Lung Ultrasound Protocol and Quality Control of Image Interpretation Using an Adjudication Panel in the Household Air Pollution Intervention Network (HAPIN) Trial.

OBJECTIVE: Lung ultrasound (LUS) is an alternative to chest radiography to confirm a diagnosis of pneumonia. For research and disease surveillance, methods to use LUS to diagnose pneumonia are needed. METHODS: In the Household Air Pollution Intervention Network (HAPIN) trial, LUS was used to confirm a clinical diagnosis of severe pneumonia in infants. We developed a standardized definition of pneumonia, protocols for recruitment and training of sonographers, along with LUS image acquisition and interpretation. We use a blinded panel approach to interpretation with LUS cine-loops randomized to non-scanning sonographers with expert review. DISCUSSION: We obtained 357 lung ultrasound scans: 159, 8 and 190 scans were collected in Guatemala, Peru and Rwanda, respectively. The diagnosis of primary endpoint pneumonia (PEP) required an expert tie breaker in 181 scans (39%). PEP was diagnosed in 141 scans (40%), not diagnosed in 213 (60%), with 3 scans (<1%) deemed uninterpretable. Agreement among the two blinded sonographers and the expert reader in Guatemala, Peru and Rwanda was 65%, 62% and 67%, with a prevalence-and-bias-corrected kappa of 0.30, 0.24 and 0.33, respectively. CONCLUSION: Use of standardized imaging protocols, training and an adjudication panel resulted in high confidence for the diagnosis of pneumonia using LUS.

Cross-sectional analysis of the association between personal exposure to household air pollution and blood pressure in adult women: Evidence from the multi-country Household Air Pollution Intervention Network (HAPIN) trial.

Elevated blood pressure (BP) is a leading risk factor for the global burden of disease. Household air pollution (HAP), resulting from the burning of biomass fuels, may be an important cause of elevated BP in resource-poor communities. We examined the exposure-response relationship of personal exposures to HAP -fine particulate matter (PM2.5), carbon monoxide (CO), and black carbon (BC) - with BP measures in women aged 40-79 years across four resource-poor settings in Guatemala, Peru, India and Rwanda. BP was obtained within a day of 24-h personal exposure measurements at baseline, when participants were using biomass for cooking. We used generalized additive models to characterize the shape of the association between BP and HAP, accounting for the interaction of personal exposures and age and adjusting for a priori identified confounders. A total of 418 women (mean age 52.2 ± 7.9 years) were included in this analysis. The interquartile range of exposures to PM2.5 was 42.9-139.5 µg/m3, BC was 6.4-16.1 µg/m3, and CO was 0.5-2.9 ppm. Both SBP and PP were positively associated with PM2.5 exposure in older aged women, achieving statistical significance around 60 years of age. The exact threshold varied by BP measure and PM2.5 exposures being compared. For example, SBP of women aged 65 years was on average 10.8 mm Hg (95% CI 1.0-20.6) higher at 232 µg/m3 of PM2.5 exposure (90th percentile) when compared to that of women of the same age with personal exposures of 10 µg/m3. PP in women aged 65 years was higher for exposures ≥90 µg/m3, with mean differences of 6.1 mm Hg (95% CI 1.8-10.5) and 9.2 mm Hg (95% CI 3.3-15.1) at 139 (75th percentile) and 232 µg/m3 (90th percentile) respectively, when compared to that of women of the same age with PM2.5 exposures of 10 µg/m3. Our findings suggest that reducing HAP exposures may help to reduce BP, particularly among older women.

Histone 3 modifications and blood pressure in the Beijing Truck Driver Air Pollution Study.

CONTEXT: Histone modifications regulate gene expression; dysregulation has been linked with cardiovascular diseases. Associations between histone modification levels and blood pressure in humans are unclear. OBJECTIVE: We examine the relationship between global histone concentrations and various markers of blood pressure. MATERIALS AND METHODS: Using the Beijing Truck Driver Air Pollution Study, we investigated global peripheral white blood cell histone modifications (H3K9ac, H3K9me3, H3K27me3, and H3K36me3) associations with pre- and post-work measurements of systolic (SBP) and diastolic (DBP) blood pressure, mean arterial pressure (MAP), and pulse pressure (PP) using multivariable mixed-effect models. RESULTS: H3K9ac was negatively associated with pre-work SBP and MAP; H3K9me3 was negatively associated with pre-work SBP, DBP, and MAP; and H3K27me3 was negatively associated with pre-work SBP. Among office workers, H3K9me3 was negatively associated with pre-work SBP, DBP, and MAP. Among truck drivers, H3K9ac and H3K27me were negatively associated with pre-work SBP, and H3K27me3 was positively associated with post-work PP. DISCUSSION AND CONCLUSION: Epigenome-wide H3K9ac, H3K9me3, and H3K27me3 were negatively associated with multiple pre-work blood pressure measures. These associations substantially changed during the day, suggesting an influence of daily activities. Blood-based histone modification biomarkers are potential candidates for studies requiring estimations of morning/pre-work blood pressure.

