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Background: Severe pediatric allergic asthma (SPAA) induces a huge economic burden in terms of direct, indirect, and intangible costs. The use of omalizumab for the treatment of these patients has produced a significant improvement in several clinical outcomes, but at the same time, the cost for the management of the disease has also increased. The aim of this report was to evaluate whether the use of omalizumab is cost-effective., Methods: A sample of 426 children with SPAA from the ANCHORS (Asthma iN CHildren: Omalizumab in Real-life in Spain) study was used to calculate the incremental cost-effectiveness ratio (ICER) for the avoidance of moderate-to-severe exacerbations (MSE) and also for the improvement in childhood Asthma Control Test (c-ACT) or the Asthma Control Questionnaire (ACQ5). We retrospectively collected data on health encounters and drug consumption before and up to 6 years after the beginning of the treatment with omalizumab., Results: The ICER per avoided MSE was €2107 after 1 year, and it consistently decreased to €656 in those followed up to 6 years. Similarly, the ICER for the minimally important difference in control tests showed a decrease from €2059 to €380 per each 0.5 points of improvement in ACQ5 and from €3141 to €2322 per each 3 points improvement in c-ACT, at years 1 and 6, respectively., Conclusion: The use of OMZ is a cost-effective option for most children with uncontrolled SPAA, especially those who have frequent exacerbations; the costs are progressively reduced in successive years of treatment., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Various studies have assessed omalizumab outcomes in the clinical practice setting but follow-up and/or number of patients included were limited. We aim to describe the long-term outcomes of pediatric patients with severe persistent allergic asthma receiving omalizumab in the largest real-life cohort reported to date., Methods: ANCHORS was a multicenter, observational, retrospective cohort study conducted in 25 Pediatric Allergy and Pulmonology units in Spain. We collected data of patients < 18 years and initiating omalizumab between 2006 and 2018, from the year prior to omalizumab initiation to discontinuation or last available follow-up. The primary outcome was the evolution of the annual number of moderate-to-severe exacerbations compared with the baseline period., Results: Of the 484 patients included, 101 (20.9%) reached 6 years of treatment. The mean ± standard deviation number of exacerbations decreased during the first year of treatment (7.9 ± 6.6 to 1.1 ± 2.0, P < .001) and remained likewise for up to 6 years. The other clinical parameters assessed also improved significantly during the first year and stabilized or continued to improve thereafter. The percentage of patients experiencing adverse events was consistently low, and the main reason for discontinuation was good disease evolution., Conclusion: In this large, long-term, observational study, moderate-to-severe exacerbations decreased significantly from the first year of treatment with omalizumab. The beneficial effect was maintained in the long term, along with a good safety profile. Our results position omalizumab as an effective long-term treatment in pediatric patients with severe persistent allergic asthma., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

The aim of the present study was to estimate the associations between the prevalence of asthma symptoms in schoolchildren and meteorological variables in west European countries that participated in the International Study of Asthma and Allergies in Children (ISAAC), Phase III 1997-2003. An ecologic study was carried out. The prevalence of asthma was obtained from this study from 48 centers in 14 countries, and meteorological variables from those stations closest to ISAAC centers, together with other socioeconomic and health care variables. Multilevel mixed-effects linear regression models were used. For schoolchildren aged 6-7 years, the prevalence rate of asthma decreased with an increase in mean annual sunshine hours, showed a positive association with rainy weather, and warm temperature, and a negative one with relative humidity and physician density (PD). Current wheeze prevalence was stronger in autumn/winter seasons and decreased with increasing PD. Severe current wheeze decreased with PD. For schoolchildren aged 13-14 years, the prevalence rates of asthma and current wheeze increased with rainy weather, and these rates decreased with increased PD. Current wheeze, as measured by a video questionnaire, was inversely associated with sunny weather, and nurse density. Severe current wheeze prevalence was stronger during autumn/winter seasons, decreased with PD, and indoor chlorinated public swimming pool density, and increased with rainy weather. Meteorological factors, including sunny and rainy weather, and PD may have some effect on the prevalence rates of asthma symptoms in children from west European countries.

