Prospective study of e-cigarette use and respiratory symptoms in adolescents and young adults.

RATIONALE: Electronic cigarette (e-cigarette) aerosol contains volatile aldehydes, including flavourings and oxidant metals with known pulmonary toxicity. OBJECTIVES: To evaluate the associations of e-cigarette use with symptoms of wheeze, bronchitic symptoms and shortness of breath (SOB) across 4 years of prospective data. METHODS: Participants completed questionnaires on respiratory symptoms and past 30-day e-cigarette, cigarette and cannabis use in 2014 (wave 1; N=2094; mean age 17.3 years, SD=0.6 years). Follow-up information was collected in 2015 (wave 2; n=1609), 2017 (wave 3; n=1502) and 2018 (wave 4; n=1637) using online surveys. Mixed-effects logistic regression models evaluated associations of e-cigarette use with respiratory symptoms. MEASUREMENTS AND MAIN RESULTS: Participants were mostly Hispanic white (51.8%) and evenly representative by sex (49.6% female; 50.4% male). Compared with never e-cigarette users, past 30-day e-cigarette users reported increased odds of wheeze (OR 1.81; 95% CI 1.28, 2.56), bronchitic symptoms (OR 2.06; 95% CI 1.58, 2.69) and SOB (OR 1.78; 95% CI 1.23, 2.57), adjusting for study wave, age, sex, race, lifetime asthma diagnosis and parental education. Effect estimates were attenuated (wheeze (OR 1.41; 95% CI 0.99, 2.01), bronchitic symptoms (OR 1.55; 95% CI 1.18, 2.05), SOB (OR 1.48; 95% CI 1.01, 2.18)), after adjusting additionally for current cigarette use, cannabis use and secondhand exposure to e-cigarettes/cigarettes/cannabis. CONCLUSIONS: E-cigarette use in young adults was associated with respiratory symptoms, independent of combustible cannabis and cigarette exposures.

Treatment patterns for patients initiating novel acute migraine specific medications (nAMSMs) in the context of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway.

BACKGROUND: New acute and preventive migraine medications are available, but data on current treatment patterns are limited. This study describes migraine treatment patterns among patients initiating novel acute migraine specific medications (nAMSMs), overall and by prior use of anti-calcitonin gene-related peptide (CGRP) pathway monoclonal antibodies (mAbs). METHODS: In this retrospective cohort study using IQVIA open-source pharmacy and medical claims data, we identified patients with ≥ 1 claim for a nAMSM (ubrogepant, rimegepant, lasmiditan) between 01/01/2020 and 09/30/2020 (index period). Patients were indexed on their first nAMSM claim and stratified into 2 cohorts: patients with prior mAb use (≥ 1 claim for erenumab, fremanezumab, galcanezumab in the 6-month pre-index period) or patients without prior mAb use. Treatment patterns were assessed during the 6-month post-index period. RESULTS: Overall, 78,574 patients were identified (63% indexed on ubrogepant, 34% on rimegepant, and 3% on lasmiditan) with 26,656 patients (34%) having had prior mAb use. In the pre-index period, 79% of patients used non-mAb preventive medications and 75% of patients used acute medications. Following the index nAMSM claim, 65% of patients had ≥ 1 refill and 21% had ≥ 4 refills of their index nAMSM; 10% of patients switched to another nAMSM. Post-index mAb use was observed in 82% of patients with a prior mAb and 15% of patients without. Among patients with pre- and post-index use of acute medications, 38% discontinued ≥ 1 acute medication class in the post-index period. Among patients with concomitant use of traditional preventive medications at index, 30% discontinued ≥ 1 concomitant preventive anti-migraine medication in the post-index period. CONCLUSIONS: Most patients initiating nAMSMs had prior treatment with acute and preventive medications. Approximately one-third of patients had prior treatment with anti-CGRP pathway mAbs. After starting nAMSMs, more than one-third of patients discontinued at least one traditional acute medication and one-third of patients discontinued at least one traditional preventive medication. Despite nAMSM initiation, most patients with prior anti-CGRP pathway mAb use continued mAb use. Around 15% of patients without a prior mAb newly started a mAb. These results provide insight into how nAMSMs and mAbs have been integrated into clinical management of migraine in the real-world.

