Irregular Cycles, Ovulatory Disorders, and Cardiometabolic Conditions in a US-Based Digital Cohort.

Importance: Polycystic ovary syndrome (PCOS), characterized by irregular menstrual cycles and hyperandrogenism, is a common ovulatory disorder. Having an irregular cycle is a potential marker for cardiometabolic conditions, but data are limited on whether the associations differ by PCOS status or potential interventions. Objective: To evaluate the association of PCOS, time to regularity since menarche (adolescence), and irregular cycles (adulthood) with cardiometabolic conditions. Design, Setting, and Participants: This cross-sectional study used a large, US-based digital cohort of users of the Apple Research application on their iPhone. Eligibility criteria were having ever menstruated, living in the US, being at age of consent of at least 18 years (or 19 years in Alabama and Nebraska or 21 years in Puerto Rico), and being able to communicate in English. Participants were enrolled between November 14, 2019, and December 13, 2022, and completed relevant surveys. Exposures: Self-reported PCOS diagnosis, prolonged time to regularity (not spontaneously establishing regularity within 5 years of menarche), and irregular cycles. Main Outcomes and Measures: The primary outcome was self-reported cardiometabolic conditions, including obesity, prediabetes, type 1 and 2 diabetes, high cholesterol, hypertension, metabolic syndrome, arrhythmia, congestive heart failure, coronary artery disease, heart attack, heart valve disease, stroke, transient ischemic attack (TIA), deep vein thrombosis, and pulmonary embolism measured using descriptive statistics and logistic regression to estimate prevalence odds ratios (PORs) and 95% CIs. Effect modification by lifestyle factors was also estimated. Results: The study sample (N = 60 789) had a mean (SD) age of 34.5 (11.1) years, with 12.3% having PCOS and 26.3% having prolonged time to regularity. Among a subset of 25 399 participants who completed the hormonal symptoms survey, 25.6% reported irregular cycles. In covariate-adjusted logistic regression models, PCOS was associated with a higher prevalence of all metabolic and several cardiovascular conditions, eg, arrhythmia (POR, 1.37; 95% CI, 1.20-1.55), coronary artery disease (POR, 2.92; 95% CI, 1.95-4.29), heart attack (POR, 1.79; 95% CI, 1.23-2.54), and stroke (POR, 1.66; 95% CI, 1.21-2.24). Among participants without PCOS, prolonged time to regularity was associated with type 2 diabetes (POR, 1.24; 95% CI, 1.05-1.46), hypertension (POR, 1.09; 95% CI, 1.01-1.19), arrhythmia (POR, 1.20; 95% CI, 1.06-1.35), and TIA (POR, 1.33; 95% CI, 1.01-1.73), and having irregular cycles was associated with type 2 diabetes (POR, 1.36; 95% CI, 1.08-1.69), high cholesterol (POR, 1.17; 95% CI, 1.05-1.30), arrhythmia (POR, 1.21; 95% CI, 1.02-1.43), and TIA (POR, 1.56; 95% CI, 1.06-2.26). Some of these associations were modified by high vs low body mass index or low vs high physical activity. Conclusions and Relevance: These findings suggest that PCOS and irregular cycles may be independent markers for cardiometabolic conditions. Early screening and intervention among individuals with irregular menstrual cycles may be beneficial.

Benzophenone-3 and ovarian reserve.