Blood pressure and expression of microRNAs in whole blood.

BACKGROUND: Blood pressure (BP) is a complex, multifactorial clinical outcome driven by genetic susceptibility, behavioral choices, and environmental factors. Many molecular mechanisms have been proposed for the pathophysiology of high BP even as its prevalence continues to grow worldwide, increasing morbidity and marking it as a major public health concern. To address this, we evaluated miRNA profiling in blood leukocytes as potential biomarkers of BP and BP-related risk factors. METHODS: The Beijing Truck Driver Air Pollution Study included 60 truck drivers and 60 office workers examined in 2008. On two days separated by 1-2 weeks, we examined three BP measures: systolic, diastolic, and mean arterial pressure measured at both pre- and post-work exams for blood NanoString nCounter miRNA profiles. We used covariate-adjusted linear mixed-effect models to examine associations between BP and increased miRNA expression in both pooled and risk factor-stratified analyses. RESULTS: Overall 43 miRNAs were associated with pre-work BP (FDR<0.05). In stratified analyses different but overlapping groups of miRNAs were associated with pre-work BP in truck drivers, high-BMI participants, and usual alcohol drinkers (FDR<0.05). Only four miRNAs were associated with post-work BP (FDR<0.05), in ever smokers. CONCLUSION: Our results suggest that many miRNAs were significantly associated with BP in subgroups exposed to known hypertension risk factors. These findings shed light on the underlying molecular mechanisms of BP, and may assist with the development of a miRNA panel for early detection of hypertension.

Traffic-derived particulate matter exposure and histone H3 modification: A repeated measures study.

BACKGROUND: Airborne particulate matter (PM) may induce epigenetic changes that potentially lead to chronic diseases. Histone modifications regulate gene expression by influencing chromatin structure that can change gene expression status. We evaluated whether traffic-derived PM exposure is associated with four types of environmentally inducible global histone H3 modifications. METHODS: The Beijing Truck Driver Air Pollution Study included 60 truck drivers and 60 office workers examined twice, 1-2 weeks apart, for ambient PM10 (both day-of and 14-day average exposures), personal PM2.5, black carbon (BC), and elemental components (potassium, sulfur, iron, silicon, aluminum, zinc, calcium, and titanium). For both PM10 measures, we obtained hourly ambient PM10 data for the study period from the Beijing Municipal Environmental Bureau's 27 representatively distributed monitoring stations. We then calculated a 24h average for each examination day and a moving average of ambient PM10 measured in the 14 days prior to each examination. Examinations measured global levels of H3 lysine 9 acetylation (H3K9ac), H3 lysine 9 tri-methylation (H3K9me3), H3 lysine 27 tri-methylation (H3K27me3), and H3 lysine 36 tri-methylation (H3K36me3) in blood leukocytes collected after work. We used adjusted linear mixed-effect models to examine percent changes in histone modifications per each µg/m3 increase in PM exposure. RESULTS: In all participants each µg/m3 increase in 14-day average ambient PM10 exposure was associated with lower H3K27me3 (ß=-1.1%, 95% CI: -1.6, -0.6) and H3K36me3 levels (ß=-0.8%, 95% CI: -1.4, -0.1). Occupation-stratified analyses showed associations between BC and both H3K9ac and H3K36me3 that were stronger in office workers (ß=4.6%, 95% CI: 0.9, 8.4; and ß=4.1%, 95% CI: 1.3; 7.0 respectively) than in truck drivers (ß=0.1%, 95% CI: -1.3, 1.5; and ß=0.9%, 95% CI: -0.9, 2.7, respectively; both pinteraction <0.05). Sex-stratified analyses showed associations between examination-day PM10 and H3K9ac, and between BC and H3K9me3, were stronger in women (ß=10.7%, 95% CI: 5.4, 16.2; and ß=7.5%, 95% CI: 1.2, 14.2, respectively) than in men (ß=1.4%, 95% CI: -0.9, 3.7; and ß=0.9%, 95% CI: -0.9, 2.7, respectively; both pinteraction <0.05). We observed no associations between personal PM2.5 or elemental components and histone modifications. CONCLUSIONS: Our results suggest a possible role of global histone H3 modifications in effects of traffic-derived PM exposures, particularly BC exposure. Future studies should assess the roles of these modifications in human diseases and as potential mediators of air pollution-induced disease, in particular BC exposure.

