Childhood asthma is not distributed evenly throughout the population, and children who grow up in crowded urban neighborhoods have higher rates of asthma and experience greater morbidity due to asthma. There are several environmental and lifestyle factors associated with urban living that are suspected to promote the development of asthma, particularly in the first few years of life. Collectively, this information suggests the hypothesis that exposure in early life to adverse environmental and lifestyle factors associated with disadvantaged urban environments modifies immune development to increase the risk for allergic diseases and asthma. The Urban Environment and Childhood Asthma birth cohort study was initiated in 2004 to test this hypothesis. The study population was recruited prenatally, and consisted of 560 families from four urban areas who were at high risk for allergies and/or asthma on the basis of parental histories, along with an additional 49 families without atopic parents. Immune development, respiratory illnesses, and exposure to stress, indoor pollutants, microbial products, and allergens were measured prospectively, and the major study outcomes are recurrent wheeze at three years of age and asthma at age seven. This review summarizes the study design, methods, and early findings of the URECA study.
Asthma and allergy are highly prevalent in industrialised countries. Longitudinal and cross-sectional studies have identified a number of potential risk factors for these conditions, including genetic and environmental factors, with significant gene-environment relationships. Birth cohort studies have been proposed as an important tool to explore these risk factors, particularly exposures in early life that are associated with later disease or protection from disease. This paper describes the establishment of a birth cohort in New Zealand.
A birth cohort was established in 1996 in Christchurch and Wellington and infants recruited between 1997–2001. Expectant mothers were recruited by midwives. Children and mothers have undergone assessment by serial questionnaires, environmental assessment including mould and allergen exposure, skin-prick testing, and at age six years are undergoing full assessment for the presence of asthma, atopy and allergic disease, including genetic assessment.
A total of 1105 children have been recruited, and the retention rate at fifteen months was 91.4%. 15.2% of the children at recruitment have been identified as Maori. A positive family history of asthma, eczema or hay fever has been reported in 84% of children. All children have now been assessed at fifteen months and 685 children from the cohort have reached age six years and have completed the six year assessment.
The cohort is fully assembled, and assessment of children is well advanced, with good retention rates. The study is well placed to address many current hypotheses about the risk factors for allergic disease and asthma.
Previous studies of how parental atopy and exposure to dampness and molds contribute to the risk of asthma have been mainly cross-sectional or prevalent case–control studies, where selection and information bias and temporality constitute problems. We assessed longitudinally the independent and joint effects of parental atopy and exposure to molds in dwellings on the development of asthma in childhood. We conducted a population-based, 6-year prospective cohort study of 1,984 children 1–7 years of age at the baseline in 1991 (follow-up rate, 77%). The study population included 1,916 children without asthma at baseline and complete outcome information. The data collection included a baseline and follow-up survey. The outcome of interest was development of asthma during the study period. The studied determinants were parental allergic diseases and four indicators of exposure at baseline: histories of water damage, presence of moisture and visible molds, and perceived mold odor in the home. A total of 138 (7.2%) children developed asthma during the study period, resulting in an incidence rate of 125 cases per 10,000 person-years [95% confidence interval (CI), 104–146]. In Poisson regression adjusting for confounding, parental atopy [adjusted incidence rate ratio (IRR) 1.52; 95% CI, 1.08–2.13] and the presence of mold odor in the home reported at baseline (adjusted IRR 2.44; 95% CI, 1.07–5.60) were independent determinants of asthma incidence, but no apparent interaction was observed. The results of this cohort study with assessment of exposure before the onset of asthma strengthen the evidence on the independent effects of parental atopy and exposure to molds on the development of asthma.
asthma; damp housing; effect modification; interaction; molds
The presence of pets in a home during the prenatal period and during early infancy has been associated with a lower prevalence of allergic sensitization and total IgE in middle childhood. No studies have examined the effect of pet exposure in a population-based cohort using multiple early life measures of serum total IgE.
To examine within-individual longitudinal trends in total IgE during early childhood and assess the effect of indoor prenatal pet exposure on those trends. Also, to employ a statistical method which was flexible enough to allow and account for unequally spaced study contacts and missing data.
