Search

Background: Little is known about the association of newborn DNA methylation (DNAm) with asthma acquisition across adolescence and early adult life., Objective: We aim to identify epigenetic biomarkers in newborns for asthma acquisition during adolescence or young adulthood., Methods: The Isle of Wight Birth Cohort (IOWBC) (n = 1456) data at ages 10, 18 and 26 years were assessed. To screen cytosine-phosphate-guanine site (CpGs) potentially associated with asthma acquisition, at the genome scale, we examined differentially methylated regions (DMR) using dmrff R package and individual CpG sites using linear regression on such associations. For CpGs that passed screening, we examined their enrichment in biological pathways using their mapping genes and tested their associations with asthma acquisitions using logistic regressions. Findings in IOWBC were tested in an independent cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort., Results: In total, 2636 unique CpGs passed screening, based on which we identified one biological pathway linked to asthma acquisition during adolescence in females (FDR adjusted p-value = .003 in IOWBC). Via logistic regressions, for females, four CpGs were shown to be associated with asthma acquisition during adolescence, and another four CpGs with asthma acquisition in young adulthood (FDR adjusted p-value < .05 in IOWBC) and these eight CpGs were replicated in ALSPAC (all p-values < .05). DNAm at all the identified CpGs was shown to be temporally consistent, and at six of the CpGs was associated with expressions of adjacent or mapping genes in females (all p-values < .05). For males, 622 CpGs were identified in IOWBC (FDR = 0.01), but these were not tested in ALSPAC due to small sample sizes., Conclusion and Clinical Relevance: Eight CpGs on LHX5, IL22RA2, SOX11, CBX4, ACPT, CFAP46, MUC4, and ATP1B2 genes have the potential to serve as candidate epigenetic biomarkers in newborns for asthma acquisition in females during adolescence or young adulthood., (© 2022 John Wiley & Sons Ltd.)

Background: Eczema is a common inflammatory skin disease with varying developmental trajectories/patterns that are influenced by different risk factors. The aim of this study was to investigate eczema development from infancy to early adulthood by identifying distinct developmental trajectories that describe disease patterns over time and evaluate the role of prenatal and early-life risk factors., Methods: The Isle of Wight Birth Cohort (n = 1456) was prospectively assessed at birth, 1, 2, 4, 10, 18 and 26 years. In all assessments, eczema was defined as chronic or chronically relapsing itchy dermatitis lasting >6 weeks with characteristic morphology and distribution in the past 12 months. Developmental trajectories of eczema between 1 or 2 and 26 years were identified separately for males and females by applying semiparametric mixture models. Associations were assessed by applying a modified Poisson regression to estimate adjusted risk ratios (aRR) and 95% confidence intervals (CI)., Results: In both males and females, the following eczema developmental trajectories were identified: unaffected/transient (males: 77.7% vs. females: 73.0%), mid-onset late-resolving (males: 7.8% vs. females: 4.4%), late-onset (males: 5.2% vs. females: 9.5%) and early-onset persistent (males: 9.3% vs. females: 5.4%). In females, an additional trajectory was identified as follows: early-onset early-resolving (7.7%). Among males, filaggrin gene (FLG) variants (aRR = 2.45, 95% CI: 1.34-4.46) and paternal eczema (2.66, 1.39-5.08) were associated with the early-onset persistent trajectory. Among females, maternal eczema (2.84, 1.42-5.70) and high birthweight (2.25, 1.08-4.69) were associated with the early-onset persistent trajectory., Conclusions: Four and five trajectories represented eczema development among males and females, respectively, with different predisposing risk factors. Our results indicate that males and females may experience a different course of eczema., (© 2021 John Wiley & Sons Ltd.)

