Exposure to air pollutants and rheumatoid arthritis biomarkers: A scoping review.

INTRODUCTION: Rheumatoid arthritis (RA) is a common autoimmune disease with a complex and poorly understood etiology that includes genetic, hormonal, and environmental factors. OBJECTIVE: Our objective was to assess current literature that investigated the association between exposure to environmental and occupational air pollutants and RA-related biomarkers rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA). DESIGN: PubMed and Web of Science were used to identify epidemiological studies that measured or estimated air pollution and at least one RA biomarker. Information was charted for comparison of evidence, including pollutant(s) studied, exposure assessment, biomarker measurement, analysis method, study population, size, dates, adjustment variables, and findings. RESULTS: Several common air pollutants (including two mixtures) and a few dozen occupational inhalants were assessed in 13 eligible studies. Associations between industrial sulfur dioxide and particulate matter less than 2.5 µm in diameter with ACPA were observed most frequently, including associations between residential proximity to pollution sources and ACPA positivity. Consistency of associations with other pollutants was either not observed or limited to single studies. Three studies evaluated the modifying impact of SE alleles (a genetic factor associated with RA) and found that pollutant associations were stronger among participants positive for SE alleles. CONCLUSION: Based on mixed results, there was no consistent link between any single pollutant and RA-related biomarker outcomes. Comparisons across studies were limited by differences in study populations (e.g., by RA status, by sociodemographic groups) and study design (including designs focused on different sources of air pollution, methodological approaches with varying levels of potential exposure misclassification, and assessments of inconsistent biomarker cut-points). However, given that multiple studies reported associations between exposure to air pollution and RA biomarkers, continued exploration utilizing studies that can be designed with a more robust causal framework, including continued consideration of effect modification by genetic status, may be necessary.

Exposure to indoor and outdoor air pollution in schools in Africa: Current status, knowledge gaps, and a call to action.

Chronic exposure to indoor and outdoor air pollution is linked to adverse human health impacts worldwide, and in children, these include increased respiratory symptoms, reduced cognitive and academic performance, and absences from school. African children are exposed to high levels of air pollution from aging diesel and gasoline second-hand vehicles, dusty roads, trash burning, and solid-fuel combustion for cooking. There is a need for more empirical evidence on the impact of air pollutants on schoolchildren in most countries of Africa. Therefore, we conducted a scoping review on schoolchildren's exposure to indoor and outdoor PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 µm and PM10 (particulate matter with an aerodynamic diameter less than 10 µm) in Africa. Following PRISMA guidelines, our search strategy yielded 2975 records, of which eight peer-reviewed articles met our selection criteria and were considered in the final analysis. We also analyzed satellite data on PM2.5 and PM10 levels in five African regions from 1990 to 2019 and compared schoolchildren's exposure to PM2.5 and PM10 levels in Africa with available data from the rest of the world. The findings showed that schoolchildren in Africa are frequently exposed to PM2.5 and PM10 levels exceeding the recommended World Health Organization air quality guidelines. We conclude with a list of recommendations and strategies to reduce air pollution exposure in African schools. Education can help to produce citizens who are literate in environmental science and policy. More air quality measurements in schools and intervention studies are needed to protect schoolchildren's health and reduce exposure to air pollution in classrooms across Africa.

Baseline associations between household air pollution exposure and blood pressure among pregnant women in the Household Air Pollution Intervention Network (HAPIN) multi-country randomized controlled trial.

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 PM2.5 (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 PM2.5/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 PM2.5, 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 PM2.5 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.

Liquefied Petroleum Gas or Biomass for Cooking and Effects on Birth Weight.

