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Household air pollution (HAP) from biomass stoves is a leading risk factor for cardiopulmonary outcomes; however, its toxicity pathways and relationship with inflammation markers are poorly understood. Among 180 adult women in rural Peru, we examined the cross-sectional exposure-response relationship between biomass HAP and markers of inflammation in blood using baseline measurements from a randomized trial. We measured markers of inflammation (CRP, IL-6, IL-10, IL-1β, and TNF-α) with dried blood spots, 48-h kitchen area concentrations and personal exposures to fine particulate matter (PM2.5), black carbon (BC), and carbon monoxide (CO), and 48-h kitchen concentrations of nitrogen dioxide (NO2) in a subset of 97 participants. We conducted an exposure-response analysis between quintiles of HAP levels and markers of inflammation. Markers of inflammation were more strongly associated with kitchen area concentrations of BC than PM2.5. As expected, kitchen area BC concentrations were positively associated with TNF-α (pro-inflammatory) concentrations and negatively associated with IL-10, an anti-inflammatory marker, controlling for confounders in single- and multi-pollutant models. However, contrary to expectations, kitchen area BC and NO2 concentrations were negatively associated with IL-1β, a pro-inflammatory marker. No associations were identified for IL-6 or CRP, or for any marker in relation to personal exposures.

Background: Per- and polyfluoroalkyl substances (PFASs) including perfluorooctanoic acid (PFOA) are ubiquitous environmental contaminants. Prior analysis in the large “C8 Health Project” population defined abnormal alanine aminotransferase (ALT) with statistically derived cutoffs (>45 IU/L in men, >34 IU/L in women). Objective: To explore the degree to which PFOA was associated with modern, clinically predictive ALT biomarker cutoffs in obese and nonobese participants, excluding those with diagnosed liver disease. Methods: We reevaluated the relationship of serum PFOA to abnormal ALT using predictive cutoff recommendations including those of the American College of Gastroenterology (ACG). Evaluations modeled lifetime cumulative exposure and measured internal PFOA exposure. Results: ACG cutoff values (≥34 IU/L for males, ≥25 IU/L for females) classified 30% of males (3815/12,672) and 21% of females (3359/15,788) above ALT cutoff values. Odds ratios (OR) for above cutoff values were consistently associated with modeled cumulative and measured serum PFOA. Linear trends were highly significant. ORs by quintile showed near monotonic increases. Trends were stronger for the overweight and obese. However, all weight classes were affected. Conclusion: Predictive cutoffs increase the OR for abnormal ALT results. Obesity increases ORs, yet association with abnormal ALT pertains to all weight classes. The results are discussed in context of current knowledge about the health implications of PFOA hepatotoxicity.

There is evidence that PM2.5 could be obesogenic. Lima is one of the most polluted cities in South America, with an increasing prevalence of childhood obesity. This study aimed to determine the association between PM2.5 exposure of children aged 6 to 59 months and being overweight or obese (O/O) in a significant dataset survey. Cases were defined when weight for height Z-score (WHZ) was >2 standard deviations (SD) from the mean, for each sex. A control was defined when WHZ was between ±2 SD. We used a conditional logistic regression model to calculate the odds ratio (OR) between extrauterine and intrauterine PM2.5 exposure and O/O. Extrauterine PM2.5 exposure was evaluated as a 6-month PM2.5 mean prior to the survey. We found a significant association between O/O and extrauterine (OR: 1.57, 1.51–1.63) and intrauterine (OR: 1.99, 1.88–2.12) PM2.5 exposure for an increment of 10 μg/m3. The ORs increased as the quartile increased in both exposures. We observed a higher association in children aged 6–11 months (OR: 3.07, 2.84–3.31). In conclusion, higher levels of PM2.5 in Lima and Callao were associated with cases of O/O in children from 6 to 59 months, with the association higher for prenatal exposure.