Using the population-based Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS) birth cohort (62% African American), we analyzed 1187 infants with one to four measurements of total IgE collected from birth to 2 years of age. Effects of pet exposure on the shape and trajectory of IgE were assessed using a multilevel longitudinal model, accommodating repeated measures, missing data, and the precise time points of data collection.
The best fit shape to the trajectory of IgE was non-linear, with an accelerated increase before 6 months. Total IgE was lower across the entire early life period when there was prenatal indoor pet exposure (p<0.001). This effect was statistically significantly stronger in children delivered by caesarean-section versus vaginally (p< 0.001 and p< 0.06, respectively) and in those born to non-African American (p< 0.001) versus African American mothers (p< 0.3).
Pet exposure and delivery mode may be markers of infant exposure to distinct microbiomes. The effect of exposures may vary by race, suggesting differential impact by ancestry.
total IgE; cohort; longitudinal; multilevel model
The National Children’s Study is considering a wide spectrum of airborne pollutants that are hypothesized to potentially influence pregnancy outcomes, neurodevelopment, asthma, atopy, immune development, obesity, and pubertal development. In this article we summarize six applicable exposure assessment lessons learned from the Centers for Children’s Environmental Health and Disease Prevention Research that may enhance the National Children’s Study: a) Selecting individual study subjects with a wide range of pollution exposure profiles maximizes spatial-scale exposure contrasts for key pollutants of study interest. b) In studies with large sample sizes, long duration, and diverse outcomes and exposures, exposure assessment efforts should rely on modeling to provide estimates for the entire cohort, supported by subject-derived questionnaire data. c) Assessment of some exposures of interest requires individual measurements of exposures using snapshots of personal and microenvironmental exposures over short periods and/or in selected microenvironments. d) Understanding issues of spatial–temporal correlations of air pollutants, the surrogacy of specific pollutants for components of the complex mixture, and the exposure misclassification inherent in exposure estimates is critical in analysis and interpretation. e) “Usual” temporal, spatial, and physical patterns of activity can be used as modifiers of the exposure/outcome relationships. f) Biomarkers of exposure are useful for evaluation of specific exposures that have multiple routes of exposure. If these lessons are applied, the National Children’s Study offers a unique opportunity to assess the adverse effects of air pollution on interrelated health outcomes during the critical early life period.
air pollution; airborne; ambient; Centers for Children’s Environmental Health and Disease Prevention Research; Children’s Centers; cohort study; direct measurement; exposure assessment; modeling; National Children’s Study; personal measurement
The glutathione S-transferase M1 (GSTM1) null variant is a common copy number variant associated with adverse pulmonary outcomes, including asthma and airflow obstruction, with evidence of important gene-by-environment interactions with exposures to oxidative stress.
To explore the joint interactive effects of GSTM1 copy number and tobacco smoke exposure on the development of asthma and asthma-related phenotypes in a family-based cohort of childhood asthmatics.
We performed quantitative PCR-based genotyping for GSTM1 copy number in children of self-reported white ancestry with mild to moderate asthma in the Childhood Asthma Management Program. Questionnaire data regarding intrauterine (IUS) and postnatal, longitudinal environmental tobacco smoke exposure were available. We performed both family-based and population-based tests of association for the interaction between GSTM1 copy number and tobacco smoke exposure with asthma and asthma-related phenotypes.
Associations of GSTM1 null variants with asthma (p= .03), younger age of asthma symptom onset (p=.03), and greater airflow obstruction (reduced FEV1/FVC, p=.01) were observed among the 50 children (10% of the cohort) with exposure to IUS. In contrast, no associations were observed between GSTM1 null variants and asthma-related phenotypes among children without IUS exposure. Presence of at least one copy of GSTM1 conferred protection.
These findings support an important gene-by-environment interaction between two common factors: increased risk of asthma and asthma-related phenotypes conferred by GSTM1-null homozygosity in children is restricted to those with a history of IUS exposure.
