Leonora Rojas-Bracho

Relationships among personal, indoor, and outdoor fine and coarse particle concentrations for individuals with COPD

This study characterizes the personal, indoor, and outdoor PM2.5, PM10, and PM2.5–10 exposures of 18 individuals with chronic obstructive pulmonary disease (COPD) living in Boston, MA. Monitoring was performed for each participant for six consecutive days in the winters of 1996 or 1997 and for six to twelve days in the summer of 1996. On each day, 12-h personal, indoor, and outdoor samples of PM2.5 and PM10 were collected simultaneously. Home characteristic information and time–activity patterns were also obtained. Personal exposures were higher than corresponding indoor and outdoor concentrations for all particle measures and for all seasons, except for winter indoor PM2.5–10 levels, which were higher than personal and outdoor levels. Higher personal exposures may be due to the proximity of the individuals to particle sources, such as cooking and cleaning. Indoor concentrations were associated with both outdoor concentrations and personal exposures (as determined by individual least square regression analyses), with associations strongest for PM2.5. Indoor PM2.5 concentrations were significantly associated with outdoor and personal levels for 12 and 15 of the 17 individuals, respectively. Both the strength and magnitude of the associations varied by individual. Also, personal PM2.5, but not PM2.5–10, exposures were associated with outdoor levels, with 10 of the 17 subjects having significant associations. The strength of the personal–outdoor association for PM2.5 was strongly related to that for indoor and outdoor levels, suggesting that home characteristics and indoor particulate sources were key determinants of the personal–outdoor association for PM2.5. Air exchange rates were found to be important determinants of both indoor and personal levels. Again, substantial interpersonal variability in the personal–outdoor relationship was found, as personal exposures varied by as much as 200% for a given outdoor level.

Impact of the improved patsari biomass stove on urinary polycyclic aromatic hydrocarbon biomarkers and carbon monoxide exposures in rural Mexican women.

Background: Cooking with biomass fuels on open fires results in exposure to health-damaging pollutants such as carbon monoxide (CO), polycyclic aromatic hydrocarbons (PAHs), and particulate matter. Objective: We compared CO exposures and urinary PAH biomarkers pre- and postintervention with an improved biomass stove, the Patsari stove. Methods: In a subsample of 63 women participating in a randomized controlled trial in central Mexico, we measured personal CO exposure for 8 hr during the day using continuous monitors and passive samplers. In addition, first-morning urine samples obtained the next day were analyzed for monohydroxylated PAH metabolites by gas chromatography/isotope dilution/high-resolution mass spectrometry. Exposure data were collected during the use of an open fire (preintervention) and after installation of the improved stove (postintervention) for 47 women, enabling paired comparisons. Results: Median pre- and postintervention values were 4 and 1 ppm for continuous personal CO and 3 and 1 ppm for passive sampler CO, respectively. Postintervention measurements indicated an average reduction of 42% for hydroxylated metabolites of naphthalene, fluorene, phenanthrene, and pyrene on a whole-weight concentration basis (micrograms per liter of urine), and a 34% reduction on a creatinine-adjusted basis (micrograms per gram of creatinine). Pre- and postintervention geometric mean values for 1-hydroxypyrene were 3.2 and 2.0 μg/g creatinine, respectively. Conclusion: Use of the Patsari stove significantly reduced CO and PAH exposures in women. However, levels of many PAH biomarkers remained higher than those reported among smokers.

In vitro biological effects of airborne PM2.5 and PM10 from a semi-desert city on the Mexico–US border

