Atopic Outcomes Research Articles

Relationships among environmental exposures, cord blood cytokine responses, allergy, and wheeze at 1 year of age in an inner-city birth cohort (Urban Environment and Childhood Asthma study).

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 μg/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.

Maternal fatty acid status in pregnancy and childhood atopic manifestations: KOALA Birth Cohort Study

Prevalence of atopic disorders has increased rapidly, but aetiological factors responsible for this increase are still largely unknown. Prenatal exposure to a pro-inflammatory fatty acid status is hypothesized although little research has been carried out. To investigate whether prenatal fatty acid exposures are associated with atopy in childhood. In the KOALA Birth Cohort Study, maternal blood samples (n=1275) at 34-36 weeks of pregnancy were assayed for n-6 and n-3 long-chain polyunsaturated fatty acids (LCPs). The full spectrum of offspring atopic manifestations (wheeze, asthma, allergic rhinoconjunctivitis, eczema, atopic dermatitis, allergic sensitization, and high total IgE) until the age of 6-7 years was assessed by repeated parental questionnaires and measurements of total and specific IgE. Associations of maternal fatty acid status with child atopic outcomes were analysed using multivariable logistic regression and generalized estimating equations for repeated measurements. High ratio of maternal n-6 vs. n-3 LCPs was associated with a lower risk of eczema in the child (P for trend 0.012). More specifically, we found a decreased risk of eczema in the first 7 months of life with increasing arachidonic acid levels (P for trend 0.013). No associations were found between maternal fatty acids and offspring airway-related atopic manifestations, sensitization, or high total IgE. The development of atopic disorders in early childhood is associated with prenatal exposure to n-6 vs. n-3 fatty acids, but with inconsistencies between different manifestations. Further exploration of associations with maternal diet and genetic variants in genes regulating fatty acid metabolism are required. This study shows that the influence of prenatal exposure to fatty acids on the risk of eczema in the child is limited to the first year of life.

Fatty acids in breast milk and development of atopic eczema and allergic sensitisation in infancy

One of the explanations for the increasing prevalence of atopic diseases is a relative low perinatal supply of n-3 fatty acids. However, this does not explain the protective effects of whole-fat dairy products or high levels of transfatty acids in breast milk, observed in some studies. We evaluated the role of perinatal supply of fatty acids in the early development of atopic eczema and allergic sensitisation. Fatty acids, including n-3 long-chain polyunsaturated fatty acids (LCPs) as well as ruminant fatty acids (rumenic acid, cis-9,trans-11-C18:2 conjugated linoleic acid; and vaccenic acid, trans-11-C18:1), were determined in breast milk sampled at 1 month postpartum from 310 mother-infant pairs in the KOALA Birth Cohort Study, the Netherlands. Children were followed for atopic outcomes until 2 years of age. Higher concentrations of n-3 LCPs as well as ruminant fatty acids were associated with lower risk of (1) parent-reported eczema, (2) atopic dermatitis (UK Working Party criteria), and (3) sensitisation at age 1 year (as revealed by specific serum IgE levels to cow's milk, hen's egg and/or peanut). In multivariable logistic regression analysis, the inverse associations between ruminant fatty acid concentrations in breast milk and atopic outcomes were found to be independent from n-3 LCPs. The results confirm a protective role of preformed n-3 LCPs in the development of atopic disease. Moreover, this is the first study in humans confirming results from animal studies of protective effects of ruminant fatty acids against the development of atopic manifestations.

Parents’ self-efficacy, outcome expectations, and self-reported task performance when managing atopic dermatitis in children: Instrument reliability and validity