Effects of policy-driven hypothetical air pollutant interventions on childhood asthma incidence in southern California.

Childhood asthma is a major public health concern and has significant adverse impacts on the lives of the children and their families, and on society. There is an emerging link between air pollution, which is ubiquitous in our environment, particularly in urban centers, and incident childhood asthma. Here, using data from 3 successive cohorts recruited from the same 9 communities in southern California over a span of 20 y (1993 to 2014), we estimated asthma incidence using G-computation under hypothetical air pollution exposure scenarios targeting nitrogen dioxide (NO2) and particulate matter <2.5 µm (PM2.5) in separate interventions. We reported comparisons of asthma incidence under each hypothetical air pollution intervention with incidence under the observed natural course of exposure; results that may be more tangible for policymakers compared with risk ratios. Model results indicated that childhood asthma incidence rates would have been statistically significantly higher had the observed reduction in ambient NO2 in southern California not occurred in the 1990s and early 2000s, and asthma incidence rates would have been significantly lower had NO2 been lower than what it was observed to be. For example, compliance with a hypothetical standard of 20 ppb NO2 was estimated to result in 20% lower childhood asthma incidence (95% CI, -27% to -11%) compared with the exposure that actually occurred. The findings for hypothetical PM2.5 interventions, although statistically significant, were smaller in magnitude compared with results for the hypothetical NO2 interventions. Our results suggest a large potential public health benefit of air pollutant reduction in reduced incidence of childhood asthma.

Compliance in Controlled E-cigarette Studies.

INTRODUCTION: E-cigarette studies have found that the use of a variety of flavors and customizable devices results in greater use frequency and user satisfaction. However, standardized research e-cigarettes are being developed as closed systems with limited flavor options, potentially limiting user satisfaction. In this study, we explore protocol compliance in an e-cigarette study using a standardized, assigned device with puff time and duration tracking (controlled e-cigarette) and potential limitations that controlled devices and e-liquids can introduce. METHODS: In a crossover study, 49 young adult e-cigarette users were recruited using convenience sampling and assigned a controlled e-cigarette device and flavored or unflavored e-liquids on standardized protocols. E-cigarette use frequency (number of puffs per day, collected from the device) and serum cotinine levels were obtained at each of three study visits over 3 weeks. The correlation of cotinine and e-cigarette use over the preceding week was calculated at each study visit. RESULTS: Correlation of nicotine intake, as measured by serum cotinine, and puff time, as measured by puffs count and duration from the e-cigarette device, as an indicator of study protocol compliance, substantially declined after the first week of the study and were no longer correlated in the remaining study weeks (R2 = 0.53 and p ≤ .01 in week 1, R2 < 0.5 and p > .05 for remaining weeks). CONCLUSIONS: There is an emerging need for controlled e-cigarette exposures studies, but low compliance in the use of assigned devices and e-liquids may be a limitation that needs to be mitigated in future studies. IMPLICATIONS: This study is the first to analyze compliance with instructions to use a standardized e-cigarette device with puff time and duration tracking (controlled e-cigarette) across all subjects and an assigned e-liquid flavor over a 3-week period. We find that protocol compliance, as measured by correlations between e-cigarette use measures and cotinine levels, was only achieved in the first week of the study and declined thereafter. These findings indicate that the assignment of a study device and instruction to only use the study device with assigned e-liquid flavor may not be sufficient to ensure participant compliance with the study protocol. We suggest that additional measures, including behavioral and biological markers, are needed to ensure sole use of the study e-cigarette and e-liquid and to be able to interpret results from controlled e-cigarette studies.

The Potential Effects of Policy-driven Air Pollution Interventions on Childhood Lung Development.