OBJECTIVE: To evaluate the association between urinary benzophenone-3 concentrations and measures of ovarian reserve (OR) among women in the Environment and Reproductive Health (EARTH) Study seeking fertility treatment at Massachusetts General Hospital in Boston, Massachusetts. DESIGN: Prospective cohort study. METHODS: Women from the EARTH cohort contributed spot urine samples before assessment of OR outcomes. Antral follicle count (AFC) and day-3 follicle stimulating hormone (FSH) levels were evaluated as part of standard infertility workups during unstimulated menstrual cycles. Quasi-Poisson and linear regression models were used to evaluate the association of specific gravity (SG)-adjusted urinary benzophenone-3 concentrations with AFC and FSH, respectively, with adjustment for age and physical activity. In secondary analyses, models were stratified by age. Sensitivity analyses assessed for confounding by season by restricting to women with exposure and outcome measured in the same season and stratifying by summer vs. non-summer months and for confounding by sunscreen use by restricting to women who filled out product questionnaires and adjusting for and stratifying by average sunscreen use score. RESULTS: The study included 142 women (mean age ± SD, 36.1 ± 4.6; range, 22-45 years) enrolled between 2009 and 2017 with both urinary benzophenone-3 and AFC and 57 women with benzophenone-3 and FSH measurements. Most women were white (78%) and highly educated (49% with a graduate degree). Women contributed a mean of 2.7 urine samples (range, 1-10) with 37% contributing 2 or more samples. Benzophenone-3 was detected in 98% of samples. Geometric mean (GM) SG-corrected urinary benzophenone-3 concentration was 85.9 µ g/L (geometric standard deviation 6.2). There were no associations of benzophenone-3 with AFC and day-3 FSH in the full cohort. In stratified models, a 1-unit increase in log GM benzophenone-3 was associated with AFC 0.91 (95% CI, 0.86, 0.97) times lower among women ≤35 years old and was associated with FSH 0.73 (95% CI, 0.12, 1.34) IU/L higher among women >35 years old. Effect estimates from models stratified by season and sunscreen use were null. CONCLUSION: In main models, urinary benzophenone-3 was not associated with OR. However, younger may be vulnerable to potential effects of benzophenone-3 on AFC. Further research is warranted.

Non-persistent endocrine disrupting chemical mixtures and uterine leiomyomata in the study of environment, lifestyle and fibroids (SELF).

BACKGROUND: Results of studies investigating associations between individual endocrine-disrupting chemicals (EDCs) and incidence of uterine leiomyomata (UL), a hormone-dependent gynecological condition, have been inconsistent. However, few studies have evaluated simultaneous exposure to a mixture of EDCs with UL incidence. METHODS: We conducted a case-cohort analysis (n = 708) of data from the Study of the Environment, Lifestyle and Fibroids (SELF), a prospective cohort study. Participants were aged 23-35 years at enrollment, had an intact uterus, and identified as Black or African American. We measured biomarker concentrations of 21 non-persistent EDCs, including phthalates, phenols, parabens, and triclocarban, in urine collected at baseline, 20-month, and 40-month clinic visits. We ascertained UL incidence and characteristics using ultrasounds at baseline and approximately every 20 months through 60 months. We used probit Bayesian Kernel Machine Regression (BKMR-P) to evaluate joint associations between EDC mixtures with cumulative UL incidence. We estimated the mean difference in the probit of UL incidence over the study period, adjusting for baseline age, education, years since last birth, parity, smoking status and body mass index. We converted probit estimates to odds ratios for ease of interpretation. RESULTS: We observed that urinary concentrations of the overall EDC mixture were inversely associated with UL incidence in the overall mixtures model, with the strongest inverse associations at the 70th percentile of all biomarkers compared with their 50th percentile (odds ratio = 0.59; 95% confidence interval: 0.36, 0.96). Strongest contributors to the joint association for the mixture were bisphenol S (BPS), ethyl paraben (EPB), bisphenol F (BPF) and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), which each demonstrated inverse associations except for MECPP. There was suggestive evidence of an interaction between MECPP and EPB. CONCLUSION: In this prospective ultrasound study, we observed evidence of an inverse association between the overall mixture of urinary biomarker concentrations of non-persistent EDCs with UL incidence.

Grouped mixtures of air pollutants and seasonal temperature anomalies and cardiovascular hospitalizations among U.S. Residents.

BACKGROUND: Air pollution is a recognized risk factor for cardiovascular disease (CVD). Temperature is also linked to CVD, with a primary focus on acute effects. Despite the close relationship between air pollution and temperature, their health effects are often examined separately, potentially overlooking their synergistic effects. Moreover, fewer studies have performed mixture analysis for multiple co-exposures, essential for adjusting confounding effects among them and assessing both cumulative and individual effects. METHODS: We obtained hospitalization records for residents of 14 U.S. states, spanning 2000-2016, from the Health Cost and Utilization Project State Inpatient Databases. We used a grouped weighted quantile sum regression, a novel approach for mixture analysis, to simultaneously evaluate cumulative and individual associations of annual exposures to four grouped mixtures: air pollutants (elemental carbon, ammonium, nitrate, organic carbon, sulfate, nitrogen dioxide, ozone), differences between summer and winter temperature means and their long-term averages during the entire study period (i.e., summer and winter temperature mean anomalies), differences between summer and winter temperature standard deviations (SD) and their long-term averages during the entire study period (i.e., summer and winter temperature SD anomalies), and interaction terms between air pollutants and summer and winter temperature mean anomalies. The outcomes are hospitalization rates for four prevalent CVD subtypes: ischemic heart disease, cerebrovascular disease, heart failure, and arrhythmia. RESULTS: Chronic exposure to air pollutant mixtures was associated with increased hospitalization rates for all CVD subtypes, with heart failure being the most susceptible subtype. Sulfate, nitrate, nitrogen dioxide, and organic carbon posed the highest risks. Mixtures of the interaction terms between air pollutants and temperature mean anomalies were associated with increased hospitalization rates for all CVD subtypes. CONCLUSIONS: Our findings identified critical pollutants for targeted emission controls and suggested that abnormal temperature changes chronically affected cardiovascular health by interacting with air pollution, not directly.

