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Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3–like protein.

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Presentation on theme: "Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3–like protein."— Presentation transcript:

1 Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3–like protein 1  Timothy S.C. Hinks, MD, Tom Brown, MD, Laurie C.K. Lau, PhD, Hitasha Rupani, MD, Clair Barber, BSc, Scott Elliott, BSc, Jon A. Ward, BSc, Junya Ono, BSc, Shoichiro Ohta, MD, Kenji Izuhara, MD, Ratko Djukanović, MD, Ramesh J. Kurukulaaratchy, MD, Anoop Chauhan, MD, Peter H. Howarth, MD  Journal of Allergy and Clinical Immunology  Volume 138, Issue 1, Pages (July 2016) DOI: /j.jaci Copyright © 2015 The Authors Terms and Conditions

2 Fig 1 Protease/antiprotease balance in asthmatic patients. MMP/tissue inhibitor of metalloproteinases (TIMP-1) ratios in sputum in asthmatic patients compared with healthy subjects for MMP1 (A), MMP3 (B), MMP8 (C), and MMP12 (D) are shown. Horizontal lines show medians. Statistical comparisons were done with Student t tests on log-transformed data. Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

3 Fig 2 Multidimensional clinicopathological clusters in asthmatic patients in the derivation data set (Southampton cohort). A topological network generated by using 22 clinical and pathological features together identifies 1 healthy (in blue) and 8 distinct clinicopathobiologic asthma clusters (A-H). The network is colored according to ACQ7 scores, with the most symptomatic subjects in red. The TDA used 145 subjects with the most complete data: metric, variance-normalized Euclidean; lenses, principal and secondary singular value decomposition (resolution, 30; gain, 3.0/3.0×, equalized) and presence/absence of asthma; node size, proportional to the number of subjects in the node. Color bars: red, highest ACQ7 score; blue, healthy participants. Features in boldface were replicated in the validation data set. GINA, Global Initiative for Asthma. Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

4 Fig 3 Bayesian belief network showing the strongest interactions between pathobiologic parameters across a range of clinical severities of asthma or health. Nodes without strong interactions are excluded. Line thickness represents the strength of the interaction (Euclidean distance). Line colors: green, positive associations; red, negative associations; black, nonlinear associations. AQLQ, Juniper Asthma Quality of Life Questionnaire; BD, bronchodilator; FGF, fibroblast growth factor; GCSF, Granulocyte-colony stimulating factor; GINA, Global Initiative for Asthma; MPO, myeloperoxidase; SPT, skin prick test; VEGF, vascular endothelial growth factor. Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

5 Fig 4 Inflammatory mediators associated with sputum YKL-40 levels. Spearman correlations between levels of sputum YKL-40 and sputum myeloperoxidase (MPO; A), IL-8 (B), vascular endothelial growth factor (VEGF; C), elastase (D), IL-6 soluble receptor (IL-6SR; E), IL-6 (F), neutrophils (G), and serum YKL-40 (H) are shown. Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

6 Fig E1 Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

7 Fig E2 Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

8 Fig E3 Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

9 Fig E4 Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

10 Fig E5 Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

11 Fig E6 Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

12 Fig E7 Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

13 Fig E8 Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

14 Fig E9 Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

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17 Fig E12 Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

18 Fig E13 Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

19 Fig E14 Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

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21 Fig E16 Journal of Allergy and Clinical Immunology  , 61-75DOI: ( /j.jaci ) Copyright © 2015 The Authors Terms and Conditions

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