Ambient air pollution and rate of spontaneous abortion.

Spontaneous abortion (SAB), defined as a pregnancy loss before 20 weeks of gestation, affects up to 30% of conceptions, yet few modifiable risk factors have been identified. We estimated the effect of ambient air pollution exposure on SAB incidence in Pregnancy Study Online (PRESTO), a preconception cohort study of North American couples who were trying to conceive. Participants completed questionnaires at baseline, every 8 weeks during preconception follow-up, and in early and late pregnancy. We analyzed data on 4643 United States (U.S.) participants and 851 Canadian participants who enrolled during 2013-2019 and conceived during 12 months of follow-up. We used country-specific national spatiotemporal models to estimate concentrations of particulate matter <2.5 µm (PM2.5), nitrogen dioxide (NO2), and ozone (O3) during the preconception and prenatal periods at each participant's residential address. On follow-up and pregnancy questionnaires, participants reported information on pregnancy status, including SAB incidence and timing. We fit Cox proportional hazards regression models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of time-varying prenatal concentrations of PM2.5, NO2, and O3 with rate of SAB, adjusting for individual- and neighborhood-level factors. Nineteen percent of pregnancies ended in SAB. Greater PM2.5 concentrations were associated with a higher incidence of SAB in Canada, but not in the U.S. (HRs for a 5 µg/m3 increase = 1.29, 95% CI: 0.99, 1.68 and 0.94, 95% CI: 0.83, 1.08, respectively). NO2 and O3 concentrations were not appreciably associated with SAB incidence. Results did not vary substantially by gestational weeks or season at risk. In summary, we found little evidence for an effect of residential ambient PM2.5, NO2, and O3 concentrations on SAB incidence in the U.S., but a moderate positive association of PM2.5 with SAB incidence in Canada.

Methylomic, Proteomic, and Metabolomic Correlates of Traffic-Related Air Pollution in the Context of Cardiorespiratory Health: A Systematic Review, Pathway Analysis, and Network Analysis.

A growing body of literature has attempted to characterize how traffic-related air pollution (TRAP) affects molecular and subclinical biological processes in ways that could lead to cardiorespiratory disease. To provide a streamlined synthesis of what is known about the multiple mechanisms through which TRAP could lead to cardiorespiratory pathology, we conducted a systematic review of the epidemiological literature relating TRAP exposure to methylomic, proteomic, and metabolomic biomarkers in adult populations. Using the 139 papers that met our inclusion criteria, we identified the omic biomarkers significantly associated with short- or long-term TRAP and used these biomarkers to conduct pathway and network analyses. We considered the evidence for TRAP-related associations with biological pathways involving lipid metabolism, cellular energy production, amino acid metabolism, inflammation and immunity, coagulation, endothelial function, and oxidative stress. Our analysis suggests that an integrated multi-omics approach may provide critical new insights into the ways TRAP could lead to adverse clinical outcomes. We advocate for efforts to build a more unified approach for characterizing the dynamic and complex biological processes linking TRAP exposure and subclinical and clinical disease and highlight contemporary challenges and opportunities associated with such efforts.

Methylomic, proteomic, and metabolomic correlates of traffic-related air pollution: A systematic review, pathway analysis, and network analysis relating traffic-related air pollution to subclinical and clinical cardiorespiratory outcomes.

A growing body of literature has attempted to characterize how traffic-related air pollution (TRAP) affects molecular and subclinical biological processes in ways that could lead to cardiorespiratory disease. To provide a streamlined synthesis of what is known about the multiple mechanisms through which TRAP could lead cardiorespiratory pathology, we conducted a systematic review of the epidemiological literature relating TRAP exposure to methylomic, proteomic, and metabolomic biomarkers in adult populations. Using the 139 papers that met our inclusion criteria, we identified the omic biomarkers significantly associated with short- or long-term TRAP and used these biomarkers to conduct pathway and network analyses. We considered the evidence for TRAP-related associations with biological pathways involving lipid metabolism, cellular energy production, amino acid metabolism, inflammation and immunity, coagulation, endothelial function, and oxidative stress. Our analysis suggests that an integrated multi-omics approach may provide critical new insights into the ways TRAP could lead to adverse clinical outcomes. We advocate for efforts to build a more unified approach for characterizing the dynamic and complex biological processes linking TRAP exposure and subclinical and clinical disease, and highlight contemporary challenges and opportunities associated with such efforts.

Air pollution and fecundability in a North American preconception cohort study.

