Objective

Racial/ethnic differences in common carotid artery intima-media thickness (CIMT) and in risk factors associated with CIMT have been predominantly observed in middle-aged and older individuals. We aimed to characterize racial/ethnic differences CIMT and other cardiovascular risk factors in a healthy, young-adult population.

Methods

College students were recruited as part of a study to characterize determinants of atherogenesis. Students were eligible if they were lifetime non-smokers, lived in the United States since six months of age, and attended high school in the United States. Blood pressure, heart rate, height, and weight were measured, B-mode carotid ultrasound was performed, questionnaires were administered and a 12-hr fasting blood sample was collected. Associations between CIMT and other variables were assessed in 768 students aged 18 to 25 years using linear regression analysis.

Results

In models adjusted for common cardiovascular risk factors, sex exhibited the strongest influence on CIMT, with men having 15.4 µm larger CIMT compared to women (95%CI 6.6, 24.2). Race/ethnicity was also strongly associated with CIMT. African Americans had 17.3 µm greater CIMT (95% CI −0.3, 34.8) compared to non Hispanic Whites, whereas Asians and Hispanic Whites had 14.3 (95%CI −24.3, −4.4) and 15.4 (95%CI −26.2, −4.7) µm smaller CIMT, respectively. BMI and systolic blood pressure were positively associated with CIMT.

Conclusion

The risk factors associated with atherogenesis later in life are already present and observable in college-aged young adults, so targeted campaigns to reduce life-long cardiovascular disease burden should be initiated earlier in life to improve public health.

The purpose of this study was to examine ethnic differences in the metabolic responses to a 16-week intervention designed to improve insulin sensitivity (SI), adiposity, and inflammation in obese African-American and Latino adolescents. A total of 100 participants (African Americans: n = 48, Latino: n = 52; age: 15.4 ± 1.1 years, BMI percentile: 97.3 ± 3.3) were randomly assigned to interventions: control (C; n = 30), nutrition (N; n = 39, 1×/week focused on decreasing sugar and increasing fiber intake), or nutrition + strength training (N+ST; n = 31, 2×/week). The following were measured at pre- and postintervention: strength, dietary intake, body composition (dual-energy X-ray absorptiometry/magnetic resonance imaging) and glucose/insulin indexes (oral glucose tolerance test (OGTT)/intravenous glucose tolerance test (IVGTT)) and inflammatory markers. Overall, N compared to C and N+ST reported significant improvements in SI (+16.5% vs. −32.3% vs. −6.9% respectively, P < 0.01) and disposition index (DI: +15.5% vs. −14.2% vs. −13.7% respectively, P < 0.01). N+ST compared to C and N reported significant reductions in hepatic fat fraction (HFF: −27.3% vs. −4.3% vs. 0% respectively, P < 0.01). Compared to N, N+ST reported reductions in plasminogen activator inhibitor-1 (PAI-1) (−38.3% vs. +1.0%, P < 0.01) and resistin (−18.7% vs. +11.3%, P = 0.02). There were no intervention effects for all other measures of adiposity or inflammation. Significant intervention by ethnicity interactions were found for African Americans in the N group who reported increases in total fat mass, 2-h glucose and glucose incremental areas under the curve (IAUC) compared to Latinos (P’s < 0.05). These interventions yielded differential effects with N reporting favorable improvements in SI and DI and N+ST reporting marked reductions in HFF and inflammation. Both ethnic groups had significant improvements in metabolic health; however some improvements were not seen in African Americans.

Rationale: The impact of asthma on chronic lung function deficits is well known. However, there has been little study of ethnic differences in these asthma-associated deficits.

Objectives: To examine whether there are ethnic differences in the effects of asthma on children's lung function.

Methods: We evaluated the impact of asthma on lung function in 3,245 Hispanic and non-Hispanic white school children (age 10–18 yr) in a longitudinal analysis of the Southern California Children's Health Study. Sex-specific mixed-effects regression spline models were fitted separately for each ethnic group.