Lung function in woodsmoke-exposed Guatemalan children following a chimney stove intervention.

RATIONALE: Household air pollution (HAP) from solid fuel combustion is a major contributor to the global burden of disease, with considerable impact from respiratory infections in children. The impact of HAP on lung function is unknown. OBJECTIVES: The Childhood Exposure to Respirable Particulate Matter (CRECER) prospective cohort study followed Guatemalan children who participated in the Randomised Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) trial of a chimney stove intervention to determine the effect of early childhood HAP exposure on growth of lung function. METHODS: RESPIRE households with pregnant women or infant children were randomised to receive a chimney stove at the beginning or at the end of the 18-month trial. During CRECER, a subset of these children, as well as children from households with newly installed stoves, were followed with spirometry beginning at age 5. Biomass smoke exposure was measured using personal carbon monoxide tubes. Two-stage regression models were employed to analyse associations with lung function growth. MEASUREMENTS AND MAIN RESULTS: Longitudinal peak expiratory flow (PEF) and FEV1 data were available for 443 and 437 children, respectively, aged 5-8 (mean follow-up 1.3 years). Decreases in PEF growth of 173 mL/min/year (95% CI -341 to -7) and FEV1 of 44 mL/year (95% CI -91 to 4) were observed with stove installation at 18 months compared with stove installation at birth in analyses adjusted for multiple covariates. No statistically significant associations were observed between personal HAP exposure and lung function. CONCLUSIONS: A significant decrease in PEF growth and a large non-significant decrease in FEV1 growth were observed with later stove installation. Additional studies including longer follow-up and cleaner stoves or fuels are needed.

Particulate Air Pollution Exposure and Expression of Viral and Human MicroRNAs in Blood: The Beijing Truck Driver Air Pollution Study.

BACKGROUND: MicroRNAs (miRNAs) are post-transcriptional gene suppressors and potential mediators of environmental effects. In addition to human miRNAs, viral miRNAs expressed from latent viral sequences are detectable in human cells. OBJECTIVE: In a highly exposed population in Beijing, China, we evaluated the associations of particulate air pollution exposure on blood miRNA profiles. METHODS: The Beijing Truck Driver Air Pollution Study (BTDAS) included 60 truck drivers and 60 office workers. We investigated associations of short-term air pollution exposure, using measures of personal PM2.5 (particulate matter ≤ 2.5 µm) and elemental carbon (EC), and ambient PM10 (≤ 10 µm), with blood NanoString nCounter miRNA profiles at two exams separated by 1-2 weeks. RESULTS: No miRNA was significantly associated with personal PM2.5 at a false discovery rate (FDR) of 20%. Short-term ambient PM10 was associated with the expression of 12 miRNAs in office workers only (FDR < 20%). Short-term EC was associated with differential expression of 46 human and 7 viral miRNAs, the latter including 3 and 4 viral miRNAs in office workers and truck drivers, respectively. EC-associated miRNAs differed between office workers and truck drivers with significant effect modification by occupational group. Functional interaction network analysis suggested enriched cellular proliferation/differentiation pathways in truck drivers and proinflammation pathways in office workers. CONCLUSIONS: Short-term EC exposure was associated with the expression of human and viral miRNAs that may influence immune responses and other biological pathways. Associations between EC exposure and viral miRNA expression suggest that latent viral miRNAs are potential mediators of air pollution-associated health effects. PM2.5/PM10 exposures showed no consistent relationships with miRNA expression.

Effects of particulate matter exposure on blood 5-hydroxymethylation: results from the Beijing truck driver air pollution study.