BACKGROUND: Exposure during pregnancy to household air pollution caused by the burning of solid biomass fuel is associated with adverse health outcomes, including low birth weight. Whether the replacement of a biomass cookstove with a liquefied petroleum gas (LPG) cookstove would result in an increase in birth weight is unclear. METHODS: We performed a randomized, controlled trial involving pregnant women (18 to <35 years of age and at 9 to <20 weeks' gestation as confirmed on ultrasonography) in Guatemala, India, Peru, and Rwanda. The women were assigned in a 1:1 ratio to use a free LPG cookstove and fuel (intervention group) or to continue using a biomass cookstove (control group). Birth weight, one of four prespecified primary outcomes, was the primary outcome for this report; data for the other three outcomes are not yet available. Birth weight was measured within 24 hours after birth. In addition, 24-hour personal exposures to fine particulate matter (particles with a diameter of ≤2.5 µm [PM2.5]), black carbon, and carbon monoxide were measured at baseline and twice during pregnancy. RESULTS: A total of 3200 women underwent randomization; 1593 were assigned to the intervention group, and 1607 to the control group. Uptake of the intervention was nearly complete, with traditional biomass cookstoves being used at a median rate of less than 1 day per month. After randomization, the median 24-hour personal exposure to fine particulate matter was 23.9 µg per cubic meter in the intervention group and 70.7 µg per cubic meter in the control group. Among 3061 live births, a valid birth weight was available for 94.9% of the infants born to women in the intervention group and for 92.7% of infants born to those in the control group. The mean (±SD) birth weight was 2921±474.3 g in the intervention group and 2898±467.9 g in the control group, for an adjusted mean difference of 19.6 g (95% confidence interval, -10.1 to 49.2). CONCLUSIONS: The birth weight of infants did not differ significantly between those born to women who used LPG cookstoves and those born to women who used biomass cookstoves. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

Exposure Contrasts of Pregnant Women during the Household Air Pollution Intervention Network Randomized Controlled Trial.

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 (n=1,605) and LPG (n=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. 24.1 µg/m3), and second follow-up visits (69.5 vs. 23.7 µg/m3) compared to controls. BC exposures were lower in the intervention arm by 72% (9.7 vs. 2.7 µg/m3) and 70% (9.6 vs. 2.8 µg/m3) at the first and second follow-up visits, respectively, and carbon monoxide exposure was 82% lower at both visits (1.1 vs. 0.2 ppm) 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 35 µg/m3. This study indicates that an LPG intervention can reduce PM2.5 exposures to levels at or below WHO targets. https://doi.org/10.1289/EHP10295.

Effects of household and participant characteristics on personal exposure and kitchen concentration of fine particulate matter and black carbon in rural Honduras.

Traditional cooking with solid fuels (biomass, animal dung, charcoals, coal) creates household air pollution that leads to millions of premature deaths and disability worldwide each year. Exposure to household air pollution is highest in low- and middle-income countries. Using data from a stepped-wedge randomized controlled trial of a cookstove intervention among 230 households in Honduras, we analyzed the impact of household and personal variables on repeated 24-h measurements of fine particulate matter (PM2.5) and black carbon (BC) exposure. Six measurements were collected approximately six-months apart over the course of the three-year study. Multivariable mixed models explained 37% of variation in personal PM2.5 exposure and 49% of variation in kitchen PM2.5 concentrations. Additionally, multivariable models explained 37% and 47% of variation in personal and kitchen BC concentrations, respectively. Stove type, season, presence of electricity, primary stove location, kitchen enclosure type, stove use time, and presence of kerosene for lighting were all associated with differences in geometric mean exposures. Stove type explained the most variability of the included variables. In future studies of household air pollution, tracking the cooking behaviors and daily activities of participants, including outdoor exposures, may explain exposure variation beyond the household and personal variables considered here.

Household air pollution from wood-burning cookstoves and C-reactive protein among women in rural Honduras.