Measurements and Main Results: Large deficits in flows were observed among children with asthma diagnosed before age 4 years regardless of ethnicity. Hispanic girls with asthma had greater deficits in flows than non-Hispanic girls and were largest for maximal midexpiratory flow (−5.13% compared with −0.58%, respectively). A bigger impact of asthma in Hispanic girls was also found for FEV1, FEF75, and PEF (P value 0.04, 0.07, and 0.005, respectively). These ethnic differences were limited to girls diagnosed after age 4 years. In boys, asthma was also associated with greater deficits in flows among Hispanic than in non-Hispanic white children (differences that were not statistically significant). Ethnic differences in prevalence of pets and pests in the home, health insurance coverage, parental education, and smoking did not explain the pattern of lung function differences.

Conclusions: Larger asthma-associated lung function deficits in Hispanics, especially among girls, merit further investigation to determine public health implications and to identify causes amenable to intervention.

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.

Introduction: Risk of testicular germ cell tumors (TGCT) is consistently associated with a history of cryptorchidism (CO) in epidemiologic studies. Factors modifying the association may provide insights regarding etiology of TGCT and suggest a basis for individualized care of CO. To identify modifiers of the CO-TGCT association, we conducted a comprehensive, quantitative evaluation of epidemiologic data.

Materials and Methods: Human studies cited in PubMed or ISI Web of Science indices through December 2011 and selected unpublished epidemiologic data were reviewed to identify 35 articles and one unpublished dataset with high-quality data on the CO-TGCT association. Association data were extracted as point and 95% confidence interval estimates of odds ratio (OR) or standardized incidence ratio (SIR), or as tabulated data. Values were recorded for each study population, and for subgroups defined by features of study design, CO and TGCT. Extracted data were used to estimate summary risk ratios (sRR) and evaluate heterogeneity of the CO-TGCT association between subgroups.

Results: The overall meta-analysis showed that history of CO is associated with four-fold increased TGCT risk [RR = 4.1(95% CI = 3.6–4.7)]. Subgroup analyses identified five determinants of stronger association: bilateral CO, unilateral CO ipsilateral to TGCT, delayed CO treatment, TGCT diagnosed before 1970, and seminoma histology.

Conclusions: Modifying factors may provide insight into TGCT etiology and suggest improved approaches to managing CO. Based on available data, CO patients and their parents or caregivers should be made aware of elevated TGCT risk following orchidopexy, regardless of age at repair, unilateral vs. bilateral non-descent, or position of undescended testes.

Background: The fractional concentration of nitric oxide in exhaled air (FeNO) potentially detects airway inflammation related to air pollution exposure. Existing studies have not yet provided conclusive evidence on the association of FeNO with traffic-related pollution (TRP).

Objectives: We evaluated the association of FeNO with residential TRP exposure in a large cohort of children.

Methods: We related FeNO measured on 2,143 children (ages 7–11 years) who participated in the Southern California Children’s Health Study (CHS) to five classes of metrics of residential TRP: distances to freeways and major roads; length of all and local roads within circular buffers around the home; traffic densities within buffers; annual average line source dispersion modeled nitrogen oxides (NOx) from freeways and nonfreeway roads; and predicted annual average nitrogen oxide, nitrogen dioxide, and NOx from a model based on intracommunity sampling in the CHS.

Results: In children with asthma, length of roads was positively associated with FeNO, with stronger associations in smaller buffers [46.7%; 95% confidence interval (CI), 14.3–88.4], 12.4% (95% CI, –8.8 to 38.4), and 4.1% (95% CI, –14.6 to 26.8) higher FeNO for 100-, 300-, and 1,000-m increases in the length of all roads in 50-, 100-, and 200-m buffers, respectively. Other TRP metrics were not significantly associated with FeNO, even though the study design was powered to detect exposures explaining as little as 0.4% of the variation in natural log-transformed FeNO (R2 = 0.004).

Conclusion: Length of road was the only indicator of residential TRP exposure associated with airway inflammation in children with asthma, as measured by FeNO.