BackgroundSupport and education for parents faced with managing a child with atopic dermatitis is crucial to the success of current treatments. Interventions aiming to improve parent management of this condition are promising. Unfortunately, evaluation is hampered by lack of precise research tools to measure change. ObjectivesTo develop a suite of valid and reliable research instruments to appraise parents’ self-efficacy for performing atopic dermatitis management tasks; outcome expectations of performing management tasks; and self-reported task performance in a community sample of parents of children with atopic dermatitis. MethodsThe Parents’ Eczema Management Scale (PEMS) and the Parents’ Outcome Expectations of Eczema Management Scale (POEEMS) were developed from an existing self-efficacy scale, the Parental Self-Efficacy with Eczema Care Index (PASECI). Each scale was presented in a single self-administered questionnaire, to measure self-efficacy, outcome expectations, and self-reported task performance related to managing child atopic dermatitis. Each was tested with a community sample of parents of children with atopic dermatitis, and psychometric evaluation of the scales’ reliability and validity was conducted. Setting and participantsA community-based convenience sample of 120 parents of children with atopic dermatitis completed the self-administered questionnaire. Participants were recruited through schools across Australia. ResultsSatisfactory internal consistency and test–retest reliability was demonstrated for all three scales. Construct validity was satisfactory, with positive relationships between self-efficacy for managing atopic dermatitis and general perceived self-efficacy; self-efficacy for managing atopic dermatitis and self-reported task performance; and self-efficacy for managing atopic dermatitis and outcome expectations. Factor analyses revealed two-factor structures for PEMS and PASECI alike, with both scales containing factors related to performing routine management tasks, and managing the child's symptoms and behaviour. Factor analysis was also applied to POEEMS resulting in a three-factor structure. Factors relating to independent management of atopic dermatitis by the parent, involving healthcare professionals in management, and involving the child in the management of atopic dermatitis were found. Parents’ self-efficacy and outcome expectations had a significant influence on self-reported task performance. ConclusionsFindings suggest that PEMS and POEEMS are valid and reliable instruments worthy of further psychometric evaluation. Likewise, validity and reliability of PASECI was confirmed.

Filaggrin gene variants and atopic diseases in early childhood assessed longitudinally from birth

Copenhagen Prospective Study on Asthma in Childhood (COPSAC) was one of the discovery cohorts of the association between eczema and variants in the filaggrin coding gene (FLG). Here, we study the FLG-associated risk of asthma symptoms in early life and describe the temporal relationship in the development of the different FLG-associated atopic outcomes: asthma, sensitization and eczema, assessed longitudinally from birth. A high-risk cohort of 411 children was assessed in a prospective clinical study from birth to school-age. Asthma, acute severe asthma exacerbations, sensitization and eczema were diagnosed prospectively by the investigators. FLG variants R501X and Del4 were determined in 382 Caucasians. Filaggrin variants increased risk of developing recurrent wheeze, asthma and asthma exacerbations (hazard ratio 1.82 [1.06-3.12], p = 0.03), which was expressed within the first 1.5 yr of life. Children with filaggrin variants had a marked and persistent increase in acute severe asthma exacerbations from 1 yr of age (incidence ratio 2.40 [1.19-4.81], p = 0.01) and increased risk of asthma by age 5 (odds ratio 2.62 [1.12-6.11], p = 0.03). FLG variants increased the risk of eczema, manifesting fully in the first year of life (point prevalence ratio for age 0-5 was 1.75 [1.29-2.37]; p-value = 0.0003) contrasting the increased risk of specific sensitization by age 4 (odds ratio 3.52 [1.72-7.25], p = 0.0007) but not age 1.5. This study describes a FLG-associated pattern of atopic diseases characterized by the early onset of asthma symptoms and eczema and later development of sensitization. The association of filaggrin variants with asthma suggests skin barrier dysfunction as a novel, and potentially modifiable, mechanism driving early childhood asthma.

Is there a role for fatty acids in early life programming of the immune system?

There may be a causal relationship between n-6 PUFA intake and allergic disease and there are biologically plausible mechanisms, involving eicosanoid mediators of the n-6 PUFA arachidonic acid, that could explain this. There is some evidence that high linoleic acid intake is linked with increased risk of atopic sensitisation and allergic manifestations. Fish and fish oils are sources of long-chain n-3 PUFA and these fatty acids act to oppose the actions of n-6 PUFA. It is considered that n-3 PUFA will protect against atopic sensitisation and against the clinical manifestations of atopy. All five epidemiological studies investigating the effect of maternal fish intake during pregnancy on atopic or allergic outcomes in infants/children of those pregnancies concluded protective associations. Epidemiological studies investigating the effects of fish intake during infancy and childhood on atopic outcomes in those infants or children are inconsistent, although the majority of the studies (9/14) showed a protective effect of fish. Fish oil provision to pregnant women is associated with immunologic changes in cord blood. Provision of fish oil during pregnancy may reduce sensitisation to common food allergens and reduce the prevalence and severity of atopic dermatitis in the first year of life. This effect may persist until adolescence with a reduction in prevalence and/or severity of eczema, hayfever and asthma. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, but whether this benefit persists as other factors come into play remains to be determined.