Background: Classification of respiratory symptoms may help to identify different underlying asthma phenotypes reflecting differences in aetiology and prognosis of wheezing disease among children., Objective: To determine childhood asthma phenotypes based on respiratory symptoms from a widely used questionnaire to further classify phenotypes in international settings., Methods: Between 2000 and 2002 cross-sectional studies were performed in four centres in Spain. Parental questionnaires were used to collect information on allergic diseases in more than 4000 children aged 8-12 years. In addition, objective markers for allergic sensitization and bronchial hyperresponsiveness (BHR) were measured. Latent class analyses (LCA) were applied to identify subgroups of children according to respiratory symptoms, and then the association of these groups with relevant clinical features such as concomitant allergic disease symptoms, atopy and BHR was studied., Results: We found seven classes, one corresponding to healthy children, three classes related to wheeze and three other classes mainly related to congestion and coughed-up phlegm. These tentative phenotypes differed in severity of symptoms and also in clinical correlates such as BHR and allergic sensitization. Atopy was more predominant in the 'wheeze phenotypes' whereas concomitant 'allergic' symptoms were most frequent in two of the 'wheeze phenotypes' and one of the 'cough phenotypes'., Conclusions: LCA on reported symptoms in a cross-sectional survey allowed different subgroups with meaningful clinical correlates to be defined. It remains to be investigated to what extent these groups also have different aetiologies, prognoses and therapeutic needs., (© 2012 Blackwell Publishing Ltd.)

The objective of this study was to estimate the relationship between the prevalence of asthma in schoolchildren aged 6-7 years and 13-14 years and the mean annual sunny hours (MASH) in Spain, and to explore predictive models for asthma prevalence. The prevalence of asthma was obtained from the International Study of Asthma and Allergies (ISAAC) Phase III 2002-2003, and climate and socio-economic variables from official sources. Nine centres were studied and a further four centres, two of which are in ISAAC, to test the predictive models. Logistic regression was used to estimate adjusted prevalence rates of asthma for each centre, and multiple regression models to study the effects of MASH and other meteorological and socio-economic variables. The adjusted prevalence rate of asthma decreased 0.6% [95% confidence interval (CI) 0.4-0.8%] for the 6-7 years group and 1.1% (95% CI 0.8-1.3%) for the 13-14 years group with an increase in the MASH of 100 h. Relative humidity was negatively associated with asthma in the older age group, and gross province product per capita (GPP) was positively associated with asthma in the younger age group. The predictive models, which included MASH, gender, relative humidity, and GPP, anticipated prevalence rates of asthma without significant differences between the levels observed and those expected in 9 of the 11 measurements carried out. The results indicate that sunny hours have a protective effect on the prevalence of asthma in schoolchildren.

The association between early exposure to paracetamol or to antibiotics and eczema is conflicting. This study aims to know whether the early exposure to those drugs is associated with eczema at school age, and whether the strength of the association is modified by the presence of asthma or rhinoconjunctivitis. Children aged 6-7 (n = 13908) from the International Study of Asthma and Allergies in Childhood in Spain provided data about current asthma, rhinoconjunctivitis and eczema. Parent-reported information was also obtained on paracetamol and antibiotic consumption during the first year of life. Logistic regression analysis with eczema as outcome and including exposure to paracetamol or to antibiotics, together with possible confounders, was carried out in the whole sample of children and in five different strata: no respiratory symptom and any respiratory symptom further subdivided into: asthma with rhinoconjunctivitis, asthma without rhinoconjunctivitis and rhinoconjunctivitis without asthma. In the whole sample, exposure to paracetamol was associated with eczema (aOR 1.56 [1.36-1.80]) as was antibiotic consumption (aOR 1.66 [1.43-1.92]). These associations did not substantially change after additionally adjusting for the other drug. A similar pattern was found among children without respiratory symptoms. In children with symptoms, adjusting for the other drug modified the association with paracetamol (aOR from 1.32 [1.03-1.71] to 1.09 [0.83-1.43]) but did not change that with antibiotics (aOR from 1.80 [1.38-2.35] to 1.81 [1.37-2.39]). Early exposure to paracetamol or to antibiotics is associated with an increased prevalence of eczema at school age. Asthma and/or rhinoconjunctivitis substantially modifies this association., (© 2010 John Wiley & Sons A/S.)