Purpose

Objectives of this study were to examine 1) whether changes in total PA (counts/minute, cpm) and time spent in moderate to vigorous PA (MVPA) are associated with changes in adiposity and 2) whether energy intake influences the relationship between changes in PA and changes in adiposity in overweight Hispanic adolescents.

Methods

Analysis included 38 overweight (BMI ≥ 85th %ile) Hispanic adolescents with complete pre- and post-test data on relevant variables after participating in a 16-week intervention. The intervention treatment did not influence physical activity, so the sample was combined and randomization group was adjusted for in the analysis. Body composition by DEXA, 7-day physical activity by accelerometry, and dietary intake by 3-day diet records were assessed pre- and post-intervention.

Results

Within individuals, the mean increase of PA (n=19) and mean decrease of PA (n=19) was approximately 105 cpm. A 100 cpm increase in total PA was associated with a decrease of 1.3 kg fat mass and 0.8% body fat after adjusting for pre-test adiposity, PA, age, sex, and treatment (p < 0.05). Controlling for energy intake modestly strengthened the relationships between total PA and fat mass and percent body fat. Changes in MVPA were not related to changes in adiposity after controlling for total PA (p>0.05).

Conclusion

Increasing total PA by 28% (100 cpm) was associated with a decrease of 1.4 kg of fat mass and 1% body fat over 16 weeks in overweight Hispanic adolescents independent of intervention group assignment. Increases in total physical activity, as compared to MVPA, may be sufficient to improve body composition in overweight Hispanic adolescents.

SUMMARY

An adequate depiction of exposure–time–response relationships is important in assessing public health implications of an occupational or environmental exposure. Recent advances have focused on flexible modeling of the overall shape of latency. Methods are needed to allow for varying shapes of latency under different exposure profiles. A tensor product spline model is proposed for describing exposure–response relationships for protracted time-dependent occupational exposure histories in epidemiologic studies. The methods use flexible multi-dimensional techniques to jointly model age, latency and exposure–response effects. In analyzing data from the Colorado Plateau Uranium Miners cohort, a model that allows for varying exposure-dependent latency shapes is found to be superior to models that only allowed for an overall latency curve. Specifically, the model suggests that, at low exposure levels risk increased at short latencies followed by a slow decline for longer latency periods. On the other hand, risk was higher but did not change much by latency for higher exposure levels. The proposed methodology has the advantage of allowing for latency functions that vary by exposure levels and, conversely, exposure–response relationships that are influenced by the latency structure.

The individual effect of functional single nucleotide polymorphisms within the catalase and myeloperoxidase genes (CAT and MPO) has been studied in relation to asthma; however, their interrelationship with ambient air pollution exposures has yet to be determined. The authors investigated the interrelationships between variants in CAT and MPO, ambient air pollutants, and acute respiratory illness. Health information, air pollution, and incident respiratory-related school absences were ascertained in January–June 1996 for 1,136 Hispanic and non-Hispanic white US elementary schoolchildren as part of the prospective Children's Health Study. Functional and tagging single nucleotide polymorphisms for the CAT and MPO loci were genotyped. The authors found epistasis between functional polymorphisms in the CAT/MPO loci, which differed by levels of oxidant-stress-producing air pollutants. Risk of respiratory-related school absences was elevated for children with the CAT (G/G) and MPO (G/A or A/A) genes (relative risk = 1.35, 95% confidence interval: 1.03, 1.77; P-interaction = 0.005). The epistatic effect of CAT and MPO variants was most evident in communities exhibiting high ambient ozone levels (P-interaction = 0.03). The association of respiratory-illness absences with functional variants in CAT and MPO that differ by air pollution levels illustrates the need to consider genetic epistasis in assessing gene-environment interactions.

Background

The interrelationships between air pollution, lung function and the incidence of childhood asthma have yet to be established. A study was undertaken to determine whether lung function is associated with new onset asthma and whether this relationship varies by exposure to ambient air pollutants.

