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Author Bisgaard, H.; Pipper, C.B.; Bonnelykke, K. url  doi
openurl 
  Title Endotyping early childhood asthma by quantitative symptom assessment Type Journal Article
  Year (down) 2011 Publication The Journal of Allergy and Clinical Immunology Abbreviated Journal J Allergy Clin Immunol  
  Volume 127 Issue 5 Pages 1155-64.e2  
  Keywords Age of Onset; Anti-Asthmatic Agents/therapeutic use; Asthma/*diagnosis/drug therapy/genetics/*physiopathology; Child; Child, Preschool; Cohort Studies; Genetic Variation; Humans; Infant; Infant, Newborn; Longitudinal Studies; Membrane Proteins/*genetics/metabolism; Prospective Studies; Severity of Illness Index; Surveys and Questionnaires  
  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.  
  Address Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen, Gentofte, Copenhagen, Denmark. Bisgaard@copsac.com  
  Corporate Author Thesis  
  Impact Factor 11,476 First Author Bisgaard, H. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Bonnelykke, K.  
  ISSN 0091-6749 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:21439619 Approved no  
  Call Number Serial 62  
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