BACKGROUND: Animal and epidemiologic studies indicate that air pollution may adversely affect fertility. However, the level of evidence is limited and specific pollutants driving the association are inconsistent across studies. METHODS: We used data from a web-based preconception cohort study of pregnancy planners enrolled during 2013-2019 (Pregnancy Study Online; PRESTO). Eligible participants self-identified as female, were aged 21-45 years, resided in the United States (U.S.) or Canada, and were trying to conceive without fertility treatments. Participants completed a baseline questionnaire and bi-monthly follow-up questionnaires until conception or 12 months. We analyzed data from 8,747 participants (U.S.: 7,304; Canada: 1,443) who had been trying to conceive for < 12 cycles at enrollment. We estimated residential ambient concentrations of particulate matter < 2.5 µm (PM2.5), nitrogen dioxide (NO2), and ozone (O3) using validated spatiotemporal models specific to each country. We fit country-specific proportional probabilities regression models to estimate the association between annual average, menstrual cycle-specific, and preconception average pollutant concentrations with fecundability, the per-cycle probability of conception. We calculated fecundability ratios (FRs) and 95% confidence intervals (CIs) and adjusted for individual- and neighborhood-level confounders. RESULTS: In the U.S., the FRs for a 5-µg/m3 increase in annual average, cycle-specific, and preconception average PM2.5 concentrations were 0.94 (95% CI: 0.83, 1.08), 1.00 (95% CI: 0.93, 1.07), and 1.00 (95% CI: 0.93, 1.09), respectively. In Canada, the corresponding FRs were 0.92 (95% CI: 0.74, 1.16), 0.97 (95% CI: 0.87, 1.09), and 0.94 (95% CI: 0.80, 1.09), respectively. Likewise, NO2 and O3 concentrations were not strongly associated with fecundability in either country. CONCLUSIONS: Neither annual average, menstrual cycle-specific, nor preconception average exposure to ambient PM2.5, NO2, and O3 were appreciably associated with reduced fecundability in this cohort of pregnancy planners.

Associations between Residential Greenspace and Fecundability in a North American Preconception Cohort Study.

BACKGROUND: Residential green space can have positive physiological effects on human health through various mechanisms, including reducing stress and/or depression or facilitating physical activity. Although green space has been consistently associated with improved birth outcomes in several studies, there has been limited study of its effect on other reproductive outcomes, including fertility. OBJECTIVE: We examined associations between residential green space and fecundability, the per-cycle probability of conception. METHODS: We analyzed data from 8,563 female participants enrolled between 2013 and 2019 in Pregnancy Study Online (PRESTO), a prospective preconception cohort study of North American couples attempting conception. Participants completed a baseline questionnaire on sociodemographic, behavioral, and reproductive factors, and bimonthly follow-up questionnaires for up to 12 months to ascertain pregnancies. Using geocoded addresses, we calculated residential green space exposure using the Normalized Difference Vegetation Index (NDVI) within 50-, 100-, 250-, and 500-m buffers across multiple temporal scales: annual maximum, seasonal maximum, and seasonal mean. We used proportional probabilities regression models to estimate fecundability ratios (FRs), adjusting for sociodemographic, behavioral, and neighborhood characteristics. We also evaluated the extent to which associations were mediated by reductions in perceived stress or depressive symptoms and increased physical activity. RESULTS: When comparing the highest (≥0.8) with the lowest (<0.2) NDVI exposures within 50m, we observed positive associations in the annual maximum NDVI [FR: 1.33; 95% confidence interval (CI): 1.06, 1.67] and seasonal maximum NDVI (FR: 1.19; 95% CI: 1.00, 1.41) models, but little association in the seasonal mean NDVI models (FR: 0.98; 95% CI: 0.73, 1.30). Restricted cubic splines showed evidence of nonlinearity in this association. Results were similar across buffer distances. Perceived stress, depressive symptoms, and physical activity explained ≤5:0% of mediation across all NDVI metrics. DISCUSSION: In this cohort, greater residential green space was associated with a modest increase in fecundability. https://doi.org/10.1289/EHP10648.

Within-City Variation in Ambient Carbon Monoxide Concentrations: Leveraging Low-Cost Monitors in a Spatiotemporal Modeling Framework.

BACKGROUND: Based on human and animal experimental studies, exposure to ambient carbon monoxide (CO) may be associated with cardiovascular disease outcomes, but epidemiological evidence of this link is limited. The number and distribution of ground-level regulatory agency monitors are insufficient to characterize fine-scale variations in CO concentrations. OBJECTIVES: To develop a daily, high-resolution ambient CO exposure prediction model at the city scale. METHODS: We developed a CO prediction model in Baltimore, Maryland, based on a spatiotemporal statistical algorithm with regulatory agency monitoring data and measurements from calibrated low-cost gas monitors. We also evaluated the contribution of three novel parameters to model performance: high-resolution meteorological data, satellite remote sensing data, and copollutant (PM2.5, NO2, and NOx) concentrations. RESULTS: The CO model had spatial cross-validation (CV) R2 and root-mean-square error (RMSE) of 0.70 and 0.02 parts per million (ppm), respectively; the model had temporal CV R2 and RMSE of 0.61 and 0.04 ppm, respectively. The predictions revealed spatially resolved CO hot spots associated with population, traffic, and other nonroad emission sources (e.g., railroads and airport), as well as sharp concentration decreases within short distances from primary roads. DISCUSSION: The three novel parameters did not substantially improve model performance, suggesting that, on its own, our spatiotemporal modeling framework based on geographic features was reliable and robust. As low-cost air monitors become increasingly available, this approach to CO concentration modeling can be generalized to resource-restricted environments to facilitate comprehensive epidemiological research. https://doi.org/10.1289/EHP10889.

Association Between Neighborhood Disadvantage and Fertility Among Pregnancy Planners in the US.