Previous studies have reported epigenetic changes induced by environmental exposures. However, previous investigations did not distinguish 5-methylcytosine (5mC) from a similar oxidative form with opposite functions, 5-hydroxymethylcytosine (5hmC). Here, we measured blood DNA global 5mC and 5hmC by ELISA and used adjusted mixed-effects regression models to evaluate the effects of ambient PM10 and personal PM2.5 and its elemental components-black carbon (BC), aluminum (Al), calcium (Ca), potassium (K), iron (Fe), sulfur (S), silicon (Si), titanium (Ti), and zinc (Zn)-on blood global 5mC and 5hmC levels. The study was conducted in 60 truck drivers and 60 office workers in Beijing, China from The Beijing Truck Driver Air Pollution Study at 2 exams separated by one to 2 weeks. Blood 5hmC level (0.08%) was ∼83-fold lower than 5mC (6.61%). An inter-quartile range (IQR) increase in same-day PM10 was associated with increases in 5hmC of 26.1% in office workers (P = 0.004), 20.2% in truck drivers (P = 0.014), and 21.9% in all participants combined (P < 0.001). PM10 effects on 5hmC were increasingly stronger when averaged over 4, 7, and 14 d preceding assessment (up to 132.6% for the 14-d average in all participants, P < 0.001). PM10 effects were also significant after controlling for multiple testing (family-wise error rate; FWER < 0.05). 5hmC was not correlated with personal measures of PM2.5 and elemental components (FWER > 0.05). 5mC showed no correlations with PM10, PM2.5, and elemental components measures (FWER > 0.05). Our study suggests that exposure to ambient PM10 affects 5hmC over time, but not 5mC. This finding demonstrates the need to differentiate 5hmC and 5mC in environmental studies of DNA methylation.

Strong and Flexible: Developing a Three-Tiered Curriculum for the Regional Central America Field Epidemiology Training Program.

Field Epidemiology Training Programs (FETPs) are recognized worldwide as an effective means to strengthen countries' capacity in epidemiology, surveillance, and outbreak response. FETPs are field-based, with minimum classroom time and maximum time in the field, providing public health services while participants achieve competency. The Central America FETP (CAFETP) uses a three-level pyramid model: basic, intermediate, and advanced. In 2006, a multidisciplinary team used a methodical process based on adult learning practices to construct a competency-based curriculum for the CAFETP. The curriculum was designed based on the tasks related to disease surveillance and field epidemiology that public health officers would conduct at multiple levels in the system. The team used a design process that engaged subject matter experts and considered the unique perspective of each country. The designers worked backwards from the competencies to define field activities, evaluation methods, and classroom components. The 2006 pyramid curriculum has been accredited for a master's of science in field epidemiology by the Universidad del Valle de Guatemala and has been adapted by programs around the world. The team found the time and effort spent to familiarize subject matter experts with key adult learning principles was worthwhile because it provided a common framework to approach curriculum design. Early results of the redesigned curriculum indicate that the CAFETP supports consistent quality while allowing for specific country needs.

Air pollution exposure and lung function in highly exposed subjects in Beijing, China: a repeated-measure study.

BACKGROUND: Exposure to ambient particulate matter (PM) has been associated with reduced lung function. Elemental components of PM have been suggested to have critical roles in PM toxicity, but their contribution to respiratory effects remains under-investigated. We evaluated the effects of traffic-related PM(2.5) and its elemental components on lung function in two highly exposed groups of healthy adults in Beijing, China. METHODS: The Beijing Truck Driver Air Pollution Study (BTDAS) included 60 truck drivers and 60 office workers evaluated in 2008. On two days separated by 1-2 weeks, we measured lung function at the end of the work day, personal PM(2.5), and nine elemental components of PM(2.5) during eight hours of work, i.e., elemental carbon (EC), potassium (K), sulfur (S), iron (Fe), silicon (Si), aluminum (Al), zinc (Zn), calcium (Ca), and titanium (Ti). We used covariate-adjusted mixed-effects models including PM(2.5) as a covariate to estimate the percentage change in lung function associated with an inter-quartile range (IQR) exposure increase. RESULTS: The two groups had high and overlapping exposure distributions with mean personal PM(2.5) of 94.6 µg/m³ (IQR: 48.5-126.6) in office workers and 126.8 µg/m³ (IQR: 73.9-160.5) in truck drivers. The distributions of the nine elements showed group-specific profiles and generally higher levels in truck drivers. In all subjects combined, forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) did not significantly correlate with PM(2.5). However, FEV1 showed negative associations with concentrations of four elements: Si (-3.07%, 95% CI: -5.00; -1.11, IQR: 1.54), Al (-2.88%, 95% CI: -4.91; -0.81, IQR: 0.86), Ca (-1.86%, 95% CI: -2.95; -0.76, IQR: 1.33), and Ti (-2.58%, 95% CI: -4.44; -0.68, IQR: 0.03), and FVC showed negative associations with concentrations of three elements: Si (-3.23%, 95% CI: -5.61; -0.79), Al (-3.26%, 95% CI: -5.73; -0.72), and Ca (-1.86%, 95% CI: -3.23; -0.47). In stratified analysis, Si, Al, Ca, and Ti showed associations with lung function only among truck drivers, and no significant association among office workers. CONCLUSION: Selected elemental components of PM(2.5) showed effects on lung function that were not found in analyses of particle levels alone.

Effects of woodsmoke exposure on airway inflammation in rural Guatemalan women.

