Childhood Air Pollution Exposure Associated with Self-Reported Bronchitic Symptoms in Adulthood.

RATIONALE: Few studies have examined the effects of long-term childhood air pollution exposure on adult respiratory health, including whether childhood respiratory effects underlie this relation. OBJECTIVES: To evaluate associations between childhood air pollution exposure and self-reported adult bronchitic symptoms, while considering child respiratory health, in the Southern California Children's Health Study. METHODS: Nitrogen dioxide (NO2), ozone, particulate matter<2.5µm (PM2.5) and <10µm (PM10) exposures assessed using inverse-distance-squared spatial interpolation based on childhood (birth-17 years) residential histories. Bronchitic symptoms (bronchitis, cough, or phlegm in last 12 months) were ascertained via questionnaire in adulthood. Associations between mean air pollution exposure across childhood and self-reported adult bronchitic symptoms were estimated using logistic regression. We further adjusted for childhood bronchitic symptoms and asthma to understand whether associations operated beyond childhood respiratory health impacts. Effect modification was assessed for family history of asthma, childhood asthma, and adult allergies. MEASUREMENTS AND MAIN RESULTS: 1308 participants were included (mostly non-Hispanic White [56%] or Hispanic [32%]). At adult assessment (age mean=32.0 years, standard deviation [SD]=4.7) 25% reported bronchitic symptoms. Adult bronchitic symptoms were associated with NO2 and PM10 childhood exposures. Odds ratios per SD increase: 1.69 (95%CI:1.14,2.49) for NO2 (SD=11.1ppb); 1.51 (95%CI:1.00,2.27) for PM10 (SD=14.2µg/m3). Adjusting for childhood bronchitic symptoms or asthma produced similar results. NO2 and PM10 associations were modified by childhood asthma, with larger associations among asthmatics. CONCLUSION: Childhood NO2 and PM10 exposures were associated with adult bronchitic symptoms. Associations were not explained by childhood respiratory health impacts; however, participants with childhood asthma had stronger associations.

Longitudinal Transitions Between Use of Combustible, Noncombustible, and Multiple Cannabis Products From Adolescence to Young Adulthood and Intersections With Nicotine Use.

Understanding transitions across use of different types of cannabis products and multiple cannabis products and how they intersect with nicotine use in young people can inform etiology and prevention. In this study, we examined transitions across use of combustible and noncombustible forms of cannabis and multiple types of cannabis from adolescence to young adulthood and the role of nicotine use in transitions. In a Southern California longitudinal cohort study (n = 3,298; baseline mean age = 16.1 (standard deviation, 0.4) years) with 9 semiannual survey waves (2015-2021), we used Markov multistate transition modeling to estimate short-term (2-wave) and long-term (9-wave) probabilities of transition across 5 cannabis use states: never use of any product, prior use with no past-6-month (P6M) use of any product, and P6M use of exclusively noncombustible products, exclusively combustible products, and multiple (noncombustible + combustible) products. Sizable transition probabilities from prior and exclusive P6M noncombustible or combustible cannabis use to P6M poly-cannabis-product use were observed in short-term (10.7%-38.9%) and long-term (43.4%-43.8%) analyses. P6M nicotine use increased risk of transitioning from never and prior use to exclusive P6M noncombustible and combustible cannabis use. Cannabis use in any form, even temporary use, during midadolescence may often be followed by poly-cannabis-product use. Nicotine use may amplify the probability of future cannabis use onset or recurrence.

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.

Recall of Flavor at First E-cigarette Use and its Association with E-cigarette Progression: The Mediating Effects of First Sensory Experience.