Importance: Decades of inequitable policies in the US have yielded disparities in neighborhood quality, and some studies show that living in a socioeconomically disadvantaged neighborhood is associated with worse health outcomes, including reproductive health outcomes. However, no US studies to date have directly examined the association between residence in disadvantaged neighborhoods and fertility. Objective: To examine the association between residence in disadvantaged neighborhoods and fecundability, a sensitive marker of fertility with many health implications. Design, Setting, and Participants: This prospective preconception cohort study used the Pregnancy Study Online, for which baseline data were collected from June 19, 2013, through April 12, 2019. The study included 6356 participants who identified as female, were 21 to 45 years of age, were attempting conception without fertility treatment, and provided a valid residential address in the contiguous US at enrollment. Exposures: A standardized area deprivation index (ADI) derived at the census block group level applied to each residential address. Main Outcomes and Measures: Fecundability, the per-cycle probability of conception, via questionnaires that were completed every 8 weeks for 12 months, until conception or a censoring event. Proportional probabilities models were used to estimate fecundability ratios and 95% CIs for associations between ADI and fecundability. Restricted cubic splines were also implemented to examine nonlinearity. Models were adjusted for demographic characteristics and factors associated with fertility. The study's a priori hypothesis was that higher levels of neighborhood disadvantage would be associated with decreased fecundability. Results: Among 6356 participants, 3725 pregnancies were observed for 27 427 menstrual cycles of follow-up. The mean (SD) baseline age was 30.0 (4.1) years, and most participants were non-Hispanic White (5297 [83.3%]) and nulliparous (4179 [65.7%]). Comparing the top and bottom deciles of disadvantaged neighborhood status, adjusted fecundability ratios were 0.79 (95% CI, 0.66-0.96) for national-level ADI rankings and 0.77 (95% CI, 0.65-0.92) for within-state ADI rankings. Restricted cubic splines showed some evidence of nonlinearity in the association. Associations were slightly stronger among participants with lower annual incomes (<$50 000). Conclusions and Relevance: In this cohort study, residence in a socioeconomically disadvantaged neighborhood was associated with moderately decreased fecundability. If confirmed in other studies, these results suggest that investments to reduce disadvantaged neighborhood status may yield positive cobenefits for fertility.

A Prospective Cohort Study of Seasonal Variation in Spontaneous Abortion.

BACKGROUND: Up to 30% of pregnancies end in spontaneous abortion, yet few risk factors have been identified. Examining seasonal patterns in risk of spontaneous abortion can generate new hypotheses regarding environmental and lifestyle determinants. METHODS: We used data from Pregnancy Study Online-a preconception cohort study of pregnancy planners from the United States and Canada-to examine seasonal variation in spontaneous abortion risk. We enrolled 12,197 women during 2013 to 2020, 6104 of whom reported a conception within 12 months of enrollment. On follow-up questionnaires, participants reported date of spontaneous abortion and weeks gestation at time of loss. We used periodic regression to estimate two aspects of seasonal occurrence: peak/low ratio-a measure of intensity of seasonal variation-and peak timing. We examined season at risk (from the date of each gestational week) in relation to spontaneous abortion; in a secondary analysis, we examined season of conception in relation to spontaneous abortion. We controlled for seasonal patterns in attempt initiation via month the pregnancy attempt began. RESULTS: Almost 20% of women experienced spontaneous abortion. Risk was highest in late August, with a peak/low ratio of 1.3 (95% confidence interval [CI] = 1.1, 1.6). This seasonal pattern was evident almost exclusively for spontaneous abortion at <8 weeks since the last menstrual period date (peak/low ratio = 1.4; 95% CI = 1.2, 1.8), and associations were stronger among women living in the Southern and Midwestern United States. CONCLUSIONS: Environmental or lifestyle factors more prevalent in late summer may be associated with increased risk of early spontaneous abortion.

Non-nutritive suck and airborne metal exposures among Puerto Rican infants.

Air pollution has been shown to impact multiple measures of neurodevelopment in young children. Its effects on particularly vulnerable populations, such as ethnic minorities, however, is less studied. To address this gap in the literature, we assess the associations between infant non-nutritive suck (NNS), an early indicator of central nervous system integrity, and air pollution exposures in Puerto Rico. Among infants aged 0-3 months enrolled in the Center for Research on Early Childhood Exposure and Development (CRECE) cohort from 2017 to 2019, we examined associations between exposure to fine particulate matter (PM2.5) and its components on infant NNS in Puerto Rico. NNS was assessed using a pacifier attached to a pressure transducer, allowing for real-time visualization of NNS amplitude, frequency, duration, cycles/burst, cycles/min and bursts/min. These data were linked to 9-month average prenatal concentrations of PM2.5 and components, measured at three community monitoring sites. We used linear regression to examine the PM2.5-NNS association in single pollutant models, controlling for infant sex, maternal age, gestational age, and season of birth in base and additionally for household smoke exposure, age at testing, and NNS duration in full models. Among 198 infants, the average NNS amplitude and burst duration was 17.1 cmH2O and 6.1 s, respectively. Decreased NNS amplitude was consistently and significantly associated with 9-month average exposure to sulfur (-1.026 ± 0.507), zinc (-1.091 ± 0.503), copper (-1.096 ± 0.535) vanadium (-1.157 ± 0.537), and nickel (-1.530 ± 0.501). Decrements in NNS frequency were associated with sulfur exposure (0.036 ± 0.018), but not other examined PM components. Our findings provide new evidence that prenatal maternal exposure to specific PM components are associated with impaired neurodevelopment in Puerto Rican infants soon after birth.

