Long-term exposure to ambient particulate matter and stroke etiology: Results from the Women's Health Initiative

Background: Ambient particulate matter (PM) air pollution is a leading cause of global disability and accounts for an annual 2.9 million deaths globally. PM is established as an important risk factor for cardiovascular disease, however the evidence supporting a link specifically between long-term exposure to ambient PM and incident stroke is less clear. We sought to evaluate the association of long-term exposure to different size fractions of ambient PM with incident stroke (overall and by etiologic subtypes) and cerebrovascular deaths within the Women's Health Initiative, a large prospective study of older women in the US. Methods: We studied 155,410 postmenopausal women without previous cerebrovascular disease enrolled into the study between 1993 and 1998, with follow-up through 2010. We assessed geocoded participant address-specific concentrations of ambient PM (fine [PM2.5], respirable [PM10] and coarse [PM10-2.5]), as well as nitrogen dioxide [NO2] using spatiotemporal models. We classified hospitalization events into ischemic, hemorrhagic, or other/unclassified stroke. Cerebrovascular mortality was defined as death from any stroke etiology. We used Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for individual and neighborhood-level characteristics. Results: During a median follow-up time of 15 years, participants experienced 4,556 cerebrovascular events. The hazard ratio for all cerebrovascular events was 2.14 (95% CI: 1.87, 2.44) comparing the top versus bottom quartiles of PM2.5. Similarly, there was a statistically significant increase in events comparing the top versus bottom quartiles of PM10 and NO2 (HR: 1.17; 95% CI: 1.03, 1.33 and HR:1.26; 95% CI: 1.12, 1.42). The strength of association did not vary substantially by stroke etiology. There was little evidence of an association between PMcoarse and incident cerebrovascular events. Conclusions: Long-term exposure to fine (PM2.5) and respirable (PM10) particulate matter as well as NO2 was associated with a significant increase of cerebrovascular events among postmenopausal women. Strength of the associations were consistent by stroke etiology

Confounding and exposure measurement error in air pollution epidemiology

Studies in air pollution epidemiology may suffer from some specific forms of confounding and exposure measurement error. This contribution discusses these, mostly in the framework of cohort studies. Evaluation of potential confounding is critical in studies of the health effects of air pollution. The association between long-term exposure to ambient air pollution and mortality has been investigated using cohort studies in which subjects are followed over time with respect to their vital status. In such studies, control for individual-level confounders such as smoking is important, as is control for area-level confounders such as neighborhood socio-economic status. In addition, there may be spatial dependencies in the survival data that need to be addressed. These issues are illustrated using the American Cancer Society Cancer Prevention II cohort. Exposure measurement error is a challenge in epidemiology because inference about health effects can be incorrect when the measured or predicted exposure used in the analysis is different from the underlying true exposure. Air pollution epidemiology rarely if ever uses personal measurements of exposure for reasons of cost and feasibility. Exposure measurement error in air pollution epidemiology comes in various dominant forms, which are different for time-series and cohort studies. The challenges are reviewed and a number of suggested solutions are discussed for both study domains

Characterizing Spatial Patterns of Airborne Coarse Particulate (PM10–2.5) Mass and Chemical Components in Three Cities: The Multi-Ethnic Study of Atherosclerosis