Background: Atopic eczema affects 5-10% of the Spanish paediatric population, and has increased in frequency over the last few decades, probably due to changes in the environment and lifestyle. Phase II of the ISAAC (International Study of Asthma and Allergies in Childhood) uses a standardised methodology to establish the prevalence of allergic disorders and factors linked to them in each centre., Objectives: To assess the prevalence and severity of atopic eczema, and to establish factors linked to atopic eczema in 10-11 year-old school children in the city of Almeria (South-East coast of Spain)., Material and Methods: An ecological study was carried out as part of ISAAC II, using homologated questionnaires and allergic tests in 1143 schoolchildren. Statistic association was assessed by means of chi(2) test, and then logistic regression analysis was performed with the most significant variables from the univariant analysis., Results: The prevalence of atopic eczema was 11.4%. The risk factors found in the multiple logistic regression analysis were: personal antecedents of severe asthma (OR 19 CI 95% 1.35-266) and severe rhinitis (OR 7.7 CI 95% 1.79-33), fungi in bedroom during the first year of life (OR 4.2 CI 95% 1.17-15.1) and atopic eczema in one parent (OR 5.2 CI 95% 2.69-10.1)., Conclusions: The prevalence of atopic eczema is similar to that found in other studies within ISAAC Phase I. The most important risk factors for atopic eczema are family and personal history of other atopic diseases and the presence of fungi in the home., (Copyright 2009 SEICAP. Published by Elsevier Espana. All rights reserved.)

Background: Allergic rhinitis affects 10-30% of children in developed countries and has increased in frequency over the last few decades, probably due to changes in the environment and life style., Aim: To assess the prevalence, severity, and factors linked to rhinitis in 10 and 11-year-old children from Almeria (Spain)., Methods: As part of ISAAC II, a cross-sectional survey was conducted among a representative sample of 1143 schoolchildren in spring and autumn of 2001, using homologated questionnaires and skin-prick testing., Results: The overall prevalence of rhinitis and rhinoconjunctivitis were 38.9% and 24.8%, respectively, 17.9% had medically diagnosed rhinitis. During the previous year symptoms disturbed daily activities and school attendance in some measure in 40% and 26% of children with rhinitis, respectively. The risk factors found in the multiple logistic regression analysis were atopy (OR 2.57; 95% CI 1.92-3.42); cat contact at home during first year of life (OR 2.4 95% CI 1.13-5.12); prior medical diagnosis of asthma (OR 2.2; 95% CI 1.22-4.02); nocturnal cough in absence of colds (OR 1.9; 95% CI 1.25-2.97); diagnosis of rhinitis in one of the parents (OR 1.8; 95% CI 1.31-2.59); wheezing at any time (OR 1.6; 95% CI 1.18-2.28); and nursery school attendance (OR 1.5; 95% CI 1.21-2.5)., Conclusions: The prevalence of rhinitis found is superior to that of other centres participating in the ISAAC Phases I and II, and coexists with asthma and eczema in many children. The independent risk factors associated to rhinitis are in accordance with previous reports., (2009 SEICAP. Published by Elsevier Espana. All rights reserved.)

The association between breastfeeding and wheezing, lung function and atopy was evaluated in the International Study of Asthma and Allergy in Childhood (ISAAC) Phase II. Cross-sectional studies were performed in 27 centres in 20 countries. Information on disease and exposure factors was collected by parental questionnaires. Data from 54,000 randomly selected school children (aged 8-12 yrs, 31,759 with skin prick testing) and a stratified subsample (n = 4,888) were used for testing the correlation of breastfeeding with bronchial hyperreactivity and lung function. Random effect models for meta-analysis were applied to calculate combined odds ratios (ORs). Any breastfeeding was associated with less wheeze both in affluent (adjusted OR (OR(adj)) 0.87, 95% confidence interval (CI) 0.78-0.97) and nonaffluent countries (OR(adj) 0.80, 95% CI 0.68-0.94). Further analyses revealed that this was true only for nonatopic wheeze in nonaffluent countries (OR(adj) 0.69, 95% CI 0.53-0.90). Breastfeeding was not associated with atopic wheeze and objective measures of allergy in both affluent and nonaffluent countries. In contrast, breastfeeding was associated with higher predicted forced expiratory volume in one second in affluent countries only (mean ratio 1.11, 95% CI 1.02-1.20). Breastfeeding is associated with protection against nonatopic wheeze, which becomes particularly evident in nonaffluent countries. Overall, breastfeeding was not related to any measure of allergy. These findings may explain some of the controversy regarding breastfeeding, since the direction of the association with breastfeeding depends on the predominating wheeze phenotype (e.g. atopic, nonatopic).

