Multiple atopy phenotypes and their associations with asthma: similar findings from two birth cohorts.

BACKGROUND: Although atopic sensitization is one of the strongest risk factors for asthma, its relationship with asthma is poorly understood. We hypothesize that 'atopy' encompasses multiple sub-phenotypes that relate to asthma in different ways. METHODS: In two population-based birth cohorts (Manchester and Isle of Wight - IoW), we used a machine learning approach to independently cluster children into different classes of atopic sensitization in an unsupervised manner, based on skin prick and sIgE tests taken throughout childhood and adolescence. We examined the qualitative cluster properties and their relationship to asthma and lung function. RESULTS: A five-class solution best described the data in both cohorts, with striking similarity between the classes across the two populations. Compared with nonsensitized class, children in the class with sensitivity to a wide variety of allergens (~1/3 of children atopic by conventional definition) were much more likely to have asthma (aOR [95% CI0; 20.1 [10.9-40.2] in Manchester and 11.9 [7.3-19.4] in IoW). The relationship between asthma and conventional atopy was much weaker (5.5 [3.4-8.8] in Manchester and 5.8 [4.1-8.3] in IoW). In both cohorts, children in this class had significantly poorer lung function (FEV1 /FVC lower by 4.4% in Manchester and 2.6% in IoW; P < 0.001), most reactive airways, highest eNO and most hospital admissions for asthma (P < 0.001). CONCLUSIONS: By adopting a machine learning approach to longitudinal data on allergic sensitization from two independent unselected birth cohorts, we identified latent classes with strikingly similar patterns of atopic response and association with clinical outcomes, suggesting the existence of multiple atopy phenotypes.

Time trends in the prevalence of peanut allergy: three cohorts of children from the same geographical location in the UK.

BACKGROUND: This article investigated the prevalence of peanut allergy in three cohorts of children born in the same geographical location, Isle of Wight, UK and seeks to determine whether the prevalence of peanut allergy has changed between 1994 and 2004. METHODS: Three cohorts of children (age 3-4 years) born on the Isle of Wight, were assessed for peanut allergy and the outcomes compared: Cohort A: Born in 1989; reviewed at 4 years of age (n = 2181). Cohort B: Born between 1994 and 1996; reviewed between 3 and 4 years of age (n = 1273). Cohort C: Born between 2001 and 2002; reviewed at 3 years of age (n = 891). RESULTS: Peanut sensitization increased significantly from 1.3% in Cohort A to 3.3% (P = 0.003) in Cohort B before falling back to 2.0% in Cohort C (P = 0.145). Similarly, clinical peanut allergy increased significantly from 0.5% in Cohort A to 1.4% (P = 0.023) in Cohort B, with a subsequent fall to 1.2% in Cohort C (P = 0.850). CONCLUSIONS: Our data from three cohorts of 3- to 4-year-old children born in the same geographical area shows that peanut allergy prevalence has changed over time. Peanut sensitization and reported allergy in children born in 1994-1996 increased from 1989 but seems to have stabilized or slightly decreased since the late 1990s, although not significant.

Characterisation of asthma that develops during adolescence; findings from the Isle of Wight Birth Cohort.

BACKGROUND: Understanding of adolescent-onset asthma remains limited. We sought to characterise this state and identify associated factors within a longitudinal birth cohort study. METHODS: The Isle of Wight Whole Population Birth Cohort was recruited in 1989 (N=1456) and characterised at 1, 2, 4, 10 and 18-years. "Adolescent-onset asthma" was defined as asthma at age 18 without prior history of asthma, "persistent-adolescent asthma" as asthma at both 10 and 18 and "never-asthma" as those without asthma at any assessment. RESULTS: Adolescent-onset asthma accounted for 28.3% of asthma at 18-years and was of similar severity to persistent-adolescent asthma. Adolescent-onset asthmatics showed elevated bronchial hyper-responsiveness (BHR) and atopy at 10 and 18 years. BHR in this group at 10 was intermediate to that of never-asthmatics and persistent-adolescent asthma. By 18 their BHR, bronchodilator reversibility and sputum eosinophilia was greater than never-asthmatics and comparable to persistent-adolescent asthma. At 10, males who later developed adolescent-onset asthma had reduced FEV(1) and FEF(25-75), while females had normal lung function but then developed impaired FEV(1) and FEF(25-75) in parallel with adolescent asthma. Factors independently associated with adolescent-onset asthma included atopy at 10 (OR=2.35; 95% CI=1.08-5.09), BHR at 10 (3.42; 1.55-7.59), rhinitis at 10 (2.35; 1.11-5.01) and paracetamol use at 18-years (1.10; 1.01-1.19). CONCLUSIONS: Adolescent-onset asthma is associated with significant morbidity. Predisposing factors are atopy, rhinitis and BHR at age 10 while adolescent paracetamol use is also associated with this state. Awareness of potentially modifiable influences may offer avenues for mitigating this disease state.

IL13 gene polymorphism association with cord serum immunoglobulin E.

Interleukin-13 (IL-13) has a pivotal role in the pathway of immunoglobulin E (IgE). Cord serum IgE has been suggested to be associated with allergy later in life, yet less affected by environmental exposures. We investigated the association of the interleukin-13 gene (IL13) polymorphisms on cord serum IgE. In the Isle of Wight birth cohort (UK, 1989-1990), cord serum IgE was measured using the ULTRA EIA kit and was dichotomized at 0.5 kU/l (n = 1358). Five single nucleotide polymorphisms (SNPs: rs1800925 in promoter, rs2066960 in intron 1, rs1295686 in intron 3, rs20541 in exon 4 and rs1295685 in exon 4) in IL13 were genotyped by pyrosequencing method. Linkage analysis using Haploview software revealed that rs1295686, rs20541 and rs1295685 were in strong linkage disequilibrium. Logistic regression and Armitage-Cochran test were used and gene association analysis included 798 children. Confounders were maternal age; maternal smoking, household dog, and household cat during pregnancy; season of birth; sex; position of child in family; and birth weight. SNP rs1295685 was associated with raised cord serum IgE (p = 0.031). This is the first report that shows an association between IL13 polymorphism and cord serum IgE.

The prevalence, characteristics of and early life risk factors for eczema in 10-year-old children.

Eczema is a common infantile disease but its nature and extent during later childhood remains unclear. In a whole-population birth cohort study (n = 1456) we examined prevalence and characteristics of eczema amongst 10-year-old children. At this age 1373 (94%) children completed ISAAC questionnaires, 1043 (72%) skin prick testing and 953 (65%) serum inhalant IgE antibody screening. At 10 years of age prevalence of eczema ever was 41.0% and for current eczema was 13.7% (combined current itchy rash and eczema ever). Most current eczema (71.0%) began before 4 years of age, but was associated with low morbidity at 10 years. Amongst children with diagnosed eczema at 4 years of age, 56.3% had current eczema at 10 years. Atopy (positive skin test) and other allergic states were associated with current eczema (p < 0.001). Risk factor analysis for current eczema identified independent significance for atopy (p = 0.01), rhinitis (p = 0.04) and food allergy (p = 0.01) at 4 years, plus maternal asthma (p = 0.03). Diagnosed rhinitis at 4 years emerged as a significant predictor of persistent disease. Eczema is not simply a transient infantile condition but a common problem at 10 years of age, often reflecting persistent disease from early childhood. Inherited predisposition towards atopy is the predominant risk factor for this state.