OBJECTIVE: To test whether the association between flavor at first vape and continued use is mediated through subjective experience at first vape. STUDY DESIGN: In a 2020 cross-sectional survey, 955 young adult ever-vapers recalled their first flavor vaped, subjective experiences at first use, current vaping behavior, nicotine dependence, and quit attempts. A latent class model grouped first-use subjective experiences into classes. Two-part negative binomial hurdle models for each vaping behavior evaluated whether the association of first flavor used with vaping outcomes was mediated by positive experience. RESULTS: Four latent classes (positive, positive and negative, negative, and minimal experience) were further reduced to "any positive experience" (only positive, positive and negative) vs "no positive experience" (negative or minimal). Class membership mediated the association of first flavor used (mint/menthol/ice [ie, "cooling"] or sweet vs other) with each vaping outcome. For example, cooling flavor (vs. other) was associated with positive class membership (OR=3.5; 95%CI:1.5,8.1), which was then associated with any past 30-day vaping (OR=3.9; 95%CI:2.7,5.8) and greater number of vaping days among current vapers (RR=1.9; 95%CI:1.3,2.7) in the two-part hurdle model. Similar results were observed for nicotine dependence and quit attempts, and for sweet (vs. other) flavor for any dependence or quit attempts, but not number of dependence symptoms or quit attempts. CONCLUSIONS: Use of a cooling or sweet flavor at first use was associated with having a positive first vaping sensory experience, and then greater likelihood as a young adult of reporting past 30-day vaping, more vaping days, and greater risk for nicotine dependence, suggesting a key mediating role of first use experience.

Types of diabetes during pregnancy and risk of depression and anxiety in offspring from childhood to young adulthood.

AIMS: To assess maternal pre-existing type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM) during pregnancy and risk of depression and anxiety from childhood to young adulthood in offspring. MATERIALS AND METHODS: This birth cohort included singletons born during 1995-2015, followed using electronic medical records through 2020. Cox regression was used to estimate hazard ratio (HR) of depression or anxiety diagnosis during follow-up associated with in-utero exposure to maternal diabetes. RESULTS: Among 439 590 offspring, 29 891 (6.8%) had depression and 51 918 (11.8%) had anxiety. T1D, followed by T2D and GDM requiring antidiabetes medication were associated with risk of depression and anxiety in offspring. Compared with no diabetes during pregnancy, the adjusted HRs (95% confidence interval) of depression in offspring associated with T1D, T2D or GDM requiring medications were 1.44 (1.09-1.91), 1.30 (1.15-1.47) and 1.18 (1.11-1.26) respectively; conversely, HRs were 0.97 (0.82-1.15) for T2D and 0.99 (0.94-1.04) for GDM without medications. The associations with anxiety followed similar patterns. The significant associations were observed for offspring ages 5-12 and >12-18 years and attenuated for 18-25 years. CONCLUSION: These data suggest that the severity of diabetes (T1D vs. T2D requiring medications vs. GDM requiring medications) during pregnancy may increase the vulnerability of offspring for depression or anxiety.

Air pollution and age-dependent changes in emotional behavior across early adolescence in the U.S.

Recent studies have linked air pollution to increased risk for behavioral problems during development, albeit with inconsistent findings. Additional longitudinal studies are needed that consider how emotional behaviors may be affected when exposure coincides with the transition to adolescence - a vulnerable time for developing mental health difficulties. This study investigates if annual average PM2.5 and NO2 exposure at ages 9-10 years moderates age-related changes in internalizing and externalizing behaviors over a 2-year follow-up period in a large, nationwide U.S. sample of participants from the Adolescent Brain Cognitive Development (ABCD) Study®. Air pollution exposure was estimated based on the residential address of each participant using an ensemble-based modeling approach. Caregivers answered questions from the Child Behavior Checklist (CBCL) at the baseline, 1-year follow-up, and 2-year follow-up visits, for a total of 3 waves of data; from the CBCL we obtained scores on internalizing and externalizing problems plus 5 syndrome scales (anxious/depressed, withdrawn/depressed, rule-breaking behavior, aggressive behavior, and attention problems). Zero-inflated negative binomial models were used to examine both the main effect of age as well as the interaction of age with each pollutant on behavior while adjusting for various socioeconomic and demographic characteristics. Against our hypothesis, there was no evidence that greater air pollution exposure was related to more behavioral problems with age over time.

Per- and polyfluoroalkyl substances, polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers and dysregulation of MicroRNA expression in humans and animals-A systematic review.