Compelling evidence indicates that exposure to urban airborne particulate matter (PM) affects health. However, how PM components interact with PM-size to cause adverse health effects needs elucidation, especially when considering soil and anthropogenic sources. We studied PM from Mexicali, Mexico, where soil particles contribute importantly to air pollution, expecting to differentiate in vitro effects related to PM-size and composition. PM samples with mean aerodynamic diameters ≤2.5μm (PM(2.5)) and ≤10μm (PM(10)) were collected in Mexicali (October 2005-March 2006) from a semi-urban (expected larger participation of soil sources) and an urban (predominately combustion sources) site. Samples were pooled by site and size, analyzed for elemental composition (particle-induced X-ray emission) and tested in vitro for: induction of human erythrocytes membrane disruption (hemolysis) (colorimetrically); inhibition of cell proliferation (ICP) (crystal violet) and TNFα/IL-6 secretion (ELISA) using J774.A1 murine monocytic cells; and DNA degradation using Balb/c3T3 cell naked DNA (electrophoretically). Results of PM elemental composition principal component analysis were used in associating cellular effects. Sixteen elements identified in PM grouped in two principal components: Component(1) (C(1)): Mg, Al, Si, P, Cl, K, Ca, Ti, V, Cr, Fe, and Component(2) (C(2)): Cu, Zn. Hemolysis was predominately induced by semi-urban-PM(10) (p<0.05) and was associated with urban-PM(10)C(1) (r=0.62, p=0.003). Major ICP resulted with semi-urban PM(2.5) (p<0.05). TNFα was mainly induced by urban samples regardless of size (p<0.05) and associated with urban-PM(2.5)C(2) (r=0.48, p=0.02). Both PM(10) samples induced highest DNA degradation (p<0.05), regardless of location. We conclude that PM-size and PM-related soil or anthropogenic elements trigger specific biological-response patterns.

Personal PM2.5 and CO exposures and heart rate variability in subjects with known ischemic heart disease in Mexico City.

Cardiovascular diseases are the main cause of death in Mexico City and have shown a rising trend over the past 20 years. Various epidemiological studies have reported an association between respirable particles and carbon monoxide (CO), with cardiorespiratory outcomes. The purpose of this study was to assess the effect of particulate matter with aerodynamic diameters of less than 2.5 μm (PM2.5), also known as respirable or fine particles and CO on heart rate variability (HRV) in 5-min periods in patients with known ischemic heart disease. 30 patients were selected from the outpatient clinic of the National Institute of Cardiology of Mexico and followed during 11 h, using electrocardiography (ECG) ambulatory electrocardiograms and personal monitors for CO and PM2.5. We calculated frequency-domain measurements using power spectral analysis and assessed the association with pollutants using mixed models analysis in 5-min periods. We found a decrease in HRV measured as high frequency (Ln) (coefficient=−0.008, 95% confidence interval (CI), −0.015, 0.0004) for each 10 μg/m3 (micrograms per cubic meter) increase of personal PM2.5 exposure. We also found a decrease of low (ln) (coefficient=−0.024, 95% CI, −0.041, −0.007) and very low frequencies (ln) (coefficient=−0.034, 95% CI, −0.061, −0.007) for 1 parts per million (p.p.m.) increase in CO personal exposure after adjustment for potential confounding factors. These results show that for this high-risk population, the alteration of the cardiac autonomic regulation was significantly associated with both PM2.5 and CO personal exposures.

Air pollution, inflammation and preterm birth: A potential mechanistic link

Preterm birth is a public health issue of global significance, which may result in mortality during the perinatal period or may lead to major health and financial consequences due to lifelong impacts. Even though several risk factors for preterm birth have been identified, prevention efforts have failed to halt the increasing rates of preterm birth. Epidemiological studies have identified air pollution as an emerging potential risk factor for preterm birth. However, many studies were limited by study design and inadequate exposure assessment. Due to the ubiquitous nature of ambient air pollution and the potential public health significance of any role in causing preterm birth, a novel focus investigating possible causal mechanisms influenced by air pollution is therefore a global health priority. We hypothesize that air pollution may act together with other biological factors to induce systemic inflammation and influence the duration of pregnancy. Evaluation and testing of this hypothesis is currently being conducted in a prospective cohort study in Mexico City and will provide an understanding of the pathways that mediate the effects of air pollution on preterm birth. The important public health implication is that crucial steps in this mechanistic pathway can potentially be acted on early in pregnancy to reduce the risk of preterm birth.