Objective: The objective of the study was to analyze the relationship between air pollutants and the prevalence of recent symptoms of asthma, allergic rhinitis, and atopic eczema in schoolchildren aged between 6 and 7 years., Patients and Methods: The prevalence of recent (previous 12 months) symptoms of allergic diseases was obtained by means of the questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC), Spain, with the participation of 7 centers (Asturias, Barcelona, Bilbao, Cartagena, La Coruña, Madrid, and Valencia) and 20 455 schoolchildren aged between 6 and 7 years, from 2002 to 2003. The pollutant detection systems of the aforementioned centers provided the mean annual concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and total suspended particulate matter., Results: The annual average concentration of SO2 showed a significant association with a higher prevalence of recent severe asthma (adjusted odds ratio [aOR] between level-1 and level-3 pollution, 1.32; 95% confidence interval [CI], 1.01-1.73), rhinitis (aOR, 1.56; 95% CI, 1.39-1.75), and rhinoconjunctivitis (aOR, 1.70; 95% CI, 1.45-2.00). The annual average concentration of CO was associated with a higher prevalence of rhinitis (aOR, 1.65; 95% CI, 1.34-2.04), rhinoconjunctivitis (aOR, 1.76; 95% CI, 1.31-2.37), and eczema (aOR, 1.55; 95% CI, 1.17-2.04). The annual average concentration for NO2 and total suspended particulate matter showed inverse associations with the prevalence of nocturnal dry cough., Conclusions: Findings suggest that air pollutants such as SO2 and CO increase the risk of recent symptoms of asthma and allergic rhinitis in schoolchildren aged between 6 and 7 years in Spain.

Few studies have focused on the long-term influence of the climate on the prevalence of asthma. The aim of this study is to establish the influence of geo-climatic conditions on the prevalence of asthma symptoms both in adolescents and schoolchildren, and to discover if this influence is associated with their time trends. Eight centres in Spain performed both ISAAC phases I (1994) and III (2002) in children 13-14 years old. Six of them also surveyed children 6-7 years old. For each age group and phase, about 3,000 children were surveyed per centre. This study examines the prevalence of current wheeze and severe current wheeze in two different geo-climatic zones, coast and plateau, considering their relative humidity and temperature range. In both age groups, the mean asthma prevalence on the coast, for phase I and III, was significantly higher than on the plateau. Living on the plateau was an independent protective factor for current wheeze and severe current wheeze for the two age groups. Within the coastal centres, the increase of the annual relative humidity was a statistical significant risk factor for current wheeze, the same trend existing for current severe wheeze. These effects were independent of the sex and of the phase of the study. The prevalence of asthma and severe asthma symptoms is more frequent on the coast of Spain as compared to the inner plateau. This finding was repeated both in 1994 and in 2002.

Background: The association between asthma and obesity in children, and the effect modification of allergy on this association have not been fully established. Aims The objective of the study was to know the effect modification of the severity of asthma and of the coexistence of rhinoconjunctivitis (RC) in the relationship between obesity and asthma., Methods: A cross-sectional study of 17 145 schoolchildren 6-7 years old from eight Spanish cities who had completed information on height and weight of the ISAAC phase III questionnaire, which also included questions about asthma and RC symptoms and on various risk factors. Body mass index (BMI) was used to define obesity according to international standards. Two different logistic regressions, using current occasional asthma (COA) and current severe asthma (CSA) as dependent variables, were made stratifying for gender and for the coexistence of RC and controlling for age, older and younger siblings, exercise, mother's education, truck traffic, cat/dog during the first year of life and smoking father or mother., Results: Obesity was a risk factor of CSA without RC, both for boys (1.92, CI 95% 1.13-3.25) and for girls (2.99, CI 95% 1.68-5.32). Every BMI unit increment increased by 6.7% the risk of CSA without RC in boys and by 12.4% in girls. Obesity was not a risk factor for CSA with RC. The association between COA and obesity was weaker and the coexistence of RC did not modify it greatly., Conclusions: Obese schoolchildren are more at risk of suffering from non-allergic asthma than the non-obese subjects.