Atopy, asthma, and lung function in relation to folate and vitamin B12 in adults

Recent studies suggested low serum folate and impaired folate metabolism as potential risk factors for development of asthma and atopic disease, but the results are inconsistent. The aim of this study was to investigate the relations of markers of folate and vitamin B₁₂ (B₁₂) deficiency with different phenotypes of asthma and atopy. A random sample of 6784 persons from a general population aged 30-60 years participated in a health examination in 1999-2001, and 4516 (66.6%) of those also participated in a follow-up examination 5 years later. The examinations included spirometry, measurements of serum folate and B₁₂, specific IgE to inhalant allergens, total IgE, and genotyping of the MTHFR-C677T polymorphism - a genetic marker of impaired folate metabolism. Information about dietary intake of folate and B₁₂, asthma diagnosis, and airway symptoms was obtained by questionnaires. Low serum folate levels and the TT genotype of the MTHFR-C677T polymorphism were associated with increased prevalence of self-reported doctor-diagnosed asthma [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.05-1.79 and OR 1.52; 95% CI 1.12-2.06, respectively] and attacks of shortness of breath (OR 1.43, 95% CI 1.14-1.79 and OR 1.47; 95% CI: 1.14-1.91, respectively). We found no significant associations with lung function or atopic outcomes. Serum levels of B₁₂ and dietary intake of folate and B₁₂ were not associated with asthma or atopy. We found that two objective markers of folate deficiency were associated with self-reported doctor-diagnosed asthma and attacks of shortness of breath, but not with lung function or atopy.

Racial/Ethnic Differences in Cord Blood IgE in an Multi-ethnic Birth Cohort

RATIONALE: There are well known racial disparities in atopic diseases such as asthma. We sought to determine whether there are also early life disparities in atopic outcomes. In particular, we sought to determine whether cord blood IgE (cbIgE) differs by race independent of socio-economic (SES) factors. METHODS: We evaluated the cbIgE levels (Phadia) in infants in a prospective, multi-ethnic Boston birth cohort. Socio-demographic information including race and annual household income (≥ or <30K) was obtained via standardized interview. Cord blood was log transformed to normalize the data for linear regression. The limit of detection of IgE in the assay was 0.1 kUA/L. Linear (log IgE) and logistic regression models (for detectable IgE) assessed the association of cbIgE with race/ethnicity, controlling for SES, and maternal (including age, atopy, education and smoking) and infant (gender and firstborn status) variables. RESULTS: The median (IQR) for cbIgE (n = 1179 infants) was 0.25 kUA/L (0-0.75kUA/L). cbIgE was detectable in 70%, 55%, 67%, and 72% of blacks, whites, Latinos, and Asian/other subjects respectively. Compared to whites, logIgE was higher in blacks (β, SE = 0.94±0.36, p = 0.009), Latinos (β, SE = 0.88±0.40, p = 0.03), and Asian/others (β, SE = 0.91±0.42, p = 0.03). When adjusted for SES, the magnitude and significance of these estimates did not change. Compared to whites, the odds of detectable cbIgE was greater in blacks (OR, SE = 2.1±0.53, p = 0.005) and Asian/others (OR, SE = 2.2±0.65, p = 0.01). Again, adjusted for SES, these estimates showed minimal change. CONCLUSIONS: Race/ethnicity has effects on cbIgE independent of SES and other prenatal factors. This finding suggests that there may be genetic or unmeasured environmental factors modifying in-utero IgE production which are differentially distributed by race/ethnicity.

Host-microbial interactions in childhood atopy: Toll-like receptor 4 (TLR4), CD14, and fecal Escherichia coli