Fine-Scale Air Pollution Models for Epidemiologic Research: Insights From Approaches Developed in the Multi-ethnic Study of Atherosclerosis and Air Pollution (MESA Air).

PURPOSE OF REVIEW: Epidemiological studies of short- and long-term health impacts of ambient air pollutants require accurate exposure estimates. We describe the evolution in exposure assessment and assignment in air pollution epidemiology, with a focus on spatiotemporal techniques first developed to meet the needs of the Multi-ethnic Study of Atherosclerosis and Air Pollution (MESA Air). Initially designed to capture the substantial variation in pollutant levels and potential health impacts that can occur over small spatial and temporal scales in metropolitan areas, these methods have now matured to permit fine-scale exposure characterization across the contiguous USA and can be used for understanding long- and short-term health effects of exposure across the lifespan. For context, we highlight how the MESA Air models compare to other available exposure models. RECENT FINDINGS: Newer model-based exposure assessment techniques provide predictions of pollutant concentrations with fine spatial and temporal resolution. These validated models can predict concentrations of several pollutants, including particulate matter less than 2.5 µm in diameter (PM2.5), oxides of nitrogen, and ozone, at specific locations (such as at residential addresses) over short time intervals (such as 2 weeks) across the contiguous USA between 1980 and the present. Advances in statistical methods, incorporation of supplemental pollutant monitoring campaigns, improved geographic information systems, and integration of more complete satellite and chemical transport model outputs have contributed to the increasing validity and refined spatiotemporal spans of available models. Modern models for predicting levels of outdoor concentrations of air pollutants can explain a substantial amount of the spatiotemporal variation in observations and are being used to provide critical insights into effects of air pollutants on the prevalence, incidence, progression, and prognosis of diseases across the lifespan. Additional enhancements in model inputs and model design, such as incorporation of better traffic data, novel monitoring platforms, and deployment of machine learning techniques, will allow even further improvements in the performance of pollutant prediction models.

Preterm birth and PM2.5 in Puerto Rico: evidence from the PROTECT birth cohort.

BACKGROUND: Preterm birth (PTB, birth before 37 weeks of gestation) has been associated with adverse health outcomes across the lifespan. Evidence on the association between PTB and prenatal exposure to air pollutants is inconsistent, and is especially lacking for ethnic/racial minority populations. METHODS: We obtained data on maternal characteristics and behaviors and PTB and other birth outcomes for women participating in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort, who lived in municipalities located along the North Coast of Puerto Rico. We assessed pre-natal PM2.5 exposures for each infant based on the nearest US Environmental Protection Agency monitor. We estimated prenatal phthalate exposures as the geometric mean of urinary measurements obtained during pregnancy. We then examined the association between PM2.5 and PTB using modified Poisson regression and assessed modification of the association by phthalate exposure levels and sociodemographic factors such as maternal age and infant gender. RESULTS: Among 1092 singleton births, 9.1% of infants were born preterm and 92.9% of mothers had at least a high school education. Mothers had a mean (standard deviation) age of 26.9 (5.5) years and a median (range) of 2.0 (1.0-8.0) pregnancies. Nearly all women were Hispanic white, black, or mixed race. Median (range) prenatal PM2.5 concentrations were 6.0 (3.1-19.8) µ g/m3. Median (interquartile range) prenatal phthalate levels were 14.9 (8.9-26.0) and 14.5 (8.4-26.0), respectively, for di-n-butyl phthalate (DBP) and di-isobutyl phthalate (DiBP). An interquartile range increase in PM2.5 was associated with a 1.2% (95% CI 0.4, 2.1%) higher risk of PTB. There was little difference in PTB risk in strata of infant sex, mother's age, family income, history of adverse birth outcome, parity, and pre-pregnancy body mass index. Pregnancy urinary phthalate metabolite levels did not modify the PM2.5-PTB association. CONCLUSION: Among ethnic minority women in Puerto Rico, prenatal PM2.5 exposure is associated with a small but significant increase in risk of PTB.

Ambient air pollution and risk of respiratory infection among adults: evidence from the multiethnic study of atherosclerosis (MESA).