The use of the population attributable fraction (PAF) of asthma owing to atopy has not been widely used in epidemiological studies on childhood asthma, especially to compare regions of the same country. The present study includes 1039 children from Cartagena, Spain (Mediterranean coast) and 663 from Madrid (centre of Spanish plateau) using the ISAAC phase II methodology (questionnaire and prick test to the most common allergens). While there were no differences in asthma symptoms between school children (aged 10-11 yr) from Madrid and Cartagena, atopy to any allergen was significantly higher in those from Madrid (40.9% vs. 29.3%, respectively, p < 0.0001). However, children from Madrid were mainly positive to pollen allergy whereas those from Cartagena were positive for mite allergy. PAF of all the different asthma symptoms owing to atopy (any positive skin test) and PAF of current wheezing owing to a more severe atopy (three positive wheals) were higher in children from Cartagena than those from Madrid (45.5% vs. 28.6% and 14.2% vs. 6.2%, respectively). Per cent of previous year wheezing attributable to atopy to specific allergens varied among those cities and was higher for D. pteronissinus, D. farinae, cat, and olive tree in children from Cartagena, and--conversely--higher for mixed grasses, mixed trees and Alternaria in those from Madrid. All of these differences remained significant even after adjusting for risk factors. PAF for asthma owing to atopy could be very different within the same country, probably depending on the allergen supply which may depend on environmental factors such as the climate.

Objective: To analyze geographic variations in the prevalence of symptoms related to asthma in Spanish children and adolescents., Population and Methods: In 2001 and 2002, the Spanish arm of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3 collected information on 28 445 children in the age bracket of 6-7 years in 10 metropolitan areas (A Coruña, Asturias, Barcelona, Bilbao, Cartagena, Castellón, Madrid, Pamplona, San Sebastián, and Valencia) and on 31 257 adolescents in the bracket 13-14 years in 11 areas (the previously named areas plus Valladolid). An asthma symptom questionnaire was filled in by parents or the adolescents themselves. Differences in symptoms between geographic areas were analyzed by fitting a logistic regression model. The relationship between symptoms and age was analyzed by linear correlation., Results: The prevalence of recent wheezing (last 12 months) ranged from 7.1% to 12.9% among 6-7-year-olds and from 7.1% to 15.3% among the 13-14-year-olds. The greatest risk of recent wheezing was observed for children in A Coruña (odds ratio [OR] =1.96 in comparison with the area of lowest prevalence; 95% confidence interval [CI], 1.65-2.33) and Bilbao (OR=1.83; 95% CI, 1.54-2.18) and for adolescents in A Coruña (OR=2.38; 95% CI, 2.04-2.79) and Asturias (OR=2.37; 95% CI, 2.03-2.77). A strong correlation (r=0.72) was observed between the prevalence of recent wheezing and age in each of the geographic areas., Conclusions: Considerable geographic variation in the prevalence of asthma symptoms can be seen in Spain even among young children. Symptoms are more frequent in children and adolescents who live on the Spain s northern Atlantic coast.

