Denver Asthma Panel Study-CHEAR Ancillary Study (part II)
ABSTRACT: Urban environments remain a poorly understood toxic environment for children with asthma, where improved exposure characterization and estimation of exposurehealth outcome relationships are clearly needed. The goal of this project is to investigate the interactions between relevant environmental exposures and asthma severity in a year-long longitudinal study of urban children with asthma. Environmental and clinical samples are being collected at 3 seasonal visits. Using these samples, we will measure the effects of multiple relevant exposures (environmental tobacco smoke (ETS), polycyclic aromatic hydrocarbons (PAHs), phthalates, and volatile organic compounds (VOCs)) on biological responses (metabolomics, oxidative stress, inflammatory markers, and endocannabinoids) and asthma outcomes. Our overall hypothesis is that relevant environmental exposures and their interactions drive disease severity in urban children with asthma. We will test this hypothesis by investigating the following aims: Aim 1: To investigate how environmental exposures (ETS, PAHs, phthalates, and VOCs) and their interactions contribute to asthma severity in urban children. Aim 2: To determine if environmental exposures in children with asthma are associated with changes in in biological responses (metabolomics, oxidative stress, inflammatory markers, and endocannabinoids). Aim 3: To determine which biological responses mediate the relationships between environmental exposures and asthma severity. Aim 4: To compare environmental exposures and biological responses in asthmatic and non-asthmatic children
Project description:Urban environments remain a poorly understood toxic environment for children with asthma, where improved exposure characterization and estimation of exposurehealth outcome relationships are clearly needed. The goal of this project is to investigate the interactions between relevant environmental exposures and asthma severity in a year-long longitudinal study of urban children with asthma. Environmental and clinical samples are being collected at 3 seasonal visits. Using these samples, we will measure the effects of multiple relevant exposures (environmental tobacco smoke (ETS), polycyclic aromatic hydrocarbons (PAHs), phthalates, and volatile organic compounds (VOCs)) on biological responses (metabolomics, oxidative stress, inflammatory markers, and endocannabinoids) and asthma outcomes. Our overall hypothesis is that relevant environmental exposures and their interactions drive disease severity in urban children with asthma. We will test this hypothesis by investigating the following aims:" "Aim 1: To investigate how environmental exposures (ETS, PAHs, phthalates, and VOCs) and their interactions contribute to asthma severity in urban children." "Aim 2: To determine if environmental exposures in children with asthma are associated with changes in in biological responses (metabolomics, oxidative stress, inflammatory markers, and endocannabinoids)." Aim 3: To determine which biological responses mediate the relationships between environmental exposures and asthma severity. Aim 4: To compare environmental exposures and biological responses in asthmatic and non-asthmatic children
Project description:Childhood asthma is a complex condition where many environmental factors are implicated in causation. The aim of this study was to complete a systematic review of the literature describing associations between environmental exposures and the development of asthma in young children.A systematic review of the literature up to November 2013 was conducted using key words agreed by the research team. Abstracts were screened and potentially eligible papers reviewed. Papers describing associations between exposures and exacerbation of pre-existing asthma were not included. Papers were placed into the following predefined categories: secondhand smoke (SHS), inhaled chemicals, damp housing/mould, inhaled allergens, air pollution, domestic combustion, dietary exposures, respiratory virus infection and medications.Children aged up to 9 years.Diagnosed asthma and wheeze.14,691 abstracts were identified, 207 papers reviewed and 135 included in the present review of which 15 were systematic reviews, 6 were meta-analyses and 14 were intervention studies. There was consistent evidence linking exposures to SHS, inhaled chemicals, mould, ambient air pollutants, some deficiencies in maternal diet and respiratory viruses to an increased risk for asthma (OR typically increased by 1.5-2.0). There was less consistent evidence linking exposures to pets, breast feeding and infant dietary exposures to asthma risk, and although there were consistent associations between exposures to antibiotics and paracetamol in early life, these associations might reflect reverse causation. There was good evidence that exposures to house dust mites (in isolation) was not associated with asthma risk. Evidence from observational and intervention studies suggest that interactions between exposures were important to asthma causation, where the effect size was typically 1.5-3.0.There are many publications reporting associations between environmental exposures and modest changes in risk for asthma in young children, and this review highlights the complex interactions between exposures that further increase risk.
Project description:To complete a systematic review of the literature describing associations between all environmental exposures and asthma symptoms and exacerbations in children up to mean age of 9 years.Systematic review.Reference lists of identified studies and reviews were searched for all articles published until November 2013 in electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Controls Trials Register).Studies were selected which examined a link between exposure to environmental factors and asthma symptoms and exacerbations where the study participants were children with a mean age of ?9 years.Indices of asthma symptoms, control and exacerbations.A total of 27 studies were identified including eight where inhaled allergens and four where environmental tobacco smoke (ETS) were the exposures of interest. There was evidence that exposure to allergen, ETS, poor air quality and unflued heaters had a modest magnitude of effect (ORs between 2 and 3). There was also evidence of interactions observed between exposures such as allergen and ETS.Exposure to inhaled allergens, ETS, unflued heaters and poor air quality has an important effect on exacerbations in young children with asthma and should be minimised or, ideally, avoided. Better understanding of the effect of exposure to damp housing, air conditioning and dietary factors plus interactions between environmental exposures associated with exacerbations is required.