Perturbations in the gut microbiota have been linked to atopic diseases. However, the development of atopic diseases depends not only on environmental factors (like microbial stimulation) but also on genetic factors. It is likely that particularly gene-environmental interactions in early life determine the development of atopy. We examine the interaction between detection of fecal Escherichia coli and genetic variations in the CD14 and Toll-like receptor 4 (TLR4) genes in relation to atopic manifestations. Within the Child, Parent and Health: Lifestyle and Genetic Constitution (KOALA) Birth Cohort Study, fecal samples of 957 one-month-old infants were collected and quantitatively screened for E coli. Fourteen haplotype-tagging polymorphisms in the genes TLR4 and CD14 were genotyped in 681 of the 957 children. Atopic outcomes were parentally reported eczema in the first 2 years of life and clinically diagnosed eczema and allergic sensitization at age 2 years. Multiple logistic regression was used to evaluate a multiplicative model of interaction. Most of the single nucleotide polymorphisms (SNPs) showed no significant interaction with E coli exposure for both eczema and allergic sensitization. A borderline significant multiplicative interaction was found between E coli and the rs2569190 (CD14/-159) SNP regarding allergic sensitization. Furthermore, a statistically significant multiplicative interaction was found for the TLR4 SNP rs10759932 (P for interaction = .001). E coli colonization was associated with a decreased risk of sensitization only in children with the rs10759932 TT genotype (adjusted odds ratio, 0.31; 95% CI, 0.14-0.68) and not in children with the minor C allele. This interaction remained statistically significant after controlling for multiple testing. The current study is the first to address the potential effect-modifying role of genetic variations in the relationship between the intestinal microbiota and allergy development.

Atopy Risk in Infants and Children in Relation to Early Exposure to Fish, Oily Fish, or Long-Chain Omega-3 Fatty Acids: A Systematic Review

There are two main families of polyunsaturated fatty acids (PUFAs), the n-6 and the n-3 families. It has been suggested that there is a causal relationship between n-6 PUFA intake and allergic disease, and there are biologically plausible mechanisms, involving eicosanoid mediators of the n-6 PUFA arachidonic acid, that could explain this. Fish and fish oils are sources of long-chain n-3 PUFAs and these fatty acids act to oppose the actions of n-6 PUFAs. Thus, it is considered that n-3 PUFAs will protect against atopic sensitization and against the clinical manifestations of atopy. Evidence to examine this has been acquired from epidemiologic studies investigating associations between fish intake in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children and from intervention studies with fish oil supplements in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children. All five epidemiological studies investigating the effect of maternal fish intake during pregnancy on atopic or allergic outcomes in infants/children of those pregnancies concluded protective associations. One study investigating the effects of maternal fish intake during lactation did not observe any significant associations. The evidence from epidemiological studies investigating the effects of fish intake during infancy and childhood on atopic outcomes in those infants or children is inconsistent, although the majority of the studies (nine of 14) showed a protective effect of fish intake during infancy or childhood on atopic outcomes in those infants/children. Fish oil supplementation during pregnancy and lactation or during infancy or childhood results in a higher n-3 PUFA status in the infants or children. Fish oil provision to pregnant women is associated with immunologic changes in cord blood and such changes may persist. Studies performed to date indicate that provision of fish oil during pregnancy may reduce sensitization to common food allergens and reduce prevalence and severity of atopic dermatitis in the first year of life, with a possible persistence until adolescence with a reduction in eczema, hay fever, and asthma. Fish oil provision to infants or children may be associated with immunologic changes in the blood but it is not clear if these are of clinical significance and whether they persist. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, but this benefit may not persist as other factors come into play. It is not clear whether fish oil can be used to treat children with asthma as the two studies conducted to date give divergent results. Further studies of increased long-chain n-3 PUFA provision in during pregnancy, lactation, and infancy are needed to more clearly identify the immunologic and clinical effects in infants and children and to identify protective and therapeutic effects and their persistence.

Stress, Traffic Related Air Pollution and Eczema and Wheeze in the First Year of Life: Project ACCESS

ISEE-0832 Background and Objective: While both chronic stress and traffic related air pollution are associated with respiratory health and atopic outcomes in children, studies exploring the joint effect of these exposures are limited. We examined the relationship between violence, conceptualized as a chronic stressor, and black carbon from traffic sources on eczema and wheeze in infancy in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS), an urban prospective birth cohort study in the US. Methods: Mothers reported physician-diagnosed eczema or wheeze in their children during the first year of life and completed the My Exposure to Violence (ETV) scale. Black carbon (BC) exposure levels were estimated using a validated spatio-temporal land use regression model, based on mother’s residence during pregnancy. Rasch modeling was used to create a summary measure of ETV. Associations between predicted BC, ETV and wheeze and eczema were examined adjusting for sociodemographics, birthweight for gestational age, season of birth, in-utero tobacco smoke and postnatal tobacco smoke exposure; infant outcomes were examined in separate regression models. Results: In the sample of 403 children, 15% were diagnosed with eczema and 25% reported wheezing. The mean ± SD predicted annual BC was 0.42 + 0.2 μg/m3. In adjusted analyses, ETV (OR 1.3, 95%CI 1.0, 1.7) and BC per interquartile range (OR 1.3, 95%CI 1.0, 1.8) were associated with wheeze; there was no significant interaction between ETV and BC. In stratified analysis, increased odds of wheeze was seen only among children with both above median ETV and above median BC exposure (OR 2.2, 95%CI 1.1, 4.1) albeit the test for an interaction was not significant. Conclusions: Violence and traffic related BC are independently associated with wheeze in the first year of life but not eczema. These environmental exposures may be operating through pathways other than a predisposition to atopy.