Background: Underlying biological mechanisms involved in sex differences in asthma status changes from pre- to post-adolescence are unclear. DNA methylation (DNAm) has been shown to be associated with the risk of asthma., Objective: We hypothesized that asthma acquisition from pre- to post-adolescence was associated with changes in DNAm during this period at asthma-associated cytosine-phosphate-guanine (CpG) sites and such an association was sex-specific., Methods: Subjects from the Isle of Wight birth cohort (IOWBC) with DNAm in blood at ages 10 and 18 years (n = 124 females, 151 males) were studied. Using a training-testing approach, epigenome-wide CpGs associated with asthma were identified. Logistic regression was used to examine sex-specific associations of DNAm changes with asthma acquisition between ages 10 and 18 at asthma-associated CpGs. The ALSPAC birth cohort was used for independent replication. To assess functional relevance of identified CpGs, association of DNAm with gene expression in blood was assessed., Results: We identified 535 CpGs potentially associated with asthma. Significant interaction effects of DNAm changes and sex on asthma acquisition in adolescence were found at 13 of the 535 CpGs in IOWBC (P-values <1.0 × 10 -3 ). In the replication cohort, consistent interaction effects were observed at 10 of the 13 CpGs. At 7 of these 10 CpGs, opposite DNAm changes across adolescence were observed between sexes in both cohorts. In both cohorts, cg20891917, located on IFRD1 linked to asthma, shows strong sex-specific effects on asthma transition (P-values <.01 in both cohorts)., Conclusion and Clinical Relevance: Gender reversal in asthma acquisition is associated with opposite changes in DNAm (males vs females) from pre- to post-adolescence at asthma-associated CpGs. These CpGs are potential biomarkers of sex-specific asthma acquisition in adolescence., (© 2020 John Wiley & Sons Ltd.)

Background: Cigarette smoke contains compounds similar to coal tar, an ancient remedy of eczema. Some studies have reported protective effects of maternal gestational smoking on offspring eczema; however, others have shown no or increased risks. Similarly, studies linking breastfeeding duration and eczema have demonstrated contradictory findings. No study has yet investigated combined effects of these two factors on eczema., Objective: Since tobacco compounds can pass to offspring via breast milk, we investigated their combined effects on eczema development from childhood to adolescence., Methods: We obtained information regarding gestational smoking, exclusive breastfeeding duration, and eczema at ages 1-or-2, 4, 10, and 18 years from the Isle of Wight (IOW) birth cohort, UK. Using generalized estimating equations, we assessed the interaction of gestational smoking and residual exclusive breastfeeding duration (Resid-BF-duration, obtained by regressing the latter on maternal smoking) on eczema over time adjusting for confounders. For the three transition periods of 1-or-2 to 4 years, 4-10, and 10-18 years, we estimated risks of persistent, incident, and remitting eczema associated with the interaction using repeated measurements., Results: If the mother smoked during gestation, longer Resid-BF-duration was associated with a lower risk of eczema, compared to if she did not smoke. The risk ratios (95% CI) if the mother smoked during gestation and exclusively breastfed for at least 3, 9, 15, 21 weeks are 0.7 (0.6, 1.7), 0.6 (0. 4, 0.9), 0.5 (0.3, 0.8), and 0.4 (0.2, 0. 8), respectively. Additionally, in all three transition periods, the risk of persistent eczema was lower with longer Resid-BF-duration if the mother smoked during gestation., Conclusions and Clinical Relevance: Results suggest a protective effect of gestational smoking combined with longer duration of exclusive breastfeeding on early-onset persistent eczema. Future studies should examine underlying biological mechanisms. Prolonged breastfeeding should be encouraged even if the mother smoked during gestation., (© 2018 John Wiley & Sons Ltd.)