Asthma; GSTM1; copy number variation (CNV); gene by environment; intrauterine smoke exposure; tobacco smoke
It is not yet known the extent to which the environment adversely affects the health of the developing individual. Difficulties in this determination are the problems of a) the assessment of exposure, b) the long latency of many diseases induced by the environment, c) the number of confounding exposures, and d) the extrapolation of animal models to critical stages of human development. Biomarkers have the potential to be quantitative dosimeters of exposure and biologic effective dose, as well as early warning signals of biologic effect. Biomarkers may document interindividual susceptibilities, as well as defining critical windows of exposure. To be useful, biomarkers need to be validated in terms of their specificity and sensitivity. Biomarkers are useful across all disciplines including asthma and respiratory problems, developmental neurotoxicity, childhood cancer, and endocrine disruptors. Biomarkers have not been developed nor used widely in pediatric environmental health. Research by our group and others has documented the validity of biomarkers in pediatric environmental health. Advances in the field of biomarkers may have important implications for the detection, prevention, and treatment of environmentally induced diseases in children. Ongoing validation of promising biomarkers should be a research priority.
Little is known about mouse allergen exposure in home environments and the development of wheezing, asthma and atopy in childhood.
To examine the relation between mouse allergen exposure and wheezing, atopy, and asthma in the first 7 years of life.
Prospective study of 498 children with parental history of allergy or asthma followed from birth to age 7 years, with longitudinal questionnaire ascertainment of reported mouse exposure and dust sample mouse urinary protein allergen levels measured at age 2–3 months.
Parental report of mouse exposure in the first year of life was associated with increased risk of transient wheeze and wheezing in early life. Current report of mouse exposure was also significantly associated with current wheeze throughout the first 7 years of life in the longitudinal analysis (P = 0.03 for overall relation of current mouse to current wheeze). However, early life mouse exposure did not predict asthma, eczema or allergic rhinitis at age 7 years. Exposure to detectable levels of mouse urinary protein in house dust samples collected at age 2–3 months was associated with a twofold increase in the odds of atopy (sensitization to >=1 allergen) at school age (95% confidence interval for odds ratio = 1.1–3.7; P = 0.03 in a multivariate analysis.
Among children with parental history of asthma or allergies, current mouse exposure is associated with increased risk of wheeze during the first 7 years of life. Early mouse exposure was associated with early wheeze and atopy later in life.
childhood asthma; indoor allergens; mouse allergen
There is increasing recognition of the importance of early environmental exposures in the development of childhood asthma. Outdoor air pollution is a recognized asthma trigger, but it is unclear whether exposure influences incident disease. We investigated the effect of exposure to ambient air pollution in utero and during the first year of life on risk of subsequent asthma diagnosis in a population-based nested case–control study.
We assessed all children born in southwestern British Columbia in 1999 and 2000 (n = 37,401) for incidence of asthma diagnosis up to 3–4 years of age using outpatient and hospitalization records. Asthma cases were age- and sex-matched to five randomly chosen controls from the eligible cohort. We estimated each individual’s exposure to ambient air pollution for the gestational period and first year of life using high-resolution pollution surfaces derived from regulatory monitoring data as well as land use regression models adjusted for temporal variation. We used logistic regression analyses to estimate effects of carbon monoxide, nitric oxide, nitrogen dioxide, particulate matter ≤ 10 μm and ≤ 2.5 μm in aerodynamic diameter (PM10 and PM2.5), ozone, sulfur dioxide, black carbon, woodsmoke, and proximity to roads and point sources on asthma diagnosis.
A total of 3,482 children (9%) were classified as asthma cases. We observed a statistically significantly increased risk of asthma diagnosis with increased early life exposure to CO, NO, NO2, PM10, SO2, and black carbon and proximity to point sources. Traffic-related pollutants were associated with the highest risks: adjusted odds ratio = 1.08 (95% confidence interval, 1.04–1.12) for a 10-μg/m3 increase of NO, 1.12 (1.07–1.17) for a 10-μg/m3 increase in NO2, and 1.10 (1.06–1.13) for a 100-μg/m3 increase in CO. These data support the hypothesis that early childhood exposure to air pollutants plays a role in development of asthma.
administrative data; air pollution; asthma; children’s health; in utero; respiratory; traffic
Phthalates, pesticides, and bisphenol-A (BPA) are three groups of chemicals, implicated in endocrine disruption and commonly found in the local environment, that have been implicated in the pathogenesis of asthma and allergies [1-3]. Multiple observational studies have demonstrated an association between exposure to phthalates and the development of asthma and allergies in humans. Associations with exposure to pesticides and BPA and the development of respiratory disease are less clear. However, recent evidence suggests that prenatal or early postnatal exposure to BPA may be deleterious to the developing immune system. Future cohort-driven epidemiological or translational research should focus on determining whether these ubiquitous chemicals contribute to the development of asthma and allergies in humans, and attempt to establish the routes and mechanisms by which they operate. Determining dose-response relationships will be important to establishing safe levels of these chemicals in the environment and in consumer products. Attempts to reduce exposures to chemicals such as phthalates, pesticides, and BPA may have environmental repercussions as well as public health impact for the developing child.