Project description:The Urban Environment and Childhood Asthma study was established to investigate the immunologic and environmental causes of asthma in inner-city children.We sought to evaluate potential atopic outcomes in the first 12 months and their relationships to environmental exposures and immune development.A birth cohort of 560 children with at least 1 parent with allergy or asthma was established in Baltimore, Boston, New York, and St Louis. Wheezing is assessed every 3 months, allergen-specific IgE yearly, and mononuclear cell cytokine responses at birth and yearly; environmental assessments include dust allergen and endotoxin, maternal stress, and indoor nicotine and nitrogen dioxide levels.Key outcomes in the first year include wheeze in 49%, 2 or more episodes of wheeze in 23%, eczema in 30%, and detectable IgE to milk, egg, and/or peanut in 32% and to cockroach in 4%. Household dust revealed levels of greater than 2 ?g/g to cockroach in 40%, mite in 19%, cat in 25%, and mouse in 29%, and 66% of homes housed at least 1 smoker. Positive associations were detected between multiple wheeze and cotinine levels, maternal stress, and maternal depression, whereas cytokine responses to a variety of innate, adaptive, and mitogenic stimuli were inversely related to eczema.This high-risk cohort of inner-city infants is exhibiting high rates of wheeze, eczema, and allergic sensitization. Low cytokine responses at birth might be a risk factor for eczema, whereas a variety of adverse environmental exposures contribute to the risk of wheezing in infancy. These findings provide evidence of specificity in the interactions between immune development, environmental exposures, and the development of early features that might predict future asthma.
Project description:Asthma is a heterogeneous clinical syndrome that includes subtypes of disease with different underlying causes and disease mechanisms. Asthma is caused by a complex interaction between genes and environmental exposures; early-life exposures in particular play an important role. Asthma is also heritable, and a number of susceptibility variants have been discovered in genome-wide association studies, although the known risk alleles explain only a small proportion of the heritability. In this review, we present evidence supporting the hypothesis that focusing on more specific asthma phenotypes, such as childhood asthma with severe exacerbations, and on relevant exposures that are involved in gene-environment interactions (GEIs), such as rhinovirus infections, will improve detection of asthma genes and our understanding of the underlying mechanisms. We will discuss the challenges of considering GEIs and the advantages of studying responses to asthma-associated exposures in clinical birth cohorts, as well as in cell models of GEIs, to dissect the context-specific nature of genotypic risks, to prioritize variants in genome-wide association studies, and to identify pathways involved in pathogenesis in subgroups of patients. We propose that such approaches, in spite of their many challenges, present great opportunities for better understanding of asthma pathogenesis and heterogeneity and, ultimately, for improving prevention and treatment of disease.
Project description:Asthma is a heterogeneous disease that results from the complex interaction between genetic factors and environmental exposures that occur at critical periods throughout life. It seems plausible to regard childhood-onset and adult-onset asthma as different entities, each with a different pathophysiology, trajectory, and outcome. This review provides an overview about the role of genetics and gene-environment interactions in these two conditions. Looking at the genetic overlap between childhood and adult onset disease gives one window into whether there is a correlation, as well as to mechanism. A second window is offered by the genetics of the relationship between each type of asthma and other phenotypes e.g., obesity, chronic obstructive pulmonary disease (COPD), atopy, vitamin D levels, and inflammatory and immune status; and third, the genetic-specific responses to the many environmental exposures that influence risk throughout life, and particularly those that occur during early-life development. These represent a large number of possible combinations of genetic and environmental factors, at least 150 known genetic loci vs. tobacco smoke, outdoor air pollutants, indoor exposures, farming environment, and microbial exposures. Considering time of asthma onset extends the two-dimensional problem of gene-environment interactions to a three-dimensional problem, since identified gene-environment interactions seldom replicate for childhood and adult asthma, which suggests that asthma susceptibility to environmental exposures may biologically differ from early life to adulthood as a result of different pathways and mechanisms of the disease.
Project description:RATIONALE:Navajo children living on the reservation have high rates of asthma prevalence and severity. Environmental influences may contribute to asthma on the Navajo Nation and are inadequately understood. OBJECTIVES:We performed a comprehensive, integrative literature review to determine the environmental factors that may contribute to increased asthma prevalence and severity among Navajo children living on the reservation. METHODS:A systematic search was conducted in four databases regarding the environmental risk factors for asthma in Navajo children living on the reservation. Relevant studies between 1990 and 2017 were examined. Nonexperimental literature was also integrated into the review to describe the environmental injustices that have historically, disproportionately, and systematically affected the Navajo people, thus contributing to respiratory disparities among Navajo children. RESULTS:Eight studies met inclusion criteria for systematic review; however, limited research regarding environmental risk factors specific to asthma and Navajo children living on the reservation was identified. Our integrative review indicated both indoor and outdoor environmental risk factors commonly found on the Navajo reservation appear to be important determinants of asthma. CONCLUSIONS:Future research should examine indoor and outdoor air pollution from wood-burning stoves and cook stoves, coal combustion, tobacco and traditional ceremonial smoke, diesel exhaust exposure from long bus rides, indoor allergens, ambient pollutants, and regional dusts. Comprehensive mitigation efforts created in partnership with the Navajo Nation are necessary to address less-recognized risk factors as well as the common risk factors known to contribute to increased childhood asthma prevalence and severity.
