Associations between repeated measures of urinary phthalate metabolites and biomarkers of oxidative stress in a rural agricultural cohort of children with asthma.

Phthalate exposure is widespread, and studies suggest an adverse relationship with asthma morbidity, including some support for oxidative stress as an underlying pathophysiological mechanism. Urinary phthalate metabolites have been associated with biomarkers of oxidative stress, but data are few in children diagnosed with asthma. We used participant data from the Home Air in Agriculture Pediatric Intervention Trial (HAPI) to examine longitudinal relationships between phthalates and oxidative stress in a cohort of Latino children with asthma residing in an agricultural community. We used linear mixed-effects models to estimate associations between 11 urinary phthalate metabolites (and one summed measure of di-2-ethylhexyl phthalate (DEHP) metabolites, ∑DEHP) and two urinary biomarkers of oxidative stress: a biomarker of lipid peroxidation via measure of 8-isoprostane and a biomarker of DNA/RNA oxidative damage via combined measure of 8-hydroxydeoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), and 8-hydroxyguanine. Seventy-nine participants provided 281 observations. In covariate-adjusted models, we observed significant positive relationships between all phthalate metabolites and 8-isoprostane, effect sizes ranging from a 9.3 % (95 % CI: 4.2 %-14.7 %) increase in 8-isoprostane for each 100 % increase (i.e., doubling) of mono-(carboxy-isooctyl) phthalate (MCIOP), to a 21.0 % (95 % CI: 14.3 %-28.2 %) increase in 8-isoprostane for each doubling of mono-n-butyl phthalate (MNBP). For each doubling of mono-(carboxy-isononyl) phthalate (MCINP) and mono-ethyl phthalate (MEP), the DNA/RNA oxidative damage biomarker increased by 6.0 % (95 % CI: 0.2 %-12.2 %) and 6.5 % (95 % CI: 1.4 %-11.9 %), respectively. In conclusion, we provide unique data suggesting phthalate exposure is positively associated with oxidative stress in children with asthma. Our repeat measures provide novel identification of a consistent effect of phthalates on oxidative stress in children with asthma via lipid peroxidation. Confirmation in future studies of children with asthma is needed to enhance understanding of the role of phthalates in childhood asthma morbidity.

Longitudinal measures of phthalate exposure and asthma exacerbation in a rural agricultural cohort of Latino children in Yakima Valley, Washington.

Phthalates are a class of widely used synthetic chemicals found in commonly used materials and products. Epidemiological studies suggest phthalate exposure is associated with asthma outcomes, though most studies have not investigated phthalates as triggers of exacerbations in children diagnosed with asthma. This study used data from the Home Air in Agriculture Pediatric Intervention Trial (HAPI) to examine relationships between phthalate exposure and outcomes related to childhood asthma exacerbation. We used measures of phthalate metabolites and respiratory health measures including fractional exhaled nitric oxide (FENO), the Asthma Control Test (ACT), caregiver report of symptoms, and urinary leukotriene E4 (uLTE4) to estimate longitudinal associations using mixed effects models, adjusted for covariates. For 100% (i.e., doubling) increases in mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-2-ethylhexyl phthalate (MEHP), and mono-ethyl phthalate (MEP), concentrations of FENO increased by 8.7% (95% CI: 0.7-17.3), 7.2% (95% CI: 0.0-14.9), and 6.4% (95% CI: 0.0-13.3), respectively. All phthalate metabolites demonstrated associations with uLTE4, effect sizes ranging from an 8.7% increase in uLTE4 (95% CI: 4.3-12.5) for a 100% increase in MEHP to an 18.1% increase in uLTE4 (95% CI: 13.3-23.1) for a 100% increase in MNBP. In models of caregiver report of symptoms, no phthalate metabolites were significantly associated in primary models. No phthalate metabolites were associated with standardized ACT score. Our results suggest urinary phthalate metabolites are significant predictors of inflammatory biomarkers related to asthma exacerbation in children but not child and caregiver report of airway symptomatology.

Randomized trial of a portable HEPA air cleaner intervention to reduce asthma morbidity among Latino children in an agricultural community.