Background: Allergic sensitization is associated with eczema, asthma, and rhinitis. However, it is unknown whether and how allergic sensitization is associated over time with acquisition, remission, and persistence of these diseases and their comorbidity., Objective: To gain a better understanding of factors including allergic sensitization transitions that influence the temporal pattern of asthma, eczema, and rhinitis and their comorbidity during childhood., Methods: In the Isle of Wight birth cohort, information on allergic sensitization to common allergens was collected at ages 4, 10, and 18 years along with asthma, rhinitis, and eczema status determined by clinical diagnosis. Logistic regressions were used to estimate subsequent and concurrent odds ratios of diseases transition with allergic sensitization transition status as the main independent variable. Two transition periods were considered, 4 to 10 years of age and 10 to 18 years of age., Results: The odds of new diagnosis of allergic disease (no-yes) was increased among subjects with acquired or persistent allergic sensitization to common allergens compared to subjects with no sensitization (acquisition of sensitization odds ratio [OR]=3.22, P < .0001; persistence of sensitization, OR=6.33, P < .0001). The odds of remission of allergic diseases (yes-no) was lower among subjects with acquired or sustained allergic sensitization (acquisition, OR=0.18, P = .0001; persistence, OR=0.085, P < .0001), compared to subjects not sensitized. Subjects with acquired or persistent allergic sensitization were also had higher odds for persistence of disease (yes-yes) than subjects not sensitized (acquisition, OR=5.49, P = .0001; persistence, OR=11.79, P < .0001)., Conclusion: Transition of allergic sensitizations to common allergens is a prognostic factor for subsequent or concurrent transition of eczema, asthma, and rhinitis. Prevention or reduction in allergic sensitization has a potential to lead to remission of these conditions., (© 2018 John Wiley & Sons Ltd.)

Background: Filaggrin loss-of-function (FLG-LOF) mutations are an established genetic cause of eczema. These mutations have subsequently been reported to increase the risk of aeroallergen sensitization and allergic airway disease. However, it is unclear whether FLG variants require both eczema and aeroallergen sensitization to influence airway disease development long-term outcomes., Objective: To examine the effects of FLG-LOF mutations on allergic airway disease outcomes, with eczema and aeroallergen sensitization as intermediate variables, using the Isle of Wight birth cohort., Methods: Study participants were evaluated at ages 1, 2, 4, 10 and 18 years to ascertain the development of allergic diseases (eczema, asthma and allergic rhinitis) and aeroallergen sensitization (determined by skin prick tests). FLG-LOF mutations were genotyped in 1150 subjects. To understand the complex associations between FLG mutations, intermediate variables (eczema and aeroallergen sensitization) and airway disease, path analysis was performed., Results: There were significant total effects of FLG-LOF mutations on both asthma and allergic rhinitis at all ages as well as on aeroallergen sensitization up till 10 years old. In the filaggrin-asthma analysis, a direct effect of FLG-LOF mutations was observed on early childhood eczema (age 1 and 2 years) (relative risk (RR) 2.01, 95% CI: 1.74-2.31, P < .001), and all significant indirect pathways on asthma outcomes passed through eczema at these ages. In contrast, for the filaggrin-rhinitis model, FLG-LOF mutations exerted significant direct effects on early eczema as well as rhinitis at 10 years (RR 1.99; 95% CI: 1.72-2.29, P = .002)., Conclusion: FLG-LOF mutations are a significant risk factor for later childhood asthma and rhinitis. However, the pathway to asthma is only through early childhood eczema while a direct effect was observed for childhood rhinitis., (© 2017 John Wiley & Sons Ltd.)

Background: Modes of infant feeding such as direct and indirect breastfeeding, and formula feeding, and their combinations may play a role in child health., Objective: The aim was to investigate which feeding patterns in the first 6 months pose risks of eczema/skin allergy in children up to 6 years compared to direct breastfeeding for at least 3 months., Methods: The Infant Feeding Practices Study II in the United States and its 6-year follow-up provided data on feeding modes in infancy and doctor's diagnosed eczema/skin allergy in the first 6 years of life (1387 infants), based on parental reports. Different feeding patterns were identified. Log-linear models were used to estimate prevalence ratios (PRs) of feeding patterns for doctor's diagnosed eczema/skin allergy in the first 6 years of life, adjusting for confounders., Results: Compared to "direct breastfeeding for at least 3 months" (DBF3m), the combination of "direct feeding at the breast (DBF), pumping and feeding breast milk (BM), and formula (FF) in the first months" (DBF/BM/FF) showed a statistically significant higher risk of eczema/skin allergy in the first 6 years of life (PR = 1.46), adjusting for confounders. DBF combined with BM for the first 3 months followed by mixed feeding also had an increased risk (PR = 1.26), although not statistically significant. Formula feeding introduced since birth had no effect on eczema. Among the confounders, paternal eczema and race/ethnicity (Hispanic vs White) were associated with a higher risk of eczema/skin allergy., Conclusions & Clinical Relevance: Mixed infant feeding may carry a higher risk of eczema/skin allergy compared to direct feeding at the breast. The recent epidemic of pumping and feeding in the United States and the use of mixed infant feeding modes requires additional studies to provide appropriate and renewed assessments of the risks of feeding modes for the future development of allergies., (© 2017 John Wiley & Sons Ltd.)

