The Cooking Energy and Ventilation Impacts on Children's Asthma (CEVICA) study is a randomized control trial investigating the effects of replacing gas with induction electric ranges in the homes of children with asthma in California's San Joaquin Valley. Indoor air quality parameters and respiratory health indicators were measured over 2-week intensive at Baseline and after consecutive 3-month study phases, with half getting electric cooking at the start of Phase 1 and others in Phase 2. Indoor air measurements included time-integrated NO2 and NOX by passive sampler and time-resolved NO2 by electrochemical sensors. In the first 40 homes, data were collected during 61 intensives for gas cooking and 55 for induction. Cooking was identified using temperature sensors above the cooktop. Pollutant events were identified from sharp rises in concentrations Time integrated NOX species were lower with electric cooking, with mean differences of 14.2 ppb for NO2 (95% CI: 9.6, 18.7; p < 0.001), 55.6 ppb for NOX (95% CI: 30.4, 80.9; p < 0.001), and 41.5 ppb for derived NO (95% CI: 19.7, 63.2; p < 0.001). A paired, within home analysis showed larger reductions in Group 2 (gas to induction) than Group 1 that remained electric across Phase 1 and Phase 2 for NO2 (mean difference in As of 10.5 ppb; 95% CI: 5.6, 15.4; p < 0.001), NOX (32.3 ppb; 95% CI: 10.0, 54.5; p=0.007), and derived NO (21.8 ppb; 95% CI: 3.6, 40.0; p=0.022). Compared to electric cooking, gas had much higher rates of associated NO2 events, and larger above-baseline NO2 peaks. These preliminary results are consistent with prior findings that shifting to induction cooking can substantially lower indoor NO2 compared with gas cooking.

Air pollution has been linked to impaired cognitive outcomes and lower academic performance in children. The Children's Health and Air Pollution Study (CHAPS) is a longitudinal cohort study following children who live in the Fresno metropolitan area of California, where air pollution is notoriously high. In this study, we investigated the relationship between estimated concentrations of three high-priority air pollutants (PM2.5, NO2, and O3) at the home and school and multiple years of standardized test scores from children in the CHAPS cohort. We analyzed data from 97 children between ages 8 to 13 who had reported at least three years of standardized testing between 2015 and 2022. To model the relationship between pollution and testing performance over multiple time points, we ran six mixed effects linear regression models differentiated by pollutant (PM2.5, NO2, and O3), and standardized tests (English Language Arts or math). Math standardized test scores were negatively associated with O3 and PM2.5, but not NO2. A one part per billion (ppb) increase in O3 was associated with a -0.078 (95% CI: -0.145 to -0.010) standard deviation decrease in test scores and a 1 μg per meter cubed (μg/m3) increase in PM2.5 was associated with a -0.074 standard deviation decrease in test score (95% CI: -0.120 to -0.032). There was a weak negative association between English Language Arts and both O3 and PM2.5, however, the confidence intervals for these associations overlapped the null. The association between O3 and math scores was eliminated after adjusting for PM2.5, and may have resulted from collinearity between O3 and PM2.5 rather than a unique association between O3 and math scores. This association between air pollutant exposure at home and school and student standardized test scores emphasizes the possible neurocognitive impact of air pollution on a measure available for nearly all California children.

BACKGROUND:Ambient air pollutants such as particulate matter (PM), ozone (O3), and nitrogen dioxide (NO2) have been associated with lower lung function among children. However, the reported associations could be due to correlation with other pollutants. OBJECTIVE:We investigate the relationships between exposures to eight ambient air pollutants and children's lung function and apply mixture analysis to identify key contributors to health effects. METHODS:The Children's Health and Air Pollution Study (CHAPS) in Fresno, California, is a prospective cohort study that recruited 299 children and assessed their lung function at two visits, at approximately 7 and 9 years of age. The children's forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio were standardized using the Global Lung Function Initiative (GLI) race-neutral calculators. We assessed the children's average daily residential exposures to PM2.5, PM10, nitrogen oxides (NOx), NO2, O3, carbon monoxide (CO), elemental carbon (EC), and polycyclic aromatic hydrocarbons (PAHs), during the 1-week, 1-month, 3-month, 6-month, and 12-month periods before each visit, and the 2 years between visits. We applied linear mixed-effect models and quantile-based g-computation (q-gcomp) for statistical analysis. RESULTS:The children's exposures to the eight ambient air pollutants exhibited high intercorrelation: Seven air pollutants were positively correlated, while O3 exposures were negatively correlated with the other pollutants. Higher PM10 was associated with lower FEV1 and FEV1/FVC ratio, and the associations were strongest for the 3-month exposure timeframe. Q-gcomp also identified PM10 as the key pollutant associated with lower FEV1 and FEV1/FVC ratio. CONCLUSION:Among the eight ambient air pollutants, PM10 was the strongest risk factor for impaired lung function among children in Fresno. Ambient air pollution levels in this community exceed regulatory standards and are harmful to children's lung function.