Background: Household air pollution (HAP) from solid fuel use is associated with adverse birth outcomes, but data for exposure–response relationships are scarce. We examined associations between HAP exposures and birthweight in rural Guatemala, India, Peru, and Rwanda during the Household Air Pollution Intervention Network (HAPIN) trial. Methods: The HAPIN trial recruited pregnant women (9–<20 weeks of gestation) in rural Guatemala, India, Peru, and Rwanda and randomly allocated them to receive a liquefied petroleum gas stove or not (ie, and continue to use biomass fuel). The primary outcomes were birthweight, length-for-age, severe pneumonia, and maternal systolic blood pressure. In this exposure–response subanalysis, we measured 24-h personal exposures to PM2·5, carbon monoxide, and black carbon once pre-intervention (baseline) and twice post-intervention (at 24–28 weeks and 32–36 weeks of gestation), as well as birthweight within 24 h of birth. We examined the relationship between the average prenatal exposure and birthweight or weight-for-gestational age Z scores using multivariate-regression models, controlling for the mother's age, nulliparity, diet diversity, food insecurity, BMI, the mother's education, neonate sex, haemoglobin, second-hand smoke, and geographical indicator for randomisation strata. Findings: Between March, 2018, and February, 2020, 3200 pregnant women were recruited. An interquartile increase in the average prenatal exposure to PM2·5 (74·5 μg/m3) was associated with a reduction in birthweight and gestational age Z scores (birthweight: –14·8 g [95% CI –28·7 to –0·8]; gestational age Z scores: –0·03 [–0·06 to 0·00]), as was an interquartile increase in black carbon (7·3 μg/m3; –21·9 g [–37·7 to –6·1]; –0·05 [–0·08 to –0·01]). Carbon monoxide exposure was not associated with these outcomes (1·7; –3·1 [–12·1 to 5·8]; –0·003 [–0·023 to 0·017]). Interpretation: Continuing efforts are needed to reduce HAP exposure alongside other drivers of low birthweight in low-income and middle-income countries. Funding: US National Institutes of Health (1UM1HL134590) and the Bill & Melinda Gates Foundation (OPP1131279).

Introduction: According to the WHO, anaemia is a severe public health problem when the prevalence is ≥ 40%. In 2019, in Peru, 40·1% of children (aged 6 to 35 months) are diagnosed as anaemic. This is a concern since, despite the efforts of the governments to reduce the prevalence, the problem has stagnated since 2011. The treatment applied to deal with anaemia is Fe supplementation. Although Fe is essential for cell function, an excess can produce adverse responses, such as gut inflammation affecting microbiota and resulting in diarrhoeic episodes. Objective: To determine the association between diarrhoea and Fe supplementation in children with and without anaemia, controlling for different socio-demographic variables. Design: We conducted via logistic regression to obtain diarrhoea prevalence ratios (PR), adjusted by age, sex, geographic region, water and sanitation service, and rurality. The survey asked for recent episodes of diarrhoea during the last 7 d; similarly, after the consumption of Fe supplements during the last 12 months before the survey. Setting: Peru. Participants: The Demographic and Family Health Survey (DHS) is conducted annually at home among 14 202 children on average (2009-2019). Results: Fe supplementation in the last 7 d (PR = 1·09) or the last 12 months (PR = 1·19) (P < 0·0001) was associated with an increased risk of diarrhoea. The same association was observed between Fe supplementation and the presence of anaemia. Conclusions: Fe supplementation is associated with diarrhoea and overuse in children should be avoided.

Cooking and heating using solid fuels can result in dangerous levels of exposure to household air pollution (HAP). HAPIN is an ongoing randomized controlled trial assessing the impact of a liquified petroleum gas stove and fuel intervention on HAP exposure and health in Guatemala, India, Peru, and Rwanda among households that rely primarily on solid cooking fuels. Given the potential impacts of HAP exposure on cardiovascular outcomes during pregnancy, we seek to characterize the relationship between personal exposures to HAP and blood pressure among pregnant women at baseline (prior to intervention) in the study. We assessed associations between PM 2.5 (particulate matter with an aerodynamic diameter ≤2.5 μm), BC (black carbon), and CO (carbon monoxide) exposures and blood pressure at baseline, prior to intervention, among 3195 pregnant women between 9 and 19 weeks of gestation. We measured 24-hour personal exposure to PM 2.5 /BC/CO and gestational blood pressure. Multivariable linear regression models were used to evaluate associations between personal exposures to three air pollutants and blood pressure parameters. Trial-wide, we found moderate increases in systolic blood pressure (SBP) and decreases in diastolic blood pressure (DBP) as exposure to PM 2.5 , BC, and CO increased. None of these associations, however, were significant at the 0.05 level. HAP exposure and blood pressure associations were inconsistent in direction and magnitude within each country. We observed effect modification by body mass index (BMI) in India and Peru. Compared to women with normal weights, obese women in India and Peru (but not in Rwanda or Guatemala) had higher SBP per unit increase in log transformed PM 2.5 and BC exposures. We did not find a cross-sectional association between HAP exposure and blood pressure in pregnant women; however, HAP may be associated with higher blood pressure in pregnant women who are obese, but this increase was not consistent across settings.

