Latent class analysis reveals clinically relevant atopy phenotypes in two birth cohorts

Publication date: Available online 19 October 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Alexander J. Hose, Martin Depner, Sabina Illi, Susanne Lau, Thomas Keil, Ulrich Wahn, Oliver Fuchs, Petra Ina Pfefferle, Elisabeth Schmaußer-Hechfellner, Jon Genuneit, Roger Lauener, Anne M. Karvonen, Caroline Roduit, Jean-Charles Dalphin, Josef Riedler, Juha Pekkanen, Erika von Mutius, Markus J. Ege, Carl Peter Bauer, Johannes Forster, Fred Zepp, Volker Wahn, Antje Schuster, Renate L. Bergmann, Karl E. Bergmann, Andreas Reich, Linus Grabenhenrich, Bianca Schaub, Georg J. Loss, Harald Renz, Michael Kabesch, Marjut Roponen, Anne Hyvärinen, Pekka Tiittanen, Sami Remes, Charlotte Braun-Fahrländer, Remo Frei, Vincent Kaulek, Marie-Laure Dalphin, Gert Doekes, Nicole Blümer, Urs Frey
BackgroundPhenotypes of childhood-onset asthma are characterized by distinct trajectories and functional features. For atopy, definition of phenotypes during childhood is less clear.ObjectiveTo define phenotypes of atopic sensitization over the first 6 years of life by a latent class analysis (LCA) integrating three dimensions of atopy: allergen specificity, time course, and levels of specific IgE.MethodsPhenotypes were defined by LCA in 680 children of the MAS and 766 of the PASTURE birth cohorts and compared to classical non-disjunctive definitions of seasonal, perennial, and food sensitization with respect to atopic diseases and lung function. Cytokine levels were measured in PASTURE.ResultsThe LCA classified predominantly by type and multiplicity of sensitization (food versus 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 in both cohorts consistently a distinct group of children with severe atopy characterized by high seasonal sIgE and a strong propensity for asthma, hay fever, eczema and impaired lung function even in children without an established asthma diagnosis. Severe atopy was associated with an elevated interleukin-5/interferon-gamma ratio. A path analysis among sensitized children revealed that among all features of severe atopy only excessive sIgE production early in life impacted on asthma risk.ConclusionsLCA 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 via excessive sIgE production and directly impacted on impaired lung function.

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Teaser

Atopic sensitization was classified with respect to disease relevance in three phenotypes of benign, symptomatic, and severe atopy, which impacted on asthma risk via excessive production of specific IgE early in life and on poor lung function.


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