Background: The natural distributions of ambient air pollutants are often correlated. Existing studies have found that exposures to various air pollutants are associated with elevated risks of asthma symptoms among children. However, most studies applied single-pollutant models, which cannot distinguish between causal effects and associations due to correlations with other measured or unmeasured pollutants. Objective: We sought to investigate air pollutant mixtures and child asthma symptoms and identify key risk factors. Methods: The Children’s Health and Air Pollution Study recruited 299 children in Fresno, California, 63 of whom had ever-diagnosed asthma. We assessed the children’s prior 12-month exposures to 8 ambient air pollutants, namely, particulate matter with aerodynamic diameter of 2.5 μm, particulate matter with aerodynamic diameter of 10 μm, nitrogen oxides, nitrogen dioxide, ozone, carbon monoxide, elemental carbon, and polycyclic aromatic hydrocarbons, and asthmatic symptoms (wheeze and cough) at 2 visits, at age approximately 7 and 9 years. We conducted repeated-measures analysis with mixture analysis methods, including principal-component analysis and quantile-based g-computation (q-gcomp). Results: The 8 air pollutants exhibited strong intercorrelation. In single-pollutant models, exposure to ozone was associated with higher risk of cough (odds ratio, 1.39; 95% CI, 1.06-1.82). Using principal-component analysis and q-gcomp, exposures to nitrogen oxides, elemental carbon, and ozone had relatively high contributions to cough and wheeze. The association between ozone and cough was consistently positive from single-pollutant models, double-pollutant models, principal-component analysis, and quantile-based g-computation with negative control. Conclusion: Ozone stands out among the 8 air pollutants and may be a driving risk factor for persistent cough among children with asthma.

BACKGROUND:Evidence in the literature suggests that air pollution exposures experienced prenatally and early in life can be detrimental to normal lung development, however the specific timing of critical windows during development is not fully understood. OBJECTIVES:We evaluated air pollution exposures during the prenatal and early-life period in association with lung function at ages 6-9, in an effort to identify potentially influential windows of exposure for lung development. METHODS:Our study population consisted of 222 children aged 6-9 from the Fresno-Clovis metro area in California with spirometry data collected between May 2015 and May 2017. We used distributed-lag non-linear models to flexibly model the exposure-lag-response for monthly average exposure to fine particulate matter (PM2.5) and ozone (O3) during the prenatal months and first three years of life in association with forced vital capacity (FVC), and forced expiratory volume in the first second (FEV1), adjusted for covariates. RESULTS:PM2.5 exposure during the prenatal period and the first 3-years of life was associated with lower FVC and FEV1 assessed at ages 6-9. Specifically, an increase from the 5th percentile of the observed monthly average exposure (7.55 μg/m3) to the median observed exposure (12.69 μg/m3) for the duration of the window was associated with 0.42 L lower FVC (95% confidence interval (CI): -0.82, -0.03) and 0.38 L lower FEV1 (95% CI: -0.75, -0.02). The shape of the lag-response indicated that the second half of pregnancy may be a particularly influential window of exposure. Associations for ozone were not as strong and typically CIs included the null. CONCLUSIONS:Our findings indicate that prenatal and early-life exposures to PM2.5 are associated with decreased lung function later in childhood. Exposures during the latter months of pregnancy may be especially influential.