Project description:Previous research has found relationships between specific indoor environmental exposures and exacerbation of asthma.In this review we provide an updated summary of knowledge from the scientific literature on indoor exposures and exacerbation of asthma.Peer-reviewed articles published from 2000 to 2013 on indoor exposures and exacerbation of asthma were identified through PubMed, from reference lists, and from authors' files. Articles that focused on modifiable indoor exposures in relation to frequency or severity of exacerbation of asthma were selected for review. Research findings were reviewed and summarized with consideration of the strength of the evidence.Sixty-nine eligible articles were included. Major changed conclusions include a causal relationship with exacerbation for indoor dampness or dampness-related agents (in children); associations with exacerbation for dampness or dampness-related agents (in adults), endotoxin, and environmental tobacco smoke (in preschool children); and limited or suggestive evidence for association with exacerbation for indoor culturable Penicillium or total fungi, nitrogen dioxide, rodents (nonoccupational), feather/down pillows (protective relative to synthetic bedding), and (regardless of specific sensitization) dust mite, cockroach, dog, and dampness-related agents.This review, incorporating evidence reported since 2000, increases the strength of evidence linking many indoor factors to the exacerbation of asthma. Conclusions should be considered provisional until all available evidence is examined more thoroughly.Multiple indoor exposures, especially dampness-related agents, merit increased attention to prevent exacerbation of asthma, possibly even in nonsensitized individuals. Additional research to establish causality and evaluate interventions is needed for these and other indoor exposures.
Project description:BACKGROUND:Allergic and nonallergic asthma severity in children can be affected by microbial exposures. OBJECTIVE:We sought to examine associations between exposures to household microbes and childhood asthma severity stratified by atopic status. METHODS:Participants (n = 196) were selected from a cohort of asthmatic children in Connecticut and Massachusetts. Children were grouped according to asthma severity (mild with no or minimal symptoms and medication or moderate to severe persistent) and atopic status (determined by serum IgE levels). Microbial community structure and concentrations in house dust were determined by using next-generation DNA sequencing and quantitative PCR. Logistic regression was used to explore associations between asthma severity and exposure metrics, including richness, taxa identification and quantification, community composition, and concentration of total fungi and bacteria. RESULTS:Among all children, increased asthma severity was significantly associated with an increased concentration of summed allergenic fungal species, high total fungal concentrations, and high bacterial richness by using logistic regression in addition to microbial community composition by using the distance comparison t test. Asthma severity in atopic children was associated with fungal community composition (P = .001). By using logistic regression, asthma severity in nonatopic children was associated with total fungal concentration (odds ratio, 2.40; 95% CI, 1.06-5.44). The fungal genus Volutella was associated with increased asthma severity in atopic children (P = .0001, q = 0.04). The yeast genera Kondoa might be protective; Cryptococcus species might also affect asthma severity. CONCLUSION:Asthma severity among this cohort of children was associated with microbial exposure, and associations differed based on atopic status.
Project description:BACKGROUND:Prenatal environmental phenol and phthalate exposures may alter immune or inflammatory responses leading to respiratory and allergic disease. OBJECTIVES:We estimated associations of prenatal environmental phenol and phthalate biomarkers with respiratory and allergic outcomes among children in the Mount Sinai Children's Environmental Health Study. METHODS:We quantified urinary biomarkers of benzophenone-3, bisphenol A, paradichlorobenzene (as 2,5-dichlorophenol), triclosan, and 10 phthalate metabolites in third trimester maternal samples and assessed asthma, wheeze, and atopic skin conditions via parent questionnaires at ages 6 and 7?years (n?=?164 children with 240 observations). We used logistic regression to estimate covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) per standard deviation difference in natural log biomarker concentrations and examined effect measure modification by child's sex. RESULTS:Associations of prenatal 2,5-dichlorophenol (all outcomes) and bisphenol A (asthma outcomes) were modified by child's sex, with increased odds of outcomes among boys but not girls. Among boys, ORs for asthma diagnosis per standard deviation difference in biomarker concentration were 3.00 (95% CI: 1.36, 6.59) for 2,5-dichlorophenol and 3.04 (95% CI: 1.38, 6.68) for bisphenol A. Wheeze in the past 12?months was inversely associated with low molecular weight phthalate metabolites among girls only (OR: 0.27, 95% CI: 0.13, 0.59) and with benzophenone-3 among all children (OR: 0.65, 95% CI: 0.44, 0.96). CONCLUSIONS:Prenatal bisphenol A and paradichlorobenzene exposures were associated with pediatric respiratory outcomes among boys. Future studies may shed light on biological mechanisms and potential sexually-dimorphic effects of select phenols and phthalates on respiratory disease development.