Personal Exposures to Particles and Their Relationships with Personal Activities for Chronic Obstructive Pulmonary Disease Patients Living in Boston

Abstract An exposure study of 18 subjects with chronic obstructive pulmonary disease (COPD) living in the Boston, MA, area was conducted. The objective was to examine determinants of personal exposures to particulate matter (PM) with aerodynamic diameters of less than 2.5 μm (PM2.5), less than 10 μm (PM10), and between 2.5 and 10 μm (PM2.5–10). In a previous publication, the analyses of the longitudinal individual-specific relationships among indoor, outdoor, and personal levels showed that the relationships varied by subject and by particle size fraction. In the present paper, statistical and physical models were used to examine personal PM2.5,PM10, and PM2.5–10 exposure covariates. Results indicated that time-weighted indoor concentrations were significant predictors of personal PM2.5,PM10, and PM2.5–10 exposures. Also, time-weighted outdoor concentrations, time spent near smokers, and time spent during transportation were important predictors for PM2.5 but not for personal PM2.5–10 exposures. In turn, time spent cleaning contributed to all size-fraction personal exposures, whereas cooking affected only personal PM2.5–10 exposures. The findings showed that the relationship between personal PM2.5 exposures and the corresponding ambient concentrations was influenced by home air exchange rates (or by ventilation status). Because the particle properties or components causing the health effects are unknown, it is not certain to what extent the risk posed by ambient particles can be reduced by controlling any one of these factors.

Variation in the composition and in vitro proinflammatory effect of urban particulate matter from different sites.

Spatial variation in particulate matter–related health and toxicological outcomes is partly due to its composition. We studied spatial variability in particle composition and induced cellular responses in Mexico City to complement an ongoing epidemiologic study. We measured elements, endotoxins, and polycyclic aromatic hydrocarbons in two particle size fractions collected in five sites. We compared the in vitro proinflammatory response of J774A.1 and THP‐1 cells after exposure to particles, measuring subsequent TNFα and IL‐6 secretion. Particle composition varied by site and size. Particle constituents were subjected to principal component analysis, identifying three components: C1 (Si, Sr, Mg, Ca, Al, Fe, Mn, endotoxin), C2 (polycyclic aromatic hydrocarbons), and C3 (Zn, S, Sb, Ni, Cu, Pb). Induced TNFα levels were higher and more heterogeneous than IL‐6 levels. Cytokines produced by both cell lines only correlated with C1, suggesting that constituents associated with soil induced the inflammatory response and explain observed spatial differences.

TNFα and IL-6 Responses to Particulate Matter in Vitro: Variation According to PM Size, Season, and Polycyclic Aromatic Hydrocarbon and Soil Content.

Background: Observed seasonal differences in particulate matter (PM) associations with human health may be due to their composition and to toxicity-related seasonal interactions. Objectives: We assessed seasonality in PM composition and in vitro PM pro-inflammatory potential using multiple PM samples. Methods: We collected 90 weekly PM10 and PM2.5 samples during the rainy-warm and dry-cold seasons in five urban areas with different pollution sources. The elements, polycyclic aromatic hydrocarbons (PAHs), and endotoxins identified in the samples were subjected to principal component analysis (PCA). We tested the potential of the PM to induce tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) secretion in cultured human monocytes (THP-1), and we modeled pro-inflammatory responses using the component scores. Results: PM composition varied by size and by season. PCA identified two main components that varied by season. Combustion-related constituents (e.g., vanadium, benzo[a]pyrene, benzo[a]anthracene) mainly comprised component 1 (C1). Soil-related constituents (e.g., endotoxins, silicon, aluminum) mainly comprised component 2 (C2). PM from the rainy-warm season was high in C2. PM (particularly PM2.5) from the dry-cold season was rich in C1. Elevated levels of cytokine production were associated with PM10 and C2 (rainy-warm season), whereas reduced levels of cytokine production were associated with PM2.5 and C1 (dry-cold season). TNFα secretion was increased following exposure to PM with high (vs. low) C2 content, but TNFα secretion in response to PM was decreased following exposure to samples containing ≥ 0.1% of C1-related PAHs, regardless of C2 content. The results of the IL-6 assays suggested more complex interactions between PM components and particle size. Conclusions: Variations in PM soil and PAH content underlie seasonal and PM size–related patterns in TNFα secretion. These results suggest that the mixture of components in PM explains some seasonal differences in associations between health outcomes and PM in epidemiologic studies. Citation: Manzano-León N, Serrano-Lomelin J, Sánchez BN, Quintana-Belmares R, Vega E, Vázquez-López I, Rojas-Bracho L, López-Villegas MT, Vadillo-Ortega F, De Vizcaya-Ruiz A, Rosas Perez I, O’Neill MS, Osornio-Vargas AR. 2016. TNFα and IL-6 responses to particulate matter in vitro: variation according to PM size, season, and polycyclic aromatic hydrocarbon and soil content. Environ Health Perspect 124:406–412; http://dx.doi.org/10.1289/ehp.1409287

Air pollution, inflammation and preterm birth in Mexico City: study design and methods.