Rationale: Although elevated air pollution exposure impairs lung-function development in childhood, it remains a challenge to use this information to estimate the potential public health benefits of air pollution interventions in exposed populations.Objectives: Apply G-computation to estimate hypothetical effects of several realistic scenarios for future air pollution reductions on lung growth.Methods: Mixed-effects linear regression was used to estimate FEV1 and FVC from age 11 to 15 years in 2,120 adolescents across 3 cohorts (1993-2001, 1997-2004, and 2007-2011). Models included regional pollutants (nitrogen dioxide [NO2] or particulate matter with an aerodynamic diameter ≤2.5 µm [PM2.5]) and other important covariates. Using G-computation, a causal inference-based method, we then estimated changes in mean lung growth in our population for hypothetical interventions on either NO2 or PM2.5. Confidence intervals (CIs) were computed by bootstrapping (N = 1,000).Measurements and Main Results: Compared with the effects of exposure from observed NO2 concentrations during the study period, had communities remained at 1994 to 1997 NO2 levels, FEV1 and FVC growth were estimated to have been reduced by 2.7% (95% CI, -3.6 to -1.8) and 4.2% (95% CI, -5.2 to -3.4), respectively. If NO2 concentrations had been reduced by 30%, we estimated a 4.4% increase in FEV1 growth (95% CI, 2.8-5.9) and a 7.1% increase in FVC growth (95% CI, 5.7-8.6). Comparable results were observed for PM2.5 interventions.Conclusions: We estimated that substantial increases in lung function would occur as a result of interventions that reduce NO2 or PM2.5 concentrations. These findings provide a quantification of potential health benefits of air quality improvement.

Risk for ischemic stroke and coronary heart disease associated with migraine and migraine medication among older adults.

BACKGROUND: Migraine has been associated with cardiovascular disease (CVD) events among middle-aged adults. The objective of this study was to determine the risk for ischemic stroke and coronary heart disease (CHD) events among older adults with versus without migraine. METHODS: This retrospective cohort study was conducted using data from US adults ≥66 years of age with Medicare health insurance between 2008 and 2017. After stratification by history of CVD, patients with a history of migraine were matched 1:4 to those without a history of migraine, based on calendar year, age, and sex. Patients were followed through December 31, 2017 for ischemic stroke and CHD events including myocardial infarction or coronary revascularization. All analyses were done separately for patients with and without a history of CVD. RESULTS: Among patients without a history of CVD (n = 109,950 including n = 21,990 with migraine and n = 87,960 without migraine), 1789 had an ischemic stroke and 3552 had a CHD event. The adjusted hazard ratio (HR) among patients with versus without migraine was 1.20 (95% confidence interval [95%CI], 1.07-1.35) for ischemic stroke and 1.02 (95%CI, 0.93-1.11) for CHD events. Compared to patients without migraine, those with migraine who were taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.43 [95%CI, 1.20-1.69]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.79 [95%CI, 0.67-0.93]). Among patients with a history of CVD (n = 79,515 including n = 15,903 with migraine and n = 63,612 without migraine), 2960 had an ischemic stroke and 7981 had a CHD event. The adjusted HRs (95%CI) for ischemic stroke and CHD events associated with migraine were 1.27 (1.17-1.39) and 0.99 (0.93-1.05), respectively. Patients with migraine taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.21 [95%CI, 1.07-1.36]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.83 [95%CI, 0.72-0.95]), each versus those without migraine. CONCLUSIONS: Older adults with migraine are at increased risk for ischemic stroke. The risk for ischemic stroke among older adults with migraine may differ by migraine medication classes.

The Dynamic Relationship Between Asthma and Obesity in Schoolchildren.

Asthma and obesity are among the most prevalent chronic health conditions in children. Although there has been compelling evidence of co-occurrence of asthma and obesity, it is uncertain whether asthma contributes to the development of obesity or obesity contributes to the onset of asthma or both. In this study, we used a joint transition modeling approach with cross-lagged structure to understand how asthma and obesity influence each other dynamically over time. Subjects for this study included 5,193 kindergarten and first-grade students enrolled from 13 communities in 2002-2003 in the Southern California Children's Health Study, with up to 10 years of follow-up. We found that nonobese children with diagnosed asthma at a study visit were at 37% higher odds of becoming obese by the next annual visit compared with children without asthma (odds ratio = 1.38; 95% credible interval: 1.12, 1.71). However, the presence of obesity at the current visit was not statistically significantly associated with asthma onset in the next visit (odds ratio = 1.25; 95% credible interval: 0.94, 1.62). In conclusion, childhood asthma appears to drive an increase in the onset of obesity among schoolchildren, while the onset of obesity does not necessarily imply the future onset of asthma, at least in the short term.