BACKGROUND: Air pollution may affect the risk of respiratory infection, though research has focused on uncommon infections or infections in children. Whether ambient air pollutants increase the risk of common acute respiratory infections among adults is uncertain, yet this may help understand whether pollutants influence spread of pandemic respiratory infections like COVID-19. OBJECTIVE: To estimate the association between ambient air pollutant exposures and respiratory infections in adults. METHODS: During five study examinations over 12 years, 6536 participants in the multiethnic study of atherosclerosis (MESA) reported upper respiratory tract infections, bronchitis, pneumonia or febrile illness in the preceding 2 weeks. Using a validated spatiotemporal model, we estimated residential concentrations of ambient PM2.5, NOx and NO2 for the 2-6 weeks (short-term) and year (long-term) prior to each examination. RESULTS: In this population aged 44-84 years at baseline, 10%-32% of participants reported a recent respiratory infection, depending on month of examination and study region. PM2.5, NOx and NO2 concentrations over the prior 2-6 weeks were associated with increased reporting of recent respiratory infection, with risk ratios (95% CIs) of 1.04 (1.00 to 1.09), 1.15 (1.10 to 1.20) and 1.21 (1.10 to 1.33), respectively, per increase from 25th to 75th percentile in residential pollutant concentration. CONCLUSION: Higher short-term exposure to PM2.5 and traffic-related pollutants are associated with increased risk of symptomatic acute respiratory infections among adults. These findings may provide an insight into the epidemiology of COVID-19.

Maternal exposure to PM2.5 during pregnancy and asthma risk in early childhood: consideration of phases of fetal lung development.

BACKGROUND: Increasingly studies suggest prenatal exposure to air pollution may increase risk of childhood asthma. Few studies have investigated exposure during specific fetal pulmonary developmental windows. OBJECTIVE: To assess associations between prenatal fine particulate matter exposure and asthma at age 4. METHODS: This study included mother-child dyads from two pregnancy cohorts-CANDLE and TIDES-within the ECHO-PATHWAYS consortium (births in 2007-2013). Three child asthma outcomes were parent-reported: ever asthma, current asthma, and current wheeze. Fine particulate matter (PM2.5) exposures during the pseudoglandular (5-16 weeks gestation), canalicular (16-24 weeks gestation), saccular (24-36 weeks gestation), and alveolar (36+ weeks gestation) phases of fetal lung development were estimated using a national spatiotemporal model. We estimated associations with Poisson regression with robust standard errors, and adjusted for child, maternal, and neighborhood factors. RESULTS: Children (n=1469) were on average 4.3 (standard deviation 0.5) years old, 49% were male, and 11.7% had ever asthma; 46% of women identified as black and 53% had at least a college/technical school degree. A 2 µg/m3 higher PM2.5 exposure during the saccular phase was associated with 1.29 times higher risk of ever asthma (95% CI: 1.06-1.58). A similar association was observed with current asthma (RR 1.27, 95% CI: 1.04-1.54), but not current wheeze (RR 1.11, 95% CI: 0.92-1.33). Effect estimates for associations during other developmental windows had confidence intervals that included the null. CONCLUSIONS: Later phases of prenatal lung development may be particularly sensitive to the developmental toxicity of PM2.5.

Patient Transfers and Their Impact on Gaps in Clinical Care: Differences by Gender in a Large Cohort of Adults Living with HIV on Antiretroviral Therapy in South Africa.

For people living with HIV (PLWH), patient transfers may affect engagement in care. We followed a cohort of PLWH in Cape Town, South Africa who tested positive for HIV in 2012-2013 from ART initiation in 2012-2016 through December 2016. Patient transfers were defined as moving from one healthcare facility to another on a different day, considering all healthcare visits and recorded HIV-visits only. We estimated incidence rates (IR) for transfers by time since ART initiation, overall and by gender, and associations between transfers and gaps of > 180 days in clinical care. Overall, 4,176 PLWH were followed for a median of 32 months, and 8% (HIV visits)-17% (all healthcare visits) of visits were patient transfers. Including all healthcare visits, transfers were highest through 3 months on ART (IR 20.2 transfers per 100 visits, 95% CI 19.2-21.2), but increased through 36 months on ART when only HIV visits were included (IR 9.7, 95% CI 8.8-10.8). Overall, women were more likely to transfer than men, and transfers were associated with gaps in care (IR ratio [IRR] 3.06 95% CI 2.83-3.32; HIV visits only). In this cohort, patient transfers were frequent, more common among women, and associated with gaps in care.

Modeling residential indoor concentrations of PM2.5 , NO2 , NOx , and secondhand smoke in the Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) Air study.

Increased outdoor concentrations of fine particulate matter (PM2.5 ) and oxides of nitrogen (NO2 , NOx ) are associated with respiratory and cardiovascular morbidity in adults and children. However, people spend most of their time indoors and this is particularly true for individuals with chronic obstructive pulmonary disease (COPD). Both outdoor and indoor air pollution may accelerate lung function loss in individuals with COPD, but it is not feasible to measure indoor pollutant concentrations in all participants in large cohort studies. We aimed to understand indoor exposures in a cohort of adults (SPIROMICS Air, the SubPopulations and Intermediate Outcome Measures in COPD Study of Air pollution). We developed models for the entire cohort based on monitoring in a subset of homes, to predict mean 2-week-measured concentrations of PM2.5 , NO2 , NOx , and nicotine, using home and behavioral questionnaire responses available in the full cohort. Models incorporating socioeconomic, meteorological, behavioral, and residential information together explained about 60% of the variation in indoor concentration of each pollutant. Cross-validated R2 for best indoor prediction models ranged from 0.43 (NOx ) to 0.51 (NO2 ). Models based on questionnaire responses and estimated outdoor concentrations successfully explained most variation in indoor PM2.5 , NO2 , NOx , and nicotine concentrations.