Recent studies have explored the potential for swimming pool disinfection by-products (DBPs), which are respiratory irritants, to cause asthma in young children. Here we describe the state of the science on methods for understanding children’s exposure to DBPs and biologics at swimming pools and associations with new-onset childhood asthma and recommend a research agenda to improve our understanding of this issue.
A workshop was held in Leuven, Belgium, 21–23 August 2007, to evaluate the literature and to develop a research agenda to better understand children’s exposures in the swimming pool environment and their potential associations with new-onset asthma. Participants, including clinicians, epidemiologists, exposure scientists, pool operations experts, and chemists, reviewed the literature, prepared background summaries, and held extensive discussions on the relevant published studies, knowledge of asthma characterization and exposures at swimming pools, and epidemiologic study designs.
Childhood swimming and new-onset childhood asthma have clear implications for public health. If attendance at indoor pools increases risk of childhood asthma, then concerns are warranted and action is necessary. If there is no such relationship, these concerns could unnecessarily deter children from indoor swimming and/or compromise water disinfection.
Current evidence of an association between childhood swimming and new-onset asthma is suggestive but not conclusive. Important data gaps need to be filled, particularly in exposure assessment and characterization of asthma in the very young. Participants recommended that additional evaluations using a multidisciplinary approach are needed to determine whether a clear association exists.
aerosols; biologics; childhood asthma; DBPs; disinfection by-products; epidemiology; study design; swimming pools
Most studies that have examined exposure to indoor allergens have focused on home environments. However, allergen exposures can be encountered in environments other than the home. For example, many children spend a large part of their time in schools and daycare facilities. Over the past two decades, a large number of studies have been conducted in school and daycare environments. However, the role of indoor exposures in allergy and asthma development or morbidity in these settings is not well characterized. The purpose of this review is to evaluate the importance of indoor allergen exposures in school and daycare settings. We summarize the key findings from recent scientific literature, describe exposure characteristics, discuss the role of these exposures in relation to asthma and allergy symptoms, and provide information on the effectiveness of published interventions.
allergen; indoor; exposure; asthma; allergy; school; daycare
Background. The literature is contradictory concerning pet exposure and the risk of development of asthma and other allergic diseases. Using longitudinal studies, we aimed to systematically review the impact of pet ownership in the critical perinatal period as a risk factor for allergies in childhood.
Methods. Medline database was searched for urban cohort studies with perinatal exposure to cats and/or dogs and subsequent asthma or allergic disease.
Results. Nine articles, comprising 6498 participants, met inclusion criteria. Six found a reduction in allergic disease associated with perinatal exposure to dogs or, cats or dogs. One study found no association. Two found increased risk only in high-risk groups. Conclusion. Longitudinal studies in urban populations suggest that perinatal pets, especially dogs, may reduce the development of allergic disease in those without a family history of allergy. Other unmeasured factors such as pet-keeping choices in allergic families may be confounding the association seen in these high-risk families, and further study is required.
OBJECTIVE: To review aspects of occupational allergies and asthma for primary care physicians recognizing, diagnosing, and managing patients with these conditions. QUALITY OF EVIDENCE: Studies in the medical literature mainly provide level 2 evidence, that is, from at least one well-designed clinical trial without randomization, from cohort or case-control analytical studies, from multiple time series, or from dramatic results in uncontrolled experiments. MAIN MESSAGE: Occupational allergies and asthma have the best prognosis with an early, accurate diagnosis and subsequent avoidance of exposure to the relevant sensitizer. These diagnoses can normally be suspected from the clinical history. Primary care physicians can also initiate investigations to make an objective diagnosis, can assess workplace exposure agents from the history, and can review appropriate data sheets on material safety. Specialist evaluation is likely to be needed for skin tests, however, and for other specialized tests (such as pulmonary function assessments at work and off work or specific challenges with the suspected workplace agent). Patients with a confirmed diagnosis need appropriate medical management of their allergic manifestations or asthma, but also often require psychosocial support during the period of investigation and management, especially in relation to required changes in their work and to compensation or insurance claims. CONCLUSIONS: Consider workplace exposure as a source of patients' allergies or asthma and aim to make an early, accurate diagnosis.