BACKGROUND: Data on pediatric asthma morbidity and effective environmental interventions in U.S. agricultural settings are few. We evaluated the effectiveness of HEPA air cleaners on asthma morbidity among a cohort of rural Latino children. METHODS: Seventy-five children with poorly controlled asthma and living in non-smoking homes were randomly assigned to asthma education alone or along with HEPA air cleaners placed in their sleeping area and home living room. The Asthma Control Test (ACT) score, asthma symptoms in prior 2 weeks, unplanned clinical utilization, creatinine-adjusted urinary leukotriene E4 (uLTE4 [ng/mg]), and additional secondary outcomes were evaluated at baseline, six, and 12 months. Group differences were assessed using multivariable-adjusted generalized estimating equations. Incident rate ratios of ever experiencing the metrics of poorer asthma health during follow-up (suboptimal asthma management) were estimated using Poisson regression models in secondary analysis. RESULTS: Mean child age was 9.2 and 8.6 years in intervention and control groups, respectively, and two-thirds of participants were male. Primary analysis of repeated measures of ACT score did not differ between groups (HEPA group mean change compared to controls 10% [95% CI: - 12-39%]). A suggestion of greater decrease in uLTE4 (ng/mg creatinine) was observed (- 10% [95% CI: - 20 -1%]). Secondary analysis showed children with HEPAs were less likely to have an ACT score meeting a clinically defined cutoff for poorly controlled asthma using repeated measures (IRR: 0.45 [95% CI: 0.21-0.97]). In Poisson models, intervention participants had reduced risk of ever meeting this cutoff (IRR: 0.43 [95% CI: 0.21-0.89]), ever having symptoms in the past 2 weeks (IRR: 0.71 [95% CI: 0.52-0.98]), and lower risk of any unplanned clinical utilization (IRR: 0.35 [95% CI: 0.13-0.94]) compared to control participants. DISCUSSION: The HAPI study showed generally improved outcomes among children in the HEPA air cleaner group. However, primary analyses did not meet statistical significance and many outcomes were subjective (self-report) in this unblinded study, so findings must be interpreted cautiously. HEPA air cleaners may provide additional benefit for child asthma health where traditional asthmagens (traffic, tobacco smoke) are not prominent factors, but larger studies with more statistical power and blinded designs are needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04919915 . Date of retrospective registration: May 19, 2021.

Effectiveness of portable HEPA air cleaners on reducing indoor endotoxin, PM10, and coarse particulate matter in an agricultural cohort of children with asthma: A randomized intervention trial.

We conducted a randomized trial of portable HEPA air cleaners in the homes of children age 6-12 years with asthma in the Yakima Valley, Washington. All families received asthma education while intervention families also received two HEPA cleaners (child's bedroom, living room). We collected 14-day integrated samples of endotoxin in settled dust and PM10 and PM10-2.5 in the air of the children's bedrooms at baseline and one-year follow-up, and used linear regression to compare follow-up levels, adjusting for baseline. Seventy-one families (36 HEPA, 35 control) completed the study. Baseline geometric mean (GSD) endotoxin loadings were 1565 (6.3) EU/m2 and 2110 (4.9) EU/m2 , respectively, in HEPA vs. control homes while PM10 and PM10-2.5 were 22.5 (1.9) µg/m3 and 9.5 (2.9) µg/m3 , respectively, in HEPA homes, and 19.8 (1.8) µg/m3 and 7.7 (2.0) µg/m3 , respectively, in control homes. At follow-up, HEPA families had 46% lower (95% CI, 31%-57%) PM10 on average than control families, consistent with prior studies. In the best-fit heterogeneous slopes model, HEPA families had 49% (95% CI, 6%-110%) and 89% lower (95% CI, 28%-177%) PM10-2.5 at follow-up, respectively, at 50th and 75th percentile baseline concentrations. Endotoxin loadings did not differ significantly at follow-up (4% lower, HEPA homes; 95% CI, -87% to 50%).

Effectiveness of portable HEPA air cleaners on reducing indoor PM2.5 and NH3 in an agricultural cohort of children with asthma: A randomized intervention trial.

We conducted a randomized trial of portable HEPA air cleaners with pre-filters designed to also reduce NH3 in non-smoking homes of children age 6-12 with asthma in Yakima Valley (Washington, USA). Participants were recruited through the Yakima Valley Farm Workers Clinic asthma education program. All participants received education on home triggers while intervention families additionally received two HEPA cleaners (child's sleeping area, main living area). Fourteen-day integrated samples of PM2.5 and NH3 were measured at baseline and one-year follow-up. We fit ANCOVA models to compare follow-up concentrations in HEPA vs control homes, adjusting for baseline concentrations. Seventy-one households (36 HEPA, 35 control) completed the study. Most were single-family homes, with electric heat and stove, A/C, dogs/cats, and mean (SD) 5.3 (1.8) occupants. In the sleeping area, baseline geometric mean (GSD) PM2.5 was 10.7 (2.3) µg/m3 (HEPA) vs 11.2 (1.9) µg/m3 (control); in the living area, it was 12.5 (2.3) µg/m3 (HEPA) vs 13.6 (1.9) µg/m3 (control). Baseline sleeping area NH3 was 62.4 (1.6) µg/m3 (HEPA) vs 65.2 (1.8) µg/m3 (control). At follow-up, HEPA families had 60% (95% CI, 41%-72%; p < .0001) and 42% (19%-58%; p = .002) lower sleeping and living area PM2.5 , respectively, consistent with prior studies. NH3 reductions were not observed.

