parental history of asthma and child’s history of allergic symptoms, sex, and early-life exposure (residence at the same home since 2 years of age) were examined as susceptibility factors. Residential exposure was assessed by proximity to a major road and by modeling exposure to local traffic-related pollutants. Residence within 75 m of a major road was associated with an increased risk of lifetime asthma [odds ratio (OR) = 1.29; 95% confidence interval (CI), 1.01–1.86], prevalent asthma (OR = 1.50; 95% CI, 1.16–1.95), and wheeze (OR = 1.40; 95% CI, 1.09–1.78). Susceptibility increased in long-term residents with no parental history of asthma for lifetime asthma (OR = 1.85; 95% CI, 1.11–3.09), prevalent asthma (OR = 2.46; 95% CI, 0.48–4.09), and recent wheeze (OR = 2.74; 95% CI, 1.71–4.39). The higher risk of asthma near a major road decreased to background rates at 150–200 m from the road. In children with a parental history of asthma and in children moving to the residence after 2 years of age, there was no increased risk associated with exposure. Effect of residential proximity to roadways was also larger in girls. A similar pattern of effects was observed with traffic-modeled exposure. These results indicate that residence near a major road is associated with asthma. The reason for larger effects in those with no parental history of asthma merits further investigation.

Childhood Asthma and Exposure to Traffic and Nitrogen Dioxide

Background: Evidence for a causal relationship between traffic-related air pollution and asthma has not been consistent across studies, and comparisons among studies have been difficult because of the use of different indicators of exposure. Methods: We examined the association between traffic-related pollution and childhood asthma in 208 children from 10 southern California communities using multiple indicators of exposure. Study subjects were randomly selected from participants in the Childrens Health Study. Outdoor nitrogen dioxide (NO2) was measured in summer and winter outside the home of each child. We also determined residential distance to the nearest freeway, traffic volumes on roadways within 150 meters, and model-based estimates of pollution from nearby roadways. Results: Lifetime history of doctor-diagnosed asthma was associated with outdoor NO2; the odds ratio (OR) was 1.83 (95% confidence interval = 1.04–3.22) per increase of 1 interquartile range (IQR = 5.7 ppb) in exposure. We also observed increased asthma associated with closer residential distance to a freeway (1.89 per IQR; 1.19–3.02) and with model-based estimates of outdoor pollution from a freeway (2.22 per IQR; 1.36–3.63). These 2 indicators of freeway exposure and measured NO2 concentrations were also associated with wheezing and use of asthma medication. Asthma was not associated with traffic volumes on roadways within 150 meters of homes or with model-based estimates of pollution from nonfreeway roads. Conclusions: These results indicate that respiratory health in children is adversely affected by local exposures to outdoor NO2 or other freeway-related pollutants.

Childhood Incident Asthma and Traffic-Related Air Pollution at Home and School

Background Traffic-related air pollution has been associated with adverse cardiorespiratory effects, including increased asthma prevalence. However, there has been little study of effects of traffic exposure at school on new-onset asthma. Objectives We evaluated the relationship of new-onset asthma with traffic-related pollution near homes and schools. Methods Parent-reported physician diagnosis of new-onset asthma (n = 120) was identified during 3 years of follow-up of a cohort of 2,497 kindergarten and first-grade children who were asthma- and wheezing-free at study entry into the Southern California Children’s Health Study. We assessed traffic-related pollution exposure based on a line source dispersion model of traffic volume, distance from home and school, and local meteorology. Regional ambient ozone, nitrogen dioxide (NO2), and particulate matter were measured continuously at one central site monitor in each of 13 study communities. Hazard ratios (HRs) for new-onset asthma were scaled to the range of ambient central site pollutants and to the residential interquartile range for each traffic exposure metric. Results Asthma risk increased with modeled traffic-related pollution exposure from roadways near homes [HR 1.51; 95% confidence interval (CI), 1.25–1.82] and near schools (HR 1.45; 95% CI, 1.06–1.98). Ambient NO2 measured at a central site in each community was also associated with increased risk (HR 2.18; 95% CI, 1.18–4.01). In models with both NO2 and modeled traffic exposures, there were independent associations of asthma with traffic-related pollution at school and home, whereas the estimate for NO2 was attenuated (HR 1.37; 95% CI, 0.69–2.71). Conclusions Traffic-related pollution exposure at school and homes may both contribute to the development of asthma.

