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Developmental profiles of eczema, wheeze, and rhinitis: two population-based birth cohort studies.

ABSTRACT: The term "atopic march" has been used to imply a natural progression of a cascade of symptoms from eczema to asthma and rhinitis through childhood. We hypothesize that this expression does not adequately describe the natural history of eczema, wheeze, and rhinitis during childhood. We propose that this paradigm arose from cross-sectional analyses of longitudinal studies, and may reflect a population pattern that may not predominate at the individual level.Data from 9,801 children in two population-based birth cohorts were used to determine individual profiles of eczema, wheeze, and rhinitis and whether the manifestations of these symptoms followed an atopic march pattern. Children were assessed at ages 1, 3, 5, 8, and 11 y. We used Bayesian machine learning methods to identify distinct latent classes based on individual profiles of eczema, wheeze, and rhinitis. This approach allowed us to identify groups of children with similar patterns of eczema, wheeze, and rhinitis over time. Using a latent disease profile model, the data were best described by eight latent classes: no disease (51.3%), atopic march (3.1%), persistent eczema and wheeze (2.7%), persistent eczema with later-onset rhinitis (4.7%), persistent wheeze with later-onset rhinitis (5.7%), transient wheeze (7.7%), eczema only (15.3%), and rhinitis only (9.6%). When latent variable modelling was carried out separately for the two cohorts, similar results were obtained. Highly concordant patterns of sensitisation were associated with different profiles of eczema, rhinitis, and wheeze. The main limitation of this study was the difference in wording of the questions used to ascertain the presence of eczema, wheeze, and rhinitis in the two cohorts.The developmental profiles of eczema, wheeze, and rhinitis are heterogeneous; only a small proportion of children (? 7% of those with symptoms) follow trajectory profiles resembling the atopic march. Please see later in the article for the Editors' Summary.

SUBMITTER: Belgrave DC

PROVIDER: S-EPMC4204810 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Developmental profiles of eczema, wheeze, and rhinitis: two population-based birth cohort studies.

Belgrave Danielle C M DC Granell Raquel R Simpson Angela A Guiver John J Bishop Christopher C Buchan Iain I Henderson A John AJ Custovic Adnan A

PLoS medicine 20141021 10

<h4>Background</h4>The term "atopic march" has been used to imply a natural progression of a cascade of symptoms from eczema to asthma and rhinitis through childhood. We hypothesize that this expression does not adequately describe the natural history of eczema, wheeze, and rhinitis during childhood. We propose that this paradigm arose from cross-sectional analyses of longitudinal studies, and may reflect a population pattern that may not predominate at the individual level.<h4>Methods and findi ...[more]

PMID: 25335105

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Project description:Rationale: The relationship between eczema, wheeze or asthma, and rhinitis is complex, and epidemiology and mechanisms of their comorbidities is unclear. Objectives: To investigate within-individual patterns of morbidity of eczema, wheeze, and rhinitis from birth to adolescence/early adulthood. Methods: We investigated onset, progression, and resolution of eczema, wheeze, and rhinitis using descriptive statistics, sequence mining, and latent Markov modeling in four population-based birth cohorts. We used logistic regression to ascertain if early-life eczema or wheeze, or genetic factors (filaggrin [FLG] mutations and 17q21 variants), increase the risk of multimorbidity. Measurements and Main Results: Single conditions, although the most prevalent, were observed significantly less frequently than by chance. There was considerable variation in the timing of onset/remission/persistence/intermittence. Multimorbidity of eczema+wheeze+rhinitis was rare but significantly overrepresented (three to six times more often than by chance). Although infantile eczema was associated with subsequent multimorbidity, most children with eczema (75.4%) did not progress to any multimorbidity pattern. FLG mutations and rs7216389 were not associated with persistence of eczema/wheeze as single conditions, but both increased the risk of multimorbidity (FLG by 2- to 3-fold, rs7216389 risk variant by 1.4- to 1.7-fold). Latent Markov modeling revealed five latent states (no disease/low risk, mainly eczema, mainly wheeze, mainly rhinitis, multimorbidity). The most likely transition to multimorbidity was from eczema state (0.21). However, although this was one of the highest transition probabilities, only one-fifth of those with eczema transitioned to multimorbidity. Conclusions: Atopic diseases fit a multimorbidity framework, with no evidence for sequential atopic march progression. The highest transition to multimorbidity was from eczema, but most children with eczema (more than three-quarters) had no comorbidities.