Comparisons of physical exposure between workers harvesting apples on mobile orchard platforms and ladders, part 1: Back and upper arm postures.

This study compared farmworkers' exposure to non-neutral postures using a new mobile platform apple harvesting method and the traditional method using ladders. Twenty-four workers were recruited and assigned into three groups: ladder workers (n = 8) picking apples from full trees using a ladder, mobile platform workers (n = 8) picking apples from upper part of the trees while standing on a moving platform, and ground-based mobile platform workers (n = 8) picking apples from lower part of the trees which the mobile platform workers left out. Upper arm and back inclinations were continuously monitored during harvesting using tri-axial accelerometers over full work shifts (~8 h). Upper arm posture was characterized as the percentage of time that upper arm flexion and abduction exceeded 30°, 60°, and 90°. Back posture was characterized as the percentage of time that torso angles (sagittal flexion or lateral bending) exceeded 10°, 20°, and 30°. The 10th, 50th, and 90th postural percentiles were also calculated. The platform workers had lower exposures to upper arm flexion and abduction than the ground and ladder workers. There were no differences in torso angles between the ladder and mobile platform workers; however, the ground workers were exposed to more and greater percentages of time in torso flexions.

Comparisons of physical exposure between workers harvesting apples on mobile orchard platforms and ladders, part 2: Repetitive upper arm motions.

Farmworkers are exposed to physical risk factors including repetitive motions. Existing ergonomic assessment methods are primarily laboratory-based and, thus, inappropriate for use in the field. This study presents an approach to characterize the repetitive motions of the upper arms based on direct measurement using accelerometers. Repetition rates were derived from upper arm inclination data and with video recordings in the field. This method was used to investigate whether harvesting with mobile platforms (teams harvesting apples from the platform and the ground) increased the farmworkers' exposure to upper arm repetitive motions compared to traditional harvesting using ladders. The ladder workers had higher repetitive motions (13.7 cycles per minute) compared to the platform and ground workers (11.7 and 12.2 cycles per minutes). The higher repetitions in the ladder workers were likely due to their ability to work independently and the additional arm movements associated with ladder climbing and walking.

The home air in agriculture pediatric intervention (HAPI) trial: Rationale and methods.

BACKGROUND: Data addressing air quality effects on children with asthma in rural U.S. communities are rare. Our community engaged research partnership previously demonstrated associations between neighborhood NH3 and ambient PM2.5 and asthma in the agricultural lower Yakima Valley of Washington. As a next step, the partnership desired an intervention approach to address concerns about pediatric asthma in this largely Latino immigrant, farm worker community. OBJECTIVE: The Home Air in Agriculture Pediatric Intervention (HAPI) sought to examine the effectiveness of enrichment of an existing asthma education program with portable high-efficiency particulate air (HEPA) cleaners designed to reduce PM2.5 and NH3. We investigated the effect of this enriched approach on these exposures and asthma health measures. DESIGN: We randomized children with poorly controlled asthma to a control arm (current asthma education program) or an intervention arm (current asthma education program + placement of two indoor air cleaners in the family's home). Outcomes included (1) 14-day integrated samples of indoor air contaminants (PM2.5 and NH3) at baseline and one-year follow-up and (2) child asthma health metrics at baseline, midpoint (4-6 months) and one-year follow-up. These included the Asthma Control Test, symptoms days, clinical utilization, oral corticosteroid use, pulmonary function, fractional exhaled nitric oxide, and urinary leukotriene E4 concentration. DISCUSSION: To our knowledge, this is the first randomized HEPA cleaner intervention designed to assess NH3 as well as PM2.5 and to evaluate health outcomes of children with asthma in an agricultural region.

Estimated time-varying exposures to air emissions from animal feeding operations and childhood asthma.

