title: Clinical and epidemiologic phenotypes of childhood asthma.
abstract: BACKGROUND
  Clinical and epidemiologic approaches have identified two distinct sets of classifications for asthma and wheeze phenotypes.
  
  
  OBJECTIVE
  To compare epidemiologic phenotype definitions identified by latent class analysis (LCA) with clinical phenotypes based on patient histories, diagnostic work-up, and treatment responses. To relate phenotypes to genetic and environmental determinants as well as diagnostic and treatment-related parameters.
  
  
  METHODS
  LCA was performed in an international multicenter birth cohort based on yearly questions about current wheeze until age 6 years. Associations of wheeze classes and clinical phenotypes with asthma-related characteristics such as atopy, lung function, fraction of exhaled nitric oxide, and medication use were calculated using regression models.
  
  
  RESULTS
  LCA identified five classes, which verified the clinically defined wheeze phenotypes with high sensitivity and specificity; the respective receiver operating characteristics curves displayed an area under the curve ranging from 84% (frequent wheeze) to 85% (asthma diagnosis) and 87% (unremitting wheeze) to 97% (recurrent unremitting wheeze). Recurrent unremitting wheeze was the most specific and unremitting wheeze at least once the most sensitive definition. The latter identified a subgroup of children with decreased lung function, increased genetic risk, and in utero smoke exposure (ODDS RATIO, 2.03; 95% CONFIDENCE INTERVAL, 1.12-3.68; P = 0.0191), but without established asthma diagnosis and treatment.
  
  
  CONCLUSIONS
  Clinical phenotypes were well supported by LCA analysis. The hypothesis-free LCA phenotypes were a useful reference for comparing clinical phenotypes. Thereby, we identified children with clinically conspicuous but undiagnosed disease. Because of their high area under the curve values, clinical phenotypes such as (recurrent) unremitting wheeze emerged as promising alternative asthma definitions for epidemiologic studies.
authors.affiliation: 1 Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Depner
authors.forename: Oliver
authors.initials: O
authors.lastname: Fuchs
authors.forename: Jon
authors.initials: J
authors.lastname: Genuneit
authors.forename: Anne M
authors.initials: AM
authors.lastname: Karvonen
authors.forename: Anne
authors.initials: A
authors.lastname: Hyvärinen
authors.forename: Vincent
authors.initials: V
authors.lastname: Kaulek
authors.forename: Caroline
authors.initials: C
authors.lastname: Roduit
authors.forename: Juliane
authors.initials: J
authors.lastname: Weber
authors.forename: Bianca
authors.initials: B
authors.lastname: Schaub
authors.forename: Roger
authors.initials: R
authors.lastname: Lauener
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
authors.forename: Petra Ina
authors.initials: PI
authors.lastname: Pfefferle
authors.forename: Urs
authors.initials: U
authors.lastname: Frey
authors.forename: Juha
authors.initials: J
authors.lastname: Pekkanen
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Dalphin
authors.forename: Josef
authors.initials: J
authors.lastname: Riedler
authors.forename: Charlotte
authors.initials: C
authors.lastname: Braun-Fahrländer
authors.forename: Erika
authors.initials: E
authors.lastname: von Mutius
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Ege
mesh_terms: D000383:Agriculture; D001249:Asthma / Q000175:diagnosis* / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004781:Environmental Exposure / Q000009:adverse effects; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D015995:Prevalence; D011446:Prospective Studies; D012044:Regression Analysis; D012135:Respiratory Sounds; D012307:Risk Factors; D012680:Sensitivity and Specificity