Background: Filaggrin gene (FLG) expression, particularly in the skin, has been linked to the development of the skin barrier and is associated with eczema risk. However, knowledge as to whether FLG expression in umbilical cord blood (UCB) is associated with eczema development and prediction is lacking., Objective: This study sought to assess whether FLG expression in UCB associates with and predicts the development of eczema in infancy., Methods: Infants enrolled in a birth cohort study (n=94) were assessed for eczema at ages 3, 6, and 12 months. Five probes measuring FLG transcripts expression in UCB were available from genomewide gene expression profiling. FLG genetic variants R501X, 2282del4, and S3247X were genotyped. Associations were assessed using Poisson regression with robust variance estimation. Area under the curve (AUC), describing the discriminatory/predictive performance of fitted models, was estimated from logistic regression., Results: Increased level of FLG expression measured by probe A&#95;24&#95;P51322 was associated with reduced risk of eczema during the first year of life (RR=0.60, 95% CI: 0.38-0.95). In contrast, increased level of FLG antisense transcripts measured by probe A&#95;21&#95;P0014075 was associated with increased risk of eczema (RR=2.02, 95% CI: 1.10-3.72). In prediction models including FLG expression, FLG genetic variants, and sex, discrimination between children who will and will not develop eczema at 3 months of age was high (AUC: 0.91, 95% CI: 0.84-0.98)., Conclusions and Clinical Relevance: This study demonstrated, for the first time, that FLG expression in UCB is associated with eczema development in infancy. Moreover, our analysis provided prediction models that were capable of discriminating, to a great extent, between those who will and will not develop eczema in infancy. Therefore, early identification of infants at increased risk of developing eczema is possible and such high-risk newborns may benefit from early stratification and intervention., (© 2017 John Wiley & Sons Ltd.)

Background: Allergic sensitization and filaggrin gene (FLG) variants are important risk factors for allergic disorders; however, knowledge on their individual and interactive effects on the coexistence of eczema, asthma, and rhinitis is lacking., Objective: This study aimed at investigating the single and combined effects of allergic sensitization and FLG variants on the development of single and multiple allergic disorders., Methods: The Isle of Wight birth cohort (n = 1456) has been examined at 1, 2, 4, 10, and 18 years of age. Repeated measurements of eczema, asthma, rhinitis, and skin prick tests were available for all follow-ups. FLG variants were genotyped in 1150 participants. Associations of allergic sensitization and FLG variants with single and multiple allergic disorders were tested in log-binomial regression analysis., Results: The prevalence of eczema-, asthma-, and rhinitis-only ranged from 5.6% to 8.5%, 4.9% to 10.2%, and 2.5% to 20.4%, respectively, during the first 18 years of life. The coexistence of allergic disorders is common, with approximately 2% of the population reporting the comorbidity of 'eczema, asthma, and rhinitis' during the study period. In repeated measurement analyses, allergic sensitization and FLG variants, when analysed separately, were associated with having single and multiple allergic disorders. Of particular significance, their combined effect increased the risk of 'eczema and asthma' (RR = 13.67, 95% CI: 7.35-25.42), 'asthma and rhinitis' (RR = 7.46, 95% CI: 5.07-10.98), and 'eczema, asthma, and rhinitis' (RR = 23.44, 95% CI: 12.27-44.78)., Conclusions and Clinical Relevance: The coexistence of allergic disorders is frequent, and allergic sensitization and FLG variants jointly increased risk of allergic comorbidities, which may represent more severe and complex clinical phenotypes. The interactive effect and the elevated proportion of allergic comorbidities associated with allergic sensitization and FLG variants emphasize their joint importance in the pathogenesis of allergic disorders., (© 2014 John Wiley & Sons Ltd.)

