Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts Alexander J. Hose, MA, MPH, Martin Depner, PhD, Sabina Illi, PhD,

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Presentation transcript:

Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts Alexander J. Hose, MA, MPH, Martin Depner, PhD, Sabina Illi, PhD, Susanne Lau, MD, PhD, Thomas Keil, MD, MScPH, Ulrich Wahn, MD, Oliver Fuchs, MD, PhD, Petra Ina Pfefferle, PhD, DrPH, Elisabeth Schmaußer-Hechfellner, BSc, Jon Genuneit, MD, Roger Lauener, MD, Anne M. Karvonen, PhD, Caroline Roduit, MD, Jean-Charles Dalphin, MD, PhD, Josef Riedler, MD, Juha Pekkanen, MD, PhD, Erika von Mutius, MD, Markus J. Ege, MD 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 Alexander J. Hose, MA, MPH, Martin Depner, PhD, Sabina Illi, PhD, Susanne Lau, MD, PhD, Thomas Keil, MD, MScPH, Ulrich Wahn, MD, Oliver Fuchs, MD, PhD, Petra Ina Pfefferle, PhD, DrPH, Elisabeth Schmaußer- Hechfellner, BSc, Jon Genuneit, MD, Roger Lauener, MD, Anne M. Karvonen, PhD, Caroline Roduit, MD, Jean-Charles Dalphin, MD, PhD, Josef Riedler, MD, Juha Pekkanen, MD, PhD, Erika von Mutius, MD, Markus J. Ege, MD 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 Alexander J. Hose, MA, MPH, Martin Depner, PhD, Sabina Illi, PhD, Susanne Lau, MD, PhD, Thomas Keil, MD, MScPH, Ulrich Wahn, MD, Oliver Fuchs, MD, PhD, Petra Ina Pfefferle, PhD, DrPH, Elisabeth Schmaußer-Hechfellner, BSc, Jon Genuneit, MD, Roger Lauener, MD, Anne M. Karvonen, PhD, Caroline Roduit, MD, Jean-Charles Dalphin, MD, PhD, Josef Riedler, MD, Juha Pekkanen, MD, PhD, Erika von Mutius, MD, Markus J. Ege, MD 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 Journal of Allergy and Clinical Immunology Volume 139, Issue 6, Pages 1935-1945.e12 (June 2017) DOI: 10.1016/j.jaci.2016.08.046 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Journal of Allergy and Clinical Immunology 2017 139, 1935-1945 Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 A and B, Selection of study populations. Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 LCs of atopy as characterized by allergen specificity, time course, and sIgE levels. Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Associations of asthma-related conditions with LCs and classical definitions of atopic sensitization at age 6 years. *Because there was no case of lifetime asthma in this LC, we calculated a conservative estimation of the odds ratio (OR) based on one case of asthma in this LC, which was simulated at random. Black point estimates with error bars mark the LCs as reference, red marks the classical definitions as a comparison. Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Atopy phenotypes in relation to the distribution of LCs in both populations. Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Absolute sIgE levels (A) and ratio of IL-5 to IFN-γ expression (B) at age 6 years. Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Path diagram comparing severe atopy with the other atopy phenotypes, including its features, lung function, and asthma in both populations. Excessive sIgE production is defined as incremental increase of seasonal sIgE production during the first 6 years. High sIgE levels are determined at age 6 years. Significant associations are shown by solid arrows. Absent associations are represented by interrupted dotted arrows. Values represent association estimates from the final model, including significant paths only. Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 7 Proportion of nonasthmatic children with reduced lung function by LCs. Reduced lung function was defined as values in the lowest decile of the FEV1 distribution. Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Distribution of LCs across study centers. Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Prediction of LCs by classical definitions of sensitization at age 6 years. Dots mark the sensitization status (from right to left: unsensitized and CAP classes 1-3). Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Associations of health conditions with LCs and classical definitions of atopic sensitization at age 6 years. *Because there was no case of late-onset wheeze in this LC, we calculated a conservative estimation of the OR based on 1 case of late-onset wheeze in this LC, which was simulated at random. Black point estimates with error bars mark the LCs as reference, and red marks the classical definitions as comparison. Late-onset wheeze was defined as described by Depner et al.3 Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Associations of LCs with parental atopy. Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 Sensitivity analyses omitting single dimensions of LCA. Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E6 Comparing disease associations across all sensitivity analyses. *Because there was no case of lifetime asthma in this LC, we calculated a conservative estimation of the odds ratio (OR) based on 1 case of asthma in this LC, which was simulated at random. Black point estimates with error bars mark the LCs as reference, and red marks the classical definitions as a comparison. Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E7 Number of sensitizations to different allergen specificities across LCs (CAP classes 1-3). Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E8 Absolute sIgE levels at age 6 years. Journal of Allergy and Clinical Immunology 2017 139, 1935-1945.e12DOI: (10.1016/j.jaci.2016.08.046) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions