Identification of atopic dermatitis subgroups in children from two longitudinal birth cohorts

Lavinia Paternoster (Lead / Corresponding author), Olga E. M. Savenije, Jon Heron, David M. Evans, Judith M. Vonk, Bert Brunekreef, Alet H. Wijga, A. John Henderson, Gerard H. Koppelman, Sara J. Brown

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    Abstract

    Background: Atopic dermatitis (AD) is a prevalent disease with variable natural history. Longitudinal birth cohort studies provide an opportunity to define subgroups based on disease trajectories, which may represent different genetic and environmental pathomechanisms.

    Objective: To investigate the existence of distinct longitudinal phenotypes of AD and test whether these findings are reproducible in two independent cohorts.

    Methods: The presence of AD was examined in two birth cohort studies including 9,894 children from the UK (ALSPAC) and 3,652 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 two cohorts. The most prevalent class was early-onset-early-resolving AD, which was associated with male gender. 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 unrecognised class of mid-onset-resolving AD, not associated with FLG mutations, but strongly associated with asthma, was identified.

    Conclusion: Six classes based on temporal trajectories of rash were consistently identified in two population-based cohorts. The differing risk factor profiles and diverse prognoses demonstrate the potential importance of a stratified medicine approach for AD.

    Clinical Implications: Atopic dermatitis ranges from a transient condition to lifelong morbidity. This study has identified distinct subphenotypes of atopic dermatitis in children, which could indicate the importance of a stratified approach to management of this complex disease.

    Original languageEnglish
    Pages (from-to)964-971
    Number of pages8
    JournalJournal of Allergy and Clinical Immunology
    Volume141
    Issue number3
    Early online date9 Nov 2017
    DOIs
    Publication statusPublished - Mar 2018

    Fingerprint

    Atopic Dermatitis
    Parturition
    Exanthema
    Cohort Studies
    Mutation
    Disease Management
    Natural History
    Netherlands
    Comorbidity
    Asthma

    Keywords

    • Atopic dermatitis
    • Eczema
    • Environmental
    • Genetic
    • Latent class analysis
    • PIAMA
    • ALSPAC

    Cite this

    Paternoster, Lavinia ; Savenije, Olga E. M. ; Heron, Jon ; Evans, David M. ; Vonk, Judith M. ; Brunekreef, Bert ; Wijga, Alet H. ; Henderson, A. John ; Koppelman, Gerard H. ; Brown, Sara J. / Identification of atopic dermatitis subgroups in children from two longitudinal birth cohorts. In: Journal of Allergy and Clinical Immunology. 2018 ; Vol. 141, No. 3. pp. 964-971.
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    title = "Identification of atopic dermatitis subgroups in children from two 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 based on disease trajectories, which may represent different genetic and environmental pathomechanisms.Objective: To investigate the existence of distinct longitudinal phenotypes of AD and test whether these findings are reproducible in two independent cohorts.Methods: The presence of AD was examined in two birth cohort studies including 9,894 children from the UK (ALSPAC) and 3,652 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 two cohorts. The most prevalent class was early-onset-early-resolving AD, which was associated with male gender. 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 unrecognised class of mid-onset-resolving AD, not associated with FLG mutations, but strongly associated with asthma, was identified.Conclusion: Six classes based on temporal trajectories of rash were consistently identified in two population-based cohorts. The differing risk factor profiles and diverse prognoses demonstrate the potential importance of a stratified medicine approach for AD.Clinical Implications: Atopic dermatitis ranges from a transient condition to lifelong morbidity. This study has identified distinct subphenotypes of atopic dermatitis in children, which could indicate the importance of a stratified approach to management of this complex disease.",
    keywords = "Atopic dermatitis, Eczema, Environmental, Genetic, Latent class analysis, PIAMA, ALSPAC",
    author = "Lavinia Paternoster and Savenije, {Olga E. M.} and Jon Heron and Evans, {David M.} and Vonk, {Judith M.} and Bert Brunekreef and Wijga, {Alet H.} and Henderson, {A. John} and Koppelman, {Gerard H.} and Brown, {Sara J.}",
    note = "This work and LP were supported by a UK Medical Research Council Fellowship (MR/J012165/1). LP & DME work in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol which is supported by the Medical Research Council and the University of Bristol (MC_UU_12013/4). DME is supported by an Australian Research Council Future Fellowship (FT130101709). SJB holds a Wellcome Trust Senior Research Fellowship in Clinical Science (106865/Z/15/Z). The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. The PIAMA birth cohort was funded by the Netherlands Organization for Health Research and Development, the Netherlands Organization for Scientific Research, the Lung Function of the Netherlands, the Netherlands Ministry of Spatial Planning, Housing, and the Environment, and the Netherlands Ministry of Health, Welfare, and Sport.",
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    Paternoster, L, Savenije, OEM, Heron, J, Evans, DM, Vonk, JM, Brunekreef, B, Wijga, AH, Henderson, AJ, Koppelman, GH & Brown, SJ 2018, 'Identification of atopic dermatitis subgroups in children from two longitudinal birth cohorts', Journal of Allergy and Clinical Immunology, vol. 141, no. 3, pp. 964-971. https://doi.org/10.1016/j.jaci.2017.09.044