Project description:BackgroundAllergic diseases (eczema, wheeze and rhinitis) in children often present as heterogeneous phenotypes. Understanding genetic associations of specific patterns of symptoms might facilitate understanding of the underlying biological mechanisms.ObjectiveTo examine associations between allergic disease-related variants identified in a recent genome-wide association study and latent classes of allergic diseases (LCADs) in two population-based birth cohorts.MethodsEight previously defined LCADs between birth and 11 years: "No disease," "Atopic march," "Persistent eczema and wheeze," "Persistent eczema with later-onset rhinitis," "Persistent wheeze with later-onset rhinitis," "Transient wheeze," "Eczema only" and "Rhinitis only" were used as the study outcome. Weighted multinomial logistic regression was used to estimate associations between 135 SNPs (and a polygenic risk score, PRS) and LCADs among 6345 individuals from The Avon Longitudinal Study of Parents and Children (ALSPAC). Heterogeneity across LCADs was assessed before and after Bonferroni correction. Results were replicated in Manchester Asthma and Allergy Study (MAAS) (n = 896) and pooled in a meta-analysis.ResultsWe found strong evidence for differential genetic associations across the LCADs; pooled PRS heterogeneity P-value = 3.3 × 10-14 , excluding "no disease" class. The associations between the PRS and LCADs in MAAS were remarkably similar to ALSPAC. Two SNPs (a protein-truncating variant in FLG and a SNP within an intron of GSDMB) had evidence for differential association (pooled P-values ≤ 0.006). The FLG locus was differentially associated across LCADs that included eczema, with stronger associations for LCADs with comorbid wheeze and rhinitis. The GSDMB locus in contrast was equally associated across LCADs that included wheeze.Conclusions and clinical relevanceWe have shown complex, but distinct patterns of genetic associations with LCADs, suggesting that heterogeneous mechanisms underlie individual disease trajectories. Establishing the combination of allergic diseases with which each genetic variant is associated may inform therapeutic development and/or predictive modelling.

Project description:The occurrence of allergic multimorbidity (coexistence of asthma, allergic rhinitis and eczema) has not been evaluated longitudinally from early childhood up to adulthood in a population-based study sample. We aimed to determine the prevalence of allergic multimorbidity up to age 20 stratified by parental allergies and sex/gender using extensive prospective follow-up data from two decades of a birth cohort study.In 1990, we recruited 1314 healthy newborns from 6 maternity wards across Germany for the population-based MAS birth cohort study. The sample was purposely risk-enriched by increasing the proportion of children at high allergy risk (i.e. at least 2 allergic family members among parents and siblings) from 19% in the source population to 38% in the final sample. The remaining 62% of all MAS children had a low or no allergy risk. Symptoms, medication and doctor's diagnoses of allergic diseases have been assessed using standardized questionnaires including validated ISAAC questions in 19 follow-up assessments up to age 20. Allergic multimorbidity at each time point was defined as the coexistence of at least 2 of the following diseases in one participant: asthma, allergic rhinitis and eczema.Response at age 20 was 72% (n = 942) of all recruited participants. At age 20, 18.5% (95% CI, 15.0-22.5%) of all participants with allergic parents had 2 or 3 concurrent allergies as compared to only 6.3% (95% CI, 4.3-9.0%) of those with non-allergic parents. At this age, allergic multimorbidity was similar in women and men (12.7% (95% CI, 9.7-16.2%) vs. 11.6% (95% CI, 8.9-14.8%)), whereas single allergic diseases were slightly more common in women than men (24.2% (95% CI, 20.2-28.5%) vs. 20.1% (95% CI, 16.6-24.0%)). Asthma occurred more frequently with coexisting allergic rhinitis and/or eczema than as a single entity from pre-puberty to adulthood.Having parents with allergies is not only a strong predictor to develop any allergy, but it strongly increases the risk of developing allergic multimorbidity. In males and females alike, coexisting allergies were increasingly common throughout adolescence up to adulthood. Particularly asthma occurred in both sexes more frequently with coexisting allergies than as a single entity.

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Developmental profiles of eczema, wheeze, and rhinitis: two population-based birth cohort studies.

Publications

Developmental profiles of eczema, wheeze, and rhinitis: two population-based birth cohort studies.

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