BACKGROUND: Persistent organic pollutants (POPs) are chemicals characterized by their environmental persistence. Evidence suggests that exposure to POPs, which is ubiquitous, is associated with microRNA (miRNA) dysregulation. miRNA are key regulators in many physiological processes. It is thus of public health concern to understand the relationships between POPs and miRNA as related to health outcomes. OBJECTIVES: This systematic review evaluated the relationship between widely recognized, intentionally manufactured, POPs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (dichlorodiphenyltrichloroethane [DDT], dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB]), with miRNA expression in both human and animal studies. METHODS: We used PubMed and Embase to systematically search the literature up to September 29th, 2023. Search results for human and animal studies were included if they incorporated at least one POP of interest in relation to at least one miRNA. Data were synthesized to determine the direction and significance of associations between POPs and miRNA. We utilized ingenuity pathway analysis to review disease pathways for miRNA that were associated with POPs. RESULTS: Our search identified 38 eligible studies: 9 in humans and 29 in model organisms. PFAS were associated with decreased expression of miR-19, miR-193b, and miR-92b, as well as increased expression of miR-128, miR-199a-3p, and miR-26b across species. PCBs were associated with increased expression of miR-15a, miR-1537, miR-21, miR-22-3p, miR-223, miR-30b, and miR-34a, as well as decreased expression of miR-130a and let-7b in both humans and animals. Pathway analysis for POP-associated miRNA identified pathways related to carcinogenesis. DISCUSSION: This is the first systematic review of the association of POPs with miRNA in humans and model organisms. Large-scale prospective human studies are warranted to examine the role of miRNA as mediators between POPs and health outcomes.

Exposure to perfluoroalkyl substances and longitudinal changes in bone mineral density in adolescents and young adults: A multi-cohort study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) may impair bone development in adolescence, which impacts life-long bone health. No previous studies have examined prospective associations of individual PFAS and their mixture with bone mineral density (BMD) changes in Hispanic young persons, a population at high risk of osteoporosis in adulthood. OBJECTIVES: To examine associations of individual PFAS and PFAS mixtures with longitudinal changes in BMD in an adolescent Hispanic cohort and examine generalizability of findings in a mixed-ethnicity young adult cohort (58.4% Hispanic). METHODS: Overweight/obese adolescents from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR; n = 304; mean follow-up = 1.4 years) and young adults from the Southern California Children's Health Study (CHS; n = 137; mean follow-up = 4.1 years) were included in this study. Plasma PFAS were measured at baseline and dual x-ray absorptiometry scans were performed at baseline and follow-up to measure BMD. We estimated longitudinal associations between BMD and five PFAS via separate covariate-adjusted linear mixed effects models, and between BMD and the PFAS mixture via quantile g-computation. RESULTS: In SOLAR adolescents, baseline plasma perfluorooctanesulfonic acid (PFOS) was associated with longitudinal changes in BMD. Each doubling of PFOS was associated with an average -0.003 g/cm2 difference in change in trunk BMD per year over follow-up (95% CI: -0.005, -0.0002). Associations with PFOS persisted in CHS young adults, where each doubling of plasma PFOS was associated with an average -0.032 g/cm2 difference in total BMD at baseline (95% CI -0.062, -0.003), though longitudinal associations were non-significant. We did not find associations of other PFAS with BMD; associations of the PFAS mixture with BMD outcomes were primarily negative though non-significant. DISCUSSION: PFOS exposure was associated with lower BMD in adolescence and young adulthood, important periods for bone development, which may have implications on future bone health and risk of osteoporosis in adulthood.

