Gene-environment interaction between an IL4R variant and school endotoxin exposure contributes to asthma symptoms in inner-city children.
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ABSTRACT:
SUBMITTER: Lai PS
PROVIDER: S-EPMC5803303 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
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Gene-environment interaction between an IL4R variant and school endotoxin exposure contributes to asthma symptoms in inner-city children.
Lai Peggy S PS Massoud Amir H AH Xia Mingcan M Petty Carter R CR Cunningham Amparito A Chatila Talal A TA Phipatanakul Wanda W
The Journal of allergy and clinical immunology 20170921 2
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Project description:BackgroundEndotoxin exposure is associated with airway inflammation. Children spend 6 to 8 h/d in school, yet the effect of school-specific endotoxin exposure on asthma morbidity is not well understood.MethodsIn this longitudinal cohort study, 248 students with asthma, from 38 inner-city schools, underwent baseline phenotyping and follow-up. Clinical outcomes were evaluated throughout the academic school year and linked to classroom-specific dust and air endotoxin levels as well as home dust endotoxin levels. The primary outcome was maximum asthma symptom-days per 2-week period.ResultsClassrooms had higher settled dust endotoxin levels compared with homes (14.3 endotoxin unit/mg vs 11.3 endotoxin unit/mg; P = .02). Airborne endotoxin levels exceeding recommended occupational exposure limits for adults were recorded in 22.0% of classrooms. Classroom air endotoxin levels were independently associated with increased maximum symptom-days in children with nonatopic asthma, but not in those with atopic asthma (interaction P = .03). Adjusting for home exposures, classroom endotoxin exposure was independently associated with a dose-dependent increase in asthma symptom-days for children with nonatopic asthma (adjusted incidence rate ratio, 1.16 [95% CI, 1.03-1.31]; P = .02). In these subjects, maximum symptom-days increased by 1.3 days for each 14-day period when comparing students in classrooms with the lowest endotoxin levels compared with average measured levels.ConclusionsInner-city children with asthma are exposed to high levels of airborne endotoxin at school, resulting in increased asthma symptoms in children with nonatopic asthma. Mitigation of school-related exposures may represent a strategy to decrease asthma morbidity in this population.Trial registryClinicalTrials.gov; No.: NCT01756391; URL: www.clinicaltrials.gov.
| S-EPMC4631040 | biostudies-literature
Project description:BackgroundTraffic proximity has been associated with adverse respiratory health outcomes. Less is known about the combined impact of residential and school exposures on pediatric asthma.ObjectiveWe sought to use spatial analysis methodology to analyze residential and school proximity to major roadways and pediatric asthma morbidity.MethodsThe School Inner-City Asthma Study (n = 350) recruited school-aged children with asthma. Each participant's school and home addresses were geocoded, and distances from major roadways were measured to calculate a composite measure accounting for both home and school traffic exposure. Generalized estimating equation models were clustered by subject and adjusted for age, race/ethnicity, sex, income, environmental tobacco smoke, controller medication, upper respiratory tract infections, and seasonality.ResultsThe majority of participants (62%) attended schools within 100 m from major roadways, and 40% also resided within 100 m of major roadways. In multivariate analyses major roadway proximity was independently associated with increased asthma symptom days. At greater than the threshold of 100 m, children had 29% less odds of a symptom day over the past 2 weeks for each 100-m increase in distance from a major roadway (odds ratio, 0.71; 95% CI, 0.58-0.87; P < .01). Children farther from a major roadway also had significantly less reported health care use (odds ratio, 0.63; 95% CI, 0.47-0.85; P < .01) and were significantly less likely to have poor asthma control (odds ratio, 0.80; 95% CI, 0.69-0.94; P < .01). There was not a meaningful association between distance to a major roadway and lung function outcomes.ConclusionsProximity to a major roadway, a composite measure of home and school exposure but primarily driven by home exposure, was associated with greater asthma morbidity. More studies are needed to evaluate the independent effect of school distance to a roadway on asthma morbidity.
