[Show abstract][Hide abstract] ABSTRACT: Asthma, rhinitis, and eczema often co-occur in children but their interrelationships at the population level have been poorly addressed. We assessed co-occurrence of childhood asthma, rhinitis, and eczema using unsupervised statistical techniques.
We included 17,209 children at 4 years and 14,585 at 8 years from seven European-population-based birth cohorts (MeDALL project). At each age period, children were grouped, using partitioning cluster analysis, according to the distribution of 23 variables covering symptoms "ever" and "in the last 12 months", doctor diagnosis, age of onset, and treatments of asthma, rhinitis, and eczema, IgE sensitisation, weight, and height. We tested the sensitivity of our estimates to subject and variable selections, and to different statistical approaches, including latent class analysis and self-organising maps.
Two groups were identified as the optimal way to cluster the data at both age periods and in all sensitivity analyses. The first (reference) group at 4 and 8 years (including 70 and 79% of children, respectively) was characterised by a low prevalence of symptoms and sensitisation, whereas the second (symptomatic) group exhibited more frequent symptoms and sensitisation. 99% children with comorbidities (co-occurrence of asthma, rhinitis, and/or eczema) were included in the symptomatic group at both ages. The children's characteristics in both groups were consistent in all sensitivity analyses.
At 4 and 8 years, at the population level, asthma, rhinitis, and eczema can be classified together as an allergic comorbidity cluster. Future research including time-repeated assessments and biological data will help understanding the interrelationships between these diseases. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Allergic diseases (asthma, rhinitis and atopic dermatitis) are complex. They are associated with allergen-specific IgE and non-allergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono or polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE-mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re-occurrence of foetal Type 2 signalling. Asthma, rhinitis and atopic dermatitis are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This paper proposes a new classification of IgE-mediated allergic diseases that allows the definition of novel phenotypes in order to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis, and (iii) propose novel strategies of treatment and prevention. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Allergy to wheat can present clinically in different forms: Sensitization to ingested wheat via the gastrointestinal tract can cause traditional food allergy or in combination with exercise, Wheat-Dependent Exercise-Induced Anaphylaxis (WDEIA). Sensitization to inhaled wheat flour may lead to occupational rhinitis and/or asthma.
We retrospectively reviewed the case notes of 156 patients (age 0.7 - 73.3 years) with a case history of wheat allergy. The population was divided into three groups, 1: Wheat allergy elicited by ingestion, 2: By inhalation and 3: WDEIA. All patients were examined with detailed case history, specific IgE (sIgE), Skin Prick Test (SPT) and wheat challenge (nasal or oral ± exercise). Details of the case history were extracted from the patients´ case records.
Group 1: Twenty one of 95 patients were challenge positive (15 children, 6 adults). All children had atopic dermatitis, and most (13/15) outgrew their wheat allergy. Most children (13/15) had other food allergies. Challenge positive patients showed significantly higher levels of sIgE to wheat and significantly more were SPT positive than challenge negative. Group 2: Eleven out of 13 adults with occupational asthma or rhinitis were challenge positive. None outgrew their allergy. Seven had positive sIgE and 10 had positive SPT to wheat. Group 3: Ten of 48 (adolescent/adults) were positive when challenged during exercise. Challenge positive patients showed significantly higher levels of sIgE to ω-5-gliadin. The natural course is presently unknown.
Wheat allergy can manifest in different disease entities, rendering a detailed case history and challenge mandatory. Patient age, occupation, concomitant allergies (food or inhalant) and atopic dermatitis are important factors for evaluation.
[Show abstract][Hide abstract] ABSTRACT: Background:
Numerous birth cohorts have been initiated in the world over the past 30 years using heterogeneous methods to assess the incidence, course and risk factors of asthma and allergies. The aim of the present work is to provide the stepwise proceedings of the development and current version of the harmonized MeDALL-Core Questionnaire (MeDALL-CQ) used prospectively in 11 European birth cohorts.
The harmonization of questions was accomplished in 4 steps: (i) collection of variables from 14 birth cohorts, (ii) consensus on questionnaire items, (iii) translation and back-translation of the harmonized English MeDALL-CQ into 8 other languages and (iv) implementation of the harmonized follow-up.
Three harmonized MeDALL-CQs (2 for parents of children aged 4-9 and 14-18, 1 for adolescents aged 14-18) were developed and used for a harmonized follow-up assessment of 11 European birth cohorts on asthma and allergies with over 13,000 children.