Exposure to per- and polyfluoroalkyl substances and alterations in plasma microRNA profiles in children.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans. OBJECTIVE: To investigate associations between PFAS concentrations and miRNA levels in children. METHODS: Data from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and 64 participants (average age 6.5 years, 39.1% female) from the Rhea study, a mother-child cohort in Greece. PFAS concentrations and miRNA levels were assessed in plasma samples from both studies. Associations between individual PFAS and plasma miRNA levels were examined after adjusting for covariates. Additionally, the cumulative effects of PFAS mixtures were evaluated using an exposure burden score. Ingenuity Pathways Analysis was employed to identify potential disease functions of PFAS-associated miRNAs. RESULTS: Plasma PFAS concentrations were associated with alterations in 475 miRNAs in the Teen-LABs study and 5 miRNAs in the Rhea study (FDR p < 0.1). Specifically, plasma PFAS concentrations were consistently associated with decreased levels of miR-148b-3p and miR-29a-3p in both cohorts. Pathway analysis indicated that PFAS-related miRNAs were linked to numerous chronic disease pathways, including cardiovascular diseases, inflammatory conditions, and carcinogenesis. CONCLUSION: Through miRNA screenings in two independent cohorts, this study identified both known and novel miRNAs associated with PFAS exposure in children. Pathway analysis revealed the involvement of these miRNAs in several cancer and inflammation-related pathways. Further studies are warranted to enhance our understanding of the relationships between PFAS exposure and disease risks, with miRNA emerging as potential biomarkers and/or mediators in these complex pathways.

Effects of exposure to snus marketing with versus without modified risk tobacco product claims on snus use intention and perceived harm among young adults.

BACKGROUND: We tested whether snus marketing with modified risk tobacco product (MRTP) claims: (a) promotes accurate knowledge about snus's health effects in young adults and (b) encourages use intentions in only those who use combustible tobacco without attracting other young adult populations. METHODS: A randomised between-subjects experiment was embedded in a 2020 web survey of participants from Los Angeles (aged 19-23 years). Participants viewed mass-marketed snus advertising materials with (n=1212) vs without (n=1225) US Food and Drug Administration-authorised MRTP claims. After advertising exposure, snus use intention and perceptions of snus harms relative to cigarettes or e-cigarettes were measured. RESULTS: Advertisements with versus without MRTP claims did not affect snus use intention (18.0% vs 19.4%) but produced a higher prevalence of perceptions that snus was less harmful than cigarettes (12.6% vs 9.1%; p=0.007) and e-cigarettes (8.0% vs 5.8%; p=0.04). MRTP claim exposure effects did not differ by past 30-day e-cigarette or combustible tobacco use. Snus use intentions after marketing exposure, collapsed across MRTP claim conditions, were higher in those who did versus did not report past 30-day use of e-cigarettes (38.4% vs 14.3%; adjusted OR (95% CI) 2.95 (2.28 to 3.81); p<0.001) or combustible tobacco (44.0% vs 16.2%; adjusted OR (95% CI) 2.26 (1.62 to 3.16); p<0.001). CONCLUSION: Although some young adults who vape or smoke may have snus use intentions, snus MRTP claims might not affect young adults' snus use intentions, regardless of whether they vape/smoke. MRTP claims might modestly increase the accuracy of perceived harms of snus relative to cigarettes while also slightly causing unsubstantiated perceptions of lower harm than e-cigarettes.

Associations of Autism Spectrum Disorder with PM2.5 Components: A Comparative Study Using Two Different Exposure Models.

This retrospective cohort study examined associations of autism spectrum disorder (ASD) with prenatal exposure to major fine particulate matter (PM2.5) components estimated using two independent exposure models. The cohort included 318 750 mother-child pairs with singleton deliveries in Kaiser Permanente Southern California hospitals from 2001 to 2014 and followed until age five. ASD cases during follow-up (N = 4559) were identified by ICD codes. Prenatal exposures to PM2.5, elemental (EC) and black carbon (BC), organic matter (OM), nitrate (NO3-), and sulfate (SO42-) were constructed using (i) a source-oriented chemical transport model and (ii) a hybrid model. Exposures were assigned to each maternal address during the entire pregnancy, first, second, and third trimester. In single-pollutant models, ASD was associated with pregnancy-average PM2.5, EC/BC, OM, and SO42- exposures from both exposure models, after adjustment for covariates. The direction of effect estimates was consistent for EC/BC and OM and least consistent for NO3-. EC/BC, OM, and SO42- were generally robust to adjustment for other components and for PM2.5. EC/BC and OM effect estimates were generally larger and more consistent in the first and second trimester and SO42- in the third trimester. Future PM2.5 composition health effect studies might consider using multiple exposure models and a weight of evidence approach when interpreting effect estimates.