Human mid‐gestation amniotic fluid contains interleukin‐16 bioactivity

CD4-positive cells are detectable in the human fetal gastrointestinal tract from 11 weeks of gestation. Interleukin-16 (IL-16) is a chemoattractant for CD4(+) cells and, via fetal swallowing of amniotic fluid, could mediate the influx of CD4(+) cells into the fetal gut. We have shown that IL-16 was detectable in human amniotic fluid at 16-18 weeks of gestation (mid-pregnancy) but was not detectable at term (late pregnancy; > 37 weeks of gestation). Similarly, mid-pregnancy, but not late pregnancy, amniotic fluid contained chemotactic activity for CD4(+) T cells, this activity was reduced by 58% in the presence of a neutralizing anti-IL-16 antibody. The levels of IL-16 in fetal plasma at 16-24 weeks of gestation were very high, and decreased significantly by 25-36 weeks but at > 37 weeks remained significantly higher than adult levels. IL-16 transcripts were detectable in whole tissue extracts of fetal gut, skin and placenta but not in amniocytes, and IL-16 immunoreactivity was detectable in cells within the lamina propria of the fetal gut and within the skin, where it was associated with the basement membrane. Neither IL-16 levels nor chemotactic activity for CD4(+) T cells in mid-pregnancy amniotic fluid was related to atopic outcomes at 1 year of age. IL-16 might have an important role in the early development of the human immune system and/or in regulating fetal and maternal immunological responsiveness during pregnancy.

Dietary patterns in pregnancy and respiratory and atopic outcomes in childhood

Background:Studies of the relation between maternal diet in pregnancy and respiratory and atopic outcomes in the offspring have focused on the effects of individual nutrients and foods rather than dietary...

Change in prevalence of atopic dermatitis between 1986 and 2001 among children

The prevalence of atopic dermatitis (AD) has increased during the last decades. Whether the prevalence is still increasing or has reached a stable level during the 1990s is still not certain. The purpose of this study was to compare the prevalence of AD in two different random samples of Danish children studied in 1986 and 2001 and to examine the associations between AD and other atopic outcomes. Two samples of children and adolescents living in urban Copenhagen were drawn at random from the civil registration list in 1986 and 2001. A total of 527 and 480 subjects participated in 1986 and 2001, respectively. Subjects were classified as AD cases when responding affirmatively to the question "Do you have, or have you ever had, significant and recurrent episodes of eczema in the folds of your elbows or knees?" Immunoglobulin E (IgE) measurements, skin-prick tests, and airway responsiveness tests were performed. The prevalence of AD increased from 17.3% in 1986 to 27.3% in 2001. For male subjects, the prevalence of AD was 16.4% in 1986 compared with 25.7% in 2001. For female subjects, the prevalence of AD was 18.1% in 1986 compared with 28.7% in 2001. Elevated levels of IgE, airway hyperresponsiveness (AHR), and rhinitis were statistically significant predictors of AD. The prevalence of AD has increased significantly from 1986 to 2001 in urban Copenhagen, Denmark. In addition, we found that AD was significantly associated with AHR, rhinitis, and elevated levels of IgE, supporting the idea of the atopic triad.

