Edward B. Rappaport

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.

Concordance for Hodgkin's disease in identical twins suggesting genetic susceptibility to the young-adult form of the disease

BACKGROUND Relatives of young adults with Hodgkins disease are at increased risk of Hodgkins disease, and lines of evidence implicate both inheritance and environment. METHODS We have identified and followed 432 sets of twins affected by Hodgkins disease. The number of cases of Hodgkins disease observed before the age of 50 years in the healthy monozygotic and dizygotic twins of the patients with Hodgkins disease was compared with the number expected from national age-specific incidence rates. RESULTS None of the 187 pairs of dizygotic twins became concordant for Hodgkins disease, whereas 10 of the 179 pairs of monozygotic twins did; in 5 of these pairs, the second case appeared after the original ascertainment. During the observation period, 0.1 (monozygotic) and 0.1 (dizygotic) cases in the unaffected twins were expected. Monozygotic twins of patients with Hodgkins disease thus had a greatly increased risk (standardized incidence ratio, 99; 95 percent confidence interval, 48 to 182), whereas no increase in the risk for dizygotic twins of patients with Hodgkins was observed. CONCLUSIONS Genetic susceptibility underlies Hodgkins disease in young adulthood.

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.).

Family history and the risk of early-onset persistent, early-onset transient, and late-onset asthma.

Family history of asthma and allergies strongly influences asthma risk in children, but the association may differ for early-onset persistent, early-onset transient, and late-onset asthma. We analyzed the relation between family history and these types of asthma using cross-sectional data from a school-based study of 5,046 Southern California children. Parental and/or sibling history of asthma and allergy were generally more strongly associated with early-onset persistent asthma compared with early-onset transient or late-onset asthma. For children with two asthmatic parents relative to those with none, the prevalence ratio for early-onset persistent asthma was 12.1 [95% confidence interval (CI) = 7.91–18.7] compared with 7.51 (95% CI = 2.62–21.5) for early-onset transient asthma and 5.38 (95% CI = 3.40–8.50) for late-onset asthma. Maternal smoking in pregnancy was predominantly related to the risk of early-onset persistent asthma in the presence of parental history of allergy and asthma, and the joint effects were more than additive (interaction contrast ratio = 3.10, 95% CI = 1.45–4.75). Our results confirm earlier data that parental history of asthma and allergy is most strongly associated with early-onset persistent asthma and suggest that among genetically predisposed children, an early-life environmental exposure, maternal smoking during pregnancy, favors the development of early-onset asthma that persists into later early childhood.

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 (FeNO) using data from a cohort of school children with large differences in air pollutant exposures from the Childrens 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 FeNO and ambient air pollution levels from central site monitors with lags of up to 30 days prior to FeNO 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 FeNO 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.

Indoor risk factors for asthma in a prospective study of adolescents.

Background. The risk of asthma associated with pets and other indoor exposures has been examined in both cross-sectional and prospective studies of younger children. However, there has been little investigation of the effect of the indoor environment on incident asthma in adolescents. Methods. Risk factors for the development of asthma were examined in a cohort of 3535 Southern California school children with no history of asthma at 1993 entry into the study, who were followed for up to 5 years. Newly diagnosed cases of asthma were identified by yearly interview report. A total of 265 children reported a new diagnosis of asthma during the follow-up period; 163 of these had reported no history of wheeze at baseline. The risk associated with indoor exposures assessed by questionnaire at entry into the study was examined using Cox proportional hazards models. Results. In children with no history of wheezing, an increased risk of developing asthma was associated with a humidifier (relative risk [RR] = 1.7; 95% confidence interval [CI] = 1.2–2.4), any pet (RR = 1.6; 95% CI = 1.0–2.5), or specifically a dog (RR = 1.4; 95% CI = 1.0–2.0) in the home. An estimated 32% of new asthma cases could be attributed to pets. Conclusions. We conclude that furry pets are a common and potentially remediable risk factor for new onset asthma in adolescents. Our results suggest that a humidifier in the home may contribute to the onset of asthma in this age group.

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

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

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

BackgroundDeterminants 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.MethodsDuring 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.ResultsFeNO 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.ConclusionFeNO 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.

Reproductive outcomes in relation to malathion spraying in the San Francisco Bay area, 1981-1982

We studied reproductive outcomes in a cohort of 7,450 pregnancies identified through three Kaiser-Permanente facilities in the San Francisco Bay Area, in relation to exposure to the pesticide malathion, applied aerially to control an infestation by the Mediterranean fruit fly. We included in the cohort all women over age 17 who were registered at these facilities and who were confirmed as pregnant during the spraying period. Residence histories throughout the pregnancy were obtained by mailed questionnaire or telephone interview from 933 women with adverse outcomes and a sample of 1,000 women with normal outcomes, and were converted to geographical coordinates. We linked the coordinates for malathion spraying corridors with the residence coordinates to create individual exposure indices for each week of pregnancy. The statistical analysis compared each of the adverse pregnancy outcome groups against an appropriate control group using logistic regression or survival time regression approaches. After adjustment for various confounders, no important association was found between malathion exposure and spontaneous abortion, intrauterine growth retardation, stillbirth, or most categories of congenital anomalies. Gastrointestinal anomalies were related to second trimester exposure (odds ratio = 2.6), based on 13 cases and not specific to any particular International Classification of Diseases code. (Epidemiology 1992;3:32–39)