Preterm birth is one of the leading causes of perinatal mortality and is associated with long-term adverse health consequences for surviving infants. Preterm birth rates are rising worldwide, and no effective means for prevention currently exists. Air pollution exposure may be a significant cause of prematurity, but many published studies lack the individual, clinical data needed to elucidate possible biological mechanisms mediating these epidemiological associations. This paper presents the design of a prospective study now underway to evaluate those mechanisms in a cohort of pregnant women residing in Mexico City. We address how air quality may act together with other factors to induce systemic inflammation and influence the duration of pregnancy. Data collection includes: biomarkers relevant to inflammation in cervico-vaginal exudate and peripheral blood, along with full clinical information, pro-inflammatory cytokine gene polymorphisms and air pollution data to evaluate spatial and temporal variability in air pollution exposure. Samples are collected on a monthly basis and participants are followed for the duration of pregnancy. The data will be used to evaluate whether ambient air pollution is associated with preterm birth, controlling for other risk factors. We will evaluate which time windows during pregnancy are most influential in the air pollution and preterm birth association. In addition, the epidemiological study will be complemented with a parallel toxicology invitro study, in which monocytic cells will be exposed to air particle samples to evaluate the expression of biomarkers of inflammation.

An assessment of air pollutant exposure methods in Mexico City, Mexico.

Geostatistical interpolation methods to estimate individual exposure to outdoor air pollutants can be used in pregnancy cohorts where personal exposure data are not collected. Our objectives were to a) develop four assessment methods (citywide average (CWA); nearest monitor (NM); inverse distance weighting (IDW); and ordinary Kriging (OK)), and b) compare daily metrics and cross-validations of interpolation models. We obtained 2008 hourly data from Mexico City’s outdoor air monitoring network for PM10, PM2.5, O3, CO, NO2, and SO2 and constructed daily exposure metrics for 1,000 simulated individual locations across five populated geographic zones. Descriptive statistics from all methods were calculated for dry and wet seasons, and by zone. We also evaluated IDW and OK methods’ ability to predict measured concentrations at monitors using cross validation and a coefficient of variation (COV). All methods were performed using SAS 9.3, except ordinary Kriging which was modeled using R’s gstat package. Overall, mean concentrations and standard deviations were similar among the different methods for each pollutant. Correlations between methods were generally high (r = 0.77 to 0.99). However, ranges of estimated concentrations determined by NM, IDW, and OK were wider than the ranges for CWA. Root mean square errors for OK were consistently equal to or lower than for the IDW method. OK standard errors varied considerably between pollutants and the computed COVs ranged from 0.46 (least error) for SO2 and PM10 to 3.91 (most error) for PM2.5. OK predicted concentrations measured at the monitors better than IDW and NM. Given the similarity in results for the exposure methods, OK is preferred because this method alone provides predicted standard errors which can be incorporated in statistical models. The daily estimated exposures calculated using these different exposure methods provide flexibility to evaluate multiple windows of exposure during pregnancy, not just trimester or pregnancy-long exposures. Implications: Many studies evaluating associations between outdoor air pollution and adverse pregnancy outcomes rely on outdoor air pollution monitoring data linked to information gathered from large birth registries, and often lack residence location information needed to estimate individual exposure. This study simulated 1,000 residential locations to evaluate four air pollution exposure assessment methods, and describes possible exposure misclassification from using spatial averaging versus geostatistical interpolation models. An implication of this work is that policies to reduce air pollution and exposure among pregnant women based on epidemiologic literature should take into account possible error in estimates of effect when spatial averages alone are evaluated.