The Relationship between Cord Blood IgE Levels and Atopic Outcomes at Age 18

The Relationship between Cord Blood IgE Levels and Atopic Outcomes at Age 18

A review of ibuprofen and acetaminophen use in febrile children and the occurrence of asthma-related symptoms

Background: Although many studies have investigated the safety and tolerability of ibuprofen or acetaminophen (paracetamol) use in children, few have specifically examined the association of ibuprofen or acetaminophen and the occurrence of asthma in pediatric populations. Objectives: The primary objective of this literature review was to ascertain whether ibuprofen use exacerbates the symptoms of asthma or asthma-related adverse events in febrile children, and how it compares with acetaminophen use. The secondary objective was to develop an algorithm that allows for the consideration of ibuprofen treatment in children by health care professionals. Methods: Twelve electronic databases (MEDLINE, EMBASE, Cochrane Database, DARE, British Nursing Index, CBIB, Derwent Drug File, International Pharmaceutical Abstracts, Pharm-Line, CINAHL, PASCAL, SCZZ-SciSearch) were searched from their year of inception to June 2007, to identify English-language articles pertaining to ibuprofen or acetaminophen use in the asthmatic pediatric population. The following search terms were used: asthma, child, pediatric, pediatrics, ibuprofen, Nurofen, Brufen, Motrin, Advil, propionic acid, paracetamol, and acetaminophen. Results: Of 472 articles retrieved, 3 were relevant for the development of the algorithm. Two were subanalyses of a major randomized controlled trial (RCT), the Boston University Fever Study. Therefore, some overlap should be noted. The third article was another RCT. Other studies and review articles identified were used for the discussion. Findings from the literature analysis indicated that the use of ibuprofen in the pediatric population does not exacerbate asthma morbidity. Two of the studies demonstrated that ibuprofen was associated with a lower risk for asthma morbidity in febrile children with or without asthma compared with acetaminophen. In one study, ibuprofen use was associated with a lower relative risk for hospitalization (0.63) and outpatient visits (0.56) for asthma compared with acetaminophen. In the second study, acetaminophen use was associated with the exacerbation of wheezing in febrile children. This observation was corroborated by the findings of other studies that revealed an increased risk for asthma, wheezing, and other atopic outcomes with acetaminophen use. Conclusions: The evidence reviewed in this article suggests a low risk for asthma-related morbidity associated with ibuprofen use in children and a possible protective and therapeutic effect compared with acetaminophen. The findings also suggest that acetaminophen use in children is associated with an increased risk for wheezing. The pediatric algorithm developed might serve as a guide for health care professionals in assessing suitability for ibuprofen use in children.

Mycobacterial infection and atopy in childhood: A systematic review

The epidemiological relation between mycobacterial infection and the prevalence of atopic disease in humans is still unclear. This is in contrast to studies in murine models in which a clear suppression of atopic symptoms was observed after exposure to mycobacteria or mycobacterial products. We therefore wanted to provide a systematic overview of the published literature on the relationship between mycobacterial infection and atopic disease and to evaluate the causal relationship in a meta-analysis. The EMBASE and MEDLINE databases were searched systematically for papers published in the English literature (1966-2005) on the relation between mycobacterial infection and atopic disease. Original observational or interventional studies involving the paediatric population were included. Two authors independently reviewed articles for data on mycobacterial exposure and atopic disease outcome. Any differences were resolved by discussion. Of a total of 1201 hits, 23 studies (19 cross-sectionals, three case-controls and one prospective cohort) met the inclusion criteria. Only a minority of studies (40%) observed an association between mycobacterial infection and the prevalence of atopic disease outcome. In the meta-analysis, only studies containing data on mycobacterial exposure and atopic disease outcome variables were included. Only cross-sectional studies, in which the relation between a positive tuberculin skin test and allergic symptoms was studied, observed statistically significant negative correlation (odds ratio 0.63; 95% confidence interval: 0.51-0.79). The results of this review show that the evidence of the relationship of mycobacterial infection and atopic disease is based on observations of cross-sectional studies. In a meta-analysis, calculations showed a high level of heterogeneity (I(2)) within studies with similar design making it difficult to pool effects. This may partly be explained by differences in the type and definition of mycobacterial infection and lack of uniformity in the definition of atopy. The results show that only a minority of studies in the literature shows any evidence of inverse relationship between mycobacterial exposure and atopic disease outcome. The fact that the present epidemiological evidence on the relationship between mycobacterial infection and the development of atopic disease is based mainly on cross-sectional observational studies indicates the need for population-based prospective studies to address this issue. This issue needs to be addressed in view of recent suggestions to developing mycobacterial-based vaccines against atopic disease in the future.