BACKGROUND: More than two-fifths of the world's population uses solid fuels, mostly biomass, for cooking. The resulting biomass smoke exposure is a major cause of chronic obstructive pulmonary disease (COPD) among women in developing countries. OBJECTIVE: To assess whether lower woodsmoke exposure from use of a stove with a chimney, compared to open fires, is associated with lower markers of airway inflammation in young women. DESIGN: We carried out a cross-sectional analysis on a sub-cohort of participants enrolled in a randomized controlled trial in rural Guatemala, RESPIRE. PARTICIPANTS: We recruited 45 indigenous women at the end of the 18-month trial; 19 women who had been using the chimney stove for 18-24 months and 26 women still using open fires. MEASUREMENTS: We obtained spirometry and induced sputum for cell counts, gene expression of IL-8, TNF-α, MMP-9 and 12, and protein concentrations of IL-8, myeloperoxidase and fibronectin. Exhaled carbon monoxide (CO) and 48-hr personal CO tubes were measured to assess smoke exposure. RESULTS: MMP-9 gene expression was significantly lower in women using chimney stoves. Higher exhaled CO concentrations were significantly associated with higher gene expression of IL-8, TNF-α, and MMP-9. Higher 48-hr personal CO concentrations were associated with higher gene expression of IL-8, TNF- α, MMP-9 and MMP-12; reaching statistical significance for MMP-9 and MMP-12. CONCLUSIONS: Compared to using an open wood fire for cooking, use of a chimney stove was associated with lower gene expression of MMP-9, a potential mediator of airway remodeling. Among all participants, indoor biomass smoke exposure was associated with higher gene expression of multiple mediators of airway inflammation and remodeling; these mechanisms may explain some of the observed association between prolonged biomass smoke exposure and COPD.

Effects of short-term exposure to inhalable particulate matter on DNA methylation of tandem repeats.

There is compelling evidence that particulate matter (PM) increases lung cancer risk by triggering systemic inflammation, and leukocyte DNA hypomethylation. However, previous investigations focused on repeated element sequences from LINE-1 and Alu families. Tandem repeats, which display a greater propensity to mutate, and are often hypomethylated in cancer patients, have never been investigated in individuals exposed to PM. We measured methylation of three tandem repeats (SATα, NBL2, and D4Z4) by polymerase chain reaction-pyrosequencing on blood samples from truck drivers and office workers (60 per group) in Beijing, China. We used lightweight monitors to measure personal PM2.5 (PM with aerodynamic diameter ≤2.5 µm) and elemental carbon (a tracer of PM from vehicular traffic). Ambient PM10 data were obtained from air quality measuring stations. Overall, an interquartile increase in personal PM2.5 and ambient PM10 levels was associated with a significant covariate-adjusted decrease in SATα methylation (-1.35% 5-methyl cytosine [5mC], P = 0.01; and -1.33%5mC; P = 0.01, respectively). Effects from personal PM2.5 and ambient PM10 on SATα methylation were stronger in truck drivers (-2.34%5mC, P = 0.02; -1.44%5mC, P = 0.06) than office workers (-0.95%5mC, P = 0.26; -1.25%5mC, P = 0.12, respectively). Ambient PM10 was negatively correlated with NBL2 methylation in truck drivers (-1.38%5mC, P = 0.03) but not in office workers (1.04%5mC, P = 0.13). Our result suggests that PM exposure is associated with hypomethylation of selected tandem repeats. Measuring tandem-repeat hypomethylation in easy-to-obtain blood specimens might identify individuals with biological effects and potential cancer risk from PM exposure.

Altered methylation in tandem repeat element and elemental component levels in inhalable air particles.

Exposure to particulate matter (PM) has been associated with lung cancer risk in epidemiology investigations. Elemental components of PM have been suggested to have critical roles in PM toxicity, but the molecular mechanisms underlying their association with cancer risks remain poorly understood. DNA methylation has emerged as a promising biomarker for environmental-related diseases, including lung cancer. In this study, we evaluated the effects of PM elemental components on methylation of three tandem repeats in a highly exposed population in Beijing, China. The Beijing Truck Driver Air Pollution Study was conducted shortly before the 2008 Beijing Olympic Games (June 15-July 27, 2008) and included 60 truck drivers and 60 office workers. On two days separated by 1-2 weeks, we measured blood DNA methylation of SATα, NBL2, D4Z4, and personal exposure to eight elemental components in PM2.5 , including aluminum (Al), silicon (Si), sulfur (S), potassium (K), calcium (Ca) titanium (Ti), iron (Fe), and zinc (Zn). We estimated the associations of individual elemental component with each tandem-repeat methylation in generalized estimating equations (GEE) models adjusted for PM2.5 mass and other covariates. Out of the eight examined elements, NBL2 methylation was positively associated with concentrations of Si [0.121, 95% confidence interval (CI): 0.030; 0.212, False Discovery Rate (FDR) = 0.047] and Ca (0.065, 95%CI: 0.014; 0.115, FDR = 0.047) in truck drivers. In office workers, SATα methylation was positively associated with concentrations of S (0.115, 95% CI: 0.034; 0.196, FDR = 0.042). PM-associated differences in blood tandem-repeat methylation may help detect biological effects of the exposure and identify individuals who may eventually experience higher lung cancer risk.