Understanding the importance of key risk factors in predicting chronic bronchitic symptoms using a machine learning approach.

BACKGROUND: Chronic respiratory symptoms involving bronchitis, cough and phlegm in children are underappreciated but pose a significant public health burden. Efforts for prevention and management could be supported by an understanding of the relative importance of determinants, including environmental exposures. Thus, we aim to develop a prediction model for bronchitic symptoms. METHODS: Schoolchildren from the population-based southern California Children's Health Study were visited annually from 2003 to 2012. Bronchitic symptoms over the prior 12 months were assessed by questionnaire. A gradient boosting model was fit using groups of risk factors (including traffic/air pollution exposures) for all children and by asthma status. Training data consisted of one observation per participant in a random study year (for 50% of participants). Validation data consisted of: (1) a random (later) year in the same participants (within-participant); (2) a random year in participants excluded from the training data (across-participant). RESULTS: At baseline, 13.2% of children had asthma and 18.1% reported bronchitic symptoms. Models performed similarly within- and across-participant. Previous year symptoms/medication use provided much of the predictive ability (across-participant area under the receiver operating characteristic curve (AUC): 0.76 vs 0.78 for all risk factors, in all participants). Traffic/air pollution exposures added modestly to prediction as did body mass index percentile, age and parent stress. CONCLUSIONS: Regardless of asthma status, previous symptoms were the most important predictors of current symptoms. Traffic/air pollution variables contribute modest predictive information, but impact large populations. Methods proposed here could be generalized to personalized exacerbation predictions in future longitudinal studies to support targeted prevention efforts.

Electronic Cigarette and Cigarette Social Environments and Ever Use of Each Product: A Prospective Study of Young Adults in Southern California.

BACKGROUND: A supportive youth cigarette social environment, for example, friends' approval of use, leads to cigarette use initiation, and cigarette users develop a more supportive social environment. Whether there is a bidirectional relationship of electronic cigarette (e-cigarette) social environment with e-cigarette use has not been studied. METHODS: Prospective data were collected from 1441 Children's Health Study participants in 2014 (median age = 17.3 years) and at follow-up 1.5 years later. Associations were examined of (1) supportive e-cigarette social environment with subsequent e-cigarette use initiation and (2) baseline e-cigarette use with supportive e-cigarette social environment at follow-up (among those with a nonsupportive baseline social environment). RESULTS: Participants with three to four friends using e-cigarettes at baseline (vs. no friends) had an odds ratio (OR) of 4.08 of subsequent initiation (95% confidence interval [CI] = 1.96 to 8.49); those with best friends who would have a very friendly (vs. unfriendly) reaction to e-cigarette use had an OR of 2.54 of initiation (95% CI = 1.57 to 4.10); and those with someone in the home using e-cigarettes had an OR of 1.94 of initiation (95% CI = 1.19 to 3.15). Participants who had ever used e-cigarettes at baseline developed a supportive social environment at follow-up (OR of 2.06 of having any friends who used e-cigarettes [95% CI = 1.29 to 3.30] and OR of 2.33 of having friends who were friendly toward use [95% CI = 1.32 to 4.11]). Similar bidirectional associations were observed between ever cigarette use and a supportive cigarette social environment. CONCLUSIONS: The bidirectional relationship between a supportive e-cigarette social environment and ever use of e-cigarettes was similar to that previously observed between cigarette social environment and cigarette use. IMPLICATIONS: Disrupting the social acceptability of youth e-cigarette use merits consideration as a strategy for preventing initiation of e-cigarette use, just as the social denormalization of cigarette use has proven to be effective in preventing cigarette initiation.

Tobacco Marketing and Subsequent Use of Cigarettes, E-Cigarettes, and Hookah in Adolescents.