Maternal stress in early life has been associated with the development of asthma in children, although it is unclear whether there are any critical periods of exposure. The association of asthma with prenatal exposure to maternal stress has not been reported.
We tested whether prenatal and postnatal anxiety and/or depression in pregnant women predicted the risk of their offspring developing asthma in childhood.
The Avon Longitudinal Study of Parents and Children is a population-based birth cohort recruited during pregnancy. Data were available on maternal anxiety scores and asthma at age 7½ years in 5810 children. Anxiety was assessed at 18 and 32 weeks of gestation by using the validated Crown-Crisp Experiential Index. Asthma was defined at age 7½ years as doctor-diagnosed asthma with current symptoms or treatment in the previous 12 months. Multivariable logistic regression was used to determine the association of prenatal anxiety with asthma (odds ratio; 95% CI).
Independent of postnatal anxiety and adjusted for a number of likely confounders, there was a higher likelihood of asthma at age 7½ years (odds ratio, 1.64; 95% CI, 1.25-2.17) in children of mothers in the highest compared with lowest quartile of anxiety scores at 32 weeks of gestation, with evidence for a dose-response (P value for trend <0.001).
Maternal anxiety symptoms as an indicator of stress during fetal life may program the development of asthma during childhood.
Anxiety; pregnancy; prenatal programming; asthma; child; ALSPAC, Avon Longitudinal Study of Parents and Children; HPA, Hypothalamo-pituitary-adrenal; OR, Odds ratio
The rising incidence of allergic disorders in developed countries is unexplained. Exposure to traffic related air pollutants may be an important cause of wheezing and asthma in childhood. Experimental evidence from human studies suggests that diesel exhaust particles, constituents of fine particulate matter less than 2.5 microns (PM2.5), may act to enhance IgE mediated aeroallergen sensitization and Th2 directed cytokine responses. To date, epidemiologic investigations indicate that children living in close proximity to heavily travelled roads are more likely to be atopic and wheeze. The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort study was initiated to test the hypothesis that early high exposure to traffic related air pollutants is associated with early aeroallergen sensitization and allergic respiratory phenotypes. Using an exposure cohort design, more than 700 infants born to atopic parents were recruited at age 1 living either less than 400 meters (high traffic pollutant exposure) or greater than 1,500 meters (low exposure) from a major road. Children were medically evaluated and underwent skin prick testing with aeroallergen at screening, and re-evaluated sequentially at ages 1, 2, 3, 4, and 7. In this study, both proximity and land use regression (LUR) models of traffic air pollutant exposure have been assessed. Proximity to stop and go traffic with large concentrations of bus and truck traffic predicted persistent wheezing during infancy. The LUR model estimated elemental carbon attributable to traffic (ECAT) as a proxy for diesel exhaust particulate exposure. High ECAT was significantly associated with wheezing at age 1 as well as persistent wheezing at age 3. High mold exposure predicted a well defined asthma phenotype at age 7.