Longitudinal relationship between personal CO and personal PM2.5 among women cooking with woodfired cookstoves in Guatemala.

Household air pollution (HAP) due to solid fuel use is a major public health threat in low-income countries. Most health effects are thought to be related to exposure to the fine particulate matter (PM) component of HAP, but it is currently impractical to measure personal exposure to PM in large studies. Carbon monoxide (CO) has been shown in cross-sectional analyses to be a reliable surrogate for particles<2.5 µm in diameter (PM2.5) in kitchens where wood-burning cookfires are a dominant source, but it is unknown whether a similar PM2.5-CO relationship exists for personal exposures longitudinally. We repeatedly measured (216 measures, 116 women) 24-hour personal PM2.5 (median [IQR] = 0.11 [0.05, 0.21] mg/m(3)) and CO (median [IQR] = 1.18 [0.50, 2.37] mg/m(3)) among women cooking over open woodfires or chimney woodstoves in Guatemala. Pollution measures were natural-log transformed for analyses. In linear mixed effects models with random subject intercepts, we found that personal CO explained 78% of between-subject variance in personal PM2.5. We did not see a difference in slope by stove type. This work provides evidence that in settings where there is a dominant source of biomass combustion, repeated measures of personal CO can be used as a reliable surrogate for an individual's PM2.5 exposure. This finding has important implications for the feasibility of reliably estimating long-term (months to years) PM2.5 exposure in large-scale epidemiological and intervention studies of HAP.

Air pollution exposure and telomere length in highly exposed subjects in Beijing, China: a repeated-measure study.

BACKGROUND: Ambient particulate matter (PM) exposure has been associated with short- and long-term effects on cardiovascular disease (CVD). Telomere length (TL) is a biomarker of CVD risk that is modified by inflammation and oxidative stress, two key pathways for PM effects. Whether PM exposure modifies TL is largely unexplored. OBJECTIVES: To investigate effects of PM on blood TL in a highly-exposed population. METHODS: We measured blood TL in 120 blood samples from truck drivers and 120 blood samples from office workers in Beijing, China. We measured personal PM(2.5) and Elemental Carbon (EC, a tracer of traffic particles) using light-weight monitors. Ambient PM(10) was obtained from local monitoring stations. We used covariate-adjusted regression models to estimate percent changes in TL per an interquartile-range increase in exposure. RESULTS: Covariate-adjusted TL was higher in drivers (mean=0.87, 95%CI: 0.74; 1.03) than in office workers (mean=0.79, 95%CI: 0.67; 0.93; p=0.001). In all participants combined, TL increased in association with personal PM(2.5) (+5.2%, 95%CI: 1.5; 9.1; p=0.007), personal EC (+4.9%, 95%CI: 1.2; 8.8; p=0.01), and ambient PM(10) (+7.7%, 95%CI: 3.7; 11.9; p<0.001) on examination days. In contrast, average ambient PM(10) over the 14 days before the examinations was significantly associated with shorter TL (-9.9%, 95%CI: -17.6; -1.5; p=0.02). CONCLUSIONS: Short-term exposure to ambient PM is associated with increased blood TL, consistent with TL roles during acute inflammatory responses. Longer exposures may shorten TL as expected after prolonged pro-oxidant exposures. The observed TL alterations may participate in the biological pathways of short- and long-term PM effects.

Effects of particulate air pollution on blood pressure in a highly exposed population in Beijing, China: a repeated-measure study.