INTRODUCTION: Tobacco marketing has expanded from cigarettes to other tobacco products through many promotional channels. Marketing exposure is associated with use of that tobacco product. However, it is unclear if marketing for one product leads to subsequent use of other tobacco products. METHODS: This prospective cohort study assessed self-reported marketing exposure for six tobacco products across five marketing channels in 11th and 12th grade students in 2014. Approximately 16 months later, a follow-up survey was conducted online (N = 1553) to assess initiation of cigarettes, electronic cigarettes (e-cigarettes), and hookah. RESULTS: Adolescent never-smokers with frequent exposure to cigarette marketing on the Internet and in stores are more than two times as likely to begin smoking as young adults (Internet OR = 2.98 [95% CI = 1.56 to 5.66]; stores OR = 2.83 [95% CI = 1.23 to 6.50]). Never users of e-cigarettes were significantly more likely to initiate use, if exposed to Internet, store, and outdoor e-cigarette marketing. Never users of hookah were more likely to use hookah after seeing it marketed in stores. Youth exposed to marketing of e-cigarettes, hookah, cigars, smokeless tobacco, and pipe tobacco in stores were two to three times more likely to begin smoking cigarettes even though the marketed products were not cigarettes. CONCLUSIONS: Adolescent exposure to marketing of tobacco products is associated with initiation of those products as young adults. Exposure to marketing for non-cigarette tobacco products is associated with subsequent cigarette smoking, even when the promoted products are not cigarettes. Future research and interventions should consider the influence of marketing from multiple tobacco products on adolescent tobacco use. IMPLICATIONS: Adolescents grow up in a rich media environment with exposure to tobacco marketing in both their homes (eg, through the Internet and television) and their communities (eg, stores and billboards). This prospective study provides evidence that adolescents exposed to tobacco marketing for multiple tobacco products are more likely to subsequently begin using those products and to begin smoking cigarettes even when the marketing they recall is for different tobacco products. Adolescent exposure to tobacco marketing can increase likelihood of cigarette smoking, e-cigarette, and hookah use with potential lifelong health effects.

Association of Changes in Air Quality With Incident Asthma in Children in California, 1993-2014.

Importance: Exposure to air pollutants is a well-established cause of asthma exacerbation in children; whether air pollutants play a role in the development of childhood asthma, however, remains uncertain. Objective: To examine whether decreasing regional air pollutants were associated with reduced incidence of childhood asthma. Design, Setting, and Participants: A multilevel longitudinal cohort drawn from 3 waves of the Southern California Children's Health Study over a period of air pollution decline. Each cohort was followed up from 4th to 12th grade (8 years): 1993-2001, 1996-2004, and 2006-2014. Final follow-up for these data was June 2014. Population-based recruitment was from public elementary schools. A total of 4140 children with no history of asthma and residing in 1 of 9 Children's Health Study communities at baseline were included. Exposures: Annual mean community-level ozone, nitrogen dioxide, and particulate matter less than 10 µm (PM10) and less than 2.5 µm (PM2.5) in the baseline year for each of 3 cohorts. Main Outcomes and Measures: Prospectively identified incident asthma, collected via questionnaires during follow-up. Results: Among the 4140 children included in this study (mean [SD] age at baseline, 9.5 [0.6] years; 52.6% female [n = 2 179]; 58.6% white [n = 2273]; and 42.2% Hispanic [n = 1686]), 525 incident asthma cases were identified. For nitrogen dioxide, the incidence rate ratio (IRR) for asthma was 0.80 (95% CI, 0.71-0.90) for a median reduction of 4.3 parts per billion, with an absolute incidence rate decrease of 0.83 cases per 100 person-years. For PM2.5, the IRR was 0.81 (95% CI, 0.67-0.98) for a median reduction of 8.1 µg/m3, with an absolute incidence rate decrease of 1.53 cases per 100 person-years. For ozone, the IRR for asthma was 0.85 (95% CI, 0.71-1.02) for a median reduction of 8.9 parts per billion, with an absolute incidence rate decrease of 0.78 cases per 100 person-years. For PM10, the IRR was 0.93 (95% CI, 0.82-1.07) for a median reduction of 4.0 µg/m3, with an absolute incidence rate decrease of 0.46 cases per 100 person-years. Conclusions and Relevance: Among children in Southern California, decreases in ambient nitrogen dioxide and PM2.5 between 1993 and 2014 were significantly associated with lower asthma incidence. There were no statistically significant associations for ozone or PM10.

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 Children's 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.).

Talking about tobacco on Twitter is associated with tobacco product use.

