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.
authors: Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen, Gentofte, Copenhagen, Denmark. Bisgaard@copsac.com
authors: Hans
authors: H
authors: Bisgaard
authors: Christian Bressen
authors: CB
authors: Pipper
authors: Klaus
authors: K
authors: Bønnelykke
mesh_terms: D017668:Age of Onset; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D011446:Prospective Studies; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires
chemical_list: D018927:Anti-Asthmatic Agents; D008565:Membrane Proteins; C464399:ORMDL3 protein, human