BACKGROUND: Particulate Matter (PM) exposure is critical in Beijing due to high population density and rapid increase in vehicular traffic. PM effects on blood pressure (BP) have been investigated as a mechanism mediating cardiovascular risks, but results are still inconsistent. The purpose of our study is to determine the effects of ambient and personal PM exposure on BP. METHODS: Before the 2008 Olympic Games (June 15-July 27), we examined 60 truck drivers and 60 office workers on two days, 1-2 weeks apart (n = 240). We obtained standardized measures of post-work BP. Exposure assessment included personal PM(2.5) and Elemental Carbon (EC, a tracer of traffic particles) measured using portable monitors during work hours; and ambient PM(10) averaged over 1-8 days pre-examination. We examined associations of exposures (exposure group, personal PM(2.5)/EC, ambient PM(10)) with BP controlling for multiple covariates. RESULTS: Mean personal PM(2.5) was 94.6 µg/m(3) (SD = 64.9) in office workers and 126.8 (SD = 68.8) in truck drivers (p-value < 0.001). In all participants combined, a 10 µg/m(3) increase in 8-day ambient PM(10) was associated with BP increments of 0.98 (95%CI 0.34; 1.61; p-value = 0.003), 0.71 (95%CI 0.18; 1.24; p-value = 0.01), and 0.81 (95%CI 0.31; 1.30; p-value = 0.002) mmHg for systolic, diastolic, and mean BP, respectively. BP was not significantly different between the two groups (p-value > 0.14). Personal PM(2.5) and EC during work hours were not associated with increased BP. CONCLUSIONS: Our results indicate delayed effects of ambient PM(10) on BP. Lack of associations with exposure groups and personal PM(2.5)/EC indicates that PM effects are related to background levels of pollution in Beijing, and not specifically to work-related exposure.

Effect of reduction in household air pollution on childhood pneumonia in Guatemala (RESPIRE): a randomised controlled trial.

BACKGROUND: Pneumonia causes more child deaths than does any other disease. Observational studies have indicated that smoke from household solid fuel is a significant risk factor that affects about half the world's children. We investigated whether an intervention to lower indoor wood smoke emissions would reduce pneumonia in children. METHODS: We undertook a parallel randomised controlled trial in highland Guatemala, in a population using open indoor wood fires for cooking. We randomly assigned 534 households with a pregnant woman or young infant to receive a woodstove with chimney (n=269) or to remain as controls using open woodfires (n=265), by concealed permuted blocks of ten homes. Fieldworkers visited homes every week until children were aged 18 months to record the child's health status. Sick children with cough and fast breathing, or signs of severe illness were referred to study physicians, masked to intervention status, for clinical examination. The primary outcome was physician-diagnosed pneumonia, without use of a chest radiograph. Analysis was by intention to treat (ITT). Infant 48-h carbon monoxide measurements were used for exposure-response analysis after adjustment for covariates. This trial is registered, number ISRCTN29007941. FINDINGS: During 29,125 child-weeks of surveillance of 265 intervention and 253 control children, there were 124 physician-diagnosed pneumonia cases in intervention households and 139 in control households (rate ratio [RR] 0·84, 95% CI 0·63-1·13; p=0·257). After multiple imputation, there were 149 cases in intervention households and 180 in controls (0·78, 0·59-1·06, p=0·095; reduction 22%, 95% CI -6% to 41%). ITT analysis was undertaken for secondary outcomes: all and severe fieldworker-assessed pneumonia; severe (hypoxaemic) physician-diagnosed pneumonia; and radiologically confirmed, RSV-negative, and RSV-positive pneumonia, both total and severe. We recorded significant reductions in the intervention group for three severe outcomes-fieldworker-assessed, physician-diagnosed, and RSV-negative pneumonia--but not for others. We identified no adverse effects from the intervention. The chimney stove reduced exposure by 50% on average (from 2·2 to 1·1 ppm carbon monoxide), but exposure distributions for the two groups overlapped substantially. In exposure-response analysis, a 50% exposure reduction was significantly associated with physician-diagnosed pneumonia (RR 0·82, 0·70-0·98), the greater precision resulting from less exposure misclassification compared with use of stove type alone in ITT analysis. INTERPRETATION: In a population heavily exposed to wood smoke from cooking, a reduction in exposure achieved with chimney stoves did not significantly reduce physician-diagnosed pneumonia for children younger than 18 months. The significant reduction of a third in severe pneumonia, however, if confirmed, could have important implications for reduction of child mortality. The significant exposure-response associations contribute to causal inference and suggest that stove or fuel interventions producing lower average exposures than these chimney stoves might be needed to substantially reduce pneumonia in populations heavily exposed to biomass fuel air pollution. FUNDING: US National Institute of Environmental Health Sciences and WHO.

Impact of reduced maternal exposures to wood smoke from an introduced chimney stove on newborn birth weight in rural Guatemala.