Tobacco-related content appears on social media in the form of advertising and messages by individuals. However, little is known about associations between posting social media messages and tobacco product use among adolescents and young adults. Self-reports of tobacco product use were obtained from the Children's Health Study of young adults in Southern California. Among the 1486 respondents in the most recent wave of the cohort (2016-2017), 284 provided tobacco product use data and their Twitter user names to access publicly available Twitter account data (mean age = 20.1 yrs. (SD = 0.6), 54% female, 49% Hispanic). We obtained the tweets that those respondents posted on Twitter, searched the tweets for 14 nicotine- and tobacco-related keywords, and coded these statements as positive or negative/neutral. Logistic regression analyses were conducted to determine whether respondents who posted positive tobacco-related tweets were more likely to report tobacco product use, relative to those who did not post any positive tobacco-related tweets. Respondents who posted any positive messages about tobacco had significantly higher odds of reporting past month use of cigarettes (OR = 3.15, 95% CI = 1.36, 7.30) and any tobacco product (OR = 2.41, 95% CI = 1.16, 5.01), relative to respondents who did not post about tobacco. This is the first study to establish an empirical link between adolescents' and young adults' tobacco-related Twitter activity and their tobacco product use. Health communications about the risks of tobacco use could target adolescents who post positive messages about tobacco products on Twitter.

Electronic Cigarette Use and Respiratory Symptoms in Adolescents.

RATIONALE: Rates of adolescent electronic (e-) cigarette use are increasing, but there has been little study of the chronic effects of use. Components of e-cigarette aerosol have known pulmonary toxicity. OBJECTIVES: To investigate the associations of e-cigarette use with chronic bronchitis symptoms and wheeze in an adolescent population. METHODS: Associations of self-reported use of e-cigarettes with chronic bronchitic symptoms (chronic cough, phlegm, or bronchitis) and of wheeze in the previous 12 months were examined in 2,086 Southern California Children's Health Study participants completing questionnaires in 11th and 12th grade in 2014. MEASUREMENTS AND MAIN RESULTS: Ever e-cigarette use was reported by 502 (24.0%), of whom 201 (9.6%) used e-cigarettes during the last 30 days (current users). Risk of bronchitic symptoms was increased by almost twofold among past users (odds ratio [OR], 1.85; 95% confidence interval [CI], 1.37-2.49), compared with never-users, and by 2.02-fold (95% CI, 1.42-2.88) among current users. Risk increased with frequency of current use (OR, 1.66; 95% CI, 1.02-2.68) for 1-2 days and 2.52 (95% CI, 1.56-4.08) for 3 or more days in past 30 days compared with never-users. Associations were attenuated by adjustment for lifetime number of cigarettes smoked and secondhand smoke exposure. However, risk of bronchitic symptoms among past e-cigarette users remained elevated after adjustment for relevant potential confounders and was also observed among never-cigarette users (OR, 1.70; 95% CI, 1.11-2.59). There were no statistically significant associations of e-cigarette use with wheeze after adjustment for cigarette use. CONCLUSIONS: Adolescent e-cigarette users had increased rates of chronic bronchitic symptoms. Further investigation is needed to determine the long-term effects of e-cigarettes on respiratory health.

Constrained Mixed-Effect Models with Ensemble Learning for Prediction of Nitrogen Oxides Concentrations at High Spatiotemporal Resolution.

Spatiotemporal models to estimate ambient exposures at high spatiotemporal resolutions are crucial in large-scale air pollution epidemiological studies that follow participants over extended periods. Previous models typically rely on central-site monitoring data and/or covered short periods, limiting their applications to long-term cohort studies. Here we developed a spatiotemporal model that can reliably predict nitrogen oxide concentrations with a high spatiotemporal resolution over a long time span (>20 years). Leveraging the spatially extensive highly clustered exposure data from short-term measurement campaigns across 1-2 years and long-term central site monitoring in 1992-2013, we developed an integrated mixed-effect model with uncertainty estimates. Our statistical model incorporated nonlinear and spatial effects to reduce bias. Identified important predictors included temporal basis predictors, traffic indicators, population density, and subcounty-level mean pollutant concentrations. Substantial spatial autocorrelation (11-13%) was observed between neighboring communities. Ensemble learning and constrained optimization were used to enhance reliability of estimation over a large metropolitan area and a long period. The ensemble predictions of biweekly concentrations resulted in an R2 of 0.85 (RMSE: 4.7 ppb) for NO2 and 0.86 (RMSE: 13.4 ppb) for NOx. Ensemble learning and constrained optimization generated stable time series, which notably improved the results compared with those from initial mixed-effects models.