Methods

A cohort of children aged 9–10 years without asthma or wheeze at study entry were identified from the Children's Health Study and followed for 8 years. The participants resided in 12 communities with a wide range of ambient air pollutants that were measured continuously. Spirometric testing was performed and a medical diagnosis of asthma was ascertained annually. Proportional hazard regression models were fitted to investigate the relationship between lung function at study entry and the subsequent development of asthma and to determine whether air pollutants modify these associations.

Results

The level of airway flow was associated with new onset asthma. Over the 10th–90th percentile range of forced expiratory flow over the mid‐range of expiration (FEF25–75, 57.1%), the hazard ratio (HR) of new onset asthma was 0.50 (95% CI 0.35 to 0.71). This protective effect of better lung function was reduced in children exposed to higher levels of particulate matter with an aerodynamic diameter <2.5 μm (PM2.5). Over the 10th–90th percentile range of FEF25–75, the HR of new onset asthma was 0.34 (95% CI 0.21 to 0.56) in communities with low PM2.5 (<13.7 μg/m3) and 0.76 (95% CI 0.45 to 1.26) in communities with high PM2.5 (⩾13.7 μg/m3). A similar pattern was observed for forced expiratory volume in 1 s. Little variation in HR was observed for ozone.

Conclusion

Exposure to high levels of PM2.5 attenuates the protective effect of better lung function against new onset asthma.

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.

Rationale: The glutathione S-transferases (GSTs) are important detoxification enzymes.

Objectives: To investigate effects of variants in GST mu genes on lung function and assess their interactions with tobacco smoke exposure.

Methods: In this prospective study, 14,836 lung function measurements were collected from 2,108 children who participated in two Southern California cohorts. For each child, tagging single nucleotide polymorphisms in GSTM2, GSTM3, GSTM4, and GSTM5 loci were genotyped. Using principal components and haplotype analyses, the significance of each locus in relation to level and growth of FEV1, maximum midexpiratory flow rate (MMEF), and FVC was evaluated. Interactions between loci and tobacco smoke on lung function were also investigated.

Measurements and Main Results: Variation in the GST mu family locus was associated with lower FEV1 (P = 0.01) and MMEF (0.04). Two haplotypes of GSTM2 were associated with FEV1 and MMEF, with effect estimates in opposite directions. One haplotype in GSTM3 showed a decrease in growth for MMEF (−164.9 ml/s) compared with individuals with other haplotypes. One haplotype in GSTM4 showed significantly decreased growth in FEV1 (−51.3 ml), MMEF (−69.1 ml/s), and FVC (−44.4 ml), compared with all other haplotypes. These results were consistent across two independent cohorts. Variation in GSTM2 was particularly important for FVC and FEV1 among children whose mothers smoked during pregnancy.

Conclusions: Genetic variation across the GST mu locus is associated with 8-year lung function growth. Children of mothers who smoked during pregnancy and had variation in GSTM2 had lower lung function growth.

Few randomized trials attempt to improve insulin sensitivity and associated metabolic risks in overweight Latino youth. The purpose of this study is to examine the effects of a modified carbohydrate nutrition program combined with strength training on insulin sensitivity, adiposity, and other type 2 diabetes risk factors in overweight Latino adolescents. In a 16-week randomized trial, 54 overweight Latino adolescents (15.5 ± 1.0 years) were randomly assigned to: (i) Control (C; n = 16), (ii) Nutrition (N; n = 21), or (iii) Nutrition + Strength training (N+ST; n = 17). The N group received modified carbohydrate nutrition classes (once per week), while the N+ST received the same nutrition classes plus strength training (twice per week). The following were measured at pre- and postintervention: strength by 1-repetition maximum, dietary intake by 3-day records, body composition by dual-energy X-ray absorptiometry, glucose/insulin indices by oral glucose tolerance test (OGTT) and intravenous glucose tolerance test with minimal modeling. Across intervention group effects were tested using analysis of covariance with post hoc pairwise comparisons. A significant overall intervention effect was found for improvement in bench press (P < 0.001) and reductions in energy (P = 0.05), carbohydrate (P = 0.04) and fat intake (P = 0.03). There were no significant intervention effects on insulin sensitivity, body composition, or most glucose/insulin indices with the exception of glucose incremental area under the curve (IAUC) (P = 0.05), which decreased in the N and N+ST group by 18 and 6.3% compared to a 32% increase in the C group. In conclusion, this intense, culturally tailored intervention resulted in no significant intervention effects on measured risk factors with the exception of a beneficial effect on glycemic response to oral glucose.