Air pollution; childhood; asthma; allergy; diesel
Because the morbidity and mortality from adult asthma have been increasing, the identification of modifiable environmental exposures that exacerbate asthma has become a priority. Limited evidence suggests that exposure to environmental tobacco smoke (ETS) may adversely affect adults with asthma. To study the effects of ETS better, we developed a survey instrument to measure ETS exposure in a cohort of adults with asthma living in northern California, where public indoor smoking is limited. To validate this survey instrument, we used a passive badge monitor that measures actual exposure to ambient nicotine, a direct and specific measure of ETS. In this validation study, we recruited 50 subjects from an ongoing longitudinal asthma cohort study who had a positive screening question for ETS exposure or potential exposure. Each subject wore a passive nicotine badge monitor for 7 days. After the personal monitoring period, we readministered the ETS exposure survey instrument. Based on the survey, self-reported total ETS exposure duration ranged from 0 to 70 hr during the previous 7 days. Based on the upper-range boundary, bars or nightclubs (55 hr) and the home (50 hr) were the sites associated with greatest maximal self-reported exposure. As measured by the personal nicotine badge monitors, the overall median 7-day nicotine concentration was 0.03 microg/m(3) (25th-75th interquartile range 0-3.69 microg/m(3)). Measured nicotine concentrations were highest among persons who reported home exposure (median 0.61 microg/m(3)), followed by work exposure (0.03 microg/m(3)), other (outdoor) exposure (0.025 microg/m(3)), and no exposure (0 microg/m(3); p = 0.03). The Spearman rank correlation coefficient between self-reported ETS exposure duration and directly measured personal nicotine concentration during the same 7-day period was 0.47, supporting the survey's validity (p = 0.0006). Compared to persons with no measured exposure, lower-level [odds ratio (OR) 1.9; 95% confidence interval (CI), 0.4-8.8] and higher-level ETS exposures (OR 6.8; 95% CI, 1.4-32.3) were associated with increased risk of respiratory symptoms. A brief, validated survey instrument can be used to assess ETS exposure among adults with asthma, even with low levels of exposure. This instrument could be a valuable tool for studying the effect of ETS exposure on adult asthma health outcomes.
Children who reside in agricultural settings are potentially exposed to higher levels of organophosphate (OP) pesticides, endotoxin, and allergens than their urban counterparts. Endotoxin and allergens stimulate maturation of the immune response in early childhood, but little is known about the effect of exposures to OPs or to the three combined.
In this study, we investigated the relationships between these exposures and T-helper 1 (Th1) and T-helper 2 (Th2) cytokines, biomarkers of allergic asthma, in the subjects of CHAMA-COS (Center for the Health Assessment of Mothers and Children of Salinas), a longitudinal birth cohort in Salinas Valley, California. Exposures were ascertained by interviewer-administered questionnaires and by home visits, and clinical diagnoses were abstracted from medical records. Blood samples were collected at 12 and 24 months of age and analyzed for Th1/Th2 status by flow cytometric detection of intracellular interferon-γ/interleukin-4 cytokine expression.
Mean Th2 levels were significantly higher in children with doctor-diagnosed asthma and children with wheezing at 2 years of age. In a multiple linear regression model, exclusive breast-feeding at 1 month and pet ownership were associated with 35.3% (p < 0.01) and 34.5% (p = 0.01) increases in Th1, respectively. Maternal agricultural work and presence of gas stove in the home were associated with a 25.9% increase (p = 0.04) and 46.5% increase (p < 0.01) in Th2, respectively.
Asthma and wheeze outcomes in children at 24 months of age are associated with elevated Th2 status in children at an early age. Our data further suggest that early exposures to an agricultural environment, breast-feeding, pets, and gas stoves affect the development of children’s Th1/Th2 immune response.
allergen; breast-feeding; children; endotoxin; flow cytometry; interferon-γ; interleukin-4; organophosphate; pesticide; T-helper cytokines
Atopic dermatitis in young children is often followed by the development of asthma (atopic march). The role of environmental exposures is unclear in this high risk population.
We aimed to determine the predictive relationship between indoor allergen exposures, particularly pets, rodents and cockroaches, to the development of asthma in a prospective pediatric cohort.
Children with atopic dermatitis and a family history of allergy were followed prospectively with questionnaire ascertainment of environmental exposure to cat, dog, cockroach, rat, and mouse. Asthma was diagnosed by study physicians based on caregiver reports of symptoms continually assessed over the course of the study period.
Fifty-five of the 299 children developed asthma by the end of the study. Cat exposure had a strong and independent effect to reduce the risk of developing asthma across all analyses (odds ratio (OR) 0.16; 95% confidence interval (CI) 0.05 – 0.53). Dog, mouse, rat and cockroach exposures did not significantly influence the development of asthma. Daycare exposure had the largest risk reduction for the development of asthma (OR 0.08; 95% CI 0.03 – 0.19). Maternal asthma (OR 2.93; 95%CI 1.29 – 6.67), baseline body mass index (BMI) (OR 1.23; 95%CI 1.08 – 1.42) and specific immunoglobulin E (sIgE) to house dust mix (HDM) at 3 years were each independent risk factors for the development of asthma.