The harmonized MeDALL follow-up produced more comparable data across different cohorts and countries in Europe and will offer the possibility to verify results of former cohort analyses. Thus, MeDALL can become the starting point to stringently plan, conduct and support future common asthma and allergy research initiatives in Europe.
International Archives of Allergy and Immunology 03/2014; 163(3):215-224. DOI:10.1159/000357732 · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Eczema, rhinitis, and asthma often coexist (comorbidity) in children, but the proportion of comorbidity not attributable to either chance or the role of IgE sensitisation is unknown. We assessed these factors in children aged 4-8 years.
In this prospective cohort study, we assessed children from 12 ongoing European birth cohort studies participating in MeDALL (Mechanisms of the Development of ALLergy). We recorded current eczema, rhinitis, and asthma from questionnaires and serum-specific IgE to six allergens. Comorbidity of eczema, rhinitis, and asthma was defined as coexistence of two or three diseases in the same child. We estimated relative and absolute excess comorbidity by comparing observed and expected occurrence of diseases at 4 years and 8 years. We did a longitudinal analysis using log-linear models of the relation between disease at age 4 years and comorbidity at age 8 years.
We assessed 16 147 children aged 4 years and 11 080 aged 8 years in cross-sectional analyses. The absolute excess of any comorbidity was 1·6% for children aged 4 years and 2·2% for children aged 8 years; 44% of the observed comorbidity at age 4 years and 50·0% at age 8 years was not a result of chance. Children with comorbidities at 4 years had an increased risk of having comorbidity at 8 years. The relative risk of any cormorbidity at age 8 years ranged from 36·2 (95% CI 26·8-48·8) for children with rhinitis and eczema at age 4 years to 63·5 (95% CI 51·7-78·1) for children with asthma, rhinitis, and eczema at age 4 years. We did longitudinal assessment of 10 107 children with data at both ages. Children with comorbidities at 4 years without IgE sensitisation had higher relative risks of comorbidity at 8 years than did children who were sensitised to IgE. For children without comorbidity at age 4 years, 38% of the comorbidity at age 8 years was attributable to the presence of IgE sensitisation at age 4 years.
Coexistence of eczema, rhinitis, and asthma in the same child is more common than expected by chance alone-both in the presence and absence of IgE sensitisation-suggesting that these diseases share causal mechanisms. Although IgE sensitisation is independently associated with excess comorbidity of eczema, rhinitis, and asthma, its presence accounted only for 38% of comorbidity, suggesting that IgE sensitisation can no longer be considered the dominant causal mechanism of comorbidity for these diseases.
EU Seventh Framework Programme.
The Lancet Respiratory Medicine 02/2014; 2(2):131-40. DOI:10.1016/S2213-2600(13)70277-7 · 9.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The causal link between body mass index (BMI) or obesity and asthma in children is still being debated. Analyses of large longitudinal studies with a sufficient number of incident cases and in which the time-dependent processes of both excess weight and asthma development can be validly analyzed are lacking. OBJECTIVE: We sought to investigate whether the course of BMI predicts incident asthma in childhood. METHODS: Data from 12,050 subjects of 8 European birth cohorts on asthma and allergies were combined. BMI and doctor-diagnosed asthma were modeled during the first 6 years of life with latent growth mixture modeling and discrete time hazard models. Subpopulations of children were identified with similar standardized BMI trajectories according to age- and sex-specific "World Health Organization (WHO) child growth standards" and "WHO growth standards for school aged children and adolescents" for children up to age 5 years and older than 5 years, respectively (BMI-SDS). These types of growth profiles were analyzed as predictors for incident asthma. RESULTS: Children with a rapid BMI-SDS gain in the first 2 years of life had a higher risk for incident asthma up to age 6 years than children with a less pronounced weight gain slope in early childhood. The hazard ratio was 1.3 (95% CI, 1.1-1.5) after adjustment for birth weight, weight-for-length at birth, gestational age, sex, maternal smoking in pregnancy, breast-feeding, and family history of asthma or allergies. A rapid BMI gain at 2 to 6 years of age in addition to rapid gain in the first 2 years of life did not significantly enhance the risk of asthma. CONCLUSION: Rapid growth in BMI during the first 2 years of life increases the risk of asthma up to age 6 years.
