Endotyping early childhood asthma by quantitative symptom assessment

Hans Bisgaard; Christian Bressen Pipper; Klaus Bønnelykke

doi:10.1016/j.jaci.2011.02.007

Endotyping early childhood asthma by quantitative symptom assessment

Hans Bisgaard, Christian Bressen Pipper, Klaus Bønnelykke

54 Citations (Scopus)

Abstract

Background: Asthmatic symptoms in young children reflect a heterogeneous group of diseases. Symptoms remain the primary end-point in both research and clinical management, but there is a need for standardized symptom assessment. Objective: We sought to explore endotyping of early childhood asthma by prospective daily diary recordings of globally assessed symptoms during the first 6 years of life. Methods: Globally assessed troublesome lung symptoms were recorded in daily diaries during the first 6 years of life in the Copenhagen Prospective Studies on Asthma in Childhood birth cohort born of mothers with asthma. Symptom recordings adjusted for missing values were used to categorize children based on the temporal symptom pattern. We propose an alternative approach of quantitating symptom frequency and longitudinal assessment of age-at-onset to segment children. These different methods were compared by estimating the risk from the well-established genetic risk variants of ORMDL3. Results: Six years of daily diary recordings were available in 307 children (75% of the birth cohort). We confirmed the archetypal temporal categories of transient early, persistent, and late-onset troublesome lung symptoms based on 3-year periods, finding no benefit from a finer temporal categorization of 2- or 1-year periods. Restricting categorization to symptoms during the summer improved specificity at the expense of sensitivity. Our alternative approach quantitating symptom frequency and age-at-onset exhibited a more powerful association with ORMDL3, whereas the study power was lost by restricting to doctor-verified wheeze. Conclusions: We propose a novel method for endotyping of early childhood asthma based on the frequency and age-of-onset of globally assessed troublesome lung symptoms analyzed longitudinally. This method showed the closest association with genetic variants, hence underlying molecular mechanisms and endotypes.

Original language	English
Journal	Journal of Allergy and Clinical Immunology
Volume	127
Issue number	5
Pages (from-to)	1155-1164
Number of pages	10
ISSN	0091-6749
DOIs	https://doi.org/10.1016/j.jaci.2011.02.007
Publication status	Published - May 2011

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10.1016/j.jaci.2011.02.007

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@article{d9dddddeb6ce49768fb5bfb4df9c3491,

title = "Endotyping early childhood asthma by quantitative symptom assessment",

abstract = "Background: Asthmatic symptoms in young children reflect a heterogeneous group of diseases. Symptoms remain the primary end-point in both research and clinical management, but there is a need for standardized symptom assessment. Objective: We sought to explore endotyping of early childhood asthma by prospective daily diary recordings of globally assessed symptoms during the first 6 years of life. Methods: Globally assessed troublesome lung symptoms were recorded in daily diaries during the first 6 years of life in the Copenhagen Prospective Studies on Asthma in Childhood birth cohort born of mothers with asthma. Symptom recordings adjusted for missing values were used to categorize children based on the temporal symptom pattern. We propose an alternative approach of quantitating symptom frequency and longitudinal assessment of age-at-onset to segment children. These different methods were compared by estimating the risk from the well-established genetic risk variants of ORMDL3. Results: Six years of daily diary recordings were available in 307 children (75% of the birth cohort). We confirmed the archetypal temporal categories of transient early, persistent, and late-onset troublesome lung symptoms based on 3-year periods, finding no benefit from a finer temporal categorization of 2- or 1-year periods. Restricting categorization to symptoms during the summer improved specificity at the expense of sensitivity. Our alternative approach quantitating symptom frequency and age-at-onset exhibited a more powerful association with ORMDL3, whereas the study power was lost by restricting to doctor-verified wheeze. Conclusions: We propose a novel method for endotyping of early childhood asthma based on the frequency and age-of-onset of globally assessed troublesome lung symptoms analyzed longitudinally. This method showed the closest association with genetic variants, hence underlying molecular mechanisms and endotypes.",

author = "Hans Bisgaard and Pipper, {Christian Bressen} and Klaus B{\o}nnelykke",

year = "2011",

month = may,

doi = "10.1016/j.jaci.2011.02.007",

language = "English",

volume = "127",

pages = "1155--1164",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

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number = "5",

}

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T1 - Endotyping early childhood asthma by quantitative symptom assessment