Background: The long-term health effects of coarse particular matter (PM10–2.5) are challenging to assess because of a limited understanding of the spatial variation in PM10–2.5 mass and its chemical components. Objectives: We conducted a spatially intensive field study and developed spatial prediction models for PM10–2.5 mass and four selected species (copper, zinc, phosphorus, and silicon) in three American cities. Methods: PM10–2.5 snapshot campaigns were conducted in Chicago, Illinois; St. Paul, Minnesota; and Winston-Salem, North Carolina, in 2009 for the Multi-Ethnic Study of Atherosclerosis and Coarse Airborne Particulate Matter (MESA Coarse). In each city, samples were collected simultaneously outside the homes of approximately 40 participants over 2 weeks in the winter and/or summer. City-specific and combined prediction models were developed using land use regression (LUR) and universal kriging (UK). Model performance was evaluated by cross-validation (CV). Results: PM10–2.5 mass and species varied within and between cities in a manner that was predictable by geographic covariates. City-specific LUR models generally performed well for total mass (CV R2, 0.41–0.68), copper (CV R2, 0.51–0.86), phosphorus (CV R2, 0.50–0.76), silicon (CV R2, 0.48–0.93), and zinc (CV R2, 0.36–0.73). Models pooled across all cities inconsistently captured within-city variability. Little difference was observed between the performance of LUR and UK models in predicting concentrations. Conclusions: Characterization of fine-scale spatial variability of these often heterogeneous pollutants using geographic covariates should reduce exposure misclassification and increase the power of epidemiological studies investigating the long-term health impacts of PM10–2.5. Citation: Zhang K, Larson TV, Gassett A, Szpiro AA, Daviglus M, Burke GL, Kaufman JD, Adar SD. 2014. Characterizing spatial patterns of airborne coarse particulate (PM10–2.5) mass and chemical components in three cities: the Multi-Ethnic Study of Atherosclerosis. Environ Health Perspect 122:823–830; http://dx.doi.org/10.1289/ehp.130728

Confounding and exposure measurement error in air pollution epidemiology

Studies in air pollution epidemiology may suffer from some specific forms of confounding and exposure measurement error. This contribution discusses these, mostly in the framework of cohort studies. Evaluation of potential confounding is critical in studies of the health effects of air pollution. The association between long-term exposure to ambient air pollution and mortality has been investigated using cohort studies in which subjects are followed over time with respect to their vital status. In such studies, control for individual-level confounders such as smoking is important, as is control for area-level confounders such as neighborhood socio-economic status. In addition, there may be spatial dependencies in the survival data that need to be addressed. These issues are illustrated using the American Cancer Society Cancer Prevention II cohort. Exposure measurement error is a challenge in epidemiology because inference about health effects can be incorrect when the measured or predicted exposure used in the analysis is different from the underlying true exposure. Air pollution epidemiology rarely if ever uses personal measurements of exposure for reasons of cost and feasibility. Exposure measurement error in air pollution epidemiology comes in various dominant forms, which are different for time-series and cohort studies. The challenges are reviewed and a number of suggested solutions are discussed for both study domains

Associations between schistosomiasis and HIV-1 acquisition risk in four prospective cohorts: a nested case-control analysis

Introduction Globally, schistosomes infect approximately 200 million people, with 90% of infections in sub-Saharan Africa. Schistosomiasis is hypothesized to increase HIV-1 acquisition risk, and multiple cross-sectional studies reported strong associations. We evaluated this hypothesis within four large prospective cohorts. Methods We conducted nested case-control analyses within three longitudinal cohorts of heterosexual HIV-1 serodiscordant couples and one female sex worker (FSW) cohort from Kenya and Uganda. The serodiscordant couples studies were conducted between 2004 and 2012 while the FSW cohort analysis included participant follow-up from 1993 to 2014. Cases HIV-1 seroconverted during prospective follow-up; three controls were selected per case. The presence of circulating anodic antigen in archived serum, collected prior to HIV-1 seroconversion, identified participants with active schistosomiasis; immunoblots determined the schistosome species. Data from serodiscordant couples cohorts were pooled, while the FSW cohort was analysed separately to permit appropriate confounder adjustment. Results We included 245 HIV-1 seroconverters and 713 controls from the serodiscordant couples cohorts and 330 HIV-1 seroconverters and 962 controls from the FSW cohort. The prevalence of active schistosomiasis was 20% among serodiscordant couples and 22% among FSWs. We found no association between schistosomiasis and HIV-1 acquisition risk among males (adjusted odds ratio (aOR) = 0.99, 95% CI 0.59 to 1.67) or females (aOR = 1.21, 95% CI 0.64 to 2.30) in serodiscordant couples. Similarly, in the FSW cohort we detected no association (adjusted incidence rate ratio (aIRR) = 1.11, 95% CI 0.83 to 1.50). Exploring schistosome species-specific effects, there was no statistically significant association between HIV-1 acquisition risk andSchistosoma mansoni(serodiscordant couples: aOR = 0.90, 95% CI 0.56 to 1.44; FSW: aIRR = 0.83, 95% CI 0.53 to 1.20) orSchistosoma haematobium(serodiscordant couples: aOR = 1.06, 95% CI 0.46 to 2.40; FSW: aIRR = 1.64, 95% CI 0.93 to 2.87) infection. Conclusions Schistosomiasis was not a strong risk factor for HIV-1 acquisition in these four prospective studies.S. mansoniwas responsible for the majority of schistosomiasis in these cohorts, and our results do not support the hypothesis thatS. mansoniinfection is associated with increased HIV-1 acquisition risk.S. haematobiuminfection was associated with a point estimate of elevated HIV-1 risk in the FSW cohort that was not statistically significant, and there was no trend towards a positive association in the serodiscordant couples cohorts.Host-parasite interactio

Schistosomiasis was not associated with higher HIV-1 plasma or genital set point viral loads among HIV seroconverters from four cohort studies

Author summary Schistosomiasis is a parasitic disease that is common in many parts of sub-Saharan Africa most affected by the HIV-1 epidemic. Schistosomiasis causes genital damage when schistosome ova become lodged in the female genital tract, inducing inflammation that may elevate HIV-1 genital viral loads and increase the risk of HIV-1 transmission. Schistosomiasis may also promote viral replication by facilitating cell-to-cell transmission of HIV-1, elevating HIV-1 plasma viral load levels. Using data from 370 individuals residing in Kenya or Uganda who acquired HIV-1 while participating in one of four prospective cohort studies, we tested the hypotheses that schistosomiasis increases plasma and genital viral load levels. We found no evidence that individuals with schistosomiasis had higher set point plasma viral load levels, a measure of viral replication obtained during the set point period 4-24 months after HIV-1 acquisition when viral load levels remain relatively stable. Additionally, we found no evidence that schistosomiasis was associated with higher female set point genital viral loads measured from vaginal or cervical swabs. Unexpectedly, we found that S. mansoni infection was associated with a decline in plasma viral load levels while S. haematobium infection was associated with a decline in cervical viral load levels. Thus, our results do not support the hypotheses that schistosomiasis increases plasma and genital HIV-1 viral loads.Background Many regions of sub-Saharan Africa experience a high prevalence of both schistosomiasis and HIV-1, leading to frequent coinfection. Higher plasma HIV-1 viral loads are associated with faster disease progression and genital HIV-1 loads are a primary determinant of HIV-1 transmission risk. We hypothesized that schistosome infection would be associated with higher HIV-1 viral loads in plasma and genital samples. Methods/Principal findings We utilized data from individuals who HIV-1 seroconverted while enrolled in one of four prospective cohort studies. Plasma and genital viral loads collected 4-24 months after the estimated date of HIV-1 acquisition, but prior to antiretroviral therapy initiation, were included. Detection of circulating anodic antigen in archived blood samples, collected prior to HIV-1 seroconversion, identified participants with active schistosomiasis; immunoblots determined the schistosome species causing infection. Our analysis included 370 HIV-1 seroconverters with plasma viral load results, of whom 82 (22%) had schistosomiasis. We did not find a statistically significant association between schistosomiasis and higher HIV-1 set point plasma viral loads (-0.17 log(10) copies/ml, 95% CI -0.38 to 0.03); S. mansoni infection was associated with a lower set point (-0.34 log(10) copies/ml, 95% CI -0.58 to -0.09). We found no association between schistosomiasis and cervical (+0.07 log(10) copies/swab, 95% CI -0.20 to 0.34) or vaginal (+0.11 log(10) copies/swab, 95% CI -0.17 to 0.39) set point viral loads; S. haematobium infection was associated with lower cervical viral loads (-0.59 log(10) copies/swab, 95% CI -1.11 to -0.06).Host-parasite interactio