Household air pollution from solid fuel combustion was estimated to cause 2.31 million deaths worldwide in 2019; cardiovascular disease is a substantial contributor to the global burden. We evaluated the cross-sectional association between household air pollution (24-h gravimetric kitchen and personal particulate matter (PM2.5) and black carbon (BC)) and C-reactive protein (CRP) measured in dried blood spots among 107 women in rural Honduras using wood-burning traditional or Justa (an engineered combustion chamber) stoves. A suite of 6 additional markers of systemic injury and inflammation were considered in secondary analyses. We adjusted for potential confounders and assessed effect modification of several cardiovascular-disease risk factors. The median (25th, 75th percentiles) 24-h-average personal PM2.5 concentration was 115 µg/m3 (65,154 µg/m3) for traditional stove users and 52 µg/m3 (39, 81 µg/m3) for Justa stove users; kitchen PM2.5 and BC had similar patterns. Higher concentrations of PM2.5 and BC were associated with higher levels of CRP (e.g., a 25% increase in personal PM2.5 was associated with a 10.5% increase in CRP [95% CI: 1.2-20.6]). In secondary analyses, results were generally consistent with a null association. Evidence for effect modification between pollutant measures and four different cardiovascular risk factors (e.g., high blood pressure) was inconsistent. These results support the growing evidence linking household air pollution and cardiovascular disease.

Estimating long-term average household air pollution concentrations from repeated short-term measurements in the presence of seasonal trends and crossover.

Estimating long-term exposure to household air pollution is essential for quantifying health effects of chronic exposure and the benefits of intervention strategies. However, typically only a small number of short-term measurements are made. We compare different statistical models for combining these short-term measurements into predictions of a long-term average, with emphasis on the impact of temporal trends in concentrations and crossover in study design. We demonstrate that a linear mixed model that includes time adjustment provides the best predictions of long-term average, which have lower error than using household averages or mixed models without time, for a variety of different study designs and underlying temporal trends. In a case study of a cookstove intervention study in Honduras, we further demonstrate how, in the presence of strong seasonal variation, long-term average predictions from the mixed model approach based on only two or three measurements can have less error than predictions based on an average of up to six measurements. These results have important implications for the efficiency of designs and analyses in studies assessing the chronic health impacts of long-term exposure to household air pollution.

Reduced Black Carbon Concentrations following a Three-Year Stepped-Wedge Randomized Trial of the Wood-Burning Justa Cookstove in Rural Honduras.

Introduction: Household air pollution from cooking-related biomass combustion remains a leading risk factor for global health. Black carbon (BC) is an important component of particulate matter (PM) in household air pollution. We evaluated the impact of the engineered, wood-burning Justa stove intervention on BC concentrations. Methods: We conducted a 3-year stepped-wedge randomized controlled trial with 6 repeated visits among 230 female primary cooks in rural Honduras. Participants used traditional stoves at baseline and were randomized to receive the Justa after visit 2 or after visit 4. At each visit, we measured 24-hour gravimetric personal and kitchen fine PM (PM2.5) concentrations and estimated BC mass concentrations (Sootscan Transmissometer). We conducted intent-to-treat analyses using linear mixed models with natural log-transformed 24-hour personal and kitchen BC. Results: BC concentrations were reduced for households assigned to the Justa vs. traditional stoves: e.g., personal BC geometric mean (GSD), 3.6 µg/m3 (6.4) vs. 11.5 µg/m3 (4.6), respectively. Following the intervention, we observed 53% (95% CI: 35-65%) lower geometric mean personal BC concentrations and 76% (95% CI: 66-83%) lower geometric mean kitchen BC concentrations. Conclusions: The Justa stove intervention substantially reduced BC concentrations, mitigating household air pollution and potentially benefitting human and climate health.

Visualizing Field Data Collection Procedures of Exposure and Biomarker Assessments for the Household Air Pollution Intervention Network Trial in India.