The Journal of allergy and clinical immunology 02/2013; 131(6). DOI:10.1016/j.jaci.2013.01.001 · 11.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have previously reported patch test reactivity to nickel sulphate in a cohort of unselected infants tested repeatedly at 3–18 months of age. A reproducible positive reaction at 12 and 18 months was selected as a sign of nickel sensitivity provided a patch test with an empty Finn chamber was negative. A reproducible positive reaction was seen in 8.6% of the infants. The objective of this study is to follow-up on infants with alleged nickel sensitivity.
A total of 562 infants were included in the cohort and patch tested with nickel sulphate (ICDRG guidelines). The 26 children with a positive patch test reaction to nickel sulphate at 12 and 18 months were offered repeated patch tests at 3 and 6 yr.
Among the 21 children tested at both 12 months, 18 months and at 3 and 6 yr only 2 of 21 had reproducible nickel reactions (one clinically relevant), 13 of 21 were negative and 6 of 21 were negative at 3 or 6 yr.
Only 9.5% of the children had reproducible nickel sulphate reactivity, while 62% became negative. The results are noteworthy and can be interpreted in different ways: Repeated nickel patch tests did not cause patch test sensitization. The test reactions in infancy are probably of irritant or non-specific nature. Hence, nickel patch tests should only be performed in small children if there is a clinical suspicion of nickel-induced allergic contact dermatitis.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
As replacement for the oral food challenge, decision-points for sensitization test have been established, but suboptimal sensitivity and/or specificity, as well as regional differences, have reduced the clinical usability. IgE toward specific peanut protein components has been reported to be of value, but data on correlation with clinical data are sparse. Our aim was to correlate IgE values with the outcome of peanut challenges.
Data from 175 positive and 30 negative peanut challenges in patients aged 1-26 years were retrospectively correlated with the levels of specific IgE to peanut and peanut components (Ara h 1-3, h 8, and h 9).
The best correlation between IgE and clinical thresholds was found for Ara h 2 (ρ(s) = -0.30, P < 0.01). A cutoff of Ara h 2 > 1.63 kU/l yielded a specificity = 1.00, with a corresponding sensitivity of 0.70. Symptom severity elicited during challenge correlated significantly with the levels of Ara h 2 (ρ(s) = 0.60, P < 0.0001), but large individual variation was found.
The level of IgE toward Ara h 2 can improve diagnostic accuracy by introducing a more clear-cut decision-point with an optimal specificity maintaining a high sensitivity. In our study, this would have reduced the necessary number of challenges to be performed from 205 to 92. Extrapolation between centers is difficult and decision-points need to be addressed in relation to settings and population. Further component-resolved diagnostic cannot replace oral challenge neither in determining thresholds nor in the assessment of severity of symptoms elicited during challenge.
[Show abstract][Hide abstract] ABSTRACT: RATIONALE: Although epidemiological studies suggest that exposure to maternal smoking during fetal and early life increases the risk of childhood wheezing and asthma, previous studies were not able to differentiate effects of prenatal from postnatal exposure. OBJECTIVES: To assess the effect of exposure to maternal smoking only during pregnancy on preschool age wheeze and asthma. METHODS: A pooled analysis was performed based on individual participant data from eight European birth cohorts. Cohort-specific effects of maternal smoking during pregnancy, but not during the first year, on wheeze and asthma at age four to six years were estimated using logistic regression and then combined using a random effects model. Adjustments were made for sex, parental education, parental asthma, birth weight and siblings. MEASUREMENTS AND MAIN RESULTS: Among the 21,600 children included in the analysis, 735 children (3.4 %) were exposed to maternal smoking exclusively during pregnancy but not in the first year after birth. In the pooled analysis, maternal smoking only during pregnancy was associated with wheeze and asthma at age four to six years, adjusted odds ratio 1.39 (95 % CI 1.08-1.77) and 1.65 (1.18-2.31), respectively. The likelihood to develop wheeze and asthma increased statistically significantly in a linear dose-dependent manner in relation to maternal daily cigarette consumption during the first trimester of pregnancy. CONCLUSIONS: Maternal smoking during pregnancy appears to increase the risk of wheeze and asthma also among children who are not exposed to maternal smoking after birth.
American Journal of Respiratory and Critical Care Medicine 09/2012; 186(10). DOI:10.1164/rccm.201203-0501OC · 13.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6-10 years.
Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. EXPOSURE DEFINITION: Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. OUTCOME DEFINITION: Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6-10 years of age.
Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models.