Background: The role of immunization with bacillus Calmette-Guérin (BCG) in the prevalence of asthma, hay fever and atopic dermatitis is not definitely established and seems to be influenced by ethnic background. The aim of this study was to analyze the relationship between this immunization and the prevalence of those diseases in a homogeneous population of Spanish schoolchildren., Methods: The International Study of Asthma and Allergies in Childhood (ISAAC) core and environmental questionnaires were used in four different centers of the Spanish North Atlantic coast. Bilbao, San Sebastián and Asturias have a universal BCG immunization policy during the first days of life, whereas La Coruña discontinued this practice in 1989. Except for this center, immunization coverage was above 90%. A random sample of schools of Asturias or all schools in the city district (rest of centers) with children 6 and 7 years old was surveyed., Results: The participation rate was above 70%. After excluding those children born outside Spain, the numbers were 6,762 immunized and 2,828 nonimmunized. After adjusting for gender, age, smoking habits of the father and mother, truck traffic near the household, older and younger siblings and having a cat or a dog during the first year of the child's life, the adjusted ORs of the BCG-immunized children suffering from asthma, hay fever and atopic dermatitis were respectively 0.87 (95% CI 0.76-1.00), 0.87 (0.75-1.01) and 0.89 (0.76-1.05)., Conclusions: BCG immunization offers a weak but significant protection against asthma and hay fever in Spanish schoolchildren., (Copyright 2005 S. Karger AG, Basel.)

Background: Most studies show a steep increase in asthma prevalence in the last decades, although few studies had applied the same methodology. Recent reports point out the possibility that the epidemic has come to an end. We have studied the prevalence of asthma in a very large sample of children, repeating the study eight years apart., Methods: Repeated cross-sectional studies using the International Study of Asthma and Allergies in Childhood (ISAAC) protocol in a sample of Spanish schoolchildren 6-7 (parent-reported) and 13-14 (self-reported) years old in 1994-95 (phase I) and 2002-2003 (phase III). The number of participants was 42 417 in phase I and 42 813 in phase III. The participation rate was over 87% (13-14 years) and 70% (6-7 years)., Results: The prevalence of wheezing in the previous year in children aged 13-14 years was 9.0 and 9.3% for boys and 9.6 and 9.2% for girls for phases I and III, respectively. Children 6-7 years of age showed a substantial increase in wheezing in the previous year (7.0 and 10.7% for boys and 5.3 and 8.2% for girls). Other symptoms and severity indexes followed the same patterns., Conclusions: In the last 8 years, the prevalence of asthma has not changed in 13-14-year-old Spanish children but has increased substantially in 6-7-year olds.

Background: The ISAAC phase I results have supplied valuable information on the prevalence of asthma and allergy in childhood throughout the world., Objectives: To describe the implementation and participation rate of normal children in each test performed in phase II of the ISAAC in the four Spanish cities participating the study, and to establish the influence of type of school and geographical situation (in a polluted or unpolluted area) in Cartagena., Methods: The ISAAC phase II included a questionnaire on symptoms, risk factors and treatment, skin examination, skin-prick test, bronchial challenge test, total and specific IgE measurement, as well as mite and bacterial endotoxin determination in house dust. The questionnaire was distributed with a letter requesting authorization from the parents in primary schools (fourth and fifth grades) in sufficient number to achieve approximately 1,000 skin prick-test authorizations in each city., Results: The participation rate for the questionnaire, skin examination, skin-prick test, blood extraction, bronchial challenge test, and dust collection was, respectively, for each city: Cartagena: 58.9, 49.2, 43.2, 33.1, 39.9 and 29.8 %; Almería: 42.5, 40.6, 39.1, 39.1 and 37.6 %; Valencia: 43.7, 30.4, 23.5, 21.5, 20.1 and 17.1 %; Madrid: 53.2, 40.8, 38.6, 27.6, 30.6 and 21.1 %. In Cartagena, participation was significantly higher in private schools receiving a state subsidy and in those in unpolluted areas., Conclusions: The participation rate was highly variable and lower than that among the European centres that have already completed the study. The rate was significantly influenced by geographical area and type of school.

Background Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case–control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood. Methods We compared 1105 wheezing and 3137 non-wheezing children aged 8–12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-analysis. Results Significant associations with wheeze in the past year were detected in only four genes ( IL4R, TLR4, MS4A2, TLR9, P<0.05), with per allele odds ratios generally <1.3. Variants in IL4R and TLR4 were also related to allergen-specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations ( P<0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies. Conclusions Despite the biological plausibility of IgE-related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema. [ABSTRACT FROM AUTHOR]