Maternal smoking during pregnancy, environmental tobacco smoke exposure and childhood lung function

BACKGROUND Exposure to environmental tobacco smoke (ETS) during childhood and in utero exposure to maternal smoking are associated with adverse effects on lung growth and development. METHODS A study was undertaken of the associations between maternal smoking during pregnancy, exposure to ETS, and pulmonary function in 3357 school children residing in 12 Southern California communities. Current and past exposure to household ETS and exposure to maternal smoking in utero were assessed by a self-administered questionnaire completed by parents of 4th, 7th, and 10th grade students in 1993. Standard linear regression techniques were used to estimate the effects of in utero and ETS exposure on lung function, adjusting for age, sex, race, Hispanic ethnicity, height, weight, asthma, personal smoking, and selected household characteristics. RESULTS In utero exposure to maternal smoking was associated with reduced peak expiratory flow rate (PEFR) (–3.0%, 95% CI –4.4 to –1.4), mean mid expiratory flow (MMEF) (–4.6%, 95% CI –7.0 to –2.3), and forced expiratory flow (FEF75) (–6.2%, 95% CI –9.1 to –3.1), but not forced expiratory volume in one second (FEV1). Adjusting for household ETS exposure did not substantially change these estimates. The reductions in flows associated with in utero exposure did not significantly vary with sex, race, grade, income, parental education, or personal smoking. Exposure to two or more current household smokers was associated with reduced MMEF (–4.1%, 95% CI –7.6 to –0.4) and FEF75 (–4.4%, 95% CI –9.0 to 0.4). Current or past maternal smoking was associated with reductions in PEFR and MMEF; however, after adjustment for in utero exposure, deficits in MMEF and FEF75 associated with all measurements of ETS were substantially reduced and were not statistically significant. CONCLUSIONS In utero exposure to maternal smoking is independently associated with decreased lung function in children of school age, especially for small airway flows.

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.

The effects of ambient air pollution on school absenteeism due to respiratory illnesses

We investigated the relations between ozone (O3), nitrogen dioxide (NO2), and respirable particles less than 10 &mgr;m in diameter (PM10) and school absenteeism in a cohort of 4th-grade school children who resided in 12 southern California communities. An active surveillance system ascertained the numbers and types of absences during the first 6 months of 1996. Pollutants were measured hourly at central-site monitors in each of the 12 communities. To examine acute effects of air pollution on absence rates, we fitted a two-stage time-series model to the absence count data that included distributed lag effects of exposure adjusted for long-term pollutant levels. Short-term change in O3, but not NO2 or PM10, was associated with a substantial increase in school absences from both upper and lower respiratory illness. An increase of 20 ppb of O3 was associated with an increase of 62.9% [95% confidence interval (95% CI) = 18.4–124.1%] for illness-related absence rates, 82.9% (95% CI = 3.9–222.0%) for respiratory illnesses, 45.1% (95% CI = 21.3–73.7%) for upper respiratory illnesses, and 173.9% (95% CI = 91.3–292.3%) for lower respiratory illnesses with wet cough. The short-term effects of a 20-ppb change of O3 on illness-related absenteeism were larger in communities with lower long-term average PM10 [223.5% (95% CI = 90.4–449.7)] compared with communities with high average levels [38.1% (95% CI = 8.5–75.8)]. Increased school absenteeism from O3 exposure in children is an important adverse effect of ambient air pollution worthy of public policy consideration.

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 Childrens 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.).

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 ile105 homozygotes but not among those with at least one val105 allele (interaction p value = 0.02). The risk was highest among ile105 homozygotes who participated in ⩾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 val105 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.