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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:139

Article

Hose, Alexander J.¹  Depner, Martin¹  Illi, Sabina¹  Lau, Susanne²  Keil, Thomas⁵  Wahn, Ulrich²  Fuchs, Oliver^1,6,7,8,9  Pfefferle, Petra Ina^10,11  Schmausser-Hechfellner, Elisabeth¹  Genuneit, Jon¹²  Lauener, Roger^13,14  Karvonen, Anne M.¹⁵  Roduit, Caroline^13,16  Dalphin, Jean-Charles¹⁷  Riedler, Josef^18,19  Pekkanen, Juha^15,20  von Mutius, Erika^1,6,7  Ege, Markus J.^1,6,7  Bauer, Carl Peter²¹  Forster, Johannes²²  Zepp, Fred²³  Wahn, Volker²⁴  Schuster, Antje²⁵  Bergmann, Renate L.⁴  Bergmann, Karl E.⁴  Reich, Andreas³  Grabenhenrich, Linus³  Loss, Georg J.^1,26  Kabesch, Michael^28,29  Roponen, Marjut³⁰  Remes, Sami³¹  Braun-Fahrlander, Charlotte^32,33  Dalphin, Marie-Laure³⁴  Doekes, Gert³⁵  Blumer, Nicole²⁷ 

[1] Ludwig Maximilians Univ Munchen, Dr von Hauner Childrens Hosp, Lindwurmstr 4, D-80337 Munich, Germany

[2] Charite Univ Med Berlin, Dept Pediat Pneumol & Immunol, Berlin, Germany

[3] Charite Univ Med Berlin, Inst Social Med Epidemiol & Hlth Econ, Berlin, Germany

[4] Charite Univ Med Berlin, Dept Obstet, Berlin, Germany

[5] Univ Wurzburg, Inst Clin Epidemiol & Biometry, Wurzburg, Germany

[6] CPC M, Munich, Germany

[7] German Ctr Lung Res DZL, Munich, Germany

[8] Univ Bern, Inselspital, Dept Pediat, Div Resp Med, Bern, Switzerland

[9] Univ Basel, Univ Childrens Hosp UKBB, Basel, Switzerland

[10] Philipps Univ Marburg, CBBM, Fachbereich Med, Zentrum Tumor & Immunbiol ZTI Marburg, Marburg, Germany

[11] German Ctr Lung Res, Marburg, Germany

[12] Ulm Univ, Inst Epidemiol & Med Biometry, Ulm, Germany

[13] CK CARE, Davos, Switzerland

[14] Childrens Hosp Eastern Switzerland, St Gallen, Switzerland

[15] Natl Inst Hlth & Welf, Dept Hlth Protect, Kuopio, Finland

[16] Univ Zurich, Childrens Hosp, Zurich, Switzerland

[17] Univ Besancon, Dept Resp Dis, Univ Hosp, UMR Chronoenvironm CNRS6249, Besancon, France

[18] Childrens Hosp Schwarzach, Schwarzach, Austria

[19] Paracelsus Med Private Univ Salzburg, Teaching Hosp, Salzburg, Austria

[20] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland

[21] Tech Univ Munich, Dept Pediat, Munich, Germany

[22] St Josefs Hosp, Dept Paediat, Freiburg, Germany

[23] Univ Med Ctr Mainz, Ctr Paediat & Adolescent Med, Mainz, Germany

[24] Charite, Univ Childrens Hosp, Berlin, Germany

[25] Univ Med Ctr Dusseldorf, Dept Paediat, Dusseldorf, Germany

[26] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA

[27] Philipps Univ Marburg, Dept Clin Chem & Mol Diagnost, Marburg, Germany

[28] KUNO Childrens Univ Hosp Regensburg, Dept Pediat Pneumol & Allergy, Campus St Hedwig, Regensburg, Germany

[29] Hannover Med Sch, Clin Pediat Pneumol & Neonatol, Hannover, Germany

[30] Univ Eastern Finland, Inhalat Toxicol Lab, Dept Environm Sci, Kuopio, Finland

[31] Kuopio Univ Hosp, Dept Pediat, Kuopio, Finland

[32] Swiss Trop & Publ Hlth Inst, Basel, Switzerland

[33] Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Davos, Switzerland

[34] Univ Besancon, Dept Pediat, Univ Hosp, Besancon, France

[35] Univ Utrecht, Div Environm Epidemiol, IRAS, Utrecht, Netherlands

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

DOI  :  10.1016/j.jaci.2016.08.046

来源: Elsevier

【 摘 要 】

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-gamma 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.

【 授权许可】

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