BACKGROUND: A growing body of evidence indicates a relationship between household indoor air pollution from cooking fires and adverse neonatal outcomes, such as low birth weight (LBW), in resource-poor countries. OBJECTIVE: We examined the effect of reduced wood smoke exposure in pregnancy on LBW of Guatemalan infants in RESPIRE (Randomized Exposure Study of Pollution Indoors and Respiratory Effects). METHODS: Pregnant women (n = 266) either received a chimney stove (intervention) or continued to cook over an open fire (control). Between October 2002 and December 2004 we weighed 174 eligible infants (69 to mothers who used a chimney stove and 105 to mothers who used an open fire during pregnancy) within 48 hr of birth. Multivariate linear regression and adjusted odds ratios (ORs) were used to estimate differences in birth weight and LBW (< 2,500 g) associated with chimney-stove versus open-fire use during pregnancy. RESULTS: Pregnant women using chimney stoves had a 39% reduction in mean exposure to carbon monoxide compared with those using open fires. LBW prevalence was high at 22.4%. On average, infants born to mothers who used a stove weighed 89 g more [95% confidence interval (CI), -27 to 204 g] than infants whose mothers used open fires after adjusting for maternal height, diastolic blood pressure, gravidity, and season of birth. The adjusted OR for LBW was 0.74 (95% CI, 0.33-1.66) among infants of stove users compared with open-fire users. Average birth weight was 296 g higher (95% CI, 109-482 g) in infants born during the cold season (after harvest) than in other infants; this unanticipated finding may reflect the role of maternal nutrition on birth weight in an impoverished region. CONCLUSIONS: A chimney stove reduced wood smoke exposures and was associated with reduced LBW occurrence. Although not statistically significant, the estimated effect was consistent with previous studies.

Intervention to lower household wood smoke exposure in Guatemala reduces ST-segment depression on electrocardiograms.

BACKGROUND: A large body of evidence suggests that fine particulate matter (PM) air pollution is a cause of cardiovascular disease, but little is known in particular about the cardiovascular effects of indoor air pollution from household use of solid fuels in developing countries. RESPIRE (Randomized Exposure Study of Pollution Indoors and Respiratory Effects) was a randomized trial of a chimney woodstove that reduces wood smoke exposure. OBJECTIVES: We tested the hypotheses that the stove intervention, compared with open fire use, would reduce ST-segment depression and increase heart rate variability (HRV). METHODS: We used two complementary study designs: a) between-groups comparisons based on randomized stove assignment, and b) before-and-after comparisons within control subjects who used open fires during the trial and received chimney stoves after the trial. Electrocardiogram sessions that lasted 20 hr were repeated up to three times among 49 intervention and 70 control women 38-84 years of age, and 55 control subjects were also assessed after receiving stoves. HRV and ST-segment values were assessed for each 30-min period. ST-segment depression was defined as an average value below -1.00 mm. Personal fine PM [aerodynamic diameter ≤ 2.5 µm (PM2.5] exposures were measured for 24 hr before each electrocardiogram. RESULTS: PM2.5 exposure means were 266 and 102 µg/m³ during the trial period in the control and intervention groups, respectively. During the trial, the stove intervention was associated with an odds ratio of 0.26 (95% confidence interval, 0.08-0.90) for ST-segment depression. We found similar associations with the before-and-after comparison. The intervention was not significantly associated with HRV. CONCLUSIONS: The stove intervention was associated with reduced occurrence of nonspecific ST-segment depression, suggesting that household wood smoke exposures affect ventricular repolarization and potentially cardiovascular health.

Effect of reducing indoor air pollution on women's respiratory symptoms and lung function: the RESPIRE Randomized Trial, Guatemala.

Exposure to household wood smoke from cooking is a risk factor for chronic obstructive lung disease among women in developing countries. The Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) is a randomized intervention trial evaluating the respiratory health effects of reducing indoor air pollution from open cooking fires. A total of 504 rural Mayan women in highland Guatemala aged 15-50 years, all using traditional indoor open fires, were randomized to either receive a chimney woodstove (plancha) or continue using the open fire. Assessments of chronic respiratory symptoms and lung function and individual measurements of carbon monoxide exposure were performed at baseline and every 6 months up to 18 months. Use of a plancha significantly reduced carbon monoxide exposure by 61.6%. For all respiratory symptoms, reductions in risk were observed in the plancha group during follow-up; the reduction was statistically significant for wheeze (relative risk = 0.42, 95% confidence interval: 0.25, 0.70). The number of respiratory symptoms reported by the women at each follow-up point was also significantly reduced by the plancha (odds ratio = 0.7, 95% confidence interval: 0.50, 0.97). However, no significant effects on lung function were found after 12-18 months. Reducing indoor air pollution from household biomass burning may relieve symptoms consistent with chronic respiratory tract irritation.