BACKGROUND/AIM: Industrial-scale animal feeding operations (AFOs) have adverse impacts on regional air quality. Air emissions include endotoxins and other pro-inflammatory components, and exposure may cause airway inflammation and respiratory effects in susceptible individuals residing nearby. We aimed to develop and validate metrics for estimating time-varying exposure to AFO air pollution in surrounding communities and, secondly, to determine whether exposure is associated with health effects in children with asthma. METHODS: We conducted a longitudinal panel study of N = 58 children with asthma in an agricultural region of Washington State with a high density of dairy AFOs. Children were followed for up to 26 months with repeated measures of respiratory health (N = 2023 interviews; N = 3853 lung function measurements); urine was collected in a subcohort (N = 16) at six-day intervals over three months and analyzed for leukotriene E4 (LTE4), a biomarker of systemic inflammation (N = 138 measurements). We developed an approach to estimate daily exposure to AFO airborne emissions based on distance to AFOs, AFO size, and daily wind speed and direction, and validated the estimates against direct measurements of ammonia, a chemical marker of AFO emissions, measured biweekly at 18 sites across the region for 14 months. Short-term relationships between AFO pollutant exposure and outcomes were assessed using regression models accounting for within-participant correlation and several potential confounders. RESULTS: Estimates of daily AFO air pollution correlated moderately well with outdoor ammonia measurements (N = 842; r = 0.62). Forced expiratory volume in 1 s (FEV1) as percent of predicted was 2.0% (95% CI: 0.5, 3.5) lower with each interquartile increase in previous day exposure, but no associations with asthma symptoms were observed. There was suggestive evidence that LTE4 concentrations were higher following days of elevated exposure to AFO emissions (p = 0.06). CONCLUSIONS: A simple metric of time-varying exposure to AFO emissions was correlated with daily outdoor ammonia levels. Children with asthma may be adversely affected by exposure to AFO emissions.

A feasibility study comparing objective and subjective field-based physical exposure measurements during apple harvesting with ladders and mobile platforms.

Although mobile orchardplatforms have been developed to improve apple harvesting productivity in the US, the physical exposures of workers usingthe mobile platforms have not been well characterized, partlydue to the lack of assessment tools specific to the tree fruitorchard environment. The purpose of this study was to evaluate the feasibility and utility of different subjective and objective methods for characterizing apple harvesting workers' posture, armrepetition, heart rate, and perceived exertion during platform- and conventional ladder-based harvesting. During a regular full shiftwork (8 hours), the objective physical exposure measures (armelevation, torso inclination, and heart rate) of 6 platform, 6 ground, and 8 ladder workers were measured with tri-axial accelerometersand heart rate monitor; and subjective perceived exertion wascollected using standardized Borg RPE and CR-10 scales, translated into Spanish. The results showed that the arm elevation, torso forward bending, repetitiveness, heart rates, and perceived exertions were lower for the platform-based workers than forthe ladder-based workers. The subjective measures (Borg RPE and Borg CR-10) appeared to be similar and mirror the general trends of the objective heart rate and posture measures.These results indicate the potential benefit of these low-cost subjective measures when direct measurements are too costly,complicated, or not permitted. This study determined that field measurements of objective and subjective physical exposures were feasible for evaluating apple harvesting work. In summary, all themethods used appear to be feasible for field use in orchard-based environments..

Ambient Ammonia Exposures in an Agricultural Community and Pediatric Asthma Morbidity.

BACKGROUND: Large-scale animal feeding operations compromise regional air quality in the rural US through emission of pollutants, such as ammonia gas. Exposure to airborne pollution from animal feeding operations may cause pediatric asthma exacerbations in surrounding communities. OBJECTIVES: To describe spatial and temporal patterns in ambient ammonia concentrations in an agricultural region, and to investigate associations between short-term fluctuations in ammonia and subsequent changes in respiratory health in children with asthma. METHODS: For 13 months in the Yakima Valley of Washington State, 14 monitors sampled ammonia in outdoor air for 24-hour periods every 6 days. School-age children with asthma (n = 51) were followed for two health outcomes: biweekly reports of asthma symptoms and quick relief medication usage, and daily measurements of forced expiratory volume in 1 second. We assessed associations between each outcome and ammonia using generalized estimating equations. RESULTS: Twenty-four-hour ammonia concentrations varied from 0.2 to 238.1 µg/m during the study period and displayed a strong correlation with proximity to animal feeding operations. The percentage of forced expiratory volume in 1 second was 3.8% lower (95% confidence interval = 0.2, 7.3) per interquartile increase in 1-day lagged ammonia concentration and 3.0% lower (95% confidence interval = 0.5, 5.8) for 2-day lagged concentration. We observed no associations between self-reported asthma symptoms or medication usage and estimated ammonia exposure. CONCLUSIONS: Ammonia concentrations were elevated in this community and strongly predicted by proximity to animal feeding operations. Ammonia's association with acute lung function decrements in children with asthma in the surrounding community may be causal or, alternatively, ammonia may be a marker for other pollutants from animal feeding operations associated with respiratory effects.