Here, we present a visual representation of standard procedures to collect population-level data on personal exposures to household air pollution (HAP) from two different study sites in a resource-constrained setting of Tamil Nadu, India. Particulate matter PM2.5 (particles smaller than 2.5 microns in aerodynamic diameter), carbon monoxide (CO), and black carbon (BC) were measured in pregnant mothers (M), other adult women (OAW), and children (C) at various times over a 4 year period. In addition, stove usage monitoring (SUMs) with data-logging thermometers and ambient measurements of air pollution were carried out. Furthermore, the feasibility of collecting biological samples (urine and dried blood spots [DBSs]) from study participants at the field sites was successfully demonstrated. Based on findings from this and earlier studies, the methods used here have enhanced the data quality and avoided issues with household air pollution and biological sample collection in resource-constrained situations. The procedures established may be a valuable educational tool and resource for researchers conducting similar air pollution and health studies in India and other low- and middle-income countries (LMICs).

Acute differences in blood lipids and inflammatory biomarkers following controlled exposures to cookstove air pollution in the STOVES study.

Household air pollution is a leading risk factor for morbidity and premature mortality. Numerous cookstoves have been developed to reduce household air pollution, but it is unclear whether such cookstoves meaningfully improve health. In a controlled exposure study with a crossover design, we assessed the effect of pollution emitted from multiple cookstoves on acute differences in blood lipids and inflammatory biomarkers. Participants (n = 48) were assigned to treatment sequences of exposure to air pollution emitted from five cookstoves and a filtered-air control. Blood lipids and inflammatory biomarkers were measured before and 0, 3, and 24 hours after treatments. Many of the measured outcomes had inconsistent results. However, compared to control, intercellular adhesion molecule-1 was higher 3 hours after all treatments, and C-reactive protein and serum amyloid-A were higher 24 hours after the highest treatment. Our results suggest that short-term exposure to cookstove air pollution can increase inflammatory biomarkers within 24 hours.

LPG stove and fuel intervention among pregnant women reduce fine particle air pollution exposures in three countries: Pilot results from the HAPIN trial.

The Household Air Pollution Intervention Network trial is a multi-country study on the effects of a liquefied petroleum gas (LPG) stove and fuel distribution intervention on women's and children's health. There is limited data on exposure reductions achieved by switching from solid to clean cooking fuels in rural settings across multiple countries. As formative research in 2017, we recruited pregnant women and characterized the impact of the intervention on personal exposures and kitchen levels of fine particulate matter (PM2.5) in Guatemala, India, and Rwanda. Forty pregnant women were enrolled in each site. We measured cooking area concentrations of and personal exposures to PM2.5 for 24 or 48 h using gravimetric-based PM2.5 samplers at baseline and two follow-ups over two months after delivery of an LPG cookstove and free fuel supply. Mixed models were used to estimate PM2.5 reductions. Median kitchen PM2.5 concentrations were 296 µg/m3 at baseline (interquartile range, IQR: 158-507), 24 µg/m3 at first follow-up (IQR: 18-37), and 23 µg/m3 at second follow-up (IQR: 14-37). Median personal exposures to PM2.5 were 134 µg/m3 at baseline (IQR: 71-224), 35 µg/m3 at first follow-up (IQR: 23-51), and 32 µg/m3 at second follow-up (IQR: 23-47). Overall, the LPG intervention was associated with a 92% (95% confidence interval (CI): 90-94%) reduction in kitchen PM2.5 concentrations and a 74% (95% CI: 70-79%) reduction in personal PM2.5 exposures. Results were similar for each site. CONCLUSIONS: The intervention was associated with substantial reductions in kitchen and personal PM2.5 overall and in all sites. Results suggest LPG interventions in these rural settings may lower exposures to the WHO annual interim target-1 of 35 µg/m3. The range of exposure contrasts falls on steep sections of estimated exposure-response curves for birthweight, blood pressure, and acute lower respiratory infections, implying potentially important health benefits when transitioning from solid fuels to LPG.

A risk assessment tool for resumption of research activities during the COVID-19 pandemic for field trials in low resource settings.

