Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts.
- Hose AJ Dr von Hauner Children's Hospital, LMU Munich, Munich, Germany. Electronic address: Alexander.Hose@med.uni-muenchen.de.
- Depner M Dr von Hauner Children's Hospital, LMU Munich, Munich, Germany.
- Illi S Dr von Hauner Children's Hospital, LMU Munich, Munich, Germany.
- Lau S Department for Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
- Keil T Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, Berlin, Germany; Institute for Clinical Epidemiology and Biometry, University of Wuerzburg, Wuerzburg, Germany.
- Wahn U Department for Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
- Fuchs O 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.
- Pfefferle PI 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.
- Schmaußer-Hechfellner E Dr von Hauner Children's Hospital, LMU Munich, Munich, Germany.
- Genuneit J Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
- Lauener R Christine Kühne Center for Allergy Research and Education (CK-CARE), Davos, Switzerland; Children's Hospital of Eastern Switzerland, St Gallen, Switzerland.
- Karvonen AM Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland.
- Roduit C Christine Kühne Center for Allergy Research and Education (CK-CARE), Davos, Switzerland; Children's Hospital, University of Zürich, Zürich, Switzerland.
- Dalphin JC Department of Respiratory Disease, University of Besançon, UMR/CNRS6249 Chrono-environment, University Hospital, Besançon, France.
- Riedler J Children's Hospital Schwarzach, and the Teaching Hospital of Paracelsus Medical Private University Salzburg, Salzburg, Austria.
- Pekkanen J Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland.
- von Mutius E 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.
- Ege MJ 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.
- 2016-10-25
Published in:
- The Journal of allergy and clinical immunology. - 2017
Atopy
IgE
asthma
atopic diseases
cytokines
epidemiology
latent class analysis
lung function
path analysis
sensitization
severe atopy
unsupervised clustering
Allergens
Child
Child, Preschool
Cohort Studies
Cytokines
Female
Forced Expiratory Volume
Humans
Hypersensitivity
Immunoglobulin E
Infant
Male
Phenotype
English
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.
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.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1016/j.jaci.2016.08.046
- PMID 27771325
- Persistent URL
- https://sonar.ch/global/documents/155439
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