Associations between solar and geomagnetic activity and cognitive function in the Normative Aging study.

BACKGROUND: Studies show that changes in solar and geomagnetic activity (SGA) influence melatonin secretion and the autonomic nervous system. We evaluated associations between solar and geomagnetic activity and cognitive function in the Normative Aging Study from 1992 to 2013. METHODS: We used logistic and linear generalized estimating equations and regressions to evaluate the associations between moving averages of sunspot number (SSN) and Kp index (a measure of geomagnetic activity) and a binary measure for Mini-Mental State Examination (MMSE) scores (≤25 or > 25) and six other cognitive tests as continuous measures, combined into one global composite score and considered separately. RESULTS: A one-IQR increase in same-day SSN and Kp index were associated with 17% (95% CI: 3%, 34%) and 19% (95% CI: 4%, 36%) increases in the odds of low MMSE score. We observed small increases in the global cognitive score with increasing SSN, although we observed decreases specifically in relation to the backwards digit span test. CONCLUSIONS: Periods of high SGA were associated with cognitive function. SGA may not equally impact all aspects of cognitive function, as evidenced by differences in associations observed for the MMSE, global cognitive score, and individual cognitive tests. Given that much of the pathology of cognitive decline in the elderly remains unexplained, studies specifically targeting decline and with longer follow-up periods are warranted.

Indoor and ambient black carbon and fine particulate matter associations with blood biomarkers in COPD patients.

BACKGROUND: Systemic inflammation contributes to cardiovascular risk and chronic obstructive pulmonary disease (COPD) pathophysiology. Associations between systemic inflammation and exposure to ambient fine particulate matter (PM ≤ 2.5 µm diameter; PM2.5), and black carbon (BC), a PM2.5 component attributable to traffic and other sources of combustion, infiltrating indoors are not well described. METHODS: Between 2012 and 2017, COPD patients completed in-home air sampling over one-week intervals, up to four times (seasonally), followed by measurement of plasma biomarkers of systemic inflammation, C-reactive protein (CRP) and interleukin-6 (IL-6), and endothelial activation, soluble vascular adhesion molecule-1 (sVCAM-1). Ambient PM2.5, BC and sulfur were measured at a central site. The ratio of indoor/ambient sulfur in PM2.5, a surrogate for fine particle infiltration, was used to estimate indoor BC and PM2.5 of ambient origin. Linear mixed effects regression with a random intercept for each participant was used to assess associations between indoor and indoor of ambient origin PM2.5 and BC with each biomarker. RESULTS: 144 participants resulting in 482 observations were included in the analysis. There were significant positive associations between indoor BC and indoor BC of ambient origin with CRP [%-increase per interquartile range (IQR);95 % CI (13.2 %;5.2-21.8 and 11.4 %;1.7-22.1, respectively)]. Associations with indoor PM2.5 and indoor PM2.5 of ambient origin were weaker. There were no associations with IL-6 or sVCAM-1. CONCLUSIONS: In homes of patients with COPD without major sources of combustion, indoor BC is mainly attributable to the infiltration of ambient sources of combustion indoors. Indoor BC of ambient origin is associated with increases in systemic inflammation in patients with COPD, even when staying indoors.

Birth outcomes in relation to neighborhood food access and individual food insecurity during pregnancy in the Environmental Influences on Child Health Outcomes (ECHO)-wide cohort study.