Background: Cluster analyses have enhanced understanding of the heterogeneity of both paediatric and adult wheezing. However, while adolescence represents an important transitional phase, the nature of young adult wheeze has yet to be clearly characterised., Objectives: To use cluster analysis to define, for the first time, clinically relevant young adult wheeze clusters in a longitudinal birth cohort., Methods: K-means cluster analysis was undertaken among 309 currently wheezing subjects at 18 years in the Isle of Wight birth cohort (N = 1456). Thirteen disease-characterising clustering variables at 18 years were used. Resulting clusters were then further characterised by severity indices plus potential risk factors for wheeze development throughout the 1st 18 years of life., Results: Six wheeze clusters were identified. Cluster 1 (12.3%) male-early-childhood-onset-atopic-wheeze-with-normal-lung-function had male predominance, normal spirometry, low bronchodilator reversibility (BDR), intermediate bronchial hyper-responsiveness (BHR), high atopy prevalence and more admissions. Cluster 2 (24.2%) early-childhood-onset-wheeze-with-intermediate-lung-function had no specific sex association, intermediate spirometry, BDR, BHR, more significant BTS step therapy and admissions. Cluster 3 (9.7%) female-early-childhood-onset-atopic-wheeze-with-impaired-lung-function showed female predominance, high allergic disease comorbidity, more severe BDR and BHR, greatest airflow obstruction, high smoking prevalence, higher symptom severity and admissions. Cluster 4 (19.4%) female-undiagnosed-wheezers had adolescent-onset non-atopic wheeze, low BDR and BHR, impaired but non-obstructed spirometry, high symptom frequency and highest smoking prevalence. Cluster 5 (24.6%) female-late-childhood-onset-wheeze-with-normal-lung-function showed no specific atopy association, normal spirometry, low BDR, BHR and symptom severity. Cluster 6 (9.7%) male-late-childhood-onset-atopic-wheeze-with-impaired-lung-function had high atopy and rhinitis prevalence, increased BDR and BHR, moderately impaired spirometry, high symptom severity and higher BTS step therapy., Conclusions and Clinical Relevance: Young adult wheeze is diverse and can be classified into distinct clusters. More severe clusters merit attention and are associated with childhood onset, atopy, impaired lung function and in some, smoking. Smoking-associated undiagnosed wheezers also merit recognition. Better understanding of young adult wheeze could facilitate better later adult respiratory health., (© 2014 John Wiley & Sons Ltd.)

Background: Skin prick testing (SPT) is fundamental to the practice of clinical allergy identifying relevant allergens and predicting the clinical expression of disease. There are only limited data on the natural history of SPT results over childhood and adolescence., Objective: We aimed to describe the natural history of SPT and patterns of sensitization over childhood and adolescence., Methods: The 1989 Isle of Wight birth cohort (1456 participants) was followed up at 1, 2, 4, 10 and 18 years. SPT was undertaken from 4 years., Results: SPT was performed on 980 (80%), 1036 (75%) and 853 (65%) of participants at 4, 10 and 18 years. The prevalence of sensitization to any allergen at these time-points was 19.7%, 26.9% and 41.3% respectively. At each time-point, boys were significantly more likely to be sensitized (P < 0.016) and sensitization significantly increased over childhood and adolescence (average annual increase of 7%). Some children outgrew their sensitization. The rate of sensitization to most individual allergens increased over childhood and adolescence. A configural frequency analysis showed that whether an individual was sensitizated was relatively fixed over childhood and adolescence. Cluster analysis at 4 years demonstrated four major groups of individuals with similar co-sensitization to specific allergens. Children who were sensitized at age 4 years generally went onto become sensitized to additional allergens at 10 and 18 years., Conclusions and Clinical Relevance: Allergic sensitization continues to increase over childhood into adolescence although the majority of children who were not sensitized at 4 years remain non-sensitized throughout childhood and adolescence. The presence of sensitization at 4 years predicted later sensitization to additional allergens., (© 2012 Blackwell Publishing Ltd.)