| S-EPMC6949366 | biostudies-literature
Project description: Not available
| S-EPMC5503799 | biostudies-literature
Project description:The aim of this study was to investigate whether neighborhood safety as perceived by primary caregivers is associated with asthma morbidity outcomes among inner-city school children with asthma.School children with asthma were recruited from 25 inner-city schools between 2009 and 2012 for the School Inner-City Asthma Study (N?=?219). Primary caregivers completed a baseline questionnaire detailing their perception of neighborhood safety and their children's asthma symptoms, and the children performed baseline pulmonary function tests. In this cross-sectional analysis, asthma control was compared between children whose caregivers perceived their neighborhood to be unsafe versus safe.After adjusting for potential confounders, those children whose primary caregivers perceived the neighborhood to be unsafe had twice the odds of having poorly controlled asthma (odds ratio [OR] adjusted?=?2.2, 95% confidence interval [CI]?=?1.2-3.9, P?=?0.009), four times the odds of dyspnea and rescue medication use (OR adjusted?=?4.7; 95% CI?=?1.7-13.0, P?=?0.003, OR adjusted?=?4.0; 95% CI?=?1.8-8.8, P?<?0.001, respectively), three times as much limitation in activity (OR adjusted?=?3.2; 95% CI?=?1.4-7.7, P?=?0.008), and more than twice the odds of night-time symptoms (OR adjusted?=?2.2; 95% CI?=?1.3-4.0, P?=?0.007) compared to participants living in safe neighborhoods. There was no difference in pulmonary function test results between the two groups.Primary caregivers' perception of neighborhood safety is associated with childhood asthma morbidity among inner-city school children with asthma. Further study is needed to elucidate mechanisms behind this association, and future intervention studies to address social disadvantage may be important.
| S-EPMC4096619 | biostudies-literature
Project description:BackgroundInner-city children are disproportionately affected by asthma and sleep-disordered breathing (SDB). However, little is known about the association of SDB symptoms with asthma morbidity in this vulnerable population.ObjectiveAssess the relationship between snoring frequency and asthma morbidity.MethodsThis study was part of the School Inner-City Asthma Study, a longitudinal prospective cohort study of children with persistent asthma who attended schools in the Northeast United States from 2008 to 2013. Participants had baseline assessments of asthma symptoms, snoring, and allergy status. Caregivers completed quarterly surveys for 12 months on symptoms of asthma, snoring, and health care outcomes. Snoring frequency (non-, rare-, sometimes-, habitual-snoring) and its relationship with asthma symptoms and asthma morbidity were assessed by mixed-effects models.ResultsThere were 1186 observations from 339 subjects. Mean age was 7.9 years; roughly half were male, and most were of minority race. Half were overweight or obese, and 65.5% had atopy. At initial snoring assessment, 24.8% reported habitual snoring, but report of snoring frequency varied over the study period. Multivariate analyses revealed increased odds of maximum asthma symptom days for habitual snoring compared with nonsnoring (1.58; 95% CI, 1.19-2.10; P < .002) and all other snoring categories. Habitual snoring was associated with greater odds of health care utilization (incidence rate ratio, 1.72; 95% CI, 1.10-2.69; P = .02) and worse asthma control (odds ratio, 1.49; 95% CI, 1.05-2.11; P = .03) compared with nonsnoring.ConclusionsSnoring is common among inner-city school-age children with asthma, and habitual snoring is associated with increased asthma symptom burden and health care utilization.
| S-EPMC8511301 | biostudies-literature
Project description:BackgroundAmbient and home exposure to nitrogen dioxide (NO2) causes asthma symptoms and decreased lung function in children with asthma. Little is known about the health effects of school classroom pollution exposure.ObjectiveWe aimed to determine the effect of indoor classroom NO2 on lung function and symptoms in inner-city school children with asthma.MethodsChildren enrolled in the School Inner-City Asthma Study were followed for 1 academic year. Subjects performed spirometry and had fraction of exhaled nitric oxide values measured twice during the school year at school. Classroom NO2 was collected by means of passive sampling for 1-week periods twice per year, coinciding with lung function testing. Generalized estimating equation models assessed lung function and symptom relationships with the temporally nearest classroom NO2 level.ResultsThe mean NO2 value was 11.1 ppb (range, 4.3-29.7 ppb). In total, exposure data were available for 296 subjects, 188 of whom had complete spirometric data. At greater than a threshold of 8 ppb of NO2 and after adjusting for race and season (spirometry standardized by age, height, and sex), NO2 levels were associated highly with airflow obstruction, such that each 10-ppb increase in NO2 level was associated with a 5% decrease in FEV1/forced vital capacity ratio (β = -0.05; 95% CI, -0.08 to -0.02; P = .01). Percent predicted forced expiratory flow between the 25th and 75th percentile of forced vital capacity was also inversely associated with higher NO2 exposure (β = -22.8; 95% CI, -36.0 to -9.7; P = .01). There was no significant association of NO2 levels with percent predicted FEV1, fraction of exhaled nitric oxide, or asthma symptoms. Additionally, there was no effect modification of atopy on lung function or symptom outcomes.ConclusionIn children with asthma, indoor classroom NO2 levels can be associated with increased airflow obstruction.