We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with "no pets" (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I(2) = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with "no pets" (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I(2) = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to "no pets" resulted in an odds ratio of 1.04 (0.59 to 1.84) (I(2) = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens.
Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6-10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.
PLoS ONE 08/2012; 7(8):e43214. DOI:10.1371/journal.pone.0043214 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Large studies of individual thresholds and risk profiles for foods are sparse. Previous reports indicate that thresholds adjusted for the protein content in foods would be comparable.
To establish and compare clinical threshold values for egg, hazelnut, milk and peanut, and correlating them to severity of symptoms.
Seven hundred eighty-one challenges were performed in 487 patients (age range, 0.5-73.5 years). Using interval censoring survival analysis, the dose distribution of thresholds was fitted to a log-normal function. Symptom score was correlated to thresholds.
Based on the 405 challenges resulting in objective signs, similar distribution of thresholds for hazelnut, milk, and peanut challenges were found, whereas individuals with egg allergy were bimodally distributed with a high or a low threshold. Eliciting dose in 10% (95% confidence interval) was 42.9 (24-76.8) mg whole eggs, 133.8 (95.9-186.6) mg whole hazelnut, 106.5 (59.7-190.6) mg roasted peanut, and 2.9 (1.5-5.4) mL milk. Adults showed more severe symptoms and signs than children, and peanut caused more severe reactions than the 3 other foods.
Thresholds for the different foods were not comparable, and eliciting dose for the 4 foods differed, even if adjusted for protein content. Increasing age but not a low threshold dose is associated with severe symptoms on challenge. Peanuts elicit more severe reactions than the other foods.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 05/2012; 108(5):332-6. DOI:10.1016/j.anai.2012.03.010 · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is well recognized that the fetus and infant are especially vulnerable to the effects of envi-ronmental risk factors that disrupt develop-mental processes, due to a) critical windows of vulnerability that occur during the rapid growth and development of organs and systems, b) immaturities in metabolism, and c) greater intake and absorption of noxious agents in children relative to their body weight (Grandjean et al. 2008). Chemical, physical, and biological hazards in the environment may lead to serious health problems at birth and during childhood, ranging from premature birth, low birth weight, and congenital anoma-lies to respiratory diseases, childhood cancer, learning disabilities, behavioral problems, and possibly even obesity (Trasande et al. 2009; Wigle et al. 2007). The economic and societal costs associated with nonoptimal child health and development are substantial. Furthermore, the effects of exposure to environmental risk factors may manifest themselves throughout a lifetime and even over generations. Common physical and mental diseases in adult life appear to have part of their origin in early life (Gillman et al. 2007; Kuh et al. 2003). Epidemiological studies worldwide have investigated the role of early environmental. We thank all other cohort researchers and tech-nical staff who have helped with the completion of the questionnaires. This work was supported by Environmental Health Risks in European Birth Cohorts (ENRIECO), a proj-ect conducted within the European Union's Seventh Framework Programme (Theme 6, Environment, including climate change), grant agreement 226285. The authors declare they have no actual or potential competing financial interests.
Environmental Health Perspectives 01/2012; 120(1):29-37. · 7.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Many patients experience reactions during penicillin treatment. The diagnosis may be difficult and is mainly based on short-term tests. The European Network for Drug Allergy (ENDA) guidelines proposed for diagnosing penicillin allergy do not include long-term challenge. In this study a total of 405 patients were evaluated. The ENDA guidelines were extended, to include a 7-day oral treatment (p.o.7) with penicillin for all patients who were negative in the ENDA programme. Among the 405 patients; 85 had an immediate reaction to penicillin, and a further 13 reacted during p.o.7. Among the 307 patients with a negative outcome, 88 had a case history of reaction to other β-lactam antibiotics and were subsequently tested with the culprit drug. Thirteen patients had a positive outcome: 3 on single-dose challenge and 10 during p.o.7. The extended penicillin diagnostic work-up was positive in 111 patients, 30.0% showed immediate reactions and 5.7% reacted during p.o.7. Approximately 20% of all patients with positive outcome during penicillin challenge are detected by adding p.o.7 with penicillin to the original ENDA guidelines.
[Show abstract][Hide abstract] ABSTRACT: Several cross-sectional studies during the past 10 years have observed an increased risk of allergic outcomes for children living in damp or mouldy environments.
The objective of this study was to investigate whether reported mould or dampness exposure in early life is associated with the development of allergic disorders in children from eight European birth cohorts.