Association of Changes in Air Quality With Bronchitic Symptoms in Children in California, 1993-2012.

IMPORTANCE: Childhood bronchitic symptoms are significant public and clinical health problems that produce a substantial burden of disease. Ambient air pollutants are important determinants of bronchitis occurrence. OBJECTIVE: To determine whether improvements in ambient air quality in Southern California were associated with reductions in bronchitic symptoms in children. DESIGN, SETTING, AND PARTICIPANTS: A longitudinal study involving 4602 children (age range, 5-18 years) from 3 cohorts was conducted during the 1993-2001, 1996-2004, and 2003-2012 years in 8 Southern California communities. A multilevel logistic model was used to estimate the association of changes in pollution levels with bronchitic symptoms. EXPOSURES: Average concentrations of nitrogen dioxide, ozone, particulate matter with an aerodynamic diameter of less than 10 µm (PM10) and less than 2.5 µm (PM2.5). MAIN OUTCOMES AND MEASURES: Annual age-specific prevalence of bronchitic symptoms during the previous 12 months based on the parent's or child's report of a daily cough for 3 months in a row, congestion or phlegm other than when accompanied by a cold, or bronchitis. RESULTS: The 3 cohorts included a total of 4602 children (mean age at baseline, 8.0 years; 2268 girls [49.3%]; 2081 Hispanic white [45.2%]) who had data from 2 or more annual questionnaires. Among these children, 892 (19.4%) had asthma at age 10 years. For nitrogen dioxide, the odds ratio (OR) for bronchitic symptoms among children with asthma at age 10 years was 0.79 (95% CI, 0.67-0.94) for a median reduction of 4.9 ppb, with absolute decrease in prevalence of 10.1%. For ozone, the OR was 0.66 (95% CI, 0.50-0.86) for a median reduction of 3.6 ppb, with an absolute decrease in prevalence of 16.3%. For PM10, the OR was 0.61 (95% CI, 0.48-0.78) for a median reduction of 5.8 µg/m3, with an absolute decrease in prevalence of 18.7%. For PM2.5, the OR was 0.68 (95% CI, 0.53-0.86) for a median reduction of 6.8 µg/m3, with absolute decrease in prevalence of 15.4%. Among children without asthma (n = 3710), the ORs were 0.84 (95% CI, 0.76-0.92) for nitrogen dioxide; 0.85 (95% CI, 0.74-0.97) for ozone, 0.80 (95% CI, 0.70-0.92) for PM10, and 0.79 (95% CI, 0.69-0.91) for PM2.5; with absolute decrease in prevalence of 1.8% for nitrogen dioxide, 1.7% for ozone, 2.2% for PM10, and 2.3% for PM2.5. The associations were similar or slightly stronger at age 15 years. CONCLUSIONS AND RELEVANCE: Decreases in ambient pollution levels were associated with statistically significant decreases in bronchitic symptoms in children. Although the study design does not establish causality, the findings support potential benefit of air pollution reduction on asthma control.

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 Children's 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.

Determinants of the Spatial Distributions of Elemental Carbon and Particulate Matter in Eight Southern Californian Communities.