AU - Bisgaard, Hans

AU - Pipper, Christian Bressen

AU - Bønnelykke, Klaus

PY - 2011/5

Y1 - 2011/5

N2 - Background: Asthmatic symptoms in young children reflect a heterogeneous group of diseases. Symptoms remain the primary end-point in both research and clinical management, but there is a need for standardized symptom assessment. Objective: We sought to explore endotyping of early childhood asthma by prospective daily diary recordings of globally assessed symptoms during the first 6 years of life. Methods: Globally assessed troublesome lung symptoms were recorded in daily diaries during the first 6 years of life in the Copenhagen Prospective Studies on Asthma in Childhood birth cohort born of mothers with asthma. Symptom recordings adjusted for missing values were used to categorize children based on the temporal symptom pattern. We propose an alternative approach of quantitating symptom frequency and longitudinal assessment of age-at-onset to segment children. These different methods were compared by estimating the risk from the well-established genetic risk variants of ORMDL3. Results: Six years of daily diary recordings were available in 307 children (75% of the birth cohort). We confirmed the archetypal temporal categories of transient early, persistent, and late-onset troublesome lung symptoms based on 3-year periods, finding no benefit from a finer temporal categorization of 2- or 1-year periods. Restricting categorization to symptoms during the summer improved specificity at the expense of sensitivity. Our alternative approach quantitating symptom frequency and age-at-onset exhibited a more powerful association with ORMDL3, whereas the study power was lost by restricting to doctor-verified wheeze. Conclusions: We propose a novel method for endotyping of early childhood asthma based on the frequency and age-of-onset of globally assessed troublesome lung symptoms analyzed longitudinally. This method showed the closest association with genetic variants, hence underlying molecular mechanisms and endotypes.

AB - Background: Asthmatic symptoms in young children reflect a heterogeneous group of diseases. Symptoms remain the primary end-point in both research and clinical management, but there is a need for standardized symptom assessment. Objective: We sought to explore endotyping of early childhood asthma by prospective daily diary recordings of globally assessed symptoms during the first 6 years of life. Methods: Globally assessed troublesome lung symptoms were recorded in daily diaries during the first 6 years of life in the Copenhagen Prospective Studies on Asthma in Childhood birth cohort born of mothers with asthma. Symptom recordings adjusted for missing values were used to categorize children based on the temporal symptom pattern. We propose an alternative approach of quantitating symptom frequency and longitudinal assessment of age-at-onset to segment children. These different methods were compared by estimating the risk from the well-established genetic risk variants of ORMDL3. Results: Six years of daily diary recordings were available in 307 children (75% of the birth cohort). We confirmed the archetypal temporal categories of transient early, persistent, and late-onset troublesome lung symptoms based on 3-year periods, finding no benefit from a finer temporal categorization of 2- or 1-year periods. Restricting categorization to symptoms during the summer improved specificity at the expense of sensitivity. Our alternative approach quantitating symptom frequency and age-at-onset exhibited a more powerful association with ORMDL3, whereas the study power was lost by restricting to doctor-verified wheeze. Conclusions: We propose a novel method for endotyping of early childhood asthma based on the frequency and age-of-onset of globally assessed troublesome lung symptoms analyzed longitudinally. This method showed the closest association with genetic variants, hence underlying molecular mechanisms and endotypes.

U2 - 10.1016/j.jaci.2011.02.007

DO - 10.1016/j.jaci.2011.02.007

M3 - Journal article

C2 - 21439619

SN - 0091-6749

VL - 127

SP - 1155

EP - 1164

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 5

ER -

Endotyping early childhood asthma by quantitative symptom assessment

Abstract

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