We analysed data from 31 742 children from eight ongoing European birth cohorts. Exposure to mould and allergic health outcomes were assessed by parental questionnaires at different time points. Meta-analyses with fixed- and random-effect models were applied. The number of the studies included in each analysis varied based on the outcome data available for each cohort.
Exposure to visible mould and/or dampness during first 2 years of life was associated with an increased risk of developing asthma: there was a significant association with early asthma symptoms in meta-analyses of four cohorts [0-2 years: adjusted odds ratios (aOR), 1.39 (95% CI, 1.05-1.84)] and with asthma later in childhood in six cohorts [6-8 years: aOR, 1.09 (95% CI, 0.90-1.32) and 3-10 years: aOR, 1.10 (95% CI, 0.90-1.34)]. A statistically significant association was observed in six cohorts with symptoms of allergic rhinitis at school age [6-8 years: aOR, 1.12 (1.02-1.23)] and at any time point between 3 and 10 years [aOR, 1.18 (1.09-1.28)].
These findings suggest that a mouldy home environment in early life is associated with an increased risk of asthma particularly in young children and allergic rhinitis symptoms in school-age children.
[Show abstract][Hide abstract] ABSTRACT: Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning.
Our goal was to create a comprehensive overview of European birth cohorts with environmental exposure data.
Birth cohort studies were included if they a) collected data on at least one environmental exposure, b) started enrollment during pregnancy or at birth, c) included at least one follow-up point after birth, d) included at least 200 mother-child pairs, and e) were based in a European country. A questionnaire collected information on basic protocol details and exposure and health outcome assessments, including specific contaminants, methods and samples, timing, and number of subjects. A full inventory can be searched on www.birthcohortsenrieco.net.
Questionnaires were completed by 37 cohort studies of > 350,000 mother-child pairs in 19 European countries. Only three cohorts did not participate. All cohorts collected biological specimens of children or parents. Many cohorts collected information on passive smoking (n = 36), maternal occupation (n = 33), outdoor air pollution (n = 27), and allergens/biological organisms (n = 27). Fewer cohorts (n = 12-19) collected information on water contamination, ionizing or nonionizing radiation exposures, noise, metals, persistent organic pollutants, or other pollutants. All cohorts have information on birth outcomes; nearly all on asthma, allergies, childhood growth and obesity; and 26 collected information on child neurodevelopment.
Combining forces in this field will yield more efficient and conclusive studies and ultimately improve causal inference. This impressive resource of existing birth cohort data could form the basis for longer-term and worldwide coordination of research on environment and child health.
Environmental Health Perspectives 08/2011; 120(1):29-37. DOI:10.1289/ehp.1103823 · 7.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced by such infectious agents on asthmatic patients, it is necessary to understand their nature and be able to identify them in clinical samples by employing accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively less or not clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved more with asthma persistence rather than with disease exacerbations. Recent data suggest that common bacteria may also be involved, but this should be confirmed. Although current information is considerable, improvements in detection methodologies, as well as the wide variation in respect to location, time and populations, underline the need for additional studies that should also take into account interacting factors.
[Show abstract][Hide abstract] ABSTRACT: The aim was to describe the relapsing pattern, sensitization and prognosis of atopic dermatitis (AD) in the first 6 yr in a population-based, prospective birth cohort. The DARC cohort includes 562 children with clinical examinations, specific-IgE and skin prick test at all follow-ups. All children were examined for the development of AD using Hanifin-Rajka criteria and for food hypersensitivity by oral challenges. Severity of AD was measured by objective SCORing Atopic Dermatitis (SCORAD). Point-prevalence of AD peaked at 18 months of age (10%) and decreased at 36 and 72 months to slightly below 7%. The 6-yr cumulative incidence was 22.8% and sensitization was found in 43% of children with AD. It was predominately sensitization to foods, however shifting toward inhalant allergens with age. Sensitization at >or=2 follow-ups affected severity, whereas short-term sensitization at one follow-up does not. Children with early, non-IgE mediated (intrinsic) AD outgrew more often their eczema; however if they develop persistent AD, they remain intrinsic. Early long-term sensitization worsens the prognosis, but 38% of all children have a debut later than 18 months of age. Boys had earlier onset of AD than girls. The large number of follow-ups gives a detailed picture of the relapsing pattern and shows that the relapses occur independently of time of onset. We could not establish any clear correlation between elimination diets and AD duration nor severity.