Background Ambient air pollutant (AAP) exposure is associated with adverse pregnancy outcomes, such as preeclampsia, preterm labor, and low birth weight. Previous studies have shown methylation of immune genes associate with exposure to air pollutants in pregnant women, but the cell-mediated response in the context of typical pregnancy cell alterations has not been investigated. Pregnancy causes attenuation in cell-mediated immunity with alterations in the Th1/Th2/Th17/Treg environment, contributing to maternal susceptibility. We recruited women ( n = 186) who were 20 weeks pregnant from Fresno, CA, an area with chronically elevated AAP levels. Associations of average pollution concentration estimates for 1 week, 1 month, 3 months, and 6 months prior to blood draw were associated with Th cell subset (Th1, Th2, Th17, and Treg) percentages and methylation of CpG sites ( IL4 , IL10, IFNγ, and FoxP3 ). Linear regression models were adjusted for weight, age, season, race, and asthma, using a Q value as the false-discovery-rate-adjusted p -value across all genes. Results Short-term and mid-term AAP exposures to fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ) carbon monoxide (CO), and polycyclic aromatic hydrocarbons (PAH 456 ) were associated with percentages of immune cells. A decrease in Th1 cell percentage was negatively associated with PM 2.5 (1 mo/3 mo: Q < 0.05), NO 2 (1 mo/3 mo/6 mo: Q < 0.05), and PAH 456 (1 week/1 mo/3 mo: Q < 0.05). Th2 cell percentages were negatively associated with PM 2.5 (1 week/1 mo/3 mo/6 mo: Q < 0.06), and NO 2 (1 week/1 mo/3 mo/6 mo: Q < 0.06). Th17 cell percentage was negatively associated with NO 2 (3 mo/6 mo: Q < 0.01), CO (1 week/1 mo: Q < 0.1), PM 2.5 (3 mo/6 mo: Q < 0.05), and PAH 456 (1 mo/3 mo/6 mo: Q < 0.08). Methylation of the IL10 gene was positively associated with CO (1 week/1 mo/3 mo: Q < 0.01), NO 2 (1 mo/3 mo/6 mo: Q < 0.08), PAH 456 (1 week/1 mo/3 mo: Q < 0.01), and PM 2.5 (3 mo: Q = 0.06) while IL4 gene methylation was positively associated with concentrations of CO (1 week/1 mo/3 mo/6 mo: Q < 0.09). Also, IFNγ gene methylation was positively associated with CO (1 week/1 mo/3 mo: Q < 0.05) and PAH 456 (1 week/1 mo/3 mo: Q < 0.06). Conclusion Exposure to several AAPs was negatively associated with T-helper subsets involved in pro-inflammatory and anti-inflammatory responses during pregnancy. Methylation of IL4, IL10 , and IFNγ genes with pollution exposure confirms previous research. These results offer insights into the detrimental effects of air pollution during pregnancy, the demand for more epigenetic studies, and mitigation strategies to decrease pollution exposure during pregnancy.

BACKGROUND:Metabolic syndrome increases the risk of cardiovascular disease in adults. Antecedents likely begin in childhood and whether childhood exposure to air pollution plays a contributory role is not well understood. OBJECTIVES:To assess whether children's exposure to air pollution is associated with markers of risk for metabolic syndrome and oxidative stress, a hypothesized mediator of air pollution-related health effects. METHODS:We studied 299 children (ages 6-8) living in the Fresno, CA area. At a study center visit, questionnaire and biomarker data were collected. Outcomes included hemoglobin A1c (HbA1c), urinary 8-isoprostane, systolic blood pressure (SBP), and BMI. Individual-level exposure estimates for a set of four pollutants that are constituents of traffic-related air pollution (TRAP) - the sum of 4-, 5-, and 6-ring polycyclic aromatic hydrocarbon compounds (PAH456), NO2, elemental carbon, and fine particulate matter (PM2.5) - were modeled at the primary residential location for 1-day lag, and 1-week, 1-month, 3-month, 6-month, and 1-year averages prior to each participant's visit date. Generalized additive models were used to estimate associations between each air pollutant exposure and outcome. RESULTS:The study population was 53% male, 80% Latinx, 11% Black and largely low-income (6% were White and 3% were Asian/Pacific Islander). HbA1c percentage was associated with longer-term increases in TRAP; for example a 4.42 ng/m3 increase in 6-month average PAH456 was associated with a 0.07% increase (95% CI: 0.01, 0.14) and a 3.62 μg/m3 increase in 6-month average PM2.5 was associated with a 0.06% increase (95% CI: 0.01, 0.10). The influence of air pollutants on blood pressure was strongest at 3 months; for example, a 6.2 ppb increase in 3-month average NO2 was associated with a 9.4 mmHg increase in SBP (95% CI: 2.8, 15.9). TRAP concentrations were not significantly associated with anthropometric or adipokine measures. Short-term TRAP exposure averages were significantly associated with creatinine-adjusted urinary 8-isoprostane. DISCUSSION:Our results suggest that both short- and longer-term estimated individual-level outdoor residential exposures to several traffic-related air pollutants, including ambient PAHs, are associated with biomarkers of risk for metabolic syndrome and oxidative stress in children.