BACKGROUND: Limited access to healthy foods, resulting from residence in neighborhoods with low-food access or from household food insecurity, is a public health concern. Contributions of these measures during pregnancy to birth outcomes remain understudied. OBJECTIVES: We examined associations between neighborhood food access and individual food insecurity during pregnancy with birth outcomes. METHODS: We used data from 53 cohorts participating in the nationwide Environmental Influences on Child Health Outcomes-Wide Cohort Study. Participant inclusion required a geocoded residential address or response to a food insecurity question during pregnancy and information on birth outcomes. Exposures include low-income-low-food-access (LILA, where the nearest supermarket is >0.5 miles for urban or >10 miles for rural areas) or low-income-low-vehicle-access (LILV, where few households have a vehicle and >0.5 miles from the nearest supermarket) neighborhoods and individual food insecurity. Mixed-effects models estimated associations with birth outcomes, adjusting for socioeconomic and pregnancy characteristics. RESULTS: Among 22,206 pregnant participants (mean age 30.4 y) with neighborhood food access data, 24.1% resided in LILA neighborhoods and 13.6% in LILV neighborhoods. Of 1630 pregnant participants with individual-level food insecurity data (mean age 29.7 y), 8.0% experienced food insecurity. Residence in LILA (compared with non-LILA) neighborhoods was associated with lower birth weight [ß -44.3 g; 95% confidence interval (CI): -62.9, -25.6], lower birth weight-for-gestational-age z-score (-0.09 SD units; -0.12, -0.05), higher odds of small-for-gestational-age [odds ratio (OR) 1.15; 95% CI: 1.00, 1.33], and lower odds of large-for-gestational-age (0.85; 95% CI: 0.77, 0.94). Similar findings were observed for residence in LILV neighborhoods. No associations of individual food insecurity with birth outcomes were observed. CONCLUSIONS: Residence in LILA or LILV neighborhoods during pregnancy is associated with adverse birth outcomes. These findings highlight the need for future studies examining whether investing in neighborhood resources to improve food access during pregnancy would promote equitable birth outcomes.

Early-Life Exposure to Air Pollution and Childhood Asthma Cumulative Incidence in the ECHO CREW Consortium.

Importance: Exposure to outdoor air pollution contributes to childhood asthma development, but many studies lack the geographic, racial and ethnic, and socioeconomic diversity to evaluate susceptibility by individual-level and community-level contextual factors. Objective: To examine early life exposure to fine particulate matter (PM2.5) and nitrogen oxide (NO2) air pollution and asthma risk by early and middle childhood, and whether individual and community-level characteristics modify associations between air pollution exposure and asthma. Design, Setting, and Participants: This cohort study included children enrolled in cohorts participating in the Children's Respiratory and Environmental Workgroup consortium. The birth cohorts were located throughout the US, recruited between 1987 and 2007, and followed up through age 11 years. The survival analysis was adjusted for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, neighborhood characteristics, and cohort. Statistical analysis was performed from February 2022 to December 2023. Exposure: Early-life exposures to PM2.5 and NO2 according to participants' birth address. Main Outcomes and Measures: Caregiver report of physician-diagnosed asthma through early (age 4 years) and middle (age 11 years) childhood. Results: Among 5279 children included, 1659 (31.4%) were Black, 835 (15.8%) were Hispanic, 2555 (48.4%) where White, and 229 (4.3%) were other race or ethnicity; 2721 (51.5%) were male and 2596 (49.2%) were female; 1305 children (24.7%) had asthma by 11 years of age and 954 (18.1%) had asthma by 4 years of age. Mean values of pollutants over the first 3 years of life were associated with asthma incidence. A 1 IQR increase in NO2 (6.1 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.25 [95% CI, 1.03-1.52]) and children younger than 11 years (HR, 1.22 [95% CI, 1.04-1.44]). A 1 IQR increase in PM2.5 (3.4 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.31 [95% CI, 1.04-1.66]) and children younger than 11 years (OR, 1.23 [95% CI, 1.01-1.50]). Associations of PM2.5 or NO2 with asthma were increased when mothers had less than a high school diploma, among Black children, in communities with fewer child opportunities, and in census tracts with higher percentage Black population and population density; for example, there was a significantly higher association between PM2.5 and asthma incidence by younger than 5 years of age in Black children (HR, 1.60 [95% CI, 1.15-2.22]) compared with White children (HR, 1.17 [95% CI, 0.90-1.52]). Conclusions and Relevance: In this cohort study, early life air pollution was associated with increased asthma incidence by early and middle childhood, with higher risk among minoritized families living in urban communities characterized by fewer opportunities and resources and multiple environmental coexposures. Reducing asthma risk in the US requires air pollution regulation and reduction combined with greater environmental, educational, and health equity at the community level.