In children with atopic dermatitis, cat and daycare exposure may reduce the risk of developing early childhood asthma.
Asthma; Atopic dermatitis; Atopy; Cat allergy; Pediatric; Allergy; Pet allergy; Daycare; epidemiology; atopic march; environmental exposure
Atopic dermatitis (AD) in young children is often followed by the development of asthma (atopic march). The role of environmental exposures is unclear in this high-risk population. We aimed to determine the predictive relationship between indoor allergen exposures, particularly pets, rodents, and cockroaches, to the development of asthma in a prospective pediatric cohort. Children with AD and a family history of allergy were followed prospectively with questionnaire ascertainment of environmental exposure to cats, dogs, cockroaches, rats, and mice. Asthma was diagnosed by study physicians based on caregiver reports of symptoms continually assessed over the course of the study period. Fifty-five of the 299 children developed asthma by the end of the study. Cat exposure had a strong and independent effect to reduce the risk of developing asthma across all analyses (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.05–0.53). Dog, mouse, rat, and cockroach exposures did not significantly influence the development of asthma. Daycare exposure had the largest risk reduction for the development of asthma (OR, 0.08; 95% CI, 0.03–0.19). Maternal asthma (OR, 2.93; 95% CI, 1.29–6.67), baseline body mass index (OR, 1.23; 95% CI, 1.08–1.42), and specific immunoglobulin E to house-dust mix at 3 years were each independent risk factors for the development of asthma. In children with AD, cat and daycare exposure may reduce the risk of developing early childhood asthma.
Allergy; asthma; atopic dermatitis; atopic march; atopy; cat allergy; daycare; environmental exposure; epidemiology; pediatric; pet allergy
An improved understanding of the contribution made by environmental exposures to disease burden in children is essential, given current increasing rates of childhood illnesses such asthma and cancer. Children must be routinely included in environmental research. Exposure assessment, both external (e.g., air, water) and internal dose (e.g., biomarkers), is an integral component of such research. Biomarker measurement has some advantages that are unique in children. These include assessment of potentially increased absorption because of behaviors that differ from adults (i.e., hand-to-mouth activity); metabolite measurement, which can help identify age-related susceptibility differences; and improved assessment of dermal exposure, an important exposure route in children. Environmental exposure assessment in children will require adaption of techniques that are currently applied in adult studies as well as development of tools and validation of strategies that are unique for children. Designs that focus on parent-child study units provide adult comparison data and allow the parent to assist with more complex study designs. Use of equipment that is sized appropriately for children, such as small air pumps and badge monitors, is also important. When biomarkers are used, biologic specimens that can be obtained noninvasively are preferable. Although the current need is primarily for small focused studies to address specific questions and optimize research tools, the future will require establishment of large prospective cohorts. Urban children are an important study cohort because of relatively high morbidity observed in the urban environment. Finally, examples of completed or possible future studies utilizing these techniques are discussed for specific exposures such as benzene, environmental tobacco smoke, aflatoxin, volatile organic compounds, and polycyclic aromatic hydrocarbons.
The pre- and postnatal environment may represent a window of opportunity for allergy and asthma prevention, and the hygiene hypothesis implies that microbial agents may play an important role in this regard. Using the cowshed-derived bacterium Acinetobacter lwoffii F78 together with a mouse model of experimental allergic airway inflammation, this study investigated the hygiene hypothesis, maternal (prenatal) microbial exposure, and the involvement of Toll-like receptor (TLR) signaling in prenatal protection from asthma. Maternal intranasal exposure to A. lwoffii F78 protected against the development of experimental asthma in the progeny. Maternally, A. lwoffii F78 exposure resulted in a transient increase in lung and serum proinflammatory cytokine production and up-regulation of lung TLR messenger RNA. Conversely, suppression of TLRs was observed in placental tissue. To investigate further, the functional relevance of maternal TLR signaling was tested in TLR2/3/4/7/9−/− knockout mice. The asthma-preventive effect was completely abolished in heterozygous offspring from A. lwoffii F78–treated TLR2/3/4/7/9−/− homozygous mother mice. Furthermore, the mild local and systemic inflammatory response was also absent in these A. lwoffii F78–exposed mothers. These data establish a direct relationship between maternal bacterial exposures, functional maternal TLR signaling, and asthma protection in the progeny.