Paired Liver:Plasma PFAS Concentration Ratios from Adolescents in the Teen-LABS Study and Derivation of Empirical and Mass Balance Models to Predict and Explain Liver PFAS Accumulation.

Animal studies have pointed at the liver as a hotspot for per- and polyfluoroalkyl substances (PFAS) accumulation and toxicity; however, these findings have not been replicated in human populations. We measured concentrations of seven PFAS in matched liver and plasma samples collected at the time of bariatric surgery from 64 adolescents in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study. Liver:plasma concentration ratios were perfectly explained (r2 > 0.99) in a multilinear regression (MLR) model based on toxicokinetic (TK) descriptors consisting of binding to tissue constituents and membrane permeabilities. Of the seven matched plasma and liver PFAS concentrations compared in this study, the liver:plasma concentration ratio of perfluoroheptanoic acid (PFHpA) was considerably higher than the liver:plasma concentration ratio of other PFAS congeners. Comparing the MLR model with an equilibrium mass balance model (MBM) suggested that complex kinetic transport processes are driving the unexpectedly high liver:plasma concentration ratio of PFHpA. Intratissue MBM modeling pointed to membrane lipids as the tissue constituents that drive the liver accumulation of long-chain, hydrophobic PFAS, whereas albumin binding of hydrophobic PFAS dominated PFAS distribution in plasma. The liver:plasma concentration data set, empirical MLR model, and mechanistic MBM modeling allow the prediction of liver from plasma concentrations measured in human cohort studies. Our study demonstrates that combining biomonitoring data with mechanistic modeling can identify underlying mechanisms of internal distribution and specific target organ toxicity of PFAS in humans.

Associations of per- and polyfluoroalkyl substances, polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers with oxidative stress markers: A systematic review and meta-analysis.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs) are intentionally produced persistent organic pollutants (POPs) that are resistant to environmental degradation. Previous in-vitro and in-vivo studies have shown that POPs can induce oxidative stress, which is linked to neurodegenerative diseases, cardiovascular diseases, and cancer. However, findings in epidemiological studies are inconsistent and an evidence synthesis study is lacking to summarize the existing literature and explore research gaps. OBJECTIVE: We evaluated the effects of PFAS, PCBs, OCPs, and PBDEs, on oxidative stress biomarkers in epidemiological studies. METHODS: A literature search was conducted in PubMed, Embase, and Cochrane CENTRAL to identify all published studies related to POPs and oxidative stress up to December 7th, 2022. We included human observational studies reporting at least one exposure to POPs and an oxidative stress biomarker of interest. Random-effects meta-analyses on standardized regression coefficients and effect direction plots with one-tailed sign tests were used for quantitative synthesis. RESULTS: We identified 33 studies on OCPs, 35 on PCBs, 49 on PFAS, and 12 on PBDEs. Meta-analyses revealed significant positive associations of α-HCH with protein carbonyls (0.035 [0.017, 0.054]) and of 4'4-DDE with malondialdehyde (0.121 [0.056, 0.187]), as well as a significant negative association between 2'4-DDE and total antioxidant capacity (TAC) (-0.042 [-0.079, -0.004]), all ß [95%CI]. Sign tests showed a significant positive association between PCBs and malondialdehyde (pone-tailed = 0.03). Additionally, we found significant negative associations of OCPs with acetylcholine esterase (pone-tailed = 0.02) and paraoxonase-1 (pone-tailed = 0.03). However, there were inconsistent associations of OCPs with superoxide dismutase, glutathione peroxidase, and catalase. CONCLUSIONS: Higher levels of OCPs were associated with increased levels of oxidative stress through increased pro-oxidant biomarkers involving protein oxidation, DNA damage, and lipid peroxidation, as well as decreased TAC. These findings have the potential to reveal the underlying mechanisms of POPs toxicity.

Effects of dual use of e-cigarette and cannabis during adolescence on cigarette use in young adulthood.