Flexible multilevel models are proposed to allow for cluster-specific smooth estimation of growth curves in a mixed-effects modeling format that includes subject-specific random effects on the growth parameters. Attention is then focused on models that examine between-cluster comparisons of the effects of an ecologic covariate of interest (e.g. air pollution) on nonlinear functionals of growth curves (e.g. maximum rate of growth). A Gibbs sampling approach is used to get posterior mean estimates of nonlinear functionals along with their uncertainty estimates. A second-stage ecologic random-effects model is used to examine the association between a covariate of interest (e.g. air pollution) and the nonlinear functionals. A unified estimation procedure is presented along with its computational and theoretical details. The models are motivated by, and illustrated with, lung function and air pollution data from the Southern California Children's Health Study.

Background

Because asthma has been associated with exercise and ozone exposure, an association likely mediated by oxidative stress, we hypothesized that GSTP1, GSTM1, exercise and ozone exposure have inter-related effects on asthma pathogenesis.

Methods

We examined associations of the well characterized null variant of GSTM1 and four SNPs that characterized common variation in GSTP1 with new-onset asthma in a cohort of 1,610 school children. Children’s exercise and ozone-exposure status were classified using participation in team sports and community-specific ozone levels, respectively.

Results

A two SNP model (rs6591255, rs1695 [Ile105Val]) best captured the association between GSTP1 and asthma. Compared to children with common alleles for both the SNPs, the risk of asthma was lower for those with the Val allele of Ile105Val (HR 0.60, 95% CI 0.4, 0.8) and higher for the variant allele of rs6591255 (HR 1.40, 95%CI 1.1–1.9). Asthma risk increased with level of exercise among ile105 homozygotes but not among those with at least one val105 allele (interaction p-value=0.02). Risk was highest among ile105 homozygotes who participated in ≥3 sports in the high-ozone communities (HR: 6.15, 95%CI: 2.2–7.4). GSTM1 null was independently associated with asthma and showed little variation with air pollution or GSTP1 genotype. These results were consistent in two independent fourth-grade cohorts in the study population 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 increased risk of asthma.

Background

Determinants of exhaled nitric oxide (FeNO) need to be understood better to maximize the value of FeNO measurement in clinical practice and research. Our aim was to identify significant predictors of FeNO in an initial cross-sectional survey of southern California schoolchildren, part of a larger longitudinal study of asthma incidence.

Methods

During one school year, we measured FeNO at 100 ml/sec flow, using a validated offline technique, in 2568 children of age 7–10 yr. We estimated online (50 ml/sec flow) FeNO using a prediction equation from a separate smaller study with adjustment for offline measurement artifacts, and analyzed its relationship to clinical and demographic characteristics.

Results

FeNO was lognormally distributed with geometric means ranging from 11 ppb in children without atopy or asthma to 16 ppb in children with allergic asthma. Although effects of atopy and asthma were highly significant, ranges of FeNO for children with and without those conditions overlapped substantially. FeNO was significantly higher in subjects aged > 9, compared to younger subjects. Asian-American boys showed significantly higher FeNO than children of all other sex/ethnic groups; Hispanics and African-Americans of both sexes averaged slightly higher than non-Hispanic whites. Increasing height-for-age had no significant effect, but increasing weight-for-height was associated with decreasing FeNO.

Conclusion

FeNO measured offline is a useful biomarker for airway inflammation in large population-based studies. Further investigation of age, ethnicity, body-size, and genetic influences is needed, since they may contribute to substantial variation in FeNO.

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.