Criteria pollutants have been associated with exacerbation of children’s asthma, but the role of air toxics in relation to asthma is less clear. Our objective was to evaluate whether exposure to outdoor air toxics in early childhood increased asthma risk or severity.
Air toxics exposure was estimated using the 2002 National Air toxics Assessment (NATA) and linked to longitudinal data (n=6950) from a representative sample of US children born in 2001 and followed through kindergarten-age in the Early Child Longitudinal Study - Birth Cohort (ECLS-B).
Overall, 17.7% of 5.5 year-olds had ever been told by a healthcare professional they had asthma, and 6.8% had been hospitalized or visited an emergency room for an asthma attack. Higher rates of asthma were observed among boys (20.1%), low-income (24.8%), and non-Hispanic black children (30.0%) (p≤0.05). Air toxics exposure was greater for minority race/ethnicity (p<0.0001), low income (p<0.0001), non-rural area (p<0.001). Across all analyses, greater air toxics exposure, as represented by total NATA respiratory hazard index, or when limited to respiratory hazard index from onroad mobile sources or diesel PM, was not associated with a greater prevalence of asthma or hospitalizations (p trend >0.05). In adjusted logistic regression models, children exposed to the highest respiratory hazard index were not more likely to have asthma compared to those exposed to the lowest respiratory hazard index of total, onroad sources, or diesel PM.
Early childhood exposure to outdoor air toxics in a national sample has not previously been studied relative to children’s asthma. Within the constraints of the study, we found no evidence that early childhood exposure to outdoor air toxics increased risk for asthma. As has been previously reported, it is evident that there are environmental justice and disparity concerns for exposure to air toxics and asthma prevalence in US children.
The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study is a birth cohort study that investigates the influence of allergen exposure on the development of allergy and asthma in the first several years of life. The objectives of this study were to investigate the relationship between a family history of allergy and/or asthma and exposure of newborn children to mite and pet allergen and to study the influence of different home and occupant characteristics on mite allergen exposure. Dust was sampled from the child's mattress and the parental mattress at 3 months after birth of the index child and analyzed for mite and pet allergens. Subjects were divided in groups according to history of asthma and allergy in their parents, and allergen exposure was studied in the different groups. Cat allergen exposure was significantly lower on parental mattresses in families with allergic mothers, but dog allergen exposure was not different. Mite allergen exposure was lower on parental mattresses in families with allergic mothers. Use of mite allergen-impermeable mattress covers reduced mite allergen exposure. Some other characteristics such as age of home and mattress were also found to influence mite allergen exposure. Parental mattresses in homes of allergic mothers had lower cat and mite (but not dog) allergen loadings than mattresses in homes of nonallergic parents. Paternal (as opposed to maternal) allergy seemed to have little influence.
There is increasing interest in the potential for in utero exposures to affect the risk of asthma. We used population data to explore the associations between perinatal conditions and the risk of hospital admission with asthma between the 2nd and 5th birthday.
The study population was 240,511 singleton infants born during 2001–2003. Birth records and longitudinally linked hospital admissions were used to identify asthma admissions and to model potential risk factors.
A total of 7245 children (3.0%) had one or more childhood admissions with asthma. In utero infectious exposures associated with childhood asthma were maternal antenatal admission with a urinary tract infection (UTI) [adjusted odds ratio (aOR) = 1.49, 95% confidence interval (1.23–1.79)] and pre-term pre-labor rupture of membranes (PROM) [aOR = 1.23 (1.04–1.45)]. There was no evidence that gestational age at time of first antenatal UTI admission (<28, ≥28 wks) affected the risk of asthma (homogeneity test p = 0.6). Pre-term birth was a risk factor for asthma admission, with the risk decreasing by 5.3% with each extra week of gestation. Autumn and winter conceptions were associated with an increased risk of childhood asthma admission: winter aOR = 1.15 (1.08–1.23), autumn aOR = 1.09 (1.02–1.16).
As in utero exposure to both UTI and PROM carry an increased risk of childhood asthma admission, this suggests that the immune system response generally is the relevant factor rather than a specific organism. The season-associated risk is consistent with early pregnancy exposures such as the winter flu season or low vitamin D.
asthma; children; population; pregnancy; risk factors