RATIONALE: The spread of severe acute respiratory syndrome coronavirus-2 has suspended many non-COVID-19 related research activities. Where restarting research activities is permitted, investigators need to evaluate the risks and benefits of resuming data collection and adapt procedures to minimize risk. OBJECTIVES: In the context of the multicountry Household Air Pollution Intervention (HAPIN) trial conducted in rural, low-resource settings, we developed a framework to assess the risk of each trial activity and to guide protective measures. Our goal is to maximize the integrity of reseach aims while minimizing infection risk based on the latest scientific understanding of the virus. METHODS: We drew on a combination of expert consultations, risk assessment frameworks, institutional guidance and literature to develop our framework. We then systematically graded clinical, behavioral, laboratory and field environmental health research activities in four countries for both adult and child subjects using this framework. National and local government recommendations provided the minimum safety guidelines for our work. RESULTS: Our framework assesses risk based on staff proximity to the participant, exposure time between staff and participants, and potential viral aerosolization while performing the activity. For each activity, one of four risk levels, from minimal to unacceptable, is assigned and guidance on protective measures is provided. Those activities that can potentially aerosolize the virus are deemed the highest risk. CONCLUSIONS: By applying a systematic, procedure-specific approach to risk assessment for each trial activity, we were able to protect our participants and research team and to uphold our ability to deliver on the research commitments we have made to our staff, participants, local communities, and funders. This framework can be tailored to other research studies conducted in similar settings during the current pandemic, as well as potential future outbreaks with similar transmission dynamics. The trial is registered with clinicaltrials.gov NCT02944682 on October 26. 2016 .

Impact of the wood-burning Justa cookstove on fine particulate matter exposure: A stepped-wedge randomized trial in rural Honduras.

TRIAL DESIGN: We evaluated the impact of a biomass stove intervention on fine particulate matter (PM2.5) concentrations using an individual-level, stepped-wedge randomized trial. METHODS: We enrolled 230 women in rural Honduran households using traditional biomass stoves and randomly allocated them to one of two study arms. The Justa stove, the study intervention, was locally-sourced, wood-burning, and included an engineered combustion chamber and chimney. At each of 6 visits over 3 years, we measured 24-hour gravimetric personal and kitchen PM2.5 concentrations. Half of the households received the intervention after Visit 2 and half after Visit 4. We conducted intent-to-treat analyses to evaluate the intervention effect using linear mixed models with log-transformed kitchen or personal PM2.5 (separately) as the dependent variable, adjusting for time. We also compared PM2.5 concentrations to World Health Organization (WHO) guidelines. RESULTS: Arms 1 and 2 each had 115 participants with 664 and 632 completed visits, respectively. Median 24-hour average personal PM2.5 exposures were 81 µg/m3 (25th-75th percentile: 50-141 µg/m3) for the traditional stove condition (n=622) and 43 µg/m3 (25th-75th percentile: 27-73 µg/m3) for the Justa stove condition (n=585). Median 24-hour average kitchen concentrations were 178 µg/m3 (25th-75th percentile: 69-440 µg/m3; n=629) and 53 µg/m3 (25th-75th percentile: 29-103 µg/m3; n=578) for the traditional and Justa stove conditions, respectively. The Justa intervention resulted in a 32% reduction in geometric mean personal PM2.5 (95% confidence interval [CI]: 20-43%) and a 56% reduction (95% CI: 46-65%) in geometric mean kitchen PM2.5. During rainy and dry seasons, 53% and 41% of participants with the Justa intervention had 24-hour average personal PM2.5 exposures below the WHO interim target-3 guideline (37.5 µg/m3), respectively. CONCLUSION: The Justa stove intervention substantially lowered personal and kitchen PM2.5 and may be a provisional solution that is feasible for Latin American communities where cleaner fuels may not be available, affordable, or acceptable for some time. Clinicaltrials.gov: NCT02658383.

Short-term differences in cardiac function following controlled exposure to cookstove air pollution: The subclinical tests on volunteers exposed to smoke (STOVES) study.

