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J Allergy Clin Immunol. 2017 Jun;139(6):1935-1945.e12. doi: 10.1016/j.jaci.2016.08.046. Epub 2016 Oct 19.

Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts.

Author information

1
Dr von Hauner Children's Hospital, LMU Munich, Munich, Germany. Electronic address: Alexander.Hose@med.uni-muenchen.de.
2
Dr von Hauner Children's Hospital, LMU Munich, Munich, Germany.
3
Department for Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
4
Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, Berlin, Germany; Institute for Clinical Epidemiology and Biometry, University of Wuerzburg, Wuerzburg, Germany.
5
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.
6
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.
7
Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
8
Christine Kühne Center for Allergy Research and Education (CK-CARE), Davos, Switzerland; Children's Hospital of Eastern Switzerland, St Gallen, Switzerland.
9
Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland.
10
Christine Kühne Center for Allergy Research and Education (CK-CARE), Davos, Switzerland; Children's Hospital, University of Zürich, Zürich, Switzerland.
11
Department of Respiratory Disease, University of Besançon, UMR/CNRS6249 Chrono-environment, University Hospital, Besançon, France.
12
Children's Hospital Schwarzach, and the Teaching Hospital of Paracelsus Medical Private University Salzburg, Salzburg, Austria.
13
Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland.
14
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.
15
Department of Pediatrics, Technical University of Munich, Munich, Germany.
16
Department of Paediatrics, St Josefs Hospital, Freiburg, Germany.
17
Centre for Paediatric and Adolescent Medicine, University Medical Centre Mainz, Mainz, Germany.
18
University Children's Hospital, Charité, Berlin, Germany.
19
Department of Paediatrics, University Medical Centre Düsseldorf, Düsseldorf, Germany.
20
Department of Obstetrics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
21
Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
22
Dr von Hauner Children's Hospital, LMU Munich, Munich, Germany; Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, Calif.
23
Department of Clinical Chemistry and Molecular Diagnostics, Philipps University of Marburg (Member of the German Center for Lung Research), Marburg, Germany.
24
Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, Calif; Clinic for Pediatric Pneumology and Neonatology, Hannover Medical School, Hannover, Germany.
25
Department of Environmental Science, Inhalation Toxicology Laboratory, University of Eastern Finland, Kuopio, Finland.
26
Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland.
27
Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
28
Christine Kühne Center for Allergy Research and Education (CK-CARE), Davos, Switzerland; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
29
Department of Pediatrics, University of Besançon, University Hospital, Besançon, France.
30
Institute for Risk Assessment Sciences (IRAS), Division of Environmental Epidemiology, Utrecht University, Utrecht, The Netherlands.
31
Department of Clinical Chemistry and Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany.
32
University Children's Hospital (UKBB), University of Basel, Basel, Switzerland.

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.

KEYWORDS:

Atopy; IgE; asthma; atopic diseases; cytokines; epidemiology; latent class analysis; lung function; path analysis; sensitization; severe atopy; unsupervised clustering

PMID:
27771325
DOI:
10.1016/j.jaci.2016.08.046
[Indexed for MEDLINE]

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