| S-EPMC5886827 | biostudies-literature
Project description:BackgroundEnvironmental exposures in early life appear to play an important role in the pathogenesis of childhood asthma, but the potentially modifiable exposures that lead to asthma remain uncertain.ObjectiveWe sought to identify early-life environmental risk factors for childhood asthma in a birth cohort of high-risk inner-city children.MethodsWe examined the relationship of prenatal and early-life environmental factors to the occurrence of asthma at 7 years of age among 442 children.ResultsHigher house dust concentrations of cockroach, mouse, and cat allergens in the first 3 years of life were associated with lower risk of asthma (for cockroach allergen: odds ratio per interquartile range increase in concentration, 0.55; 95% CI, 0.36-0.86; P < .01). House dust microbiome analysis using 16S ribosomal RNA sequencing identified 202 and 171 bacterial taxa that were significantly (false discovery rate < 0.05) more or less abundant, respectively, in the homes of children with asthma. A majority of these bacteria were significantly correlated with 1 of more allergen concentrations. Other factors associated significantly positively with asthma included umbilical cord plasma cotinine concentration (odds ratio per geometric SD increase in concentration, 1.76; 95% CI, 1.00-3.09; P = .048) and maternal stress and depression scores.ConclusionAmong high-risk inner-city children, higher indoor levels of pet or pest allergens in infancy were associated with lower risk of asthma. The abundance of a number of bacterial taxa in house dust was associated with increased or decreased asthma risk. Prenatal tobacco smoke exposure and higher maternal stress and depression scores in early life were associated with increased asthma risk.
| S-EPMC6521865 | biostudies-literature
Project description:Asthma is the most common chronic disease of childhood in the United States, causes significant morbidity, particularly in the inner-city, and accounts for billions of dollars in health care utilization. Home environments are established sources of exposure that exacerbate symptoms and home-based interventions are effective. However, elementary school children spend 7 to 12h a day in school, primarily in one classroom. From the observational School Inner-City Asthma Study we learned that student classroom-specific exposures are associated with worsening asthma symptoms and decline in lung function. We now embark on a randomized, blinded, sham-controlled school environmental intervention trial, built on our extensively established school/community partnerships, to determine the efficacy of a school-based intervention to improve asthma control. This factorial school/classroom based environmental intervention will plan to enroll 300 students with asthma from multiple classrooms in 40 northeastern inner-city elementary schools. Schools will be randomized to receive either integrated pest management versus control and classrooms within these schools to receive either air purifiers or sham control. The primary outcome is asthma symptoms during the school year. This study is an unprecedented opportunity to test whether a community of children can benefit from school or classroom environmental interventions. If effective, this will have great impact as an efficient, cost-effective intervention for inner city children with asthma and may have broad public policy implications.
| S-EPMC5557648 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-02-02 | GSE40736 | GEO
Project description:BackgroundChildren with asthma in low-income urban areas have high morbidity. Phenotypic analysis in these children is lacking, but may identify characteristics to inform successful tailored management approaches.ObjectiveWe sought to identify distinct asthma phenotypes among inner-city children receiving guidelines-based management.MethodsNine inner-city asthma consortium centers enrolled 717 children aged 6 to 17 years. Data were collected at baseline and prospectively every 2 months for 1 year. Participants' asthma and rhinitis were optimally managed by study physicians on the basis of guidelines. Cluster analysis using 50 baseline and 12 longitudinal variables was performed in 616 participants completing 4 or more follow-up visits.ResultsFive clusters (designated A through E) were distinguished by indicators of asthma and rhinitis severity, pulmonary physiology, allergy (sensitization and total serum IgE), and allergic inflammation. In comparison to other clusters, cluster A was distinguished by lower allergy/inflammation, minimally symptomatic asthma and rhinitis, and normal pulmonary physiology. Cluster B had highly symptomatic asthma despite high step-level treatment, lower allergy and inflammation, and mildly altered pulmonary physiology. Cluster C had minimally symptomatic asthma and rhinitis, intermediate allergy and inflammation, and mildly impaired pulmonary physiology. Clusters D and E exhibited progressively higher asthma and rhinitis symptoms and allergy/inflammation. Cluster E had the most symptomatic asthma while receiving high step-level treatment and had the highest total serum IgE level (median, 733 kU/L), blood eosinophil count (median, 400 cells/mm3), and allergen sensitizations (15 of 22 tested).ConclusionsAllergy distinguishes asthma phenotypes in urban children. Severe asthma often coclusters with highly allergic children. However, a symptomatic phenotype with little allergy or allergic inflammation was identified.
| S-EPMC5104222 | biostudies-literature