INTRODUCTION: E-cigarette and cannabis use by adolescents are risk factors for smoking initiation. We hypothesised that increasingly common dual use of e-cigarette and cannabis in adolescence leads to more frequent cigarette smoking in young adulthood. METHODS: Data are from a prospective cohort study in Southern California, where 1164 participants who ever used nicotine products in their lifetime completed surveys in 12th grade (T1:2016), and at 24-month (T2) and 42-month (T3) follow-ups. Past 30-day use (number of days: range=0-30) of cigarettes, e-cigarettes and cannabis, and nicotine dependence, were assessed in each survey. Nicotine dependence for cigarettes and e-cigarettes was assessed using original and modified (for e-cigarette) Hooked on Nicotine Checklists (number of dependent products: range=0-2). Path analysis examined the mediation process via nicotine dependence linking baseline e-cigarette and cannabis use to subsequent increased cigarette use. RESULTS: Baseline exclusive use of e-cigarettes (baseline prevalence, 2.5%) was associated with 2.61-fold increase in frequency of smoking days at T3 (95% CI 1.04 to 13.1), exclusive cannabis use (26.0%) with 2.58-fold increase (95% CI 1.43 to 4.98), and dual use (7.4%) with 5.84-fold increase (95% CI 3.16 to 12.81), compared with baseline non-users. Nicotine dependence at T2 mediated 10.5% (95% CI 6.3 to 14.7) and 23.2% (95% CI 9.6 to 36.3) of the association of cannabis and dual use, respectively, with increased smoking at T3. DISCUSSION: Adolescent e-cigarette and cannabis use was associated with more frequent smoking during young adulthood, with larger effects of dual use. Associations were partially mediated through nicotine dependence. Dual use of cannabis and e-cigarettes may contribute to the development of nicotine dependence and increased use of combustible cigarettes.

Effect of a hypothetical modified risk tobacco product claim on heated tobacco product use intention and perceptions in young adults.

INTRODUCTION: Modified risk tobacco product (MRTP) claims for heated tobacco products (HTPs) that convey reduced exposure compared with conventional cigarettes may promote product initiation and transition among young people. We assessed the effects of a hypothetical MRTP claim for HTPs on young adults' intention and perceptions of using HTPs and whether these effects differed by their current cigarette and e-cigarette use. METHODS: We embedded a randomised between-subjects experiment into a web-based survey administered among a cohort of 2354 Southern California young adults (aged 20-23) in 2020. Participants viewed depictions of HTPs with an MRTP claim (n=1190) or no claim (n=1164). HTP use intention and HTP-related harm and use perceptions relative to cigarettes and e-cigarettes were assessed. RESULTS: Overall, participants who viewed versus did not view the claim did not differ in HTP use intention (28.5% vs 28.7%) but were more likely to perceive HTPs as less harmful than cigarettes (11.4% vs 7.0%; p<0.001). The experimental effect on HTP use intention did not differ among past 30-day cigarette smokers versus non-smokers (interaction adjusted OR (AOR)=0.78, 95% CI 0.36 to 1.76) but differed among past 30-day e-cigarette users versus non-users (interaction AOR=1.67, 95% CI 1.02 to 2.68). DISCUSSION: The hypothetical MRTP claim may lower young adults' HTP harm perceptions compared with cigarettes but may not change HTP use intention overall or differentially for cigarette smokers. The larger effect on HTP use intention among e-cigarette users than non-users raises the question of whether MRTP claims may promote HTP use or HTP and e-cigarette dual use among young e-cigarette users.

The Effects of Coexposure to Extremes of Heat and Particulate Air Pollution on Mortality in California: Implications for Climate Change.

