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

Lavinia Paternoster; 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

doi:10.1016/j.jaci.2017.09.044

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

Lavinia Paternoster, 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 language	English
Number of pages	8
Journal	Journal of Allergy and Clinical Immunology
Early online date	10 Nov 2017
DOIs	https://doi.org/10.1016/j.jaci.2017.09.044
Publication status	E-pub ahead of print - 10 Nov 2017

Bibliographical note

JACI Editor's choice
IEC top 10 research articles published in 2017

Keywords

Atopic dermatitis
eczema
environmental
genetic
latent class analysis
PIAMA
ALSPAC

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MRC UoB UNITE Unit - programme 4
Davey Smith, G. & Evans, D.
1/06/13 → 1/04/18
Project: Research
MRC Population Health Scientist Fellowship
Paternoster, L.
1/10/12 → 1/10/16
Project: Research

Dr Lavinia Paternoster
- lavinia.paternosterbristol.acuk
- Bristol Medical School (PHS) - Associate Professor in Genetic Epidemiology
- Bristol Population Health Science Institute
- MRC Integrative Epidemiology Unit
Person: Academic , Member

Cite this

@article{098ea470c7244c70bef39ae0973c28d3,

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 = "JACI Editor's choice IEC top 10 research articles published in 2017",

year = "2017",

month = nov,

day = "10",

doi = "10.1016/j.jaci.2017.09.044",

language = "English",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

}

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 - JACI Editor's choice IEC top 10 research articles published in 2017

PY - 2017/11/10

Y1 - 2017/11/10

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 (Academic Journal)

C2 - 29129583

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

ER -

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

Abstract

Bibliographical note

Keywords

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Projects

MRC UoB UNITE Unit - programme 4

MRC Population Health Scientist Fellowship

Profiles

Dr Lavinia Paternoster

Cite this