Background: Longitudinal studies of the natural history of childhood and adolescent rhinitis are lacking., Objectives: To investigate the natural history of rhinitis up to 18 years of age, and how that is influenced by gender and atopy., Methods: The Isle of Wight birth cohort was recruited in 1989 (n=1456). Questionnaire data on nasal symptoms (rhinitis) were collected at 1, 2, 4, 10 and 18 years of age. To define atopy, skin prick tests were conducted at 4, 10 and 18 years. The 12-month period prevalence plus positive and negative transitions (defined as change in disease status in two consecutive study assessments) were stratified by gender and atopic status., Results: Overall rhinitis prevalence increased from 5.4% at 4 years to 35.8% at 18 years (P<0.001), without gender difference. Atopic rhinitis prevalence increased steadily from 3.4% at 4 years to 27.3% at 18 years (P<0.001), was commoner in boys at 18 years (P=0.02) and associated with greater positive transition in boys from 10 to 18 years (P=0.01). Prevalence of non-atopic rhinitis also increased from 4 to 18 years (P=0.003) and was greater in girls at 18 years (P<0.001) reflecting higher female positive transition from 10 to 18 years (P<0.001). Non-atopic rhinitis negative transition (remission) was highest in early life and reduced in later childhood/adolescence., Conclusion: Atopic rhinitis becomes increasingly common as children grow into adolescents, with stronger associations to male gender. Non-atopic rhinitis shows a female predominance at 18 years as girls 'grow into' it more during adolescence. Our findings suggest differential gender effects on the increasing prevalence of both atopic and non-atopic rhinitis in adolescence., Clinical Relevance: A better understanding of how gender and atopic status influence rhinitis during adolescence emerges from this study. Application of such knowledge could help to improve clinical recognition, judge prognosis and ultimately improve management of this common condition., (© 2011 Blackwell Publishing Ltd.)

Background: Trends in the prevalence of eczema in the course of childhood and adolescence are not clear although often a net remission during childhood is assumed., Objectives: To investigate the dynamics of change in eczema from 1 to 18 years in a prospective study and to understand the influence of gender and atopy., Methods: Detailed information regarding eczema were collected at ages 1, 2, 4, 10 and 18 years from the 1989 Isle of Wight birth cohort (n=1456). Skin prick testing was performed at 4, 10 and 18 years of age. The 12-month period prevalence, positive and negative transitions (defined as change in disease status in two consecutive study assessments) were stratified by gender and atopic status., Results: The period prevalence of eczema from birth to 18 years of age remained relatively constant (11.9-14.2%) with minimal remission. Up to 10 years of age, gender did not influence prevalence. From 10 to 18 years, eczema became more prevalent among girls (16.3% for girls vs. 8.3% for boys, P<0.001) as a result of a greater positive transition in girls (9.4% for girls vs. 4.3% for boys, P=0.001) and greater negative transition in boys (65.4% for boys vs. 50% for girls, P=0.04). The higher positive transition of eczema in girls was most pronounced for non-atopic eczema (5.9% for girls vs. 1.5% for boys, P=0.002)., Conclusions: We found only a minimal reduction in the prevalence of eczema during childhood and adolescence. During adolescence, more girls develop eczema and more boys outgrow it suggesting a role for gender-specific pubertal factors., (© 2010 Blackwell Publishing Ltd.)

In 2009 the journal published in the region of 200 papers including reviews, editorials, opinion pieces and original papers that ran the full gamut of allergic disease. It is instructive to take stock of this output to determine patterns of interest and where the cutting edge lies. We have surveyed the field of allergic disease as seen through the pages of Clinical and Experimental Allergy (CEA) highlighting trends, emphasizing notable observations and placing discoveries in the context of other key papers published during the year. The review is divided into similar sections as the journal. In the field of Asthma and Rhinitis CEA has contributed significantly to the debate about asthma phenotypes and expressed opinions about the cause of intrinsic asthma. It has also added its halfpennyworth to the hunt for meaningful biomarkers. In Mechanisms the considerable interest in T cell subsets including Th17 and T regulatory cells continues apace and the discipline of Epidemiology continues to invoke a steady stream of papers on risk factors for asthma with investigators still trying to explain the post-second world war epidemic of allergic disease. Experimental Models continue to make important contributions to our understanding of pathogenesis of allergic disease and in the Clinical Allergy section various angles on immunotherapy are explored. New allergens continue to be described in the allergens section to make those allergen chips even more complicated. A rich and vibrant year helpfully summarized by some of our associate editors., (© 2010 Blackwell Publishing Ltd.)