Rationale: Extremes of heat and particulate air pollution threaten human health and are becoming more frequent because of climate change. Understanding the health impacts of coexposure to extreme heat and air pollution is urgent. Objectives: To estimate the association of acute coexposure to extreme heat and ambient fine particulate matter (PM2.5) with all-cause, cardiovascular, and respiratory mortality in California from 2014 to 2019. Methods: We used a case-crossover study design with time-stratified matching using conditional logistic regression to estimate mortality associations with acute coexposures to extreme heat and PM2.5. For each case day (date of death) and its control days, daily average PM2.5 and maximum and minimum temperatures were assigned (0- to 3-day lag) on the basis of the decedent's residence census tract. Measurements and Main Results: All-cause mortality risk increased 6.1% (95% confidence interval [CI], 4.1-8.1) on extreme maximum temperature-only days and 5.0% (95% CI, 3.0-8.0) on extreme PM2.5-only days, compared with nonextreme days. Risk increased by 21.0% (95% CI, 6.6-37.3) on days with exposure to both extreme maximum temperature and PM2.5. Increased risk of cardiovascular and respiratory mortality on extreme coexposure days was 29.9% (95% CI, 3.3-63.3) and 38.0% (95% CI, -12.5 to 117.7), respectively, and were more than the sum of individual effects of extreme temperature and PM2.5 only. A similar pattern was observed for coexposure to extreme PM2.5 and minimum temperature. Effect estimates were larger over age 75 years. Conclusions: Short-term exposure to extreme heat and air pollution alone were individually associated with increased risk of mortality, but their coexposure had larger effects beyond the sum of their individual effects.

Secondhand nicotine vaping at home and respiratory symptoms in young adults.

RATIONALE: Despite high prevalence of e-cigarette use (vaping), little is currently known regarding the health effects of secondhand nicotine vape exposure. OBJECTIVE: To investigate whether exposure to secondhand nicotine vape exposure is associated with adverse respiratory health symptoms among young adults. METHOD: We investigated the effect of secondhand nicotine vape exposure on annually reported wheeze, bronchitic symptoms and shortness of breath in the prospective Southern California Children Health Study cohort. Data were collected from study participants (n=2097) with repeated annual surveys from 2014 (average age: 17.3 years) to 2019 (average age: 21.9). We used mixed effect logistic regression to evaluate the association between secondhand nicotine vape and respiratory symptoms after controlling for relevant confounders. RESULTS: Prevalence of secondhand nicotine vape increased from 11.7% to 15.6% during the study period in this population. Prevalence of wheeze, bronchitic symptoms and shortness of breath ranged from 12.3% to 14.9%, 19.4% to 26.0% and 16.5% to 18.1%, respectively, during the study period. Associations of secondhand nicotine vape exposure with bronchitic symptoms (OR 1.40, 95% CI 1.06 to 1.84) and shortness of breath (OR 1.53, 95% CI 1.06 to 2.21) were observed after controlling for vaping, active and passive exposure to tobacco or cannabis, and demographic characteristics (age, gender, race/ethnicity and parental education). Stronger associations were observed when analysis was restricted to participants who were neither smokers nor vapers. There were no associations with wheezing after adjustment for confounders. CONCLUSION: Secondhand nicotine vape exposure was associated with increased risk of bronchitic symptoms and shortness of breath among young adults.

In Utero Exposure to Mercury Is Associated With Increased Susceptibility to Liver Injury and Inflammation in Childhood.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of liver disease in children. Mercury (Hg), a ubiquitous toxic metal, has been proposed as an environmental factor contributing to toxicant-associated fatty liver disease. APPROACH AND RESULTS: We investigated the effect of prenatal exposure to Hg on childhood liver injury by combining epidemiological results from a multicenter mother-child cohort with complementary in vitro experiments on monocyte cells that are known to play a key role in liver immune homeostasis and NAFLD. We used data from 872 mothers and their children (median age, 8.1 years; interquartile range [IQR], 6.5-8.7) from the European Human Early-Life Exposome cohort. We measured Hg concentration in maternal blood during pregnancy (median, 2.0 µg/L; IQR, 1.1-3.6). We also assessed serum levels of alanine aminotransferase (ALT), a common screening tool for pediatric NAFLD, and plasma concentrations of inflammation-related cytokines in children. We found that prenatal Hg exposure was associated with a phenotype in children that was characterized by elevated ALT (≥22.1 U/L for females and ≥25.8 U/L for males) and increased concentrations of circulating IL-1ß, IL-6, IL-8, and TNF-α. Consistently, inflammatory monocytes exposed in vitro to a physiologically relevant dose of Hg demonstrated significant up-regulation of genes encoding these four cytokines and increased concentrations of IL-8 and TNF-α in the supernatants. CONCLUSIONS: These findings suggest that developmental exposure to Hg can contribute to inflammation and increased NAFLD risk in early life.