BACKGROUND:Previous research has revealed links between air pollution exposure and metabolic syndrome in adults; however, these associations are less explored in children. OBJECTIVE:This study aims to investigate the association between traffic-related air pollutants (TRAP) and biomarkers of metabolic dysregulation, oxidative stress, and lung epithelial damage in children. METHODS:We conducted cross-sectional analyses in a sample of predominantly Latinx, low-income children (n = 218) to examine associations between air pollutants (nitrogen dioxide (NO2), nitrogen oxides (NOx), elemental carbon, polycyclic aromatic hydrocarbons, carbon monoxide (CO), fine particulates (PM2.5)) and biomarkers of metabolic function (high-density lipoprotein (HDL), hemoglobin A1c (HbA1c), oxidative stress (8-isoprostane), and lung epithelial damage (club cell protein 16 (CC16)). RESULTS:HDL cholesterol showed an inverse association with NO2 and NOx, with the strongest relationship between HDL and 3-month exposure to NO2 (-15.4 mg/dL per IQR increase in 3-month NO2, 95% CI = -27.4, -3.4). 8-isoprostane showed a consistent pattern of increasing values with 1-day and 1-week exposure across all pollutants. Non-significant increases in % HbA1c were found during 1-month time frames and decreasing CC16 in 3-month exposure time frames. CONCLUSION:Our results suggest that TRAP is significantly associated with decreased HDL cholesterol in longer-term time frames and elevated 8-isoprostane in shorter-term time frames. TRAP could have the potential to influence lifelong metabolic patterns, through metabolic effects in childhood.

Particulate matter (PM) varies in chemical composition and mass concentration based on location, source, and particle size. This study sought to evaluate the in vitro and in vivo toxicity of coarse (PM10-2.5) and fine (PM25) PM samples collected at 5 diverse sites within California. Coarse and fine PM samples were collected simultaneously at 2 rural and 3 urban sites within California during the summer. A human pulmonary microvascular endothelial cell line (HPMEC-ST1.6R) was exposed to PM suspensions (50 μg/mL) and analyzed for reactive oxygen species (ROS) after 5 hours of treatment. In addition, FVB/N mice were exposed by oropharyngeal aspiration to 50 μg PM, and lavage fluid was collected 24 hrs post-exposure and analyzed for total protein and %PMNs. Correlations between trace metal concentrations, endotoxin, and biological endpoints were calculated, and the effect of particle size range, locale (urban vs. rural), and location was determined. Absolute principal factor analysis was used to identify pollution sources of PM from elemental tracers of those sources. Ambient PM elicited an ROS and pro-inflammatory-related response in the cell and mouse models, respectively. These responses were dependent on particle size, locale, and location. Trace elements associated with soil and traffic markers were most strongly linked to the adverse effects in vitro and in vivo. Particle size, location, source, and composition of PM collected at 5 locations in California affected the ROS response in human pulmonary endothelial cells and the inflammatory response in mice.

Background Reactive oxygen species (ROS) have been shown to be important in wound healing by promoting angiogenesis (also mentioned by Ushio-Fukai and Nakamura). Likewise ROS have been implicated by toxicological studies as a primary mechanism of air pollution-associated morbidity. We sought to determine how exposure to a reactive diesel exhaust chemical (phenanthrenequinone [PQ]), which promotes formation of ROS and is considered an air pollutant, would affect wound healing. Since wound healing is compromised in diabetic (db) individuals, we examined the effects of PQ on wound healing in a db mouse model. Methods db mice consumed PQ-containing chow for a short period (2 weeks) before wounding and through generations. Wound closure rates and wound vascularization were evaluated 10 days after wounding. The effects of PQ on endothelial cell proliferation and ROS generation in vitro were also measured. Results db mice exposed to short-term PQ and PQ-exposed first-generation db mice demonstrated the highest closure rates, significantly better than control db mice (P < 0.05). Furthermore, a higher concentration of PQ in sera of db mice coincides with the higher rate of closure. PQ was also shown to produce ROS in cell culture and stimulate endothelial cell proliferation at nanomolar concentrations. Second- and third-generation db mice exposed to PQ did not show improved wound healing. Conclusions This study suggests that the free radical-generating air pollutant PQ enhances wound closure in the db mouse model possibly by stimulating angiogenesis, as suggested by in vitro results. We speculate that PQ may increase oxidation levels systemically and therefore help modulate inflammation at the wound site. Alternatively, antioxidant mechanisms recruited for wound healing may interfere with PQ metabolism and elimination as it accumulates in sera. Generational resistance to improve wound healing in PQ-exposed db mice could also be due to disturbances in metabolism caused by continuous exposure. In either case, these results introduce a new perspective on the effects of air pollution on wound healing.