Background: Identifying the protective effect of a higher number of siblings is a significant finding in understanding the aetiology of allergic sensitization, asthma, eczema, and hayfever. Knowledge about causes behind the sibling effect may allow us to prevent atopic manifestations., Objective: We tested the hypothesis that rising order of live offspring increases maternal immune tolerance (immune non-reactivity) against allergens. To this end, we investigated whether maternal IgE levels are associated with the number of live offspring., Methods: In a cohort of 1456 newborns recruited between January 1989 and February 1990 on the Isle of Wight, UK, we determined maternal and cord serum IgE, and the order of live offspring. The data were analysed by means of linear and path analysis., Results: Maternal and cord serum IgE were available in 820 mother-infant pairs with birth order information. We found that the number of live offspring significantly reduces maternal IgE. The decline was more prominent in mothers with atopy (n=268). The geometric means of IgE after the first, second, and third or higher delivery were 74.4, 66.6, and 43.0 kU/L, respectively. Findings of path analysis suggest a significant direct effect of birth order on maternal IgE, but no direct effect of birth order on cord serum IgE., Conclusion: The findings support that maternal immune tolerance against allergens may increase with increasing order of live offspring and thus pass on a lower risk of developing atopy in children of higher birth order.

Background: Sensitization to dust mites predisposes to asthma and allergic rhinitis, and prevention of this sensitization might reduce the rising prevalence of these disorders., Objective: To test the effectiveness of dust mite avoidance measures on the development of sensitization to dust mites in children., Methods: As part of a multicentre study (Study of Prevention of Allergy in Children of Europe), 242 children, aged 5-7 years, in three European countries (United Kingdom, Greece and Lithuania), were randomized to prophylactic group (n = 127) and control group (n = 115). At randomization these children were required to have a family history of atopy and positive skin test to an aeroallergen but not to house dust mite. Children in the prophylactic group were provided with dust mite impermeable mattress covers and advice on environmental measures to reduce exposure to dust-mite allergen. Control group children were given non-specific advice. After 12 months a standardized questionnaire was completed and skin prick tests were performed., Results: Ten children in the prophylactic group and 19 in the control group were lost to follow-up. Three of 117 (2.56%) children in the prophylactic group and nine of 96 (9.38%) in the control group developed sensitization to dust mites. Logistic regression analysis confirmed an independent effect of prophylactic measures (adjusted odds ratio (OR): 0.14, 95% confidence interval (CI): 0.03-0.79, P = 0.03). Fifteen children need to be treated to prevent sensitization in one child., Conclusion: Dust mite sensitization can be reduced in school age children with simple mite avoidance measures.

Background: Several studies have reported an association between a child's risk of atopic disorders and family size. However, the inverse association might not be the same in populations with a different genetic disposition for atopic disorders., Objective: This longitudinal study was designed to assess risk factors of atopy., Methods: Lifetime prevalence of asthma, hay fever and eczema of 1440 families including 3165 offspring was ascertained by means of standardized questionnaires., Results: After possible confounders had been controlled for, an inverse association between atopic disorders and the number of older siblings was found only in the offspring of atopic fathers (trend for older siblings: chi2 = 13.38, degrees of freedom [d.f.] = 1, P= 0.0002; odds ratio 'no older sibling'= 2.87 (95% confidence interval 2.18-3.78); '1 older sibling' = 2.11 [1.52-2.92], '2 older siblings' = 1.29 [0.74-2.23]; '3 or more older siblings' = 0. 15 [0.02-0.981). No such relationship was found for children without a history of paternal atopy (trend for older siblings: chi2 = 1.5 1, d.f. = 1, P = 0.22; odds ratio 'no older sibling' = 1 [reference]; '1 older sibling' =0.82 [0.63-1.06]; '2 older siblings' = 0.97 [0.67-1.40]; '3 or more older siblings' = 0.64 [0.31-1.33]). The trend for older siblings in the case of paternal atopy was significantly different from the trend for older siblings without a history of paternal atopy (chi2 = 8.68, d.f. = 1, P = 0.003). The number of younger siblings was not related to child's risk of atopy (trend for younger siblings: chi2 = 0.001, d.f. = 1, P = 0.97)., Conclusions: Data from this study suggest a protective effect of sibship size only in children with a history of paternal atopy and if older siblings are present. The reason for this combined effect remains unclear. Thus, further investigations are needed to interpret the biological cause of the so called 'sibling effect'.