Rationale: In late October 2003, Southern California wildfires burned more than 3,000 km2. The wildfires produced heavy smoke that affected several communities participating in the University of Southern California Children's Health Study (CHS).

Objectives: To study the acute effects of fire smoke on the health of CHS participants.

Methods: A questionnaire was used to assess smoke exposure and occurrence of symptoms among CHS high-school students (n = 873; age, 17–18 yr) and elementary-school children (n = 5,551; age, 6–7 yr), in a total of 16 communities. Estimates of particulate matter (PM10) concentrations during the 5 d with the highest fire activity were used to characterize community smoke level.

Main Results: All symptoms (nose, eyes, and throat irritations; cough; bronchitis; cold; wheezing; asthma attacks), medication usage, and physician visits were associated with individually reported exposure differences within communities. Risks increased monotonically with the number of reported smoky days. For most outcomes, reporting rates between communities were also associated with the fire-related PM10 levels. Associations tended to be strongest among those without asthma. Individuals with asthma were more likely to take preventive action, such as wearing masks or staying indoors during the fire.

Conclusions: Exposure to wildfire smoke was associated with increased eye and respiratory symptoms, medication use, and physician visits.

Rationale: Although involuntary exposure to maternal smoking during the in utero period and to secondhand smoke are associated with occurrence of childhood asthma, few studies have investigated the role of active cigarette smoking on asthma onset during adolescence.

Objectives: To determine whether regular smoking is associated with the new onset of asthma during adolescence.

Methods: We conducted a prospective cohort study among 2,609 children with no lifetime history of asthma or wheezing who were recruited from fourth- and seventh-grade classrooms and followed annually in schools in 12 southern California communities. Regular smoking was defined as smoking at least seven cigarettes per day on average over the week before and 300 cigarettes in the year before each annual interview. Incident asthma was defined using new cases of physician-diagnosed asthma.

Measurements and Main Results: Regular smoking was associated with increased risk of new-onset asthma. Children who reported smoking 300 or more cigarettes per year had a relative risk (RR) of 3.9 (95% confidence interval [95% CI], 1.7–8.5) for new-onset asthma compared with nonsmokers. The increased risk from regular smoking was greater in nonallergic than in allergic children. Regular smokers who were exposed to maternal smoking during gestation had the largest risk from active smoking (RR, 8.8; 95% CI, 3.2–24.0).

Conclusions: Regular smoking increased risk for asthma among adolescents, especially for nonallergic adolescents and those exposed to maternal smoking during the in utero period.

Background

Although numerous epidemiologic studies now use models of intraurban exposure, there has been little systematic evaluation of the performance of different models.

Objectives

In this present article we proposed a modeling framework for assessing exposure model performance and the role of spatial autocorrelation in the estimation of health effects.

Methods

We obtained data from an exposure measurement substudy of subjects from the Southern California Children’s Health Study. We examined how the addition of spatial correlations to a previously described unified exposure and health outcome modeling framework affects estimates of exposure–response relationships using the substudy data. The methods proposed build upon the previous work, which developed measurement–error techniques to estimate long-term nitrogen dioxide exposure and its effect on lung function in children. In this present article, we further develop these methods by introducing between- and within-community spatial autocorrelation error terms to evaluate effects of air pollution on forced vital capacity. The analytical methods developed are set in a Bayesian framework where multistage models are fitted jointly, properly incorporating parameter estimation uncertainty at all levels of the modeling process.

Results

Results suggest that the inclusion of residual spatial error terms improves the prediction of adverse health effects. These findings also demonstrate how residual spatial error may be used as a diagnostic for comparing exposure model performance.

Rationale: Exposure to second-hand smoke (SHS) has been associated with increased risk of respiratory illness in children including respiratory illness–related school absences. The role of genetic susceptibility in risk for adverse effects from SHS has not been extensively investigated in children.

Objective: To determine whether the tumor necrosis factor (TNF) G-308A genotype influences the risk for respiratory illness–related school absences associated with SHS exposure.