Long-term exposure to traffic-related air pollution and non-accidental mortality: A systematic review and meta-analysis

Background: The health effects of traffic-related air pollution (TRAP) continue to be of important public health interest across the globe. Following its 2010 review, the Health Effects Institute appointed a new expert Panel to systematically evaluate the epidemiological evidence regarding the associations between long-term exposure to TRAP and selected health outcomes. This paper describes the main findings of the systematic review on non-accidental mortality. Methods: The Panel used a systematic approach to conduct the review. An extensive search was conducted of literature published between 1980 and 2019. A new exposure framework was developed to determine whether a study was sufficiently specific to TRAP, which included studies beyond the near-roadway environment. We performed random-effects meta-analysis when at least three estimates were available of an association between a specific exposure and outcome. We evaluated confidence in the evidence using a modified Office of Health Assessment and Translation (OHAT) approach, supplemented with a broader narrative synthesis. Results: Thirty-six cohort studies were included. Virtually all studies adjusted for a large number of individual and area-level covariates—including smoking, body mass index, and individual and area-level socioeconomic status—and were judged at a low or moderate risk for bias. Most studies were conducted in North America and Europe, and a few were based in Asia and Australia. The meta-analytic summary estimates for nitrogen dioxide, elemental carbon and fine particulate matter—pollutants with more than 10 studies—were 1.04 (95% CI 1.01, 1.06), 1.02 (1.00, 1.04) and 1.03 (1.01, 1.05) per 10, 1 and 5 µg/m3, respectively. Effect estimates are interpreted as the relative risk of mortality when the exposure differs with the selected increment. The confidence in the evidence for these pollutants was judged as high, because of upgrades for monotonic exposure–response and consistency across populations. The consistent findings across geographical regions, exposure assessment methods and confounder adjustment resulted in a high confidence rating using a narrative approach as well. Conclusions: The overall confidence in the evidence for a positive association between long-term exposure to TRAP and non-accidental mortality was high

Long-term exposure to traffic-related air pollution and selected health outcomes: A systematic review and meta-analysis

The health effects of traffic-related air pollution (TRAP) continue to be of important public health interest. Following its well-cited 2010 critical review, the Health Effects Institute (HEI) appointed a new expert Panel to systematically evaluate the epidemiological evidence regarding the associations between long-term exposure to TRAP and selected adverse health outcomes. Health outcomes were selected based on evidence of causality for general air pollution (broader than TRAP) cited in authoritative reviews, relevance for public health and policy, and resources available. The Panel used a systematic approach to search the literature, select studies for inclusion in the review, assess study quality, summarize results, and reach conclusions about the confidence in the evidence. An extensive search was conducted of literature published between January 1980 and July 2019 on selected health outcomes. A new exposure framework was developed to determine whether a study was sufficiently specific to TRAP. In total, 353 studies were included in the review. Respiratory effects in children (118 studies) and birth outcomes (86 studies) were the most commonly studied outcomes. Fewer studies investigated cardiometabolic effects (57 studies), respiratory effects in adults (50 studies), and mortality (48 studies). The findings from the systematic review, meta-analyses, and evaluation of the quality of the studies and potential biases provided an overall high or moderate-to-high level of confidence in an association between long-term exposure to TRAP and the adverse health outcomes all-cause, circulatory, ischemic heart disease and lung cancer mortality, asthma onsetin chilldren and adults, and acute lower respiratory infections in children. The evidence was considered moderate, low or very low for the other selected outcomes. In light of the large number of people exposed to TRAP – both in and beyond the near-road environment - the Panel concluded that the overall high or moderate-to-high confidence in the evidence for an association between long-term exposure to TRAP and several adverse health outcomes indicates that exposures to TRAP remain an important public health concern and deserve greater attention from the public and from policymakers. © 2022 The Author(s