title: Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts.
abstract: BACKGROUND
  Phenotypes of childhood-onset asthma are characterized by distinct trajectories and functional features. For atopy, definition of phenotypes during childhood is less clear.
  
  
  OBJECTIVE
  We sought to define phenotypes of atopic sensitization over the first 6 years of life using a latent class analysis (LCA) integrating 3 dimensions of atopy: allergen specificity, time course, and levels of specific IgE (sIgE).
  
  
  METHODS
  Phenotypes were defined by means of LCA in 680 children of the Multizentrische Allergiestudie (MAS) and 766 children of the Protection against allergy: Study in Rural Environments (PASTURE) birth cohorts and compared with classical nondisjunctive definitions of seasonal, perennial, and food sensitization with respect to atopic diseases and lung function. Cytokine levels were measured in the PASTURE cohort.
  
  
  RESULTS
  The LCA classified predominantly by type and multiplicity of sensitization (food vs inhalant), allergen combinations, and sIgE levels. Latent classes were related to atopic disease manifestations with higher sensitivity and specificity than the classical definitions. LCA detected consistently in both cohorts a distinct group of children with severe atopy characterized by high seasonal sIgE levels and a strong propensity for asthma; hay fever; eczema; and impaired lung function, also in children without an established asthma diagnosis. Severe atopy was associated with an increased IL-5/IFN-γ ratio. A path analysis among sensitized children revealed that among all features of severe atopy, only excessive sIgE production early in life affected asthma risk.
  
  
  CONCLUSIONS
  LCA revealed a set of benign, symptomatic, and severe atopy phenotypes. The severe phenotype emerged as a latent condition with signs of a dysbalanced immune response. It determined high asthma risk through excessive sIgE production and directly affected impaired lung function.
authors: Dr von Hauner Children's Hospital, LMU Munich, Munich, Germany. Electronic address: Alexander.Hose@med.uni-muenchen.de.
authors: Alexander J
authors: AJ
authors: Hose
authors: Dr von Hauner Children's Hospital, LMU Munich, Munich, Germany.
authors: Martin
authors: M
authors: Depner
authors: Dr von Hauner Children's Hospital, LMU Munich, Munich, Germany.
authors: Sabina
authors: S
authors: Illi
authors: Department for Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Susanne
authors: S
authors: Lau
authors: Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, Berlin, Germany; Institute for Clinical Epidemiology and Biometry, University of Wuerzburg, Wuerzburg, Germany.
authors: Thomas
authors: T
authors: Keil
authors: Department for Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Ulrich
authors: U
authors: Wahn
authors: Dr von Hauner Children's Hospital, LMU Munich, and the Comprehensive Pneumology Center, Munich (CPC-M), Germany (Member of the German Center for Lung Research [DZL]), Munich, Germany; Division of Respiratory Medicine, Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland; University Children's Hospital (UKBB), University of Basel, Basel, Switzerland.
authors: Oliver
authors: O
authors: Fuchs
authors: Comprehensive Biomaterial Bank Marburg CBBM, Fachbereich Medizin der Philipps Universität Marburg, Zentrum für Tumor und Immunbiologie ZTI Marburg (Member of the German Center for Lung Research), Marburg, Germany.
authors: Petra Ina
authors: PI
authors: Pfefferle
authors: Dr von Hauner Children's Hospital, LMU Munich, Munich, Germany.
authors: Elisabeth
authors: E
authors: Schmaußer-Hechfellner
authors: Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
authors: Jon
authors: J
authors: Genuneit
authors: Christine Kühne Center for Allergy Research and Education (CK-CARE), Davos, Switzerland; Children's Hospital of Eastern Switzerland, St Gallen, Switzerland.
authors: Roger
authors: R
authors: Lauener
authors: Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland.
authors: Anne M
authors: AM
authors: Karvonen
authors: Christine Kühne Center for Allergy Research and Education (CK-CARE), Davos, Switzerland; Children's Hospital, University of Zürich, Zürich, Switzerland.
authors: Caroline
authors: C
authors: Roduit
authors: Department of Respiratory Disease, University of Besançon, UMR/CNRS6249 Chrono-environment, University Hospital, Besançon, France.
authors: Jean-Charles
authors: JC
authors: Dalphin
authors: Children's Hospital Schwarzach, and the Teaching Hospital of Paracelsus Medical Private University Salzburg, Salzburg, Austria.
authors: Josef
authors: J
authors: Riedler
authors: Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland.
authors: Juha
authors: J
authors: Pekkanen
authors: Dr von Hauner Children's Hospital, LMU Munich, and the Comprehensive Pneumology Center, Munich (CPC-M), Germany (Member of the German Center for Lung Research [DZL]), Munich, Germany.
authors: Erika
authors: E
authors: von Mutius
authors: Dr von Hauner Children's Hospital, LMU Munich, and the Comprehensive Pneumology Center, Munich (CPC-M), Germany (Member of the German Center for Lung Research [DZL]), Munich, Germany.
authors: Markus J
authors: MJ
authors: Ege
mesh_terms: D000485:Allergens / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007223:Infant; D008297:Male; D010641:Phenotype
chemical_list: D000485:Allergens; D016207:Cytokines; D007073:Immunoglobulin E
keywords: Atopy; IgE; asthma; atopic diseases; cytokines; epidemiology; latent class analysis; lung function; path analysis; sensitization; severe atopy; unsupervised clustering