Methods: Incident school absences were collected, using an active surveillance system, between January and June 1996, as part of the Air Pollution and Absence Study, a prospective cohort study nested in the Children's Health Study. Buccal cells and absence reports were collected on 1,351 students from 27 elementary schools in California.

Measurements and Main Results: Illness-related school absences were classified as nonrespiratory and respiratory illness–related, which were further categorized into upper or lower respiratory illness–related absences based on symptoms. The effect of SHS exposure on respiratory illness–related absences differed by TNF genotype (p interaction, 0.02). In children possessing at least one copy of the TNF-308 A variant, exposure to two or more household smokers was associated with a twofold risk of a school absence due to respiratory illness (relative risk, 2.13; 95% confidence interval, 1.34, 3.40) and a fourfold risk of lower respiratory illness–related school absence (relative risk, 4.15; 95% confidence interval, 2.57, 6.71) compared with unexposed children homozygous for the common TNF-308 G allele.

Conclusions: These results indicate that a subgroup of genetically susceptible children are at substantially greater risk of respiratory illness if exposed to SHS.

Background

Experimental data suggest that asthma exacerbation by ambient air pollutants is enhanced by exposure to endotoxin and allergens; however, there is little supporting epidemiologic evidence.

Methods

We evaluated whether the association of exposure to air pollution with annual prevalence of chronic cough, phlegm production, or bronchitis was modified by dog and cat ownership (indicators of allergen and endotoxin exposure). The study population consisted of 475 Southern California children with asthma from a longitudinal cohort of participants in the Children’s Health Study. We estimated average annual ambient exposure to nitrogen dioxide, ozone, particulate matter < 10, 2.5, and 10–2.5 μm in aerodynamic diameter (PM10, PM2.5, and PM10–2.5, respectively), elemental and organic carbon, and acid vapor from monitoring stations in each of the 12 study communities. Multivariate models were used to examine the effect of yearly variation of each pollutant. Effects were scaled to the variability that is common for each pollutant in representative communities in Southern California.

Results

Among children owning a dog, there were strong associations between bronchitic symptoms and all pollutants examined. Odds ratios ranged from 1.30 per 4.2 μg/m3 for PM10–2.5 [95% confidence interval (CI), 0.91–1.87) to 1.91 per 1.2 μg/m3 for organic carbon (95% CI, 1.34–2.71). Effects were somewhat larger among children who owned both a cat and dog. There were no effects or small effects with wide CIs among children without a dog and among children who owned only a cat.

Conclusion

Our results suggest that dog ownership, a source of residential exposure to endotoxin, may worsen the relationship between air pollution and respiratory symptoms in asthmatic children.

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.

Idiopathic male infertility may be due to exposure to environmental toxicants that alter spermatogenesis or sperm function. We studied the relationship between air pollutant levels and semen quality over a 2-year period in Los Angeles, California, by analyzing repeated semen samples collected by sperm donors. Semen analysis data derived from 5,134 semen samples from a sperm donor bank were correlated with air pollutant levels (ozone, nitrogen dioxide, carbon monoxide, and particulate matter < 10 μm in aerodynamic diameter) measured 0–9, 10–14, and 70–90 days before semen collection dates in Los Angeles between January 1996 and December 1998. A linear mixed-effects model was used to model average sperm concentration and total motile sperm count for the donation from each subject. Changes were analyzed in relationship to biologically relevant time points during spermatogenesis, 0–9, 10–14, and 70–90 days before the day of semen collection. We estimated temperature and seasonality effects after adjusting for a base model, which included donor’s date of birth and age at donation. Forty-eight donors from Los Angeles were included as subjects. Donors were included if they collected repeated semen samples over a 12-month period between January 1996 and December 1998. There was a significant negative correlation between ozone levels at 0–9, 10–14, and 70–90 days before donation and average sperm concentration, which was maintained after correction for donor’s birth date, age at donation, temperature, and seasonality (p < 0.01). No other pollutant measures were significantly associated with sperm quality outcomes. Exposure to ambient ozone levels adversely affects semen quality.