Sensitive development windows of prenatal air pollution and cognitive functioning in preschool age Mexican children.

Introduction: Neurotoxicity resulting from air pollution is of increasing concern. Considering exposure timing effects on neurodevelopmental impairments may be as important as the exposure dose. We used distributed lag regression to determine the sensitive windows of prenatal exposure to fine particulate matter (PM2.5) on children's cognition in a birth cohort in Mexico. Methods: Analysis included 553 full-term (≥37 weeks gestation) children. Prenatal daily PM2.5 exposure was estimated using a validated satellite-based spatiotemporal model. McCarthy Scales of Children's Abilities (MSCA) were used to assess children's cognitive function at 4-5 years old (lower scores indicate poorer performance). To identify susceptibility windows, we used Bayesian distributed lag interaction models to examine associations between prenatal PM2.5 levels and MSCA. This allowed us to estimate vulnerable windows while testing for effect modification. Results: After adjusting for maternal age, socioeconomic status, child age, and sex, Bayesian distributed lag interaction models showed significant associations between increased PM2.5 levels and decreased general cognitive index scores at 31-35 gestation weeks, decreased quantitative scale scores at 30-36 weeks, decreased motor scale scores at 30-36 weeks, and decreased verbal scale scores at 37-38 weeks. Estimated cumulative effects (CE) of PM2.5 across pregnancy showed significant associations with general cognitive index (CE^ = -0.35, 95% confidence interval [CI] = -0.68, -0.01), quantitative scale (CE^ = -0.27, 95% CI = -0.74, -0.02), motor scale (CE^ = -0.25, 95% CI = -0.44, -0.05), and verbal scale (CE^ = -0.2, 95% CI = -0.43, -0.02). No significant sex interactions were observed. Conclusions: Prenatal exposure to PM2.5, particularly late pregnancy, was inversely associated with subscales of MSCA. Using data-driven methods to identify sensitive window may provide insight into the mechanisms of neurodevelopmental impairment due to pollution.

Exposure-response associations between chronic exposure to fine particulate matter and risks of hospital admission for major cardiovascular diseases: population based cohort study.

OBJECTIVE: To estimate exposure-response associations between chronic exposure to fine particulate matter (PM2.5) and risks of the first hospital admission for major cardiovascular disease (CVD) subtypes. DESIGN: Population based cohort study. SETTING: Contiguous US. PARTICIPANTS: 59 761 494 Medicare fee-for-service beneficiaries aged ≥65 years during 2000-16. Calibrated PM2.5 predictions were linked to each participant's residential zip code as proxy exposure measurements. MAIN OUTCOME MEASURES: Risk of the first hospital admission during follow-up for ischemic heart disease, cerebrovascular disease, heart failure, cardiomyopathy, arrhythmia, valvular heart disease, thoracic and abdominal aortic aneurysms, or a composite of these CVD subtypes. A causal framework robust against confounding bias and bias arising from errors in exposure measurements was developed for exposure-response estimations. RESULTS: Three year average PM2.5 exposure was associated with increased relative risks of first hospital admissions for ischemic heart disease, cerebrovascular disease, heart failure, cardiomyopathy, arrhythmia, and thoracic and abdominal aortic aneurysms. For composite CVD, the exposure-response curve showed monotonically increased risk associated with PM2.5: compared with exposures ≤5 µg/m3 (the World Health Organization air quality guideline), the relative risk at exposures between 9 and 10 µg/m3, which encompassed the US national average of 9.7 µg/m3 during the study period, was 1.29 (95% confidence interval 1.28 to 1.30). On an absolute scale, the risk of hospital admission for composite CVD increased from 2.59% with exposures ≤5 µg/m3 to 3.35% at exposures between 9 and 10 µg/m3. The effects persisted for at least three years after exposure to PM2.5. Age, education, accessibility to healthcare, and neighborhood deprivation level appeared to modify susceptibility to PM2.5. CONCLUSIONS: The findings of this study suggest that no safe threshold exists for the chronic effect of PM2.5 on overall cardiovascular health. Substantial benefits could be attained through adherence to the WHO air quality guideline.

Association between prenatal and childhood PM2.5 exposure and preadolescent anxiety and depressive symptoms.