Emerging evidence indicates that near-roadway pollution (NRP) in ambient air has adverse health effects. However, specific components of the NRP mixture responsible for these effects have not been established. A major limitation for health studies is the lack of exposure models that estimate NRP components observed in epidemiological studies over fine spatial scale of tens to hundreds of meters. In this study, exposure models were developed for fine-scale variation in biologically relevant elemental carbon (EC). Measurements of particulate matter (PM) and EC less than 2.5 µm in aerodynamic diameter (EC2.5) and of PM and EC of nanoscale size less than 0.2 µm were made at up to 29 locations in each of eight Southern California Children's Health Study communities. Regression-based prediction models were developed using a guided forward selection process to identify traffic variables and other pollutant sources, community physical characteristics and land use as predictors of PM and EC variation in each community. A combined eight-community model including only CALINE4 near-roadway dispersion-estimated vehicular emissions accounting for distance, distance-weighted traffic volume, and meteorology, explained 51% of the EC0.2 variability. Community-specific models identified additional predictors in some communities; however, in most communities the correlation between predicted concentrations from the eight-community model and observed concentrations stratified by community were similar to those for the community-specific models. EC2.5 could be predicted as well as EC0.2. EC2.5 estimated from CALINE4 and population density explained 53% of the within-community variation. Exposure prediction was further improved after accounting for between-community heterogeneity of CALINE4 effects associated with average distance to Pacific Ocean shoreline (to 61% for EC0.2) and for regional NOx pollution (to 57% for EC2.5). PM fine spatial scale variation was poorly predicted in both size fractions. In conclusion, models of exposure that include traffic measures such as CALINE4 can provide useful estimates for EC0.2 and EC2.5 on a spatial scale appropriate for health studies of NRP in selected Southern California communities.

Spatial Variation in Particulate Matter Components over a Large Urban Area.

To characterize exposures to particulate matter (PM) and its components, we performed a large sampling study of small-scale spatial variation in size-resolved particle mass and composition. PM was collected in size ranges of < 0.2, 0.2-to-2.5, and 2.5-to-10 µm on a scale of 100s to 1000s of meters to capture local sources. Within each of eight Southern California communities, up to 29 locations were sampled for rotating, month-long integrated periods at two different times of the year, six months apart, from Nov 2008 through Dec 2009. Additional sampling was conducted at each community's regional monitoring station to provide temporal coverage over the sampling campaign duration. Residential sampling locations were selected based on a novel design stratified by high- and low-predicted traffic emissions and locations over- and under-predicted from previous dispersion model and sampling comparisons. Primary vehicle emissions constituents, such as elemental carbon (EC), showed much stronger patterns of association with traffic than pollutants with significant secondary formation, such as PM2.5 or water soluble organic carbon. Associations were also stronger during cooler times of the year (Oct through Mar). Primary pollutants also showed greater within-community spatial variation compared to pollutants with secondary formation contributions. For example, the average cool-season community mean and standard deviation (SD) for EC were 1.1 and 0.17 µg/m3, respectively, giving a coefficient of variation (CV) of 18%. For PM2.5, average mean and SD were 14 and 1.3 µg/m3, respectively, with a CV of 9%. We conclude that within-community spatial differences are important for accurate exposure assessment of traffic-related pollutants.

Parental stress increases the detrimental effect of traffic exposure on children's lung function.

RATIONALE: Emerging evidence indicates that psychosocial stress enhances the effect of traffic exposure on the development of asthma. OBJECTIVES: We hypothesized that psychosocial stress would also modify the effect of traffic exposure on lung function deficits. METHODS: We studied 1,399 participants in the Southern California Children's Health Study undergoing lung function testing (mean age, 11.2 yr). We used hierarchical mixed models to assess the joint effect of traffic-related air pollution and stress on lung function. MEASUREMENTS AND MAIN RESULTS: Psychosocial stress in each child's household was assessed based on parental response to the perceived stress scale (range, 0-16) at study entry. Exposures to nitric oxide, nitrogen dioxide, and total oxides of nitrogen (NOx), surrogates of the traffic-related pollution mixture, were estimated at schools and residences based on a land-use regression model. Among children from high-stress households (parental perceived stress scale > 4) deficits in FEV1 of 4.5 (95% confidence interval, -6.5 to -2.4) and of 2.8% (-5.7 to 0.3) were associated with each 21.8 ppb increase in NOx at homes and schools, respectively. These pollutant effects were significantly larger in the high-stress compared with lower-stress households (interaction P value 0.007 and 0.05 for residential and school NOx, respectively). No significant NOx effects were observed in children from low-stress households. A similar pattern of association was observed for FVC. The observed associations for FEV1 and FVC remained after adjusting for sociodemographic factors and after restricting the analysis to children who do not have asthma. CONCLUSIONS: A high-stress home environment is associated with increased susceptibility to lung function effects of air pollution both at home and at school.