Growing evidence suggests that fine particulate matter (PM2.5) likely increases the risks of dementia, yet little is known about the relative contributions of different constituents. Here, we conducted a nationwide population-based cohort study (2000 to 2017) by integrating the Medicare Chronic Conditions Warehouse database and two independently sourced datasets of high-resolution PM2.5 major chemical composition, including black carbon (BC), organic matter (OM), nitrate (NO3 -), sulfate (SO4 2-), ammonium (NH4 +), and soil dust (DUST). To investigate the impact of long-term exposure to PM2.5 constituents on incident all-cause dementia and Alzheimer's disease (AD), hazard ratios for dementia and AD were estimated using Cox proportional hazards models, and penalized splines were used to evaluate potential nonlinear concentration-response (C-R) relationships. Results using two exposure datasets consistently indicated higher rates of incident dementia and AD for an increased exposure to PM2.5 and its major constituents. An interquartile range increase in PM2.5 mass was associated with a 6 to 7% increase in dementia incidence and a 9% increase in AD incidence. For different PM2.5 constituents, associations remained significant for BC, OM, SO4 2-, and NH4 + for both end points (even after adjustments of other constituents), among which BC and SO4 2- showed the strongest associations. All constituents had largely linear C-R relationships in the low exposure range, but most tailed off at higher exposure concentrations. Our findings suggest that long-term exposure to PM2.5 is significantly associated with higher rates of incident dementia and AD and that SO4 2-, BC, and OM related to traffic and fossil fuel combustion might drive the observed associations.

Introduction: Organophosphate (OP) insecticides, including chlorpyrifos, have been linked with numerous harmful health effects on maternal and child health. Limited data are available on the biological mechanisms and endogenous pathways underlying the toxicity of chlorpyrifos exposures on pregnancy and birth outcomes. In this study, we measured a urinary chlorpyrifos metabolite and used high-resolution metabolomics (HRM) to identify biological perturbations associated with chlorpyrifos exposure among pregnant women in Thailand, who are disparately exposed to high levels of OP insecticides. Methods: This study included 50 participants from the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE). We used liquid chromatography-high resolution mass spectrometry to conduct metabolic profiling on first trimester serum samples collected from participants to evaluate metabolic perturbations in relation to chlorpyrifos exposures. We measured 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of chlorpyrifos and chlorpyrifos-methyl, in first trimester urine samples to assess the levels of exposures. Following an untargeted metabolome-wide association study workflow, we used generalized linear models, pathway enrichment analyses, and chemical annotation to identify significant metabolites and pathways associated with urinary TCPy levels. Results: In the 50 SAWASDEE participants, the median urinary TCPy level was 4.36 μg TCPy/g creatinine. In total, 691 unique metabolic features were found significantly associated with TCPy levels (p < 0.05) after controlling for confounding factors. Pathway analysis of metabolic features associated with TCPy indicated perturbations in 24 metabolic pathways, most closely linked to the production of reactive oxygen species and cellular damage. These pathways include tryptophan metabolism, fatty acid oxidation and peroxisome metabolism, cytochromes P450 metabolism, glutathione metabolism, and vitamin B3 metabolism. We confirmed the chemical identities of 25 metabolites associated with TCPy levels, including glutathione, cystine, arachidic acid, itaconate, and nicotinamide adenine dinucleotide. Discussion: The metabolic perturbations associated with TCPy levels were related to oxidative stress, cellular damage and repair, and systemic inflammation, which could ultimately contribute to health outcomes, including neurodevelopmental deficits in the child. These findings support the future development of sensitive biomarkers to investigate the metabolic underpinnings related to pesticide exposure during pregnancy and to understand its link to adverse outcomes in children.

Background: Exposure to PM2.5 arising from solid fuel combustion is estimated to result in ∼2.3 million premature deaths and 91 million lost disability-adjusted life years annually. Interventions attempting to mitigate this burden have had limited success in reducing exposures to levels thought to provide substantive health benefits. Objectives: This paper reports exposure reductions achieved by a liquified petroleum gas (LPG) stove and fuel intervention for pregnant mothers in the Household Air Pollution Intervention Network (HAPIN) randomized controlled trial. Methods: The HAPIN trial included 3,195 households primarily using biomass for cooking in Guatemala, India, Peru, and Rwanda. Twenty-four-hour exposures to PM2.5, carbon monoxide (CO), and black carbon (BC) were measured for pregnant women once before randomization into control ( =1,605) and LPG ( =1,590) arms and twice thereafter (aligned with trimester). Changes in exposure were estimated by directly comparing exposures between intervention and control arms and by using linear mixed-effect models to estimate the impact of the intervention on exposure levels. Results: Median postrandomization exposures of particulate matter (PM) with aerodynamic diameter ≤2.5μm (PM2.5) in the intervention arm were lower by 66% at the first (71.5 vs. 24.1μg/m3), and second follow-up visits (69.5 vs. 23.7μg/m3) compared to controls. BC exposures were lower in the intervention arm by 72% (9.7 vs. 2.7μg/m3) and 70% (9.6 vs. 2.8μg/m3) at the first and second follow-up visits, respectively, and carbon monoxide exposure was 82% lower at both visits (1.1 vs. 0.2ppm) in comparison with controls. Exposure reductions were consistent over time and were similar across research locations. Discussion: Postintervention PM2.5 exposures in the intervention arm were at the lower end of what has been reported for LPG and other clean fuel interventions, with 69% of PM2.5 samples falling below the World Health Organization Annual Interim Target 1 of 35μg/m3. This study indicates that an LPG intervention can reduce PM2.5 exposures to levels at or below WHO targets.