To investigate the year-to-year variation of mite antigen density (Der p I, Der fI) in dust from mattresses and the relevance of residential factors for antigen load, information derived from an epidemiologic study including two surveys carried out in the households of a cohort of elementary school children (n = 1291) was analysed. When considering residences with measurements taken in both years in question (n = 1050), rank-correlation indicated a predominance of stability for both antigens (Der p I: rs = 0.82, P = 0.0001; Der f I: rs = 0.72, P = 0.0001). Using multiple regression analyses, significant associations between antigen concentrations and a variety of residential factors were found. Use of a blanket of animal hair, use of a cover or underblanket, wet spots in the bedroom, higher relative humidity and a low storey level were significantly associated with increased concentrations of Der p I, whereas inverse relationships between this antigen and room temperature, number of persons per m2 as well as use of underfloor heating were seen. Regarding Der fI, older mattresses, use of a cover or underblanket, higher weight of sampled dust, high educational level and higher ratio of inhabitants per m2 were significantly associated with increased concentrations of the antigen. On the other hand, lower Der fI concentrations were found when interior sprung mattresses were used and when the mattress was 'treated regularly'. In conclusion, two measurements, 1 year apart from each other, show that stability of mite antigen concentrations predominated.(ABSTRACT TRUNCATED AT 250 WORDS)

The coincidence of allergic sensitization was investigated in 302 school-aged children and their parents. Specific sensitization to four common inhalant allergens (grass and birch pollens, cat dander, Dermatophagoides pteronyssinus) was ascertained by means of skin-prick tests (SPT) carried out on the complete family unit at the beginning of a 22-month follow-up period. The same test procedure was then repeated on the children twice at 11-month intervals to provide cumulative prevalences of sensitization. A clinical history of atopy in the children (hay fever or asthma; n = 47), which was derived from an interview, is associated with sensitization (positive SPT in 89%). For three allergens (grass and birch pollens, cat dander) sensitization occurs significantly more frequently in the children of mothers who are sensitized to the same allergen (odds-ratios (ORs), 2.5-4.1). Additionally, in three of the four explanatory models related to a single antigen, maternal sensitization to one of the complementary allergens is of importance (ORs, 2.7-3.7). In contrast to this finding, none of the paternal sensitizations has statistical significance. Based on a reaction to at least one of the four allergens, the child's relative risk to be sensitized is increased in case of maternal (OR, 2.88; P = 0.001) but not of paternal (OR, 1.06; P = 0.83) sensitization. In conclusion, our data indicate that the maternal status is more predictive than that of the father with regard to the child's risk of sensitization.

The skin prick test (SPT) is a commonly used procedure for assessing a specific sensitization. The longitudinal variability of test results is of interest for clinical as well as epidemiological investigations. The sensitization to four common aeroallergens (grass pollen, birch pollen, Dermatophagoides pteronyssinus, cat dander) is investigated within the framework of three consecutive SPTs at 11-month intervals for a population of 587 schoolchildren. The prevalence of sensitization based on a weal diameter of at least 2 mm was between 12.9% (cat dander) and 23.9% (grass pollen) in the initial testing. The positive predictive values of the initial SPT were between 75.3% (birch pollen) and 88.2% (cat dander) for the two subsequent SPTs. In the case of initially negative tests with positive second and third SPTs the incidence ranged between 3.2% (cat dander) and 4.3% (birch pollen) per year. A clear increase in the intensity of reaction in subsequent tests was observed in a number of probands testing positively in the initial SPT. In conclusion, our data indicate a high long-term stability of a specific sensitization to aeroallergens in SPT.