First E-Cigarette Flavor and Device Type Used: Associations With Vaping Persistence, Frequency, and Dependence in Young Adults.

INTRODUCTION: Type of e-cigarette flavoring and device during first use might differentiate later e-cigarette use and dependence. This retrospective cross-sectional study examined associations of recalled first nicotine vaping device and flavor used with current vaping frequency/dependence. AIMS AND METHODS: A young adult cohort from Los Angeles, California, USA completed web-based surveys (N = 2553). Using cross-sectional data from 971 reporting ever vaping nicotine, multivariable hurdle regressions tested associations between recalled first flavor (fruit/sweet, menthol/mint, other) and device (Juul, disposable, mod, box, pod, pen, other) vaped with past-30-day vaping status (yes/no) and frequency (1-30 days), and with any vaping dependence symptoms (yes/no) and count (1-10 symptoms). RESULTS: The most common first-flavor was sweet (71%); the most common first-device was a vape pen (37%), then Juul (22%). First-flavor of mint/menthol (vs. other; adjusted odds ratio [AOR]: 2.22[95% CI = 1.16 to 4.25]), and first-device mod (AOR = 2.40[95% CI = 1.34 to 4.31]) and non-Juul pod (2.64[95% CI = 1.41 to 4.92]) (vs. pen) were associated with past-30-day vaping, and twice as many vaping days (adjusted rate ratios [ARRs] range: 1.96-2.12; ps < .05). First flavor of mint/menthol (vs. other; AOR: 1.95[95% CI = 1.003 to 3.79) and first device mod, box, non-Juul pod, and other (AORs range: 2.36-4.01; ps < .05) were associated with nicotine dependence. First device Juul, mod, box, and non-Juul pod were also associated with more dependence symptoms (ARRs range:1.38-1.59; ps < .05). CONCLUSIONS: Exposure to mint/menthol and certain devices (mod, box, Juul, and non-Juul pods) at first e-cigarette use may be associated with more frequent e-cigarette use and nicotine dependence symptoms in young adulthood. Mint/menthol and certain devices warrant consideration in regulation of e-cigarettes based on product characteristics. IMPLICATIONS: Characteristics (flavor and device type) of first e-cigarette product used were associated with higher usage and more dependence. Pending replication with prospective designs, the findings suggest certain flavors (mint/menthol) and devices (pods, mods) merit consideration in regulation because of their possible link with continued use and dependence among young people.

Evidence of susceptibility to autism risks associated with early life ambient air pollution: A systematic review.

BACKGROUND: Many studies have found associations between early life air pollution exposure and subsequent onset of autism spectrum disorder (ASD). However, characteristics that affect susceptibility remain unclear. OBJECTIVE: This systematic review examined epidemiologic studies on the modifying roles of social, child, genetic and maternal characteristics in associations between prenatal and early postnatal air pollution exposure and ASD. METHODS: A systematic literature search in PubMed and Embase was conducted. Studies that examined modifiers of the association between air pollution and ASD were included. RESULTS: A total of 19 publications examined modifiers of the associations between early life air pollution exposures and ASD. In general, estimates of effects on risk of ASD in boys were larger than in girls (based on 11 studies). Results from studies of effects of family education (2 studies) and neighborhood deprivation (2 studies) on air pollution-ASD associations were inconsistent. Limited data (1 study) suggest pregnant women with insufficient folic acid intake might be more susceptible to ambient particulate matter less than 2.5 µm (PM2.5) and 10 µm (PM10) in aerodynamic diameter, and to nitrogen dioxide (NO2). Children of mothers with gestational diabetes had increased risk of ozone-associated ASD (1 study). Two genetic studies reported that copy number variations may amplify the effect of ozone, and MET rs1858830 CC genotype may augment effects of PM and near-roadway pollutants on ASD. CONCLUSIONS: Child's sex, maternal nutrition or diabetes, socioeconomic factors, and child risk genotypes were reported to modify the effect of early-life air pollutants on ASD risk in the epidemiologic literature. However, the sparsity of studies on comparable modifying hypotheses precludes conclusive findings. Further research is needed to identify susceptible populations and potential targets for preventive intervention.