BACKGROUND: Exposure to household air pollution from solid fuel combustion for cooking and heating is an important risk factor for premature death and disability worldwide. Current evidence supports an association of ambient air pollution with cardiovascular disease but is limited for household air pollution and for cardiac function. Controlled exposure studies can complement evidence provided by field studies. OBJECTIVES: To investigate effects of short-term, controlled exposures to emissions from five cookstoves on measures of cardiac function. METHODS: Forty-eight healthy adults (46% female; 20-36 years) participated in six, 2-h exposures ('treatments'), including emissions from five cookstoves and a filtered-air control. Target fine particulate matter (PM2.5) exposure-concentrations per treatment were: control, 0 µg/m3; liquefied petroleum gas, 10 µg/m3; gasifier, 35 µg/m3; fan rocket, 100 µg/m3; rocket elbow, 250 µg/m3; and three stone fire, 500 µg/m3. Participants were treated in a set (pre-randomized) sequence as groups of 4 to minimize order bias and time-varying confounders. Heart rate variability (HRV) and cardiac repolarization metrics were calculated as 5-min means immediately and at 3 h following treatment, for analysis in linear mixed-effects models comparing cookstove to control. RESULTS: Short-term differences in SDNN (standard deviation of duration of all NN intervals) and VLF (very-low frequency power) existed for several cookstoves compared to control. While all cookstoves compared to control followed a similar trend for SDNN, the greatest effect was seen immediately following three stone fire (ß = -0.13 ms {%}; 95% confidence interval = -0.22, -0.03%), which reversed in direction at 3 h (0.03%; -0.06, 0.13%). VLF results were similar in direction and timing to SDNN; however, other HRV or cardiac repolarization results were not similar to those for SDNN. DISCUSSION: We observed some evidence of short-term, effects on HRV immediately following cookstove treatments compared to control. Our results suggest that cookstoves with lower PM2.5 emissions are potentially capable of affecting cardiac function, similar to stoves emitting higher PM2.5 emissions.

Cross-validation of biomonitoring methods for polycyclic aromatic hydrocarbon metabolites in human urine: Results from the formative phase of the Household Air Pollution Intervention Network (HAPIN) trial in India.

The Household Air Pollution Intervention Network (HAPIN) trial is evaluating health benefits of a liquefied petroleum gas (LPG) stove intervention in biomass cook-fuel using homes (n = 3200) in four low-and middle-income countries (LMICs) that include Peru, Guatemala, Rwanda and India. Longitudinal urine samples (n = 6000) collected from enrolled pregnant women, infants and older women will be analyzed for biomarkers associated with exposure and health outcomes. We report results from cross-validation of a lower cost high-performance liquid chromatography with fluorescence detection (HPLC-FLD) method with a higher resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the measurement of 1-hydroxypyrene (1PYR) and 2-naphthol (2NAP). Twenty-five split urine samples were analyzed by HPLC-FLD method at the India trial site in Chennai, India and by LC-MSMS method at the trial wide Biomarker Coordinating Center, Emory University, USA. The limits of detection (LOD) for the HPLC-FLD method were 0.02 ng/mL and 0.07 ng/mL for 2NAP and 1PYR, respectively. Bland-Altman analysis estimated a bias of 2.98 ng/ml for 2NAP (95% CI: -5.22, -0.75) and 0.09 ng/mL for 1PYR (95% CI: -0.02, 0.21) with HPLC-FLD levels being lower than LC-MSMS levels at higher concentrations. Analyses of additional urine samples (n = 119) collected during the formative phase of the HAPIN trial in India, showed 2NAP and 1PYR levels to be consistently above the limit of quantification (LOQ) and demonstrated the applicability of the method. The HPLC-FLD method can serve as a cost-effective and reliable analytical method to measure 2NAP and 1PYR in human urine in LMICs, within and beyond the HAPIN trial.

Air Pollutant Exposure and Stove Use Assessment Methods for the Household Air Pollution Intervention Network (HAPIN) Trial.