Background: Fine particulate matter (PM2.5) exposure has been linked to anxiety and depression in adults; however, there is limited research in the younger populations, in which symptoms often first arise. Methods: We examined the association between early-life PM2.5 exposure and symptoms of anxiety and depression in a cohort of 8-11-year-olds in Mexico City. Anxiety and depressive symptoms were assessed using the Spanish versions of the Revised Children's Manifest Anxiety Scale and Children's Depression Inventory. Daily PM2.5 was estimated using a satellite-based exposure model and averaged over several early and recent exposure windows. Linear and logistic regression models were used to estimate the change in symptoms with each 5-µg/m3 increase in PM2.5. Models were adjusted for child's age, child's sex, maternal age, maternal socioeconomic status, season of conception, and temperature. Results: Average anxiety and depressive symptom T-scores were 51.0 (range 33-73) and 53.4 (range 44-90), respectively. We observed consistent findings for exposures around the fourth year of life, as this was present for both continuous and dichotomized anxiety symptoms, in both independent exposure models and distributed lag modeling approaches. This window was also observed for elevated depressive symptoms. An additional consistent finding was for PM2.5 exposure during early pregnancy in relation to both clinically elevated anxiety and depressive symptoms, this was seen in both traditional and distributed lag modeling approaches. Conclusion: Both early life and recent PM2.5 exposure were associated with higher mental health symptoms in the child highlighting the role of PM2.5 in the etiology of these conditions.

Individual and joint effects of prenatal PM2.5 and maternal stress on child temperament.

Prenatal fine particulate matter (PM2.5) and maternal psychological functioning have been associated with child cognitive outcomes, though their independent and joint impacts on earlier behavioral outcomes remains less studied. We used data from 382 mother-child pairs from a prospective birth cohort in Mexico City. Temperament was measured at 24 months using the Carey Toddler Temperament Scale (TTS). Exploratory factor analysis (EFA) was used to update the factor structure of the TTS. During pregnancy, mothers completed the Crisis in Family Systems-Revised, Edinburgh Depression Scale, pregnancy-specific anxiety scale, and the Perceived Stress Scale. Pregnancy PM2.5 was assessed using estimates from a satellite-based exposure model. We assessed the association between prenatal maternal stress and PM2.5 on temperament, in both independent and joint models. Quantile g-computation was used to estimate the joint associations. Models were adjusted for maternal age, SES, education, child sex, and child age. In EFA, we identified three temperament factors related to effortful control, extraversion, and negative affect. Our main results showed that higher levels of PM2.5 and several of the maternal psychological functioning measures were related to both effortful control and negative affect in the child, both individually and as a mixture. For instance, a one quartile increase in the prenatal mixture was associated with higher negative affect scores in the child (0.34, 95% CI: 0.16, 0.53). We observed modification of these associations by maternal SES, with associations seen only among lower SES participants for both effortful control (-0.45, 95% CI: -0.70, -0.20) and negative affect outcomes (0.60, 95% CI: 0.35, 0.85). Prenatal PM2.5 and maternal psychological functioning measures were associated with toddler temperament outcomes, providing evidence for impacts of chemical and non-chemical stressors on early child health.

Protocol for the air purification for eosinophilic COPD study (APECS): a randomised controlled trial of home air filtration by HEPA.

INTRODUCTION: Exposure to particulate matter (PM) pollution has been associated with lower lung function in adults with chronic obstructive pulmonary disease (COPD). Patients with eosinophilic COPD have been found to have higher levels of airway inflammation, greater responsiveness to anti-inflammatory steroid inhalers and a greater lung function response to PM pollution exposure compared with those with lower eosinophil levels. This study will evaluate if reducing home PM exposure by high-efficiency particulate air (HEPA) air filtration improves respiratory health in eosinophilic COPD. METHODS AND ANALYSIS: The Air Purification for Eosinophilic COPD Study (APECS) is a double-blinded randomised placebo-controlled trial that will enrol 160 participants with eosinophilic COPD living in the area of Boston, Massachusetts. Real and sham air purifiers will be placed in the bedroom and living rooms of the participants in the intervention and control group, respectively, for 12 months. The primary trial outcome will be the change in forced expiratory volume in 1 s (FEV1). Lung function will be assessed twice preintervention and three times during the intervention phase (at 7 days, 6 months and 12 months postrandomisation). Secondary trial outcomes include changes in (1) health status by St. George's Respiratory Questionnaire; (2) respiratory symptoms by Breathlessness, Cough and Sputum Scale (BCSS); and (3) 6-Minute Walk Test (6MWT). Inflammatory mediators were measured in the nasal epithelial lining fluid (NELF). Indoor PM will be measured in the home for the week preceding each study visit. The data will be analysed to contrast changes in outcomes in the intervention and control groups using a repeated measures framework. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Review Board of Beth Israel Deaconess Medical Centre (protocol #2019P0001129). The results of the APECS trial will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION: NCT04252235. Version: October 2023.

