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Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts.

ABSTRACT: BACKGROUND:Atopic dermatitis (AD) is a prevalent disease with variable natural history. Longitudinal birth cohort studies provide an opportunity to define subgroups on the basis of disease trajectories, which may represent different genetic and environmental pathomechanisms. OBJECTIVES:We sought to investigate the existence of distinct longitudinal phenotypes of AD and test whether these findings are reproducible in 2 independent cohorts. METHODS:The presence of AD was examined in 2 birth cohort studies including 9894 children from the United Kingdom (ALSPAC) and 3652 from the Netherlands (PIAMA). AD was defined by parental report of a typical itchy and/or flexural rash. Longitudinal latent class analysis was used to investigate patterns of AD from birth to the age of 11 to 16 years. We investigated associations with known AD risk factors, including FLG null mutations, 23 other established AD-genetic risk variants, and atopic comorbidity. RESULTS:Six latent classes were identified, representing subphenotypes of AD, with remarkable consistency between the 2 cohorts. The most prevalent class was early-onset-early-resolving AD, which was associated with male sex. Two classes of persistent disease were identified (early-onset-persistent and early-onset-late-resolving); these were most strongly associated with the AD-genetic risk score as well as personal and parental history of atopic disease. A yet unrecognized class of mid-onset-resolving AD, not associated with FLG mutations, but strongly associated with asthma, was identified. CONCLUSIONS:Six classes based on temporal trajectories of rash were consistently identified in 2 population-based cohorts. The differing risk factor profiles and diverse prognoses demonstrate the potential importance of a stratified medicine approach for AD.

SUBMITTER: Paternoster L

PROVIDER: S-EPMC5840507 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts.

Paternoster Lavinia L Savenije Olga E M OEM Heron Jon J Evans David M DM Vonk Judith M JM Brunekreef Bert B Wijga Alet H AH Henderson A John AJ Koppelman Gerard H GH Brown Sara J SJ

The Journal of allergy and clinical immunology 20171110 3

<h4>Background</h4>Atopic dermatitis (AD) is a prevalent disease with variable natural history. Longitudinal birth cohort studies provide an opportunity to define subgroups on the basis of disease trajectories, which may represent different genetic and environmental pathomechanisms.<h4>Objectives</h4>We sought to investigate the existence of distinct longitudinal phenotypes of AD and test whether these findings are reproducible in 2 independent cohorts.<h4>Methods</h4>The presence of AD was exam ...[more]

PMID: 29129583

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Project description:PurposeEvidence supporting a link between indoor formaldehyde exposure and atopic dermatitis (AD) in humans is limited. The purpose of this longitudinal study was to investigate whether AD symptoms in children could be affected by indoor formaldehyde levels in ordinary households.MethodsFifty-five children with moderate-to-severe AD aged under 18 years were enrolled as a panel. They were followed up from February 2019 through February 2020. Indoor formaldehyde levels of patients' houses and their AD symptoms were repeatedly measured on a daily basis. The generalized linear mixed model was utilized for statistical analysis. Subdivision analysis was performed by stratifying patients by sex, body mass index, presence of parental allergy, and indoor environments including mold/dampness, temperature, and relative humidity (RH).ResultsA total of 4,789 person-days of AD symptom data were collected. The average concentration of formaldehyde was 13.6 ± 16.4 ppb, with the highest value found in spring (18.1 ± 20.6 ppb). Higher levels of formaldehyde were observed when there was parental smoking, increased indoor temperature over 25.5°C, or RH over 60% (P < 0.0001). When the effect size was compared between each season after controlling for ambient particulate matter, temperature, and RH, an increase in 10 ppb of formaldehyde increased AD symptoms by 79.2% (95% confidence interval [CI], 19.6-168.4) in spring and by 39.9% (95% CI, 14.3-71.2) in summer. AD symptoms in children aged 6-18 years appeared to increase significantly, whereas there was no significant increase in children under 6 years. When indoor temperature was over 25.5°C, an increase in formaldehyde by 10 ppb increased AD symptoms by 17.8% (95% CI, 3.9-33.6).ConclusionsIndoor formaldehyde can exacerbate AD symptom in children with moderate-to-severe AD, particularly in spring and summer, even at allowable levels. Thus, minimizing exposure to indoor formaldehyde may be needed for the proper management of AD in children.

Project description:BackgroundLongitudinal modelling of the presence/absence of current eczema through childhood has identified similar phenotypes, but their characteristics often differ between studies.ObjectivesTo demonstrate that a more comprehensive description of longitudinal pattern of symptoms may better describe trajectories than binary information on eczema presence.MethodsWe derived six multidimensional variables of eczema spells from birth to 18 years of age (including duration, temporal sequencing and the extent of persistence/recurrence). Spells were defined as consecutive observations of eczema separated by no eczema across 5 epochs in five birth cohorts: infancy (first year); early childhood (age 2-3 years); preschool/early school age (4-5 years); middle childhood (8-10 years); adolescence (14-18 years). We applied Partitioning Around Medoids clustering on these variables to derive clusters of the temporal patterns of eczema. We then investigated the stability of the clusters, within-cluster homogeneity and associated risk factors, including FLG mutations.ResultsAnalysis of 7464 participants with complete data identified five clusters: (i) no eczema (51.0%); (ii) early transient eczema (21.6%); (iii) late-onset eczema (LOE; 8.1%); (iv) intermittent eczema (INT; 7.5%); and (v) persistent eczema (PE; 11.8%). There was very-high agreement between the assignment of individual children into clusters when using complete or imputed (n = 15 848) data (adjusted Rand index = 0.99; i.e. the clusters were very stable). Within-individual symptom patterns across clusters confirmed within-cluster homogeneity, with consistent patterns of symptoms among participants within each cluster and no overlap between the clusters. Clusters were characterized by differences in associations with risk factors (e.g. parental eczema was associated with all clusters apart from LOE; sensitization to inhalant allergens was associated with all clusters, with the highest risk in the PE cluster). All clusters apart from LOE were associated with FLG mutations. Of note, the strongest association was for PE [relative risk ratio (RRR) 2.70, 95% confidence interval (CI) 2.24-3.26; P < 0.001] followed by INT (RRR 2.29, 95% CI 1.82-2.88; P < 0.001).ConclusionsClustering of multidimensional variables identified stable clusters with different genetic architectures. Using multidimensional variables may capture eczema development and derive stable and internally homogeneous clusters. However, deriving homogeneous symptom clusters does not necessarily mean that these are underpinned by completely unique mechanisms.

Dataset Information

Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts.

Publications

Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts.

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