Estimating retention in HIV care accounting for clinic transfers using electronic medical records: evidence from a large antiretroviral treatment programme in the Western Cape, South Africa.

BACKGROUND: Estimates of retention in antiretroviral treatment (ART) programmes may be biased if patients who transfer to healthcare clinics are misclassified as lost to follow-up (LTFU) at their original clinic. In a large cohort, we estimated retention in care accounting for patient transfers using medical records. METHODS: Using linked electronic medical records, we followed adults living with HIV (PLWH) in Cape Town, South Africa from ART initiation (2012-2016) through database closure at 36 months or 30 June 2016, whichever came first. Retention was defined as alive and with a healthcare visit in the 180 days between database closure and administrative censoring on 31 December 2016. Participants who died or did not have a healthcare visit in > 180 days were censored at their last healthcare visit. We estimated the cumulative incidence of retention using Kaplan-Meier methods considering (i) only records from a participant's ART initiation clinic (not accounting for transfers) and (ii) all records (accounting for transfers), over time and by gender. We estimated risk differences and bootstrapped 95% confidence intervals to quantify misclassification in retention estimates due to patient transfers. RESULTS: We included 3406 PLWH initiating ART. Retention through 36 months on ART rose from 45.4% (95% CI 43.6%, 47.2%) to 54.3% (95% CI 52.4%, 56.1%) after accounting for patient transfers. Overall, 8.9% (95% CI 8.1%, 9.7%) of participants were misclassified as LTFU due to patient transfers. CONCLUSIONS: Patient transfers can appreciably bias estimates of retention in HIV care. Electronic medical records can help quantify patient transfers and improve retention estimates.

CONTEXTE: Les estimations de la rétention dans les programmes de traitement antirétroviral (ART) peuvent être biaisées si les patients qui sont transférés dans des cliniques de soins de santé sont classés à tort comme perdus au suivi (PS) dans leur clinique d'origine. Dans une large cohorte, nous avons estimé la rétention dans les soins en tenant compte des transferts de patients à l'aide des dossiers médicaux. MÉTHODES: A l'aide de dossiers médicaux électroniques reliés entre eux, nous avons suivi des adultes vivant avec le VIH (PVVIH) à Cape Town, en Afrique du Sud, depuis le début de l'ART (2012-2016) jusqu'à la clotûre de la base de données à 36 mois ou au 30 juin 2016, selon la première éventualité. La rétention a été définie comme étant en vie et avec une visite médicale dans les 180 jours entre la clôture de la base de données et recensement administrative le 31 décembre 2016. Les participants qui sont décédés ou qui n'ont pas eu de visite médicale dans un délai de plus de 180 jours ont été recensés lors de leur dernière visite médicale. Nous avons estimé l'incidence cumulative de la rétention en utilisant les méthodes de Kaplan-Meier en considérant: (i) uniquement les dossiers de la clinique d'initiation de l'ART d'un participant (sans tenir compte des transferts) et (ii) tous les dossiers (en tenant compte des transferts), au cours du temps et par sexe. Nous avons estimé les différences de risque et avons considéré des intervalles de confiance à 95% pour quantifier les erreurs de classification dans les estimations de rétention dues aux transferts de patients. RÉSULTAT: Nous avons inclus 3.406 PVVIH qui ont commencé un ART. La rétention sous ART est passée de 45,4% (IC 95%: 43,6-47,2) à 54,3% (IC 95%: 52,4-56,1) après avoir tenu compte des transferts de patients. Dans l'ensemble, 8,9% (IC 95%: 8,1-9,7) des participants ont été classés à tort dans la catégorie PS en raison des transferts de patients. CONCLUSIONS: Les transferts de patients peuvent biaiser sensiblement les estimations de la rétention dans les soins liés au VIH. Les dossiers médicaux électroniques peuvent aider à quantifier les transferts de patients et à améliorer les estimations de rétention.

Residential proximity to major roads and fecundability in a preconception cohort.

Emerging evidence from animal and human studies indicates that exposure to traffic-related air pollution may adversely affect fertility. METHODS: Among 7,342 female pregnancy planners from the United States and 1,448 from Canada, we examined the association between residential proximity to major roads and fecundability, the per-cycle probability of conception. From 2013 to 2019, women 21-45 years old who were trying to conceive without fertility treatment completed an online baseline questionnaire and follow-up questionnaires every 8 weeks for up to 12 months or until pregnancy. We geocoded residential addresses reported at baseline and during follow-up, and calculated distance to nearest major roads and length of major roads within buffers of 50, 100, 300, and 400 meters around the residence as proxies for traffic-related air pollution. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for individual- and neighborhood-level characteristics. RESULTS: In the United States, the FR comparing women who lived <50 meters with those who lived ≥400 meters from the closest major road was 0.88 (95% CI = 0.80, 0.98). The association among Canadian women was similar in magnitude, but less precise (FR = 0.93; 95% CI = 0.74, 1.16). Likewise, length of major roads within buffers of 50 and 100 meters was associated with lower fecundability in both countries; associations were attenuated within larger buffers. CONCLUSIONS: These results are consistent with the hypothesis that traffic-related air pollution or other near-road exposures may adversely affect fecundability.