Association between gestational exposure to solar activity and pregnancy loss using live births from a Massachusetts-based medical center.

BACKGROUND: Solar activity has been linked to biological mechanisms important to pregnancy, including folate and melatonin levels and inflammatory markers. Thus, we aimed to investigate the association between gestational solar activity and pregnancy loss. METHODS: Our study included 71,963 singleton births conceived in 2002-2016 and delivered at an academic medical center in Eastern Massachusetts. We studied several solar activity metrics, including sunspot number, Kp index, and ultraviolet radiation, with data from the NASA Goddard Space Flight Center and European Centre for Medium-Range Weather Forecasts. We used a novel time series analytic approach to investigate associations between each metric from conception through 24 weeks of gestation and the number of live birth-identified conceptions (LBICs) -the total number of conceptions in each week that result in a live birth. This approach fits distributed lag models to data on LBICs, adjusted for time trends, and allows us to infer associations between pregnancy exposure and pregnancy loss. RESULTS: Overall, the association between solar activity during pregnancy and pregnancy loss varied by exposure metric. For sunspot number, we found that an interquartile range increase in sunspot number (78·7 sunspots) in all of the first 24 weeks of pregnancy was associated with 14·0 (95% CI: 6·5, 21·3) more pregnancy losses out of the average 92 LBICs in a week, and exposure in weeks ten through thirteen was identified as a critical window. Although not statistically significant, higher exposure to Kp index and to UV radiation across all 24 weeks of pregnancy was associated with more and less pregnancy losses, respectively. CONCLUSION: While exposure to certain metrics of solar activity (i.e., sunspot number) throughout the first 24 weeks of pregnancy may be associated with pregnancy losses, exposure to other metrics were not. Solar activity is a complex phenomenon, and more studies are needed to clarify underlying pathways.

Prenatal exposure to air pollution and BWGA Z-score: Modifying effects of placenta leukocyte telomere length and infant sex.

BACKGROUND: Air pollutants, such as fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3), have been associated with adverse birth outcomes, including low birth weight, often exhibiting sex-specific effects. However, the modifying effect of placental telomere length (TL), reflecting cumulative lifetime oxidative stress in mothers, remains unexplored. METHOD: Using data from a Northeastern U.S. birth cohort (n = 306), we employed linear regression and weighted quantile sum models to assess trimester-average air pollution exposures and birth weight for gestational age (BWGA) z-scores. Placental TL, categorized by median split, was considered as an effect modifier. Interactions among air pollutants, placental TL, infant sex, and BWGA z-score were evaluated. RESULTS: Without placental TL as a modifier, only 1st trimester O3 was significantly associated with BWGA z-scores (coefficient: 0.33, 95% CI: 0.03, 0.63). In models considering TL interactions, a significant modifying effect was observed between 3rd trimester NO2 and BWGA z-scores (interaction p-value = 0.02). Specifically, a one interquartile range (1-IQR) increase in 3rd trimester NO2 was linked to a 0.28 (95% CI: 0.06, 0.52) change in BWGA z-score among shorter placental TL group, with no significant association among longer TL group. Among male infants, there were significant associations between 3rd trimester PM2.5 exposure and BWGA z-scores in the longer TL group (coefficient: -0.34, 95% CI: -0.61, -0.02), and between 1st trimester O3 exposure and BWGA z-scores among males in the shorter TL group (coefficient: 0.59, 95% CI: 0.06, 1.08). For females, only a negative association in 2nd trimester mixture model was observed within the longer TL group (coefficient: -0.10, 95% CI: -0.21, -0.01). CONCLUSION: These findings highlight the need to consider the complex interactions among prenatal air pollutant exposures, placental TL, and fetal sex to better elucidate those at greatest risk for adverse birth outcomes.

Radon decay product particle radioactivity and oxidative stress biomarkers in patients with COPD.

Radon decay products include α-radiation emitting radionuclides that attach to airborne particles that have potential to promote oxidative tissue damage after inhalation. To assess associations between α-particle radioactivity (α-PR) with urinary biomarkers of oxidative tissue damage, 140 patients with chronic obstructive pulmonary disease (COPD) had up to four 1-week seasonal assessments (N = 413) of indoor (home) and ambient (central site) PM2.5 and black carbon (BC). Following environmental sampling, urine samples were analyzed for total and free malondialdehyde (MDA), biomarkers of lipid oxidation, and 8-hydroxyl-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage. Particle radioactivity was measured as α-activity on PM2.5 filter samples. Linear mixed-effects regression models adjusted for urinary creatinine and other personal characteristics were used to assess associations. Indoor α-PR was associated with an increase in 8-OhdG (8.53%; 95% CI: 3.12, 14.23); total MDA (5.59%; 95% CI: 0.20, 11.71); and free MDA (2.17%; 95% CI: 2.75, 7.35) per interquartile range (IQR) of α-PR [median 1.25 mBq/m3; IQR 0.64], similar adjusting for PM2.5 or BC. The ratio of indoor/ambient α-PR was positively associated with each biomarker and associations with ambient α-PR were positive but weaker than with indoor concentrations. These findings are consistent with a contribution of radon decay products as measured by α-PR to oxidative stress in patients with COPD, with a greater contribution of indoor radon decay products.

An epigenome-wide analysis of DNA methylation, racialized and economic inequities, and air pollution.

Importance: DNA methylation (DNAm) provides a plausible mechanism by which adverse exposures become embodied and contribute to health inequities, due to its role in genome regulation and responsiveness to social and biophysical exposures tied to societal context. However, scant epigenome-wide association studies (EWAS) have included structural and lifecourse measures of exposure, especially in relation to structural discrimination. Objective: Our study tests the hypothesis that DNAm is a mechanism by which racial discrimination, economic adversity, and air pollution become biologically embodied. Design: A series of cross-sectional EWAS, conducted in My Body My Story (MBMS, biological specimens collected 2008-2010, DNAm assayed in 2021); and the Multi Ethnic Study of Atherosclerosis (MESA; biological specimens collected 2010-2012, DNAm assayed in 2012-2013); using new georeferenced social exposure data for both studies (generated in 2022). Setting: MBMS was recruited from four community health centers in Boston; MESA was recruited from four field sites in: Baltimore, MD; Forsyth County, NC; New York City, NY; and St. Paul, MN. Participants: Two population-based samples of US-born Black non-Hispanic (Black NH), white non-Hispanic (white NH), and Hispanic individuals (MBMS; n=224 Black NH and 69 white NH) and (MESA; n=229 Black NH, n=555 white NH and n=191 Hispanic). Exposures: Eight social exposures encompassing racial discrimination, economic adversity, and air pollution. Main outcome: Genome-wide changes in DNAm, as measured using the Illumina EPIC BeadChip (MBMS; using frozen blood spots) and Illumina 450k BeadChip (MESA; using purified monocytes). Our hypothesis was formulated after data collection. Results: We observed the strongest associations with traffic-related air pollution (measured via black carbon and nitrogen oxides exposure), with evidence from both studies suggesting that air pollution exposure may induce epigenetic changes related to inflammatory processes. We also found suggestive associations of DNAm variation with measures of structural racial discrimination (e.g., for Black NH participants, born in a Jim Crow state; adult exposure to racialized economic residential segregation) situated in genes with plausible links to effects on health. Conclusions and Relevance: Overall, this work suggests that DNAm is a biological mechanism through which structural racism and air pollution become embodied and may lead to health inequities.

On statistical inference with high-dimensional sparse CCA.

We consider asymptotically exact inference on the leading canonical correlation directions and strengths between two high-dimensional vectors under sparsity restrictions. In this regard, our main contribution is developing a novel representation of the Canonical Correlation Analysis problem, based on which one can operationalize a one-step bias correction on reasonable initial estimators. Our analytic results in this regard are adaptive over suitable structural restrictions of the high-dimensional nuisance parameters, which, in this set-up, correspond to the covariance matrices of the variables of interest. We further supplement the theoretical guarantees behind our procedures with extensive numerical studies.