Atopic Diseases, Allergic Sensitization, and Individual Estimated Exposure to Traffic-Related Air Pollutants in Children

ISEE-116 Objective: In vitro studies, animal experiments, and human exposure studies have shown increased risks for atopic outcomes. However, results derived from observational studies are not consistent. We aim to assess the relationship between individual-based exposure to traffic-related air pollutants and allergic outcomes in a prospective birth cohort study during the first 6 years of life. Material and Methods: In a population-based cohort of 3577 newborns in the Munich metropolitan area, we followed-up 2860 children at the age of 4 years and 3061 children at the age of 6 years to investigate atopic diseases and allergic sensitization. Long-term exposure to fine particles with a 50% cutoff aerodynamic diameter of 2.5 μm (PM2.5), PM2.5 absorbance, and nitrogen dioxide (NO2) was assessed at residential addresses using geographic information systems-based regression models and air pollution measurements. In addition, the distance to the nearest main road was used as a surrogate for traffic-related air pollutants. Results: Strong positive associations were found between distances to the nearest main roads and asthmoid bronchitis, hay fever, eczema, and sensitization. A distance-dependent relationship could be identified with the highest ORs for children living less than 50 m from busy streets. For PM2.5, statistically significant effects were found for the symptoms of asthmoid bronchitis and eczema as well as for allergic sensitization to inhalant allergens due to pollen sensitization. PM2.5 absorbance was statistically associated with eczema and allergic sensitization to inhalant allergens. NO2 exposure was associated with hay fever only at 4 years of age, whereas no association was found for allergic sensitization. Conclusions: In conclusion, there is a strong evidence for an increased risk of atopic diseases and allergic sensitization when children are exposed to traffic-related particulate matter during the first 6 years of life.

The role of the intestinal microbiota in the development of atopic disorders

The prevalence of atopic diseases, including eczema, allergic rhinoconjunctivitis and asthma, has increased worldwide, predominantly in westernized countries. Recent epidemiological studies and experimental research suggest that microbial stimulation of the immune system influences the development of tolerance to innocuous allergens. The gastrointestinal microbiota composition may be of particular interest, as it provides an early and major source of immune stimulation and seems to be a prerequisite for the development of oral tolerance. In this review the observational studies of the association between the gut microbiota and atopic diseases are discussed. Although most studies indicated an association between the gut microbiota composition and atopic sensitization or symptoms, no specific harmful or protective microbes can be identified yet. Some important methodological issues that have to be considered are the microbiological methods used (traditional culture vs molecular techniques), the timing of examining the gut microbiota, the definition of atopic outcomes, confounding and reverse causation. In conclusion, the microbiota hypothesis in atopic diseases is promising and deserves further attention. To gain more insight into the role of the gut microbiota in the etiology of atopy, large-scale prospective birth cohort studies using molecular methods to study the gut microbiota are needed.

Original article: Polymorphisms in eosinophil pathway genes, asthma and atopy

Background: Eosinophilic inflammation is considered to play an important role in the development as well as in the perpetuation of asthma. As eosinophil production and survival is under genetic control we investigated whether polymorphisms in eosinophil regulation pathway genes (IL‐3, IL‐5, GM‐CSF and their respective enhancers and receptors) may influence the development of atopic diseases.Methods: In two large study populations of children, the German part of the International Study of Asthma and Allergy in Childhood (ISAAC II) and the German Multicentre Atopy Study (MAS), 3099 and 824 children, seven polymorphisms previously associated with the development of atopic diseases were genotyped: two in and around the GM‐CSF gene (Ile117Thr and T3085G), one in IL‐3 (Pro27Ser), in IL‐5 (C‐746T), and in the IL‐5 high affinity receptor chain IL‐5R (G‐80A) and two in the common receptor chain CSFR2b for IL‐3, IL‐5, and GM‐CSF (Asp312Asn and Glu249Gln). Statistical analyses were performed using chi‐squared tests and variance analyses. Gene by gene interactions were evaluated in logistic regression models.Results: The T allele at position −746 in the IL‐5 gene was significantly protective for atopy in the ISAAC II population (P = 0.006). Furthermore, the risk for atopic asthma was decreased in carriers of the T allele (P = 0.036) and evidence for interaction with the enhancer polymorphism 3085 bp 3′ of GM‐CSF was detected.Conclusions: IL‐5 C‐746T influenced atopic outcomes and showed evidence for gene by gene interaction. No significant associations were found with all other tested polymorphisms in the eosinophil regulation pathway after correction for multiple testing.