Association of Long-term Ambient Ozone Exposure With Respiratory Morbidity in Smokers.

Importance: Few studies have investigated the association of long-term ambient ozone exposures with respiratory morbidity among individuals with a heavy smoking history. Objective: To investigate the association of historical ozone exposure with risk of chronic obstructive pulmonary disease (COPD), computed tomography (CT) scan measures of respiratory disease, patient-reported outcomes, disease severity, and exacerbations in smokers with or at risk for COPD. Design, Setting, and Participants: This multicenter cross-sectional study, conducted from November 1, 2010, to July 31, 2018, obtained data from the Air Pollution Study, an ancillary study of SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). Data analyzed were from participants enrolled at 7 (New York City, New York; Baltimore, Maryland; Los Angeles, California; Ann Arbor, Michigan; San Francisco, California; Salt Lake City, Utah; and Winston-Salem, North Carolina) of the 12 SPIROMICS clinical sites. Included participants had historical ozone exposure data (n = 1874), were either current or former smokers (≥20 pack-years), were with or without COPD, and were aged 40 to 80 years at baseline. Healthy persons with a smoking history of 1 or more pack-years were excluded from the present analysis. Exposures: The 10-year mean historical ambient ozone concentration at participants' residences estimated by cohort-specific spatiotemporal modeling. Main Outcomes and Measures: Spirometry-confirmed COPD, chronic bronchitis diagnosis, CT scan measures (emphysema, air trapping, and airway wall thickness), 6-minute walk test, modified Medical Research Council (mMRC) Dyspnea Scale, COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), postbronchodilator forced expiratory volume in the first second of expiration (FEV1) % predicted, and self-report of exacerbations in the 12 months before SPIROMICS enrollment, adjusted for demographics, smoking, and job exposure. Results: A total of 1874 SPIROMICS participants were analyzed (mean [SD] age, 64.5 [8.8] years; 1479 [78.9%] white; and 1013 [54.1%] male). In adjusted analysis, a 5-ppb (parts per billion) increase in ozone concentration was associated with a greater percentage of emphysema (ß = 0.94; 95% CI, 0.25-1.64; P = .007) and percentage of air trapping (ß = 1.60; 95% CI, 0.16-3.04; P = .03); worse scores for the mMRC Dyspnea Scale (ß = 0.10; 95% CI, 0.03-0.17; P = .008), CAT (ß = 0.65; 95% CI, 0.05-1.26; P = .04), and SGRQ (ß = 1.47; 95% CI, 0.01-2.93; P = .048); lower FEV1% predicted value (ß = -2.50; 95% CI, -4.42 to -0.59; P = .01); and higher odds of any exacerbation (odds ratio [OR], 1.37; 95% CI, 1.12-1.66; P = .002) and severe exacerbation (OR, 1.37; 95% CI, 1.07-1.76; P = .01). No association was found between historical ozone exposure and chronic bronchitis, COPD, airway wall thickness, or 6-minute walk test result. Conclusions and Relevance: This study found that long-term historical ozone exposure was associated with reduced lung function, greater emphysema and air trapping on CT scan, worse patient-reported outcomes, and increased respiratory exacerbations for individuals with a history of heavy smoking. The association between ozone exposure and adverse respiratory outcomes suggests the need for continued reevaluation of ambient pollution standards that are designed to protect the most vulnerable members of the US population.

Quantifying the HIV treatment cascade in a South African health sub-district by gender: retrospective cohort study.

OBJECTIVES: To quantify the HIV care cascade in a Cape Town sub-district to understand rates of linkage to and engagement in HIV care. METHODS: We used routinely collected data to reconstruct the treatment cascade for 8382 infected individuals who tested HIV + in 2012/2013. We obtained data on patient gender, year of initial HIV-positive test, age at testing and initial CD4 cell count and defined five stages of the HIV care cascade. We quantified attrition across cascade stages. RESULTS: Two-thirds of the sample (5646) were women. Men were older at time of first testing (36.5 vs. 31.3 years) and had more advanced HIV disease at diagnosis (298 vs. 404 CD4 cells/µL for women). The median duration of follow-up was 818 days. Among women, 90.5% attended an initial HIV care visit, 54.6% became eligible for antiretroviral therapy under local guidelines during follow-up, 49.3% initiated ART and 45.6% achieved a therapeutic response. Among men, 88.0% attended an initial HIV care visit, 67.4% became ART eligible during follow-up, 48.0% initiated ART and 42.4% achieved a therapeutic response. Approximately 3% of women and 5% of men died during follow-up. CONCLUSIONS: We were able to reconstruct the HIV treatment cascade using routinely collected data. In this setting, rates of engagement in care differ by gender in key stages of the cascade, with men faring worse than women at each cascade point. This highlights the need for interventions aimed at encouraging earlier testing, linkage, ART initiation and retention among men.