BACKGROUND: High quality personal exposure data is fundamental to understanding the health implications of household energy interventions, interpreting analyses across assigned study arms, and characterizing exposure-response relationships for household air pollution. This paper describes the exposure data collection for the Household Air Pollution Intervention Network (HAPIN), a multicountry randomized controlled trial of liquefied petroleum gas stoves and fuel among 3,200 households in India, Rwanda, Guatemala, and Peru. OBJECTIVES: The primary objectives of the exposure assessment are to estimate the exposure contrast achieved following a clean fuel intervention and to provide data for analyses of exposure-response relationships across a range of personal exposures. METHODS: Exposure measurements are being conducted over the 3-y time frame of the field study. We are measuring fine particulate matter [PM < 2.5µm in aerodynamic diameter (PM2.5)] with the Enhanced Children's MicroPEM™ (RTI International), carbon monoxide (CO) with the USB-EL-CO (Lascar Electronics), and black carbon with the OT21 transmissometer (Magee Scientific) in pregnant women, adult women, and children <1 year of age, primarily via multiple 24-h personal assessments (three, six, and three measurements, respectively) over the course of the 18-month follow-up period using lightweight monitors. For children we are using an indirect measurement approach, combining data from area monitors and locator devices worn by the child. For a subsample (up to 10%) of the study population, we are doubling the frequency of measurements in order to estimate the accuracy of subject-specific typical exposure estimates. In addition, we are conducting ambient air monitoring to help characterize potential contributions of PM2.5 exposure from background concentration. Stove use monitors (Geocene) are being used to assess compliance with the intervention, given that stove stacking (use of traditional stoves in addition to the intervention gas stove) may occur. CONCLUSIONS: The tools and approaches being used for HAPIN to estimate personal exposures build on previous efforts and take advantage of new technologies. In addition to providing key personal exposure data for this study, we hope the application and learnings from our exposure assessment will help inform future efforts to characterize exposure to household air pollution and for other contexts. https://doi.org/10.1289/EHP6422.

Design and Rationale of the HAPIN Study: A Multicountry Randomized Controlled Trial to Assess the Effect of Liquefied Petroleum Gas Stove and Continuous Fuel Distribution.

BACKGROUND: Globally, nearly 3 billion people rely on solid fuels for cooking and heating, the vast majority residing in low- and middle-income countries (LMICs). The resulting household air pollution (HAP) is a leading environmental risk factor, accounting for an estimated 1.6 million premature deaths annually. Previous interventions of cleaner stoves have often failed to reduce exposure to levels that produce meaningful health improvements. There have been no multicountry field trials with liquefied petroleum gas (LPG) stoves, likely the cleanest scalable intervention. OBJECTIVE: This paper describes the design and methods of an ongoing randomized controlled trial (RCT) of LPG stove and fuel distribution in 3,200 households in 4 LMICs (India, Guatemala, Peru, and Rwanda). METHODS: We are enrolling 800 pregnant women at each of the 4 international research centers from households using biomass fuels. We are randomly assigning households to receive LPG stoves, an 18-month supply of free LPG, and behavioral reinforcements to the control arm. The mother is being followed along with her child until the child is 1 year old. Older adult women (40 to <80 years of age) living in the same households are also enrolled and followed during the same period. Primary health outcomes are low birth weight, severe pneumonia incidence, stunting in the child, and high blood pressure (BP) in the older adult woman. Secondary health outcomes are also being assessed. We are assessing stove and fuel use, conducting repeated personal and kitchen exposure assessments of fine particulate matter with aerodynamic diameter ≤2.5µm (PM2.5), carbon monoxide (CO), and black carbon (BC), and collecting dried blood spots (DBS) and urinary samples for biomarker analysis. Enrollment and data collection began in May 2018 and will continue through August 2021. The trial is registered with ClinicalTrials.gov (NCT02944682). CONCLUSIONS: This study will provide evidence to inform national and global policies on scaling up LPG stove use among vulnerable populations. https://doi.org/10.1289/EHP6407.

