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.

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.