Development of a unique multi-contaminant air sampling device for a childhood asthma cohort in an agricultural environment.

This research describes the design, deployment, performance, and acceptability of a novel outdoor active air sampler to provide simultaneous measurements of multiple contaminants at timed intervals for the Aggravating Factors of Asthma in Rural Environment (AFARE) study-a longitudinal cohort of 50 children in Yakima Valley, Washington. The sampler was constructed of multiple sampling media connected to individual critical orifices and a rotary vane vacuum pump. It was connected to a timed control valve system to collect 24 hours samples every six days over 18 months. We describe a spatially representative approach with both quantitative and qualitative location criteria to deploy a network of 14 devices at participant residences in a rural region (20 × 60 km). Overall the sampler performed well, as the concurrent mean sample flow rates were within or above the ranges of recommended sampling rates for each exposure metric of interest. Acceptability was high among the study population of Hispanic farmworker participant households. The sampler design may prove useful for future urban and rural community-based studies with aims at collecting multiple contaminant data during specific time periods.

Comparison of polyurethane foam and XAD-2 sampling matrices to measure airborne organophosphorus pesticides and their oxygen analogs in an agricultural community.

Side-by-side active air sampling for the organophosphorus (OP) pesticide, chlorpyrifos (CPF) and its oxygen analog, chlorpyrifos-oxon (CPF-O) was conducted with two recommended air sampling matrices: OSHA Versatile Sampling (OVS) tubes with XAD-2 resin, polyurethane foam (PUF) tubes, and passive PUF deposition disks. The study compared the proportion of artificially transformed CPF-O in the laboratory and in the field during a tree fruit application in Washington State. Lab results demonstrated that the NIOSH-recommended OVS tubes artificially transformed up to 32% of CPF to CPF-O during the sampling process, whereas PUF tubes had little to no artificial transformation (⩽0.1%). In the field, the proportion of CPF-O in the sample was significantly higher on OVS tubes than on PUF tubes (p<0.001), confirming that OVS tubes were converting a significant portion of CPF to CPF-O. In addition, PUF tubes reported measurable levels CPF-O in the field even when no artificial transformation was expected. We conclude that the PUF matrix is the superior sampling medium for OP oxygen analogs when compared to XAD-two resin. Community-located PUF tube samples 24h post-application had considerably higher levels CPF-O (16-21ngm(-3)) than near field samples during application (2-14ngm(-3)), suggesting that the oxygen analog is volatile and formed during atmospheric transport. It is recommended that worker and community risk assessments begin to take into consideration the presence of the more toxic oxygen analogs when measuring for OP pesticide mixtures.

Presence of organophosphorus pesticide oxygen analogs in air samples.

A number of recent toxicity studies have highlighted the increased potency of oxygen analogs (oxons) of several organophosphorus (OP) pesticides. These findings were a major concern after environmental oxons were identified in environmental samples from air and surfaces following agricultural spray applications in California and Washington State. This paper reports on the validity of oxygen analog measurements in air samples for the OP pesticide, chlorpyrifos. Controlled environmental and laboratory experiments were used to examine artificial formation of chlorpyrifos-oxon using OSHA Versatile Sampling (OVS) tubes as recommended by NIOSH method 5600. Additionally, we compared expected chlorpyrifos-oxon attributable to artificial transformation to observed chlorpyrifos-oxon in field samples from a 2008 Washington State Department of Health air monitoring study using non-parametric statistical methods. The amount of artificially transformed oxon was then modeled to determine the amount of oxon present in the environment. Toxicity equivalency factors (TEFs) for chlorpyrifos-oxon were used to calculate chlorpyrifos-equivalent air concentrations. The results demonstrate that the NIOSH-recommended sampling matrix (OVS tubes with XAD-2 resin) was found to artificially transform up to 30% of chlorpyrifos to chlorpyrifos-oxon, with higher percentages at lower concentrations (< 30 ng/m3) typical of ambient or residential levels. Overall, the 2008 study data had significantly greater oxon than expected by artificial transformation, but the exact amount of environmental oxon in air remains difficult to quantify with the current sampling method. Failure to conduct laboratory analysis for chlorpyrifos-oxon may result in underestimation of total pesticide concentration when using XAD-2 resin matrices for occupational or residential sampling. Alternative methods that can accurately measure both OP pesticides and their oxygen analogs should be used for air sampling, and a toxicity equivalent factor approach should be used to determine potential health risks from exposures.