Design and Rationale of the Biomarker Center of the Household Air Pollution Intervention Network (HAPIN) Trial.

BACKGROUND: Biomarkers of exposure, susceptibility, and effect are fundamental for understanding environmental exposures, mechanistic pathways of effect, and monitoring early adverse outcomes. To date, no study has comprehensively evaluated a large suite and variety of biomarkers in household air pollution (HAP) studies in concert with exposure and outcome data. The Household Air Pollution Intervention Network (HAPIN) trial is a liquified petroleum gas (LPG) fuel/stove randomized intervention trial enrolling 800 pregnant women in each of four countries (i.e., Peru, Guatemala, Rwanda, and India). Their offspring will be followed from birth through 12 months of age to evaluate the role of pre- and postnatal exposure to HAP from biomass burning cookstoves in the control arm and LPG stoves in the intervention arm on growth and respiratory outcomes. In addition, up to 200 older adult women per site are being recruited in the same households to evaluate indicators of cardiopulmonary, metabolic, and cancer outcomes. OBJECTIVES: Here we describe the rationale and ultimate design of a comprehensive biomarker plan to enable us to explore more fully how exposure is related to disease outcome. METHODS: HAPIN enrollment and data collection began in May 2018 and will continue through August 2021. As a part of data collection, dried blood spot (DBS) and urine samples are being collected three times during pregnancy in pregnant women and older adult women. DBS are collected at birth for the child. DBS and urine samples are being collected from the older adult women and children three times throughout the child's first year of life. Exposure biomarkers that will be longitudinally measured in all participants include urinary hydroxy-polycyclic aromatic hydrocarbons, volatile organic chemical metabolites, metals/metalloids, levoglucosan, and cotinine. Biomarkers of effect, including inflammation, endothelial and oxidative stress biomarkers, lung cancer markers, and other clinically relevant measures will be analyzed in urine, DBS, or blood products from the older adult women. Similarly, genomic/epigenetic markers, microbiome, and metabolomics will be measured in older adult women samples. DISCUSSION: Our study design will yield a wealth of biomarker data to evaluate, in great detail, the link between exposures and health outcomes. In addition, our design is comprehensive and innovative by including cutting-edge measures such as metabolomics and epigenetics. https://doi.org/10.1289/EHP5751.

Acute changes in lung function following controlled exposure to cookstove air pollution in the subclinical tests of volunteers exposed to smoke (STOVES) study.

Background: Exposure to household air pollution generated as a result of cooking and heating is a leading contributor to global disease. The effects of cookstove-generated air pollution on adult lung function, however, remain uncertain.Objectives: We investigated acute responses in lung function following controlled exposures to cookstove-generated air pollution.Methods: We recruited 48 healthy adult volunteers to undergo six two-hour treatments: a filtered-air control and emissions from five different stoves with fine particulate matter (PM2.5) targets from 10 to 500 µg/m3. Spirometry was conducted prior to exposure and immediately, and three and 24 h post-exposure. Mixed-effect models were used to estimate differences in post-exposure lung function for stove treatments versus control.Results: Immediately post-exposure, lung function was lower compared to the control for the three highest PM2.5-level stoves. The largest differences were for the fan rocket stove (target 250 µg/m3; forced vital capacity (FVC): -60 mL, 95% confidence interval (95% CI) -135, 15; forced expiratory volume (FEV1): -51 mL, 95% CI -117, 16; mid-expiratory flow (FEF25-75): -116 mL/s, 95% CI -239, 8). At 3 h post-exposure, lung function was lower compared to the control for all stove treatments; effects were of similar magnitude for all stoves. At 24 h post-exposure, results were consistent with a null association for FVC and FEV1; FEF25-75 was lower relative to the control for the gasifier, fan rocket, and three stone fire.Conclusions: Patterns suggesting short-term decreases in lung function follow from exposure to cookstove air pollution even for stove exposures with low PM2.5 levels.