    Identification of atopic dermatitis subgroups in children from two longitudinal birth cohorts. / Paternoster, Lavinia (Lead / Corresponding author); Savenije, Olga E. M.; Heron, Jon; Evans, David M.; Vonk, Judith M.; Brunekreef, Bert; Wijga, Alet H.; Henderson, A. John; Koppelman, Gerard H.; Brown, Sara J.

    In: Journal of Allergy and Clinical Immunology, Vol. 141, No. 3, 03.2018, p. 964-971.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Identification of atopic dermatitis subgroups in children from two longitudinal birth cohorts

    AU - Paternoster, Lavinia

    AU - Savenije, Olga E. M.

    AU - Heron, Jon

    AU - Evans, David M.

    AU - Vonk, Judith M.

    AU - Brunekreef, Bert

    AU - Wijga, Alet H.

    AU - Henderson, A. John

    AU - Koppelman, Gerard H.

    AU - Brown, Sara J.

    N1 - This work and LP were supported by a UK Medical Research Council Fellowship (MR/J012165/1). LP & DME work in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol which is supported by the Medical Research Council and the University of Bristol (MC_UU_12013/4). DME is supported by an Australian Research Council Future Fellowship (FT130101709). SJB holds a Wellcome Trust Senior Research Fellowship in Clinical Science (106865/Z/15/Z). The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. The PIAMA birth cohort was funded by the Netherlands Organization for Health Research and Development, the Netherlands Organization for Scientific Research, the Lung Function of the Netherlands, the Netherlands Ministry of Spatial Planning, Housing, and the Environment, and the Netherlands Ministry of Health, Welfare, and Sport.

    PY - 2018/3

    Y1 - 2018/3

    N2 - Background: Atopic dermatitis (AD) is a prevalent disease with variable natural history. Longitudinal birth cohort studies provide an opportunity to define subgroups based on disease trajectories, which may represent different genetic and environmental pathomechanisms.Objective: To investigate the existence of distinct longitudinal phenotypes of AD and test whether these findings are reproducible in two independent cohorts.Methods: The presence of AD was examined in two birth cohort studies including 9,894 children from the UK (ALSPAC) and 3,652 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 two cohorts. The most prevalent class was early-onset-early-resolving AD, which was associated with male gender. 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 unrecognised class of mid-onset-resolving AD, not associated with FLG mutations, but strongly associated with asthma, was identified.Conclusion: Six classes based on temporal trajectories of rash were consistently identified in two population-based cohorts. The differing risk factor profiles and diverse prognoses demonstrate the potential importance of a stratified medicine approach for AD.Clinical Implications: Atopic dermatitis ranges from a transient condition to lifelong morbidity. This study has identified distinct subphenotypes of atopic dermatitis in children, which could indicate the importance of a stratified approach to management of this complex disease.

    AB - Background: Atopic dermatitis (AD) is a prevalent disease with variable natural history. Longitudinal birth cohort studies provide an opportunity to define subgroups based on disease trajectories, which may represent different genetic and environmental pathomechanisms.Objective: To investigate the existence of distinct longitudinal phenotypes of AD and test whether these findings are reproducible in two independent cohorts.Methods: The presence of AD was examined in two birth cohort studies including 9,894 children from the UK (ALSPAC) and 3,652 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 two cohorts. The most prevalent class was early-onset-early-resolving AD, which was associated with male gender. 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 unrecognised class of mid-onset-resolving AD, not associated with FLG mutations, but strongly associated with asthma, was identified.Conclusion: Six classes based on temporal trajectories of rash were consistently identified in two population-based cohorts. The differing risk factor profiles and diverse prognoses demonstrate the potential importance of a stratified medicine approach for AD.Clinical Implications: Atopic dermatitis ranges from a transient condition to lifelong morbidity. This study has identified distinct subphenotypes of atopic dermatitis in children, which could indicate the importance of a stratified approach to management of this complex disease.

    KW - Atopic dermatitis

    KW - Eczema

    KW - Environmental

    KW - Genetic

    KW - Latent class analysis

    KW - PIAMA

    KW - ALSPAC

    U2 - 10.1016/j.jaci.2017.09.044

    DO - 10.1016/j.jaci.2017.09.044

    M3 - Article

    VL - 141

    SP - 964

    EP - 971

    JO - Journal of Allergy and Clinical Immunology

    JF - Journal of Allergy and Clinical Immunology

    SN - 0091-6749

    IS - 3

    ER -