OBJECTIFS: Quantifier la cascade des soins du VIH dans un sous-district de Cape Town pour comprendre les taux de liaisons et d'engagement avec les soins du VIH. MÉTHODES: Nous avons utilisé des données collectées en routine pour reconstruire la cascade de traitement pour 8.382 personnes infectées, testées positives pour le VIH en 2012/13. Nous avons obtenu des données sur le sexe du patient, l'année du premier test positif pour le VIH, l'âge au moment de ce test et le nombre initial de cellules CD4, et avons défini cinq étapes de la cascade des soins du VIH. Nous avons quantifié l'attrition au long des étapes de la cascade. RÉSULTATS: Deux tiers de l'échantillon (5.646) étaient des femmes. Les hommes étaient plus âgés au moment du premier test (36,5 contre 31,3 ans) et avaient la maladie du VIH plus avancée au moment du diagnostic (298 contre 404 cellules CD4/µL pour les femmes). La durée médiane de suivi était de 818 jours. Parmi les femmes, 90,5% ont pris part à une première visite pour des soins du VIH, 54,6% sont devenues éligibles au traitement antirétroviral selon les directives locales au cours du suivi, 49,3% ont commencé une ART et 45,6% ont atteint une réponse thérapeutique. Chez les hommes, 88,0% ont pris part à une première visite pour les soins du VIH; 67,4% sont devenus éligibles à l'ART au cours du suivi, 48,0% ont commencé l'ART et 42,4% ont atteint une réponse thérapeutique. Environ 3% des femmes et 5% des hommes sont décédés au cours du suivi. CONCLUSIONS: Nous avons pu reconstruire la cascade de traitement du VIH en utilisant des données collectées en routine. Dans ce contexte, les taux d'engagement dans les soins diffèrent selon le sexe dans les étapes clés de la cascade, les hommes s'en tirant moins bien que les femmes à chaque point de la cascade. Cela met en évidence la nécessité d'interventions visant à encourager le dépistage précoce, la liaison, l'initiation de l'ART et la rétention chez les hommes.

Association Between Long-term Exposure to Ambient Air Pollution and Change in Quantitatively Assessed Emphysema and Lung Function.

Importance: While air pollutants at historical levels have been associated with cardiovascular and respiratory diseases, it is not known whether exposure to contemporary air pollutant concentrations is associated with progression of emphysema. Objective: To assess the longitudinal association of ambient ozone (O3), fine particulate matter (PM2.5), oxides of nitrogen (NOx), and black carbon exposure with change in percent emphysema assessed via computed tomographic (CT) imaging and lung function. Design, Setting, and Participants: This cohort study included participants from the Multi-Ethnic Study of Atherosclerosis (MESA) Air and Lung Studies conducted in 6 metropolitan regions of the United States, which included 6814 adults aged 45 to 84 years recruited between July 2000 and August 2002, and an additional 257 participants recruited from February 2005 to May 2007, with follow-up through November 2018. Exposures: Residence-specific air pollutant concentrations (O3, PM2.5, NOx, and black carbon) were estimated by validated spatiotemporal models incorporating cohort-specific monitoring, determined from 1999 through the end of follow-up. Main Outcomes and Measures: Percent emphysema, defined as the percent of lung pixels less than -950 Hounsfield units, was assessed up to 5 times per participant via cardiac CT scan (2000-2007) and equivalent regions on lung CT scans (2010-2018). Spirometry was performed up to 3 times per participant (2004-2018). Results: Among 7071 study participants (mean [range] age at recruitment, 60 [45-84] years; 3330 [47.1%] were men), 5780 were assigned outdoor residential air pollution concentrations in the year of their baseline examination and during the follow-up period and had at least 1 follow-up CT scan, and 2772 had at least 1 follow-up spirometric assessment, over a median of 10 years. Median percent emphysema was 3% at baseline and increased a mean of 0.58 percentage points per 10 years. Mean ambient concentrations of PM2.5 and NOx, but not O3, decreased substantially during follow-up. Ambient concentrations of O3, PM2.5, NOx, and black carbon at study baseline were significantly associated with greater increases in percent emphysema per 10 years (O3: 0.13 per 3 parts per billion [95% CI, 0.03-0.24]; PM2.5: 0.11 per 2 µg/m3 [95% CI, 0.03-0.19]; NOx: 0.06 per 10 parts per billion [95% CI, 0.01-0.12]; black carbon: 0.10 per 0.2 µg/m3 [95% CI, 0.01-0.18]). Ambient O3 and NOx concentrations, but not PM2.5 concentrations, during follow-up were also significantly associated with greater increases in percent emphysema. Ambient O3 concentrations, but not other pollutants, at baseline and during follow-up were significantly associated with a greater decline in forced expiratory volume in 1 second per 10 years (baseline: 13.41 mL per 3 parts per billion [95% CI, 0.7-26.1]; follow-up: 18.15 mL per 3 parts per billion [95% CI, 1.59-34.71]). Conclusions and Relevance: In this cohort study conducted between 2000 and 2018 in 6 US metropolitan regions, long-term exposure to ambient air pollutants